2nd european conference on brain stimulation in psychiatry...

2nd European Conference on BrainStimulation in Psychiatry (ECBSP):Individualizing Neuromodulation

12–14 October 2017, Munich, Germany

Hosted by the

Deutsche Gesellschaft fur Hirnstimulation in der

Psychiatrie (DGHP) e.V.

SUPPLEMENT 1 TO VOLUME 267 � 2017

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In collaboration with

Stimulation Transcranienne en Psy-

chiatrie STEP, and the German Center for Brain

Stimulation (GCBS) funded by the Federal Ministry

of Education and Research (BMBF)

Scientific committee:

Berthold Langguth

Chris Baeken

Emmanuel Poulet

Jerome Brunelin

Djamila Bennabi

Martijn Arns

Local Organizing Committee:

Frank Padberg

Daniel Keeser

Anna-Katharine Brem

Ulrich Palm

Alkomiet Hasan

Oliver Pogarell

ORGANISATION/COMMITTEES

Eur Arch Psychiatry Clin Neurosci

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Symposia and keynote abstracts

KN-01 Individualizing brain stimulation—two perspectives from Boston: A

KN-02 Individualizing brain stimulation: two perspectives from Boston: B

KN-03 Translational research in brain stimulation

KN-04 European guidelines on the therapeutic use of rTMS and tDCS

S-1a Clinical applications 1: tDCS

S-1a-01 Transcranial direct current stimulation for depression: recent findings and perspectives

S-1a-02 tDCS in schizophrenia

S-1a-03 Combining transcranial alternating current stimulation with attention bias modification in tobacco-use

disorder

S-1a-04 Non invasive cortical stimulation in multiple sclerosis: current challenges and future perspectives

S-1b Neuroimaging and closed loop approaches

S-1b-01 State-informed NTBS: perspectives and challenges

S-1b-02 Brain-state dependent brain-stimulation with EEG triggered TMS: demonstration of a new real-time

closed-loop method for individualized therapy

S-1b-03 Brain oscillation synchronized stimulation of the frontal cortex (BOSSFRONT): validation results from a

personalised TMS pilot study with 17 patients with depression

S-1b-04 Using EEG to identify individuals who are likely to benefit from electrical stimulation

S-2a Clinical applications 2: TMS

S-2a-01 rTMS in elderly patients

S-2a-02 rTMS for the treatment of negative symptoms in residual schizophrenia

S-2a-03 Can meta-regression identify the optimal protocols for deep transcranial magnetic stimulation (DTMS)

in studies with neuropsychiatric disorders?

S-2a-04 Effect of repetitive transcranial magnetic stimulation over the left DLPFC on subjective craving,

physiological cue reactivity, and cognitive control in gambling disorder

S-2a-05 Modified deep TMS coils for the treatment of OCD and ADHD: electrophysiological correlates and

prognostic biomarkers

S-2b Brain stimulation with the double cone coil

S-2b-01 Beyond DLPFC-rTMS: more targets, more indications, more remissions

S-2b-02 A literature review on ACDC stimulation targeting the anterior cingulate by double cone coil rTMS

S-2b-03 Comparison of figure-8 and DC coil: physiological and physical data

CONTENTS


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S-3a Clinical applications 3: convulsive therapy and deep brain stimulation

S-3a-01 Stimulation strategies in electroconvulsive therapy

S-3a-02 Resting state networks, brain oscillatory activity and functional connectivity in patients with depression

under electroconvulsive therapy

S-3a-03 Magnetic seizure therapy in psychiatric disorders

S-3a-04 DBS

S-3a-05 Progress and drawbacks in deep brain stimulation for obsessive–compulsive disorder and Tourette

syndrome

S-3b Safety and NIBS across lifespan

S-3b-01 Safety of tES

S-3b-02 Transcranial electrical stimulation in pediatric brain: age or individual differences?

S-3b-03 NIBS in neurodevelopmental disorders

S-3b-04 Transcranial stimulation targeting memory-relevant sleep oscillations as therapeutic approach in aging

and mild cognitive impairment

S-4a Multimodal imaging

S-4a-01 Accounting for interindividual variation in NIBS using computational models

S-4a-02 How to reach deep brain structures: modulation of salience coding of food by rTMS

S-4a-03 Imaging transcranial direct current stimulation: contributions and challenges

S-4a-04 Towards causality: combining non-invasive brain stimulation and neuroimaging to understand

neuroplasticity

SOP-01 Effects of non-invasive neurostimulation on brain activity

SOP-01-01 Modulation of spontaneous and task-related alpha-band oscillations using transcranial alternating

current stimulation (tACS)

SOP-01-02 The effects of frontal tACS on reversal learning

SOP-01-03 The effects of rTMS treatment for auditory verbal hallucinations on inner speech related brain networks

SOP-01-04 Antidepressant effects and change in brain activation of transcranial pulsed electromagnetic fields

for treatment resistant depression

SOP-01-05 Quadri-pulse theta burst stimulation using ultra-high frequency bursts at I-wave periodicity induces

direction dependent bi-directional plasticity in human motor cortex

SOP-02 Clinical applications

SOP-02-01 The Bipolar Depression Electrical Treatment Trial (BETTER): results from a randomized clinical trial

SOP-02-02 Attitudes and educational work regarding rTMS

SOP-02-03 Creating an interventional psychiatry service

S-5a Individualizing treatment

S-5a-01 Understanding and predicting rTMS effect for the treatment of negative symptoms in schizophrenia

S-5a-02 Stimulation genetics: new perspectives for an individualized brain stimulation


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S-5a-03 Individualized treatment of positive symptoms in schizophrenia: potentials and pitfalls

S-5a-04 Computational modelling studies for non-invasive brain stimulation

S-5b Cognition and psychotherapy, state dependency

S-5b-01 Trait rumination moderates the effects of anodal tDCS over the right dorsolateral prefrontal cortex on

cognitive processing of emotional information

S-5b-02 The psychomotor retardation may be a marker of response to rTMS treatment in patients with major

depressive disorder

S-5b-03 Challenging control over emotions in borderline personality disorder with tDCS

S-5b-04 Cognitive and electrophysiological mechanisms of enhancing fluid intelligence

S-5b-05 Towards neurocognitive stimulation to treat affective disorders

S-6a Clinical applications: other

S-6a-01 A multimodal investigation on the biological markers associated with the antidepressant effects of

transcranial direct current stimulation

S-6a-02 The impact of accelerated HF-rTMS on neurochemicals in major depression: insights from 1H MR

spectroscopy

S-6a-03 Transcranial direct current stimulation (tDCS) for obsessive–compulsive disorder

S-6a-04 Cognitive brain stimulation

S-6b NIBS in cells and animals

S-6b-01 Testing neuromodulation avenues in model rats

S-6b-02 Cellular effects of low-dose tDCS: implications for neuroplasticity

S-6b-03 rTMS restores alterations in synaptic excitation/inhibition-balance

S-7a Optimizing NIBS treatment: biomarkers and RDoC approaches

S-7a-01 Matching patient subtypes to neural circuits for novel brain stimulation treatments in affective disorders

S-7a-02 Optimizing TMS treatment for depression using neuro-cardiac guided TMS (NCG TMS)

S-7a-03 Central and plasmatic plasticity markers and response to NIBS

S-7a-04 Personalizing and enhancing rTMS treatment response: EEG predictors, biomarkers and role of

combining interventions

GCBS-1

GCBS-1-01 Neuromodulation in model rats

GCBS-1-02 rTMS animals (WP1B)

GCBS-1-03 Optimizing physiological tDCS effects

GCBS-1-04 Lasting amelioration of deficient cognitive control in depression by transcranial direct current

stimulation (tDCS)-enhanced training


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S-8a Reproducibility of NIBS

S-8a-01 Effects of prefrontal tDCS on resting-state functional connectivity: variability, non-linearity and state-

dependency

S-8a-02 Efficacy and interindividual variability following LTP-like plasticity inducing PAS and anodal tDCS

S-8a-03 What does it tell you when your transcranial electric stimulation experiment failed?

S-8a-04 Reproducibility of tDCS

GCBS-2

GCBS-2-01 Disorder-tailored transcranial direct current stimulation (tDCS) of the prefrontal cortex: goals and

achievements

GCBS-2-02 PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal

transcranial direct current stimulation (tDCS) in major depressive disorder: study design and

methodology of a multicenter double-blind randomized placebo controlled trial

GCBS-2-03 Design and methods of an ongoing randomized controlled study of tDCS in major depression: the

DepressionDC Trial

Poster abstracts

P-01 Exploring the parameter space of physiological effects of cathodal transcranial direct current stimulation

over the primary motor cortex

P-02 Electrode montage dependent effects of transcranial direct current stimulation on working memory

P-03 Exploring the effects of transcranial direct current stimulation on cognitive control training

P-04 The effect of transcranial direct current stimulation on cognitive control and emotion regulation in

depressed patients

P-05 General effects of cathodal tDCS on implicit associations

P-06 Brain stimulation over frontopolar cortex enhances motivation to exert effort for reward

P-07 The influence of tDCS on prosocial behaviour when being socially excluded: experimental design

P-08 Prefrontal MRI-compatible tDCS reduces ventromedial cortical perfusion after being criticized

P-09 Does electrode localization in tDCS research matter? A comparison between 10–20 EEG system and

MRI-guided neuronavigation

P-10 Effects of different prefrontal-tDCS electrode-montages on resting-state connectivity and cognitive control

P-11 Neurophysiological impact of a fronto-temporal transcranial direct current stimulation in healthy subjects:

a multimodal PET-MR imaging approach

P-12 Modulation of brain metabolites and resting state functional MRI connectivity by transcranial direct current

stimulation (tDCS) over the left dorsolateral prefrontal cortex in healthy subjects

P-13 Effects of transcranial direct current stimulation (tDCS) on working memory performance in patients with

schizophrenia

P-14 Transcranial direct current stimulation in three patients with Gilles de la Tourette syndrome

P-15 tDCS-enhanced working memory training in subjective cognitive decline

P-16 Transcranial direct current stimulation (tDCS) as treatment for major depression: a prospective

multicenter double blind randomized placebo controlled trial (DepressionDC)—early quality control of

technical data from a blind selection of active tDCS sessions

P-17 Targeting fatigue, mood and cognition in multiple sclerosis using tDCS

P-18 Frontal EEG coherence after beta-tACS during reversal learning

P-19 Online effects of transcranial alternating current stimulation on event-related alpha power modulations: a

concurrent tACS-MEG study

P-20 Long-term effect of 3 daily sessions of transcranial random noise stimulation (tRNS) on inhibitory control


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P-21 Effects of transcranial direct current stimulation applied to the prefrontal cortex on TMS evoked potentials

P-22 Changes in firing properties and synaptic plasticity in different brain regions of schizophrenia model and

control rats after transcranial magnetic stimulation

P-23 Advances in TMS technology: from flexible pulse shape design to high speed individualized biphasic

quadri-pulse stimulation

P-24 The role of the parietal cortex in memory confidence

P-25 Time lapse of individualized rTMS effects on resting state functional connectivity of healthy brains

P-26 The effect of seed determination on functional connectivity analyses to study the effect of transcranial

magnetic stimulation

P-27 The relation between brain morphological factors and efficacy of rTMS treatment in patients with

schizophrenia and auditory verbal hallucinations

P-28 Abnormal brain asymmetry and behavior in ADHD: a TMS-EEG study

P-29 Anxiety symptoms correlates with transcallosal inhibition in patients with multiple sclerosis

P-30 Impaired corticospinal excitability revealed by transcranial magnetic stimulation in patients with major

depressive disorder

P-31 Individualized connectivity between rTMS targets and the subgenual cingulate is unrelated to

antidepressant response

P-32 Imagery guided personalized robotic rTMS in depression: preliminary results of a feasibility study

P-33 A nationwide questionnaire survey on attitudes of Japanese psychiatric specialists toward repetitive

transcranial magnetic stimulation therapy for depression

P-34 Clinical application of deep transcranial magnetic stimulation (DTMS) in neuropsychiatric disorders: a

systematic literature review and meta-analysis

P-35 Acute efficacy of deep transcranial magnetic stimulation (DTMS) in unipolar vs. bipolar major depressive

disorder (MDD): a systematic literature review and meta-analysis

P-36 Predicting deep transcranial magnetic stimulation (dTMS) efficiency in depressed using brain network

activation (BNA) analysis

P-37 Cognitive effects of high-frequency-rTMS in chronic schizophrenic patients

P-38 Transcranial magnetic stimulation has different short-term efficacy on different major depressive disorder

symptoms: a nested prospective cohort study in Croatia

P-39 Efficacy and tolerability of repetitive transcranial magnetic stimulation with and without the Brainsway H1-

coil in treatment of major depressive disorder: presentation of the protocol and interim analysis

P-40 Interaction of serotonin and age is significant predictor of transcranial magnetic stimulation effect on major

depressive disorder: a prospective cohort study in Croatia

P-41 Treatment of pediatric catatonia with ECT: a case series and review

P-42 Adjustment of pulse wave parameters to optimize effective ECT treatment

P-43 Transcranial direct current stimulation (tDCS) replaces electroconvulsive therapy (ECT) in a patient with

corpus callosum agenesis and catatonic schizophrenia: a longitudinal network-metric approach

P-44 Individualized thresholds: calibrating brain stimulation through concurrent TMS/fMRI

P-45 Is hippocampal neurogenesis mediating clinical efficacy and memory outcome after electroconvulsive

therapy in depression?

P-46 Real-time fMRI neurofeedback in patients with alcohol use disorder: craving-related modulations

P-47 LMU scripts • ready-made HPC-applicable pipeline for structural and functional data analyses


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2nd European Conference on Brain Stimulation in Psychiatry(ECBSP): Individualizing Neuromodulation

Symposia and keynote abstracts

KN-01Individualizing brain stimulation—two perspectivesfrom Boston: A

M. D. Fox1,2,3

1Berenson-Allen Center for Noninvasive Brain Stimulation,

Department of Neurology, Harvard Medical School and Beth Israel

Deaconess Medical Center, Boston, USA; 2Department of Neurology,

Massachusetts General Hospital, Harvard Medical School, Boston,

USA; 3Athinoula A. Martinos Center for Biomedical Imaging,

Massachusetts General Hospital, Charlestown, USA

It has become increasingly clear that the therapeutic targets for brain

stimulation are connected brain networks, not isolated brain regions.

Lesions causing the same symptom, but occurring in different loca-

tions, are part of the same connected brain network. Similarly, brain

stimulation sites treating the same symptom, but administered to

different brain locations, are part of the same connected brain net-

work. Brain connectivity with patient-specific stimulation sites can be

used to predict the response of individual patients with depression to

transcranial magnetic stimulation or the response of individual

patients with Parkinson’s disease to deep brain stimulation. As such,

brain connectivity can be used to identify and optimize therapeutic

targets. Because not all patients have the same symptoms or the same

brain connectivity, these principles can be applied towards identifying

individualized patient-specific stimulation sites to optimize thera-

peutic response.

Policy of full disclosure: This work was supported by the NIH

(R21MH099196, K23NS083741 and R21MH098174), by Harvard

Clinical and Translational Science Center/Harvard Catalyst (National

Center for Advancing Translational Sciences, NIH Award

UL1RR025758); Additional assistance came from the Sidney R. Baer

Jr. Foundation, the Dystonia Medical Research Foundation, and the

Nancy Lurie Marks Foundation. MDF is listed as an inventor on

submitted or pending patents using brain imaging to guide brain

stimulation.

KN-02Individualizing brain stimulation: two perspectivesfrom Boston: B

H. Liu1,2

1Harvard Medical School, Boston, USA; 2Laboratory For the Study of

the Brain Basis of Individual Differences, Massachusetts General

Hospital, Boston, USA

A major obstacle for exploring subtle aspects of network organization

and translating insights into clinical applications is the lack of tools

for mapping networks in individual subjects. Until recently, most

studies of human brain organization have focused on averaging data

over many individuals to estimate network properties. However,

marked inter-individual variability has been demonstrated in the

organization of functional systems of the brain, particularly in higher

order association areas. A functional mapping technique with high

sensitivity to the individual’s unique functional organization will

facilitate the discovery of meaningful biomarkers for disease states

and provide personalized therapeutic targets for various neurological

and psychiatric disorders.

We developed a novel brain parcellation approach to accurately

map functional organization at the individual level using resting-state

fMRI. Functional networks mapped by this approach were highly

reproducible within subjects and effectively captured the variability

across subjects. Using the functional regions localized in each indi-

vidual subject, we were able to identify connectivity markers that are

highly predictive of global and dimension-specific symptom severity

in various psychiatric disorders, including psychosis and obsessive–

compulsive disorder (OCD). These individually-identified functional

circuits may lead to novel, personalized targets for neuromodulation

treatments. Finally, I will discuss our data on evaluating the effect of

deep brain stimulation (DBS) on individual patients’ functional

networks.

Policy of full disclosure: The authors do not have disclosures to

report.

KN-03Translational research in brain stimulation

S. H. Lisanby1

1National Institute of Mental Health, Bethesda, USA

No abstract for publication.

KN-04European guidelines on the therapeutic use of rTMS and tDCS

J.-P. Lefaucheur1

1Clinical Neurophysiology, Henri Mondor Hospital, Creteil, France

Since the first therapeutic application of repetitive transcranial mag-

netic stimulation (rTMS) in the mid-1990s and transcranial direct

current stimulation (tDCS) a decade later, many studies showed the

efficacy of these techniques to treat a variety of clinical conditions. A

group of European experts was commissioned to grade the level of

evidence of this therapeutic potential in neurological and psychiatric

diseases1,2. Despite unavoidable methodological heterogeneities, a

level A of evidence (definite efficacy) was found for: (1) the analgesic

effect of high-frequency (HF) rTMS of the primary motor cortex (M1)

contralateral to the pain side and (2) the antidepressant effect of HF-

rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B

recommendation (probable efficacy) was found for: (1) the antide-

pressant effect of low-frequency (LF) rTMS of the right DLPFC, (2)

HF-rTMS of the left DLPFC for negative symptoms of schizophrenia,

(3) LF-rTMS of contralesional M1 in chronic motor stroke, (4) anodal

ABSTRACTS


https://doi.org/10.1007/s00406-017-0856-0

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https://doi.org/10.1007/s00406-017-0856-0

tDCS of the left M1 (with right orbitofrontal cathode) in fibromyalgia,

(5) anodal tDCS of the left DLPFC (with right orbitofrontal cathode)

in major depressive episodes without drug resistance, (6) anodal tDCS

of the right DLPFC (with left DLPFC cathode) in addiction/craving.

In a number of indications, the effects of rTMS (e.g., LF-rTMS of the

left temporoparietal cortex in tinnitus and auditory hallucinations) or

tDCS (e.g., anodal tDCS of the left M1 in chronic neuropathic pain)

reach level C of evidence (possible efficacy). It remains to determine

how to optimize rTMS and tDCS protocols to give them relevance in

routine clinical practice. Inappropriate applications of these tech-

niques should be avoided by ensuring rigorous training of the

professionals.

References:

1. Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C,

Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder

D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelai-

nen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A,

Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-

Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Zie-

mann U, Paulus W, Garcia-Larrea L (2014) Evidence-based

guidelines on the therapeutic use of repetitive transcranial magnetic

stimulation (rTMS). Clin Neurophysiol 125:2150–2206

2. Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J,

Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B,

Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E,

Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-

Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use

of transcranial direct current stimulation (tDCS). Clin Neurophysiol

Policy of full disclosure: The author does not have disclosures to

report.

S-1a Clinical applications 1: tDCS

Chairs: Palm and Brunelin

S-1a-01Transcranial direct current stimulation for depression: recentfindings and perspectives

A. Brunoni1,2

1Service of Interdisciplinary Neuromodulation, Department and

Institute of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil;2Department of Psychiatry and Psychotherapy, LMU Munich,

Munich, Germany

Major depressive disorder is a highly prevalent, disabling condition.

Pharmacological treatments are only moderately effective and asso-

ciated with important adverse effects. These issues reinforce the need

of developing novel treatment alternatives. One of them is transcra-

nial direct current stimulation (tDCS), a non-pharmacological

technique that might be clinically useful as it is easy to use, affordable

and tolerable. TDCS as a treatment for depression has been inten-

sively investigated during the past decade. In this talk, Dr. Brunoni

will discuss the most recent findings, based on the results of ran-

domized clinical trials and meta-analyses. The evidence suggests that

tDCS might be effective in specific groups of depressed patients;

although it is still inferior to pharmacotherapy. Future perspectives on

how to improve tDCS efficacy will be discussed.

Policy of full disclosure: ARB receives a CAPES-Humboldt fellow-

ship for experienced researchers and is a consultant of the Neurocare

(Munich, Germany) group.

S-1a-02tDCS in schizophrenia

U. Palm1

1LMU Munich, Munich, Germany

Transcranial direct current stimulation (tDCS) is an emerging tool in

neuromodulation and has been investigated to treat various

schizophrenia symptoms, e.g. catatonia, auditory verbal hallucina-

tions (AVH), negative symptoms (NS). To date, most evidence is

available for the treatment of AVH with the anode placed over the left

dorsolateral prefrontal cortex (DLPFC) and the cathode placed over

the left temporo-parietal junction (TPJ). Several randomized con-

trolled trials suggest a reduction of AVH and improvement of NS

after a tDCS series. However, overall sample sizes are too small to

draw a final conclusion and at least two failed studies do not show

superiority of active compared to sham stimulation. For the treatment

of NS, two randomized controlled trials and one open label study

showed a decrease of negative symptoms by more than 30% after a

tDCS series of the left DLPFC. Although these results are consistent,

samples sizes are far too small to draw any conclusion. There are

several studies showing an improvement of cognitive performance

after anodal stimulation of the left DLPFC in schizophrenia. There is

no clinical data available for the treatment of schizophrenia in chil-

dren and adolescents. Overall, samples sizes are small, study designs

and samples are heterogeneous and results do not allow a suggestion

of tDCS for regular treatment of schizophrenia symptoms until

stronger evidence from randomized controlled trials becomes

available.


report.

S-1a-03Combining transcranial alternating current stimulationwith attention bias modification in tobacco-use disorder

M. Mondino1, S. Fecteau1

1Faculte de medecine, Universite Laval, Centre Interdisciplinaire de

Recherche en Readaptation et Integration, Centre CERVO de

l’Institut Universitaire en Sante Mentale de Quebec, Quebec, Canada

Craving is a central feature in tobacco use disorder (TUD). Previous

studies have successfully reduced craving in adults with TUD either

by using an attention bias modification paradigm (ABM)1 or by

applying noninvasive brain stimulation (NIBS) over the dorsolateral

prefrontal cortex (DLPFC)2. Recent work showed that combining

NIBS with ABM lead to greater effects than NIBS alone3. Our

objective was to test whether NIBS applied over the DLPFC com-

bined with ABM might reduce craving intensity in adults with TUD.

We chose to use transcranial alternating current stimulation (tACS), a

NIBS technique that offers the opportunity to modulate brain oscil-

lations in humans.

In a crossover study, 19 subjects with TUD were allocated to

receive one session combining active tACS with ABM and one

combining sham tACS with ABM in a randomized order and sepa-

rated with 1 week. tACS (10 Hz, 2 mA, electrodes applied on F3 and

F4) and ABM (modified dot-probe task) were administered simulta-

neously during 30 min. Craving intensity was assessed after and

before the intervention using the Questionnaire of Smoking Urges.

We also assessed the attentional bias towards smoking cues using an

eye-tracking device during visual scanning of neutral and smoking

cues and decision-making processes using the Delay-Discounting

task.


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Active tACS combined with ABM significantly reduced desire to

smoke, as compared to sham tACS combined with ABM. No sig-

nificant effects were reported on other dimensions of craving. Both

active tACS combined with ABM and sham tACS combined with

ABM reduced the attentional bias for smoking cues. A significant

decrease of impulsive choices at the Delay-Discounting task was

reported after active tACS combined with ABM as compared to sham

tACS combined with ABM.

The combination of active tACS and ABM might reduce desire to

smoke and impulsivity in adults with TUD.

References:

1. Attwood AS, O’Sullivan H, Leonards U, Mackintosh B, Munafo

MR (2008) Attentional bias training and cue reactivity in cigarette

smokers. Addiction 103(11):1875–1882

2. Hone-Blanchet A, Ciraulo DA, Pascual-Leone A, Fecteau S (2015)

Noninvasive brain stimulation to suppress craving in substance use

disorders: review of human evidence and methodological considera-

tions for future work. Neurosci Biobehav Rev 59:184–200

3. Heeren A, Baeken C, Vanderhasselt M-A, Philippot P, de Raedt R

(2015) Impact of anodal and cathodal transcranial direct current

stimulation over the left dorsolateral prefrontal cortex during attention

bias modification: an eye-tracking study. PLoS One 10(4):e0124182


report.

S-1a-04Non invasive cortical stimulation in multiple sclerosis: currentchallenges and future perspectives

S. S. Ayache1,2,3, J.-P. Lefaucheur1,2, M. A. Chalah1,2

1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-

Est-Creteil, Creteil, France; 2Service de Physiologie-Explorations

Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux

de Paris, Creteil, France; 3Neurology Division, Lebanese American

University Medical Center-Rizk Hospital (LAUMC-RH), Beirut,

Lebanon

Multiple sclerosis (MS) is a chronic inflammatory disease of the

central nervous system. During its course, several invalidating

symptoms take place and might seriously impact the patients’ quality

of life. Among these symptoms, neuropathic pain, spasticity,

sphincter dysfunction, depression, fatigue and cognitive disorders are

difficult to deal with and represent a real challenge for the persons in

charge of this population.

Therefore, noninvasive brain stimulation (NIBS) techniques have

been proposed in this context, with the aim to improve the therapeutic

strategies, limit drug interactions and prevent the accumulation of

side effects1. While repetitive transcranial magnetic stimulation

(rTMS) has been mostly tried to ameliorate spasticity, dexterity and

motor performance; transcranial direct current stimulation (tDCS)

studies have primarily focused on the improvement of fatigue, pain

and cognitive functions. rTMS was applied at high frequency over the

primary motor cortex and led to encouraging results, with a significant

decrease of the Ashworth spasticity scores, and better performance on

the nine hole pegboard task1. Concerning tDCS, this technique was

found to have an interesting impact on chronic neuropathic pain,

fatigue and to a lesser extent on cognitive performance. In fact, anodal

stimulation of the motor or the left prefrontal cortex was able to

reduce pain intensity2. As for fatigue, anodal stimulation of the motor

or sensori-motor cortex was found to be efficacious3. However, some

controversies exist concerning the efficacy of anodal left prefrontal

tDCS on MS fatigue3. Regarding cognition, coupling cognitive tasks

with left prefrontal anodal tDCS could be of particular help. In

addition, vigilance could be ameliorated by the anodal stimulation of

the right parietal cortex.

In conclusion, some promising outcomes have been reported fol-

lowing the application of various NIBS paradigms over different brain

areas. However, the scarcity of the available literature prompts further

investigations of the place of these techniques in the management of

MS symptoms.

References:

1. Palm U, Ayache SS, Padberg F, Lefaucheur JP (2014) Non-inva-

sive brain stimulation therapy in multiple sclerosis: a review of tDCS,

rTMS and ECT results. Brain Stimul 7:849–854

2. Ayache SS, Palm U, Chalah MA, Al-Ani T, Brignol A, Abdellaoui

M, Dimitri D, Sorel M, Creange A, Lefaucheur JP (2016) Prefrontal

tDCS decreases pain in patients with multiple sclerosis. Front Neu-

rosci 10:147

3. Ayache SS, Chalah MA (2017) Fatigue in multiple sclerosis—

insights into evaluation and management. Neurophysiol Clin

47:139–171

Policy of full disclosure: Samar S. Ayache declares having received

grants or compensation from Genzyme, Biogen, Novartis and Roche.

The remaining authors have nothing to disclose.

S-1b Neuroimaging and closed loop approaches

Chairs: Siebner and Zrenner

S-1b-01State-informed NTBS: perspectives and challenges

H.R. Siebner1,2

1Danish Research Centre for Magnetic Resonance, Centre for

Functional and Diagnostic Imaging and Research, Copenhagen

University Hospital Hvidovre, Hvidovre, Denmark; 2Department of

Neurology, Copenhagen University Hospital Bispebjerg,

Copenhagen, Denmark

A wide range of non-invasive transcranial brain stimulation (NTBS)

methods is used as interventional tools to modify human brain

function. While NTBS has shown potential in the treatment of brain

diseases such as depression or stroke, substantial inter-individual

variation in the therapeutic response to NTBS is currently the greatest

obstacle for a more wide-spread therapeutic use of NTBS. This calls

for innovative approaches which fully exploit the potential of NTBS

to shape the architecture of human brain networks. (1) Biophysically

adjusted NTBS: Advanced modelling of the electrical fields that are

induced by NTBS in individual brains can be used to optimally target

the cortical network of interest. (2) State-informed NTBS: Using

electroencephalography (EEG) and functional magnetic resonance

imaging (fMRI) can be used to identify the spatiotemporal signatures

of functional and dysfunctional brain states at an individual level and

to trace the dynamic expression of these ‘‘state signatures’’ during

NTBS. This information will allow for a dynamic adaptation of the

spatiotemporal properties of NTBS to the intrinsically expressed brain

states. Biophysically adjusted State-informed Cortex stimulation

(BaSiCs) has the potential to reinforce the expression of beneficial

brain states and to attenuate the expression of dysfunctional brain

states. This will yield important discoveries regarding the neural

underpinnings of brain (dys)function and push the frontiers of NTBS

as interventional tool to optimize the function of human brain

networks.

Policy of full disclosure: HRS has received honoraria as editor from

Elsevier Publishers, Amsterdam, The Netherlands and Springer


123

Publishing, Stuttgart, Germany, and has received a research fund from

Biogen-idec.

S-1b-02Brain-state dependent brain-stimulation with EEG triggeredTMS: demonstration of a new real-time closed-loop methodfor individualized therapy

C. Zrenner1, D. Desideri1, P. Belardinelli1, P. Caldana Gordon1,

U. Ziemann1

1Department of Neurology and Stroke, and Hertie Institute for

Clinical Brain Research, University of Tubingen, Tubingen, Germany

TMS has been shown in numerous studies to be an effective treatment

for a range of neuropsychiatric conditions. However, even when a

clear clinical benefit can be demonstrated at group level, current

stimulation protocols suffer from a vexing inter- and intra-subject

outcome variability and it is difficult to predict whether or not a

particular individual patient will respond to a standardized treatment

protocol (pharmacotherapy, of course, faces the same issue).

Using a custom millisecond-resolution real-time EEG-TMS

closed-loop set-up, we present recent results demonstrating that the

effect of a TMS pulse is determined by the instantaneous brain-state

at the time of the stimulus: Corticospinal excitability fluctuates with

the phase of 10 Hz mu-rhythm oscillations over sensorimotor cortex

with the EEG surface negative peak corresponding to a high-ex-

citability state during which a TMS pulse over the primary motor

cortex evokes larger motor evoked potentials. More importantly,

repetitive stimulation with 200 EEG-triggered 100 Hz triple pulses at

an individually EEG-triggered rate of * 1 Hz, results in LTP-like

effects lasting more than 30 min after stimulation when the bursts are

triggered by the negative peak (high excitability state) vs. no effect

when they are triggered by the positive peak (low excitability state) or

at a random phase of ongoing 10 Hz oscillations.

This result has implications for the development of EEG-guided

individualized therapeutic stimulation protocols: if the goal is to

therapeutically modulate pathological brain network dynamics of a

patient, then this requires individual optimization of both the exact

MRI-guided anatomical locus of stimulation as well as of the precise

EEG-guided time (i.e. during which brain-network state?) when the

application of each pulse will best achieve the desired therapeutic

effect (see Fig. 1).


report.

S-1b-03Brain oscillation synchronized stimulation of the frontal cortex(BOSSFRONT): validation results from a personalised TMS pilotstudy with 17 patients with depression

B. Zrenner1, P. Gordon1, A. Kempf1, P. Belardinelli1, B. S. Chander2,

C. Plewnia2, S. R. Soekadar2, A. Fallgatter2, C. Zrenner1,

U. Ziemann1, F. Muller-Dahlhaus1,3


Clinical Brain Research, University of Tubingen, Tubingen,

Germany; 2Department of Psychiatry and Psychotherapy, University

Hospital of Tubingen, Tubingen, Germany; 3Department of

Psychiatry and Psychotherapy, Johannes Gutenberg University

Medical Center Mainz, Mainz, Germany

Major depressive disorder (MDD) is characterized by increased alpha

power and reduced cortical excitability in left frontal cortex1. High-

frequency repetitive transcranial magnetic stimulation (TMS) of left

dorsolateral prefrontal cortex (DLPFC) shows definite antidepressant

effects at the group level but its clinical efficacy is limited due to high

inter-individual variability and an average response rate of only 29%2.

Brain-state dependent EEG-triggered TMS, i.e. TMS triggered

dependent on the phase of instantaneous alpha oscillations as detected

by real-time EEG analysis, has been shown to consistently increase

motor cortical excitability3, and may thus be used to personalize TMS

therapy and potentially increase treatment effects in patients with

MDD.

Here, we present a proof-of-principle study of brain-state depen-

dent TMS of left DLPFC in 17 patients with unipolar treatment-

Fig. S-1b-02: A Combination of EEG und TMS using a real-time EEG signal analysis system; B closed-loop EEG-triggered stimulation;

C high-density EEG in combination with individual MRI-segmented anatomy; D real-time source reconstruction; E phase-triggered stimulation.


123

resistant MDD to test its feasibility, safety and immediate neuro-

physiological effects. Subjects underwent three separate single

sessions of either (1) brain-state dependent TMS triggered at the

trough of instantaneous alpha oscillations (alpha-trough TMS), (2)

intermittent theta-burst stimulation (iTBS), or (3) a control condition

(replay), in which TMS was applied with the same temporal stimulus

sequence as during alpha-trough TMS (i.e. not phase-locked to the

current oscillatory neural activity during replay). Triggering TMS by

real-time EEG analysis of instantaneous alpha oscillations at the F5

electrode was feasible in all subjects. Side effects reported were

limited to mild discomfort at the site of stimulation. Alpha-trough

TMS selectively reduced resting alpha power at the site of stimulation

as compared to iTBS and replay, which were not significantly dif-

ferent. These findings suggest that brain-state dependent alpha-trough

TMS of left DLPFC can be applied safely and reduces pathological

alpha activity in MDD. Future studies need to test clinical effects of

brain-state dependent TMS in alleviating symptoms of MDD.

References:

1. Jaworska N, Blier P, Fusee W, Knott V (2012) Alpha power, alpha

asymmetry and anterior cingulate cortex activity in depressed males

and females. J Psychiatr Res 46:1483–1491

2. Lefaucheur JP, Andre-Obadia N, Antal A, Ayache S et al (2014)

Evidence-based guidelines on the therapeutic use of repetitive tran-

scranial magnetic stimulation. Clin Neurophysiol 125:2150–2206

3. Zrenner C, Desideri D, Belardinelli P, Ziemann U (2017) Real-time

EEG-defined excitability states determine efficacy of TMS-induced

plasticity in human motor cortex. Under revision


report.

S-1b-04Using EEG to identify individuals who are likely to benefitfrom electrical stimulation

S. Harty1,2

1University of Oxford, Department of Experimental Psychology,

University of Oxford, Oxford, UK; 2Trinity College Institute of

Neuroscience and School of Psychology, Trinity College Dublin,

Dublin 2, Ireland

Inter-individual variability in responsiveness to interventions poses

great challenges for translational neuroscience, and health care in

general. Reliable and cost-effective screening procedures that can

identify individuals who are more likely to benefit from an inter-

vention could have substantial real-world benefits. In this talk I will

present data from a study wherein we sought to examine the potential

for high-frequency transcranial random noise stimulation (tRNS) to

modulate sustained attention in a manner that was informed by

individual differences in EEG signals. This approach may constitute a

feasible means of using individual differences in neurophysiology to

inform predictions about outcomes from electrical stimulation, and

other targeted cognitive interventions.


report.

S-2a Clinical applications 2: TMS

Chairs: Langguth and Cordes

S-2a-01rTMS in elderly patients

J. Hoppner1

1Department of Gerontopsychiatry and -psychotherapy, Helios Clinic

Schwerin, Schwerin, Germany

Because of the clinical specific characteristics in elderly depressive

patients, who have greater cognitive and physical impairments, and

who often show inadequate response to antidepressive medication and

more side effects, new innovative non-psychopharmacologic and non-

psychotherapeutic treatments are required. Therefore, especially non-

invasive brain stimulation techniques are required. However, the age

of the patients is one of the most intensive discussed negative pre-

dictor for response to rTMS treatment, the older the patients the

higher the level of non-response. Neurobiological reasons for age-

related non-response to rTMS are cortical atrophy and changes in

myelination, cerebrovascular dysfunctions, and reduction of cortical

excitability. Furthermore, human motor cortex shows age–dependent

reduction of cortical plasticity.

Therefore, only very few studies are available, which directly

compare the antidepressive rTMS effect in association with the age of

the patients. Nevertheless, recent data suggest no deficits in response

to rTMS in the elderly, and no greater risk for side effects.

Because of its shorter stimulation duration time and lower inten-

sity, and because of only very few side effects (low seizure and

adverse event risk) in comparison to rTMS, especially Theta Burst

Stimulation (TBS) could be both effective and well tolerated in older

depressive patients. Our own clinical experiences are in line with this

hypothesis. Clinical randomized and placebo controlled studies

should be of high interest for this subgroup of depressive patients.


report.

S-2a-02rTMS for the treatment of negative symptoms in residualschizophrenia

J. Cordes1

1Department of Psychiatry and Psychotherapy, Medical Faculty,

Heinrich-Heine-University, Dusseldorf, Germany

Negative symptoms can be divided into those, which derive from

schizophrenia itself (primary symptoms) and those, which are caused

by consequences of the disorder (secondary), such as side effects of

medication. We still have only limited understanding of the patho-

physiological mechanisms underlying negative symptoms and

therefore there is a lack of evidence-based treatments. The treatment

of negative symptoms with non-invasive brain stimulation techniques,

such as rTMS, is a promising new approach, especially because of the

positive side effect profile.

Although there are many encouraging findings, there are several

heterogeneous studies concerning the improvement of negative

symptoms. However, it is still unclear if results patterns are robust,

which stimulation parameters hold the highest efficacy and which

patients benefit most from rTMS. This presentation gives a detailed

overview over recent literature regarding rTMS for the treatment of


123

negative symptoms in schizophrenia patients and derives recom-

mendations for clinical practice.


report.

S-2a-03Can meta-regression identify the optimal protocols for deeptranscranial magnetic stimulation (DTMS) in studieswith neuropsychiatric disorders?

K. K. Kedzior1

1Institute of Psychology and Transfer, University of Bremen, Bremen,

Germany

Deep transcranial magnetic stimulation (DTMS) with the H-coil

system is an FDA-approved treatment for unipolar major depressive

disorder (MDD). DTMS efficacy in MDD is well-established possibly

due to a consistent protocol utilised in all studies so far, including 20

daily sessions of high-frequency (18–20 Hz) and high-intensity

(120% of the resting motor threshold) stimulation with H1-coil.

Recent studies show that DTMS may also have favourable clinical

outcomes in other neuropsychiatric disorders than MDD. However,

unlike MDD, these studies utilise highly variable stimulation

protocols.

The aim of this talk is to present the clinical outcomes of DTMS in

neuropsychiatric disorders focusing on the stimulation protocols in

studies published until mid 2017. The clinical outcome in each study

is expressed as an effect size (a standardised change in severity of

disorder from baseline to the last daily DTMS session).

According to a multivariate meta-regression analysis (random-

effects with inverse-variance weights) of data from k = 30 studies,

only 13% of variability in effect sizes is explained by the stimulation

protocols (frequency, intensity, and the number of sessions). When

controlling for other predictors in the model, effect sizes improve

with higher frequency of stimulation, with lower intensity, and do not

depend on the number of stimulation sessions. The remaining 87% of

variability in effect sizes could be due to the demographic and the

clinical characteristics of patients as well as other stimulation

parameters (location, number of stimuli).

The results of this meta-regression suggest that efficacy of DTMS

depends on stimulation frequency and that ‘more (intensity)’ may not

necessarily produce ‘better’ outcomes. Future primary and secondary

research should focus on identifying the optimal stimulation protocols

for acute and long-lasting efficacy of DTMS in neuropsychiatric

disorders.


report.

S-2a-04Effect of repetitive transcranial magnetic stimulation over the leftDLPFC on subjective craving, physiological cue reactivity,and cognitive control in gambling disorder

A. Gay1,2, A. Barcet1, C. Boutet3,4,5, J. Brunelin6,7,8,9,

C. Massoubre1,2

1University Hospital Center of Saint-Etienne, University Department

of Psychiatry and Addiction, Saint-Etienne, France; 2TAPE

Laboratory, EA7423, Jean Monnet University, Saint-Etienne, France;3INSERM, U1059, Saint-Etienne, France; 4University of Lyon, Saint-

Etienne, France; 5Radiology Department, University Hospital, Center

of Saint-Etienne, Saint-Etienne, France; 6INSERM, U1028, CNRS,

UMR5292, Lyon Neuroscience Research Center, WR2 Team, Lyon,

France; 7University of Lyon, Lyon, France; 8Lyon 1 University,

Villeurbanne, France; 9Hospital Center Le Vinatier, Bron, France

Background: Repetitive transcranial magnetic stimulation (rTMS)

over the dorsolateral prefrontal cortex (DLPFC) has alleviated crav-

ing and improved cognition in patients with substance use disorders.

Craving is a key symptom in Gambling Disorder (GD), a common

disabling behavioral addiction with no pharmacological treatment.

We hypothesized that rTMS over the left DLPFC in patients with GD

would reduce gambling craving, automatic cue reactivity and improve

cognitive control. As an exploratory outcome, we investigated if

baseline self-regulation capacity would help identify rTMS

responders.

Methods: In a randomized sham-controlled crossover study, 22

treatment-seeking patients with GD received real or sham treatment

with high frequency rTMS over the left DLPFC and the other treat-

ment a week later. Before and after each rTMS session, participants

performed cognitive tasks (Go/NoGo and Iowa Gambling Task) and

rated their gambling craving before and after viewing a gambling

video used as a cue. We used heart rate variability (HRV) to evaluate

physiological cue-reactivity during viewing. Resting-state HRV was

also used as a marker of self-regulation capacity to subtype partici-

pants and identify potential responders.

Results: Real versus sham rTMS significantly decreased cue-induced

craving but affected neither HRV cue reactivity nor cognitive task

performance. Only patients with low regulation capacity, based on

low resting-state HRV, showed decreased motor impulsivity.

Conclusions: Following one active session of high frequency rTMS

over the left DLPFC, patients with GD reported decreased cue-in-

duced craving with no apparent effect on physiological cue-reactivity.

Despite no overall improvement on cognitive control, subjects with

impaired regulation capacity could be better rTMS responders on this

dimension. Determining the utility of rTMS in GD requires further

large randomized controlled studies with repeated sessions.


report.

S-2a-05Modified deep TMS coils for the treatment of OCD and ADHD:electrophysiological correlates and prognostic biomarkers

A. Zangen1, U. Alyagon1, L. Carmi12, J. Zohar2

1Department of Life Sciences and the Zlotowski Center for

Neuroscience, Ben-Gurion University of the Negev, Beersheba,

Israel; 2Division of Psychiatry, State of Israel Ministry of Health,

Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv

University, Tel-Aviv, Israel

Converging evidence suggests that OCD patients suffer from dys-

function of the cortico-striato-thalamo-cortical (CSTC) circuit,

including the medial prefrontal cortex (mPFC) and the anterior cin-

gulate cortex (ACC). Reduced excitability of the right prefrontal

cortex (rPFC) has been implicated in attention deficit/hyperactivity

disorder (ADHD). We have designed different deep TMS coils to

target large volumes of these regions in an attempt to induce lasting

modulations and evaluate potential clinical benefits using various

stimulation parameters.

This lecture will briefly summarize clinical outcomes of treat-

ments using different stimulation parameters in two longitudinal

studies in drug-free ADHD subjects and in medication-resistant OCD

patients. In the ADHD study, EEG recordings were taken before,

during, and after the first and the last days of treatment. In addition,

EEG was recorded during a Stop Signal task (SST), following single

TMS pulses over the rPFC, and during the treatment session itself. In


123

the OCD study, EEG recording were performed during a Stroop task

before and after treatment to examine changes in error-related

activity.

In the ADHD study, 20 Hz dTMS (but not focal TMS), to the

rPFC over 3 weeks induced significant clinical improvements and

TMS evoked potential (TEP) in the rPFC was enhanced accordingly.

Moreover, specific EEG bands recorded at rest and during the first

treatment session were highly correlated with the clinical benefit;

yielding a prognostic marker that explains 90% of variance in ther-

apeutic outcome.

In the OCD study, 20 Hz (not 1 Hz) dTMS to the mPFC and ACC

over 6 weeks induced significant improvement in the Yale–Brown-

Obsessive–Compulsive Scale (YBOCS) scores. The clinical results

were replicated in a relatively large (n = 94) double-blind multi-

center study. Notably, the clinical response correlated with increased

Error Related Negativity (ERN) in the Stroop task, an electrophysi-

ological component that is attributed to ACC activity.

These studies demonstrate the value of EEG recordings before and

during rTMS treatment as a tool for predicting response and poten-

tially even tailoring stimulation parameters for individual subjects

based on initial electrophysiological measures before and during the

first treatment session.

Policy of full disclosure: This research is partly supported by grants

from the MAGNET program of the Israeli OCS.

S-2b Brain stimulation with the double cone coil

Chairs: Downar and Schecklmann

S-2b-01Beyond DLPFC-rTMS: more targets, more indications, moreremissions

J. Downar1

1MRI-Guided rTMS Clinic, Toronto Western Hospital, Toronto,

Canada

In clinical practice, the most common use of rTMS is for major

depression, targeting the dorsolateral prefrontal cortex (DLFPC).

However, many other target brain regions and networks are also

accessible to rTMS, particularly using deeper-field coils such as the

double-cone coil. Several of these other prefrontal targets are also

implicated in major depression, and indeed may be involved trans-

diagnostically across a wide variety of Axis I and II disorders. Here

we will review recent evidence that two resting-state functional net-

works, the salience network (SN) and lateral orbitofrontal network

(LOFTN), are involved transdiagnostically across several psychiatric

illnesses including major depression. We will review recent tech-

niques for targeting these networks via double-cone rTMS of the

orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex

(DMPFC). We will review evidence that OFC- and DMPFC-rTMS

may achieve marked improvement not only in major depression but in

other comorbid illnesses, specifically including OCD, bulimia ner-

vosa, PTSD, and borderline personality disorder. Finally, we will

review evidence that a substantial proportion of DLPFC-rTMS non-

responders may achieve remission with DMPFC- or OFC-rTMS, such

that sequential courses of stimulation may achieve aggregate remis-

sion rates approaching or exceeding 50%.

Policy of full disclosure: Research funding from NIH, CIHR, Brain

Canada, Ontario Brain Institute, Klarman Family Foundation, Edge-

stone Foundation, and Toronto General and Western Hospital

Foundation, In-kind equipment support for investigator-initiated trials

from MagVenture, advisory role with equity in BrainCheck.

S-2b-02A literature review on ACDC stimulation targeting the anteriorcingulate by double cone coil rTMS

P. Kreuzer1

1University of Regensburg, Regensburg, Germany

Background: Repetitive transcranial magnetic stimulation (rTMS) has

been shown to modulate the neural activity in the dorsal anterior

cingulate (dACC) by placing a double cone coil (DCC) over the

dorsomedial prefrontal cortex (dmPFC). ACDC-stimulation (anterior-

cingulate stimulation by double cone coil rTMS) has been suggested

as a name for this form of rTMS.

Objective: To provide a systematic and comprehensive review on the

application of ACDC stimulation in different indications.

Methods: We systematically searched the MEDLINE� database (

http://www.ncbi.nlm.nih.gov/pubmed/accession date: 5th of June

2016). Due to the heterogeneous naming of ACDC stimulation a

variety of search terms was applied resulting in a total of 239 hits.

Results: ACDC stimulation has been proven to be safe and feasible in

various psychiatric disorders. Clinical results are encouraging, but

have to be considered as preliminary as data from sham-controlled

clinical trials and knowledge about the neurobiological underpinning

are still scarce.

Conclusion: ACDC stimulation represents a promising approach out

of the fast evolving toolbox of non-invasive brain stimulation tech-

niques allowing the functional modulation of a brain area that is

vitally involved in affect- and salience regulation. This may hold

great potential for both neuroscientific research and clinical applica-

tions in the treatment of psychiatric disorders.


report.

S-2b-03Comparison of figure-8 and DC coil: physiological and physicaldata

M. Schecklmann1, M. Schmaußer1, F. Klinger2, P. Kreuzer1,

L. Krenkel2, B. Langguth1

1Department of Psychiatry and Psychotherapy, University of

Regensburg, Regensburg, Germany; 2Fakultat Maschinenbau,

Ostbayrische Technische Hochschule, Regensburg, Germany

As indicated by TMS manufacturers and simulation studies stimula-

tion with the double-cone coil is indicated to be able to stimulate

deeper structures of the brain with higher intensity and lower focality

in contrast to a standard figure-of-8 coil. This challenges the clinical

practice of using motor threshold of the hand area as measured with a

standard figure-of-8 coil as stimulation intensity for treatment of the

Anterior Cingulate cortex with Double Cone coil (ACDC). Here, we

present data of 24 healthy subjects whose resting motor thresholds of

the first dorsal interosseous and of the tibialis anterior muscle were

compared by using a standard figure-of-8 and a double cone coil. We

found significant effects for coil type (higher motor threshold for the

figure-of-8 coil), stimulation site (higher motor threshold for the

tibialis anterior muscle), and the interaction coil type by stimulation

site as indicated by higher differences between the coil types for the

tibialis stimulation site. No significant effects were found for stimu-

lation side (left vs. right). Magnetic field measurements affirmed the

physiological data showing higher magnetic field strengths for the


123

http://www.ncbi.nlm.nih.gov/pubmed/accession

double cone coil. These findings concretize the differences in motor

thresholds obtained with different coil types and in different brain

areas.


report.

S-3a Clinical applications 3: convulsive therapy

and deep brain stimulation

Chairs: Kayser and Schlapfer

S-3a-01Stimulation strategies in electroconvulsive therapy

M. Grozinger1

1Department of Psychiatry, Psychotherapy and Psychosomatics,

RWTH Aachen University, Aachen, Germany

Stimulation strategies in Electroconvulsive Therapy (ECT) vary in

numerous parameters starting with the handling of prior medication,

electrode position, anesthesiologic substances, hyperventilation, and

many others. The initial charge has been determined mainly in two

ways. The first takes advantage of known characteristics of the patient

like age and gender, the second is based on measuring the seizure

threshold by titration. Another aspect of the stimulation strategies

concerns the handling of the anticonvulsive effect. In the past, three

classes of methods were applied: constant high dose, automatic

increase of dosage, and multiple titration.

During the last three decades more and more evidence has

emerged in ECT research that seizures can be differently effective in

improving severe mental illness. Physiological measurements during

the ictal phase like the amplitude of the Electroencephalogram (EEG)

and the pulse rate describing the strength of the seizure have been

shown to be associated with the outcome. This finding can be used to

design a different class of stimulation strategies determining the

stimulus intensity from the quality of the prior seizure and the clinical

status of the patient. This approach aims at continually providing high

quality seizures to optimize the outcome.


report.

S-3a-02Resting state networks, brain oscillatory activity and functionalconnectivity in patients with depression under electroconvulsivetherapy

O. Pogarell1, S. Karch1, B. Kirsch1, A. Chrobok1, D. Krause1,

A. Berman2, V. Kirsch3, H. Engelbregt1,4, D. Keeser1,2

1Department of Psychiatry and Psychotherapy, University of Munich,

Munich, Germany; 2Institute of Clinical Radiology, University of

Munich, Munich, Germany; 3Department of Neurology, Ludwig-

Maximilians-University, Munich, Germany; 4Hersencentrum,

Amsterdam, The Netherlands

Objectives: Dysfunctions of neuronal circuits, brain oscillatory

activity and functional connectivity have been demonstrated to con-

tribute to the pathophysiology of psychiatric disorders. In patients

with depression, studies showed increased functional MRI and EEG

connectivity. Electroconvulsive therapy (ECT) is highly effective in

patients with depression and there is evidence that ECT impacts on

neuronal networks considered to play an important role in the neu-

robiology of depression.

Methods: Using resting state EEG, we investigated neuronal spec-

trotemporal dynamics and brain functional connectivity in sensor and

source space in a large sample of patients with major depression

(n = 240) compared to gender- and age-matched healthy subjects

(n = 292); a subsample of the subjects (n = 20) was investigated

before and during ECT. Quantitative measures, calculated from

artefact-free EEG recordings, included delta (d), theta (h), alpha (a),beta (b) and gamma (c) power (lV2), hemispheric asymmetry,

coherence, phase and eLORETA current source density (CSD)

analyses.

Results: There was an increase in cortical slow-wave activity in

sensor and source space in patients with depression revealing marked

differences in prefrontal cortical networks. Differences in CSD were

found for d, h, a-bands in the subgenual and the rostral anterior

cingulate cortex (ACC) with increased CSD in the patients. Func-

tional d, h and a- connectivity (coherence and phase) were altered

with a predominance in the left hemisphere. Upon ECT there was an

increased delta and theta power in frontal sensor EEG electrodes,

whereas EEG connectivity significantly decreased in both sensor and

source space.

Conclusions: Dysfunctions of the ACC, together with alterations in

fcEEG may contribute to the pathophysiology of major depression.

ECT is associated with changes in both brain electric activity and

EEG connectivity in frontal brain regions, a key anatomical region in

the pathophysiology of depression. Low frequency power increases

and EEG connectivity decreases may be a neurophysiological corre-

late of the mechanisms of action of ECT.


report.

S-3a-03Magnetic seizure therapy in psychiatric disorders

Sarah Kayser1

1Department of Psychiatry and Psychotherapy, University Medical

Center of Mainz, Mainz, Germany

Magnetic Seizure Therapy (MST) in Psychiatric Disorders. A failure

to respond to two different antidepressant treatments is defined as

treatment-resistant depression (TRD). Currently, electroconvulsive

therapy (ECT) is recommended in the treatment of TRD. However,

due to its stigma and the fear of cognitive side effects, ECT is often

used only as a treatment of last resort. Through the modulation of

several stimulation parameters cognitive side effects could be

reduced, but even when applying the gold standard, the right unilat-

eral (RUL) electrode placement, in particular, anterograde and

retrograde amnesia occur frequently. The underlying mechanism of

amnesia induced by ECT is an affection of the temporal lobe, the

hippocampus, during treatments. Thus, distinct brain regions may be

associated with cognitive side effects and others with the efficacy of

ECT.

Magnetic seizure therapy (MST) is a further development of the

repetitive transracial magnetic stimulation (rTMS). It generates a

strong focal magnetic field that is robust enough to elicit generalized

tonic–clonic seizures under anaesthesia and muscle relaxation. Unlike

ECT‘s electrical stimulation, the magnetic field crosses the skull and

soft tissue unimpeded to reach brain tissues. In preclinical data, the

focality of the electrical stimulation induced by MST and the superior

cognitive side effect profile compared to electroconvulsive shock

(ECS) were demonstrated. In this symposium, cognitive, clinical and

neuroimaging effects of MST in patients with TRD and other psy-

chiatric disorders were presented and discussed.


123


report.

S-3a-04DBS

Thomas Schlapfer1

1Division of Interventional Biological Psychiatry, University of

Freiburg, Freiburg, Germany

The recent introduction of Deep Brain Stimulation (DBS) for treat-

ment resistant psychiatric disorders might very well lead to the most

significant development in clinical psychiatry of the last 40 years—

possibly offering a rise of hope for patients to whom medicine had

hitherto little to offer. Furthermore, translational research on neuro-

modulation will allow us to glean something about the underlying

cause of patient’s illnesses before figuring out a treatment that

addresses the source of the problem. Major depression offers perhaps

the best example of the rapid progress being made in understanding

the biology of mental illness. Studies on the underlying neurobiology

of major depression have typically focused on the description of

biological differences between patients and healthy subjects such as

alterations of monoaminergic or endocrine systems. Psychotropic

drugs work by altering neurochemistry to a large extent in widespread

regions of the brain, many of which may be unrelated to depression.

We believe that more focused, targeted treatment approaches that

modulate specific networks in the brain—specifically structures

mediating rewarding responses to emotional stimuli—will prove a

more effective approach to help treatment-resistant patients. In other

words, whereas existing depression treatments approach this disease

as a general brain dysfunction, a more complete and appropriate

treatment will arise from thinking of depression as a dysfunction of

specific brain networks that mediate mood and reward signals. A

better understanding of defined dysfunctions in these networks will

invariably lead to a better understanding of patients afflicted with

depression and perhaps contribute to a de-stigmatization of psychi-

atric patients and the medical specialty treating them.

Policy of full disclosure: This work was partly supported by Med-

tronic Inc. in the framework of an Investigator Initiated Trials. The

authors have no further conflicts of interest.

S-3a-05Progress and drawbacks in deep brain stimulation for obsessive–compulsive disorder and Tourette syndrome

Juan Carlos Baldermann1

1Department of Psychiatry and Psychotherapy, University of Cologne,

Cologne, Germany

After more than 15 years of deep brain stimulation for obsessive

compulsive disorder and Tourette syndrome the field has made major

progress and there is increasing evidence that this neuromodulative

treatment is an effective treatment option for both indications. Still,

there are several drawbacks for research and the clinical application

that need to be addressed.

We highlight key clinical trials, discuss different brain structures

as surgical targets, and summarize recent hypotheses on mechanisms

underlying clinical effects. For obsessive–compulsive disorder, deep

brain stimulation of the ventral striatum has been approved by the

European authorities for severe treatment-refractory patients and

appears to be safe and effective. Whether other brains structures

represent a better alternative or constitute complementary targets

remains open. Deep brain stimulation for Tourette syndrome may

have left its experimental character, but difficulties in designing larger

controlled clinical trials and the numerous targets used by different

centres are relevant obstacles to prove efficacy.

To step forward, researchers must face inconvenient questions and

outperform previous clinical research in this field in terms of cohort

size and experimental design. Relevant topics for future investigations

for both indications include treatment predictors, augmentation

techniques, building up international registries and a better under-

standing of adverse events.


report.

S-3b Safety and NIBS across lifespan

Chairs: Antal and Moliadze

S-3b-01Safety of tES

A. Antal1

1Department of Clinical Neurophysiology, University Medical

Center, Gottingen, Germany

Given the growing interest in the non-invasive low intensity tran-

scranial electrical stimulation (TES) technologies, the aim of this

session is to summarize safety issues surrounding the use of TES for

the treatment of nervous system disorders as well as for non-thera-

peutic uses, Low intensity TES, encompassing transcranial direct

current (tDCS), transcutaneous spinal Direct Current Stimulation

(tsDCS), transcranial alternating current (tACS), and transcranial

random noise (tRNS) stimulation or their combinations so far appears

to be a safe technique. The prevalence of published AEs is different in

studies specifically assessing AEs vs. those not assessing them.

Nevertheless, the profile of adverse events (AEs) in terms of fre-

quency and type is comparable in healthy and clinical populations.

Typical adverse effects are itching, burning sensations under the

electrode or transient, mild headaches and fatigue. Mild AEs are

mainly skin burns, which can be controlled by improving skin–elec-

trode contact. Very rarely mania or hypomania was induced in

patients with depression. Co-application of neuroimaging electro-

physiological measurements was not associated with further safety

problems. Using AC stimulation fewer AEs were reported compared

to DC. According to recent studies safety is established for low-

intensity TES defined as\ 4 mA, up to 60 min duration per day.


report.

S-3b-02Transcranial electrical stimulation in pediatric brain: ageor individual differences?

V. Moliadze1

1Department of Medical Psychology and Medical Sociology,

Schleswig-Holstein University Hospital (UK-SH), Christian-

Albrechts-University, Kiel, Germany

Since the developing brain shows a greater capacity of brain plas-

ticity, transcranial electrical brain stimulation (tES) might induce

greater benefits in children. So far, applications of tES in pediatric

studies are not well developed. The talk will give an overview of how

age and individual differences impact tES effects in healthy children


123

and adolescents. Additionally, the research consortium STIPED

(stimulation in pediatrics, European Union’s Horizon 2020, Grant

Agreement No. 731827) will be introduced which aims (1) to char-

acterize interaction between brain development and effects of

transcranial direct current stimulation (tDCS) on neuropsychological

function and (2) to apply individual head modelling and electrical

current estimation to guide individualized treatment with tDCS in

different stages of development.


report.

S-3b-03NIBS in neurodevelopmental disorders

K. Krauel1

1Department of Child and Adolescent Psychiatry and Psychotherapy,

University of Magdeburg, Magdeburg, Germany

Non-invasive brain stimulation (NIBS) allows inducing changes in

regional cortical excitability, plasticity as well as in functional con-

nectivity of brain networks in healthy and clinical populations.

Recently, the use of NIBS has been also suggested for children and

adolescents with neurodevelopmental disorders such as attention

deficit hyperactivity disorder (ADHD) and autism spectrum disorder

(ASD). In ADHD, particularly the dorsolateral prefrontal cortex and

the inferior frontal gyrus have been used as target regions for tran-

scranial direct current stimulation (tDCS) to improve

neuropsychological and clinical parameters. The current research

consortium STIPED (stimulation in pediatrics, European Union’s

Horizon 2020, Grant Agreement No. 731827) aims to investigate both

the clinical relevance and functional mechanisms of NIBS in ADHD

and ASD, identify predictors of individual responsivity to NIBS, and

develop home-treatment solutions to improve accessibility to NIBS.


report.

S-3b-04Transcranial stimulation targeting memory-relevant sleeposcillations as therapeutic approach in aging and mild cognitiveimpairment

J. Ladenbauer1,2,3, N. Kulzow1,2, S. Paßmann1, J. Ladenbauer4,5,

A. Floel1,2,3

1Department of Neurology, Charite Universitatsmedizin Berlin,

Berlin, Germany; 2NeuroCure Cluster of Excellence, Charite

Universitatsmedizin Berlin, Berlin, Germany; 3Department of

Neurology, University Medicine Greifswald, Greifswald, Germany;4Department of Software Engineering and Theoretical Computer

Science, Technische Universitat Berlin, Berlin, Germany; 5Bernstein

Center for Computational Neuroscience Berlin, Berlin, Germany

Memory-relevant sleep oscillations, in particular cortical slow oscil-

lations (SO) and thalamo-cortical spindle activity, decrease during

aging, which is accompanied by a decline in declarative memory

consolidation. These changes are profoundly accelerated in Alzhei-

mer’s dementia and its precursor mild cognitive impairment (MCI).

We investigated the potential of slow oscillatory transcranial

direct current stimulation, applied during a daytime nap and night-

time sleep in a brain-state-dependent manner, to modulate these

activity patterns and sleep-related memory consolidation in healthy

elderly and MCI patients.

We consistently found positive immediate effects on SO as well as

fast spindle activity. Stimulation further enhanced the functional

coupling between SO and spindle activity, a mechanistic component

considered crucial for the transfer of memories from hippocampus to

cortical long-term storage networks. Regarding memory performance,

we observed that stimulation during a daytime nap significantly

improved visual recognition performance, while stimulation during

night-time sleep unexpectedly resulted in a negative memory effect.

An explanation for this discrepancy and the relation to other rel-

evant studies will be discussed.

Our findings indicate a well-tolerated therapeutic approach for

disordered sleep physiology and memory deficits and advance our

understanding of offline memory consolidation.


report.

S-4a Multimodal imaging

Chairs: Stagg and Opitz

S-4a-01Accounting for interindividual variation in NIBS usingcomputational models

A. Opitz1

1University of Minnesota, Minneapolis, USA

The response to non-invasive brain stimulation (NIBS) shows large

variation across individuals. Thus, novel stimulation protocols tai-

loring NIBS to the individual are clearly needed. In this talk, I will

discuss how computational models can be used to account for

interindividual variation in anatomy and function in NIBS. I will

further outline challenges lying ahead such that models can fully

guide individualized NIBS protocols.

Policy of full disclosure: A.O. is an inventor on patents and patent

applications describing methods and devices for noninvasive brain

stimulation.

S-4a-02How to reach deep brain structures: modulation of saliencecoding of food by rTMS

T. Kammer1

1Department of Psychiatry, University of Ulm, Ulm, Germany

In the context of hedonic (over-)eating the ventral tegmental area

(VTA) as a core part of the dopaminergic reward system plays a

central role in coding incentive salience of high-caloric food. Tran-

scranial magnetic stimulation does not directly reach such a deep

structure. Therefore, using seed-based resting-state fMRI with a

functionally defined portion of the VTA serving as seed region we

identified an area in the right mid-ventrolateral prefrontal cortex (mid-

VLPFC) connected to the VTA. In the main experiment we investi-

gated whether theta burst TMS over right mid-VLPFC can induce

modulation of calorie-sensitive brain activation in the VTA. Depen-

dent variables were reaction times as well as BOLD activity profiles.

In a sample of 15 healthy male participants, modulation of calorie-

sensitive VTA activation did not significantly differ between the two

TBS protocols. Comparisons with baseline revealed that both TBS

protocols significantly affected calorie-sensitive neural processing of

the mid-VLPFC in a rather similar way. In the VTA significant

modulation of calorie-sensitive activation was observed after con-

tinuous TBS, whereas the modulatory effect of intermittent TBS was


123

less reliable but also associated with a decrease of activation for high-

caloric food images. Neurostimulation of right mid-VLPFC is sug-

gestive as a main entry point of downstream signal changes for high-

and low-caloric food cues that could enforce a shift in valuating

stimuli of initially different incentive salience.


report.

S-4a-03Imaging transcranial direct current stimulation: contributionsand challenges

Daniel Keeser1,2, Frank Padberg1

1Department of Psychiatry and Psychotherapy, Ludwig Maximilian

University Munich, Munich, Germany; 2Department of Radiology,

Ludwig Maximilian University Munich, Munich, Germany

Non-invasive transcranial brain stimulation (NIBS) methods (e.g.

transcranial direct current stimulation—tDCS, repetitive transcranial

magnetic stimulation—rTMS and others) provide a unique in vivo

intervention for probing the functional role of regions and hubs in

human neural systems that play a role in the pathophysiology of

psychiatric disorders. Recent research has shown that the individual

human brain functional MRI connectivity (fcMRI) shows distinct

patterns of within- and between-subjects variability1,2,3. Anatomically

targeted analyses of NIBS in neuropsychiatric patients and healthy

subjects have generated promising results5,6,7. Even combining sev-

eral neuroimaging methods (resting state fcMRI, task-based fMRI,

Magnetic Resonance Spectroscopy (MRS)) may be useful to detect

classifiers that can be reliably used to predict NIBS effects. These

neuroimaging methods allow individual brain properties as well as the

evaluation of state-dependency4. By combining neuroimaging and

NIBS (term: imaging stimulation) new functional models are expec-

ted to be developed and compared in different states of health and

pathology, e.g. during the course of psychiatric disorders from pre-

clinical stages to relapsing–remitting or chronic disorders.

References:

1. Mueller S, Wang D, Fox MD et al (2013) Individual variability in

functional connectivity architecture of the human brain. Neuron

77(3):586–595

2. Laumann TO, Gordon EM, Adeyemo B, Snyder AZ, Joo SJ, Chen

MY, Gilmore AW, McDermott KB, Nelson SM, Dosenbach NU,

Schlaggar BL, Mumford JA et al (2015) Functional system and areal

organization of a highly sampled individual human brain. Neuron

5(87):657–670

3. Worsching J, Padberg F, Helbich K et al (2017) Test–retest relia-

bility of prefrontal transcranial Direct Current Stimulation (tDCS)

effects on functional MRI connectivity in healthy subjects. NeuroI-

mage. http://doi.org/10.1016/j.neuroimage.2017.04.052

4. Worsching J, Padberg F, Ertl-Wagner B et al (2016) Imaging

transcranial direct current stimulation (tDCS) of the prefrontal cortex-

correlation or causality in stimulation-mediated effects? Neurosci

Biobehav Rev 69:333–356

5. Fox MD, Buckner RL, White MP et al. Efficacy of transcranial

magnetic stimulation targets for depression is related to intrinsic

functional connectivity with the subgenual cingulate. Biol Psychiatry

72(7):595–603

6. Fox MD, Buckner RL, Liu H et al (2014) Resting-state networks

link invasive and noninvasive brain stimulation across diverse psy-

chiatric and neurological diseases. Proc Natl Acad Sci USA

111(41):E4367–E4375

7. Drysdale AT, Grosenick L, Downar J et al (2017) Resting-state

connectivity biomarkers define neurophysiological subtypes of

depression. Nat Med 23:28–38

Policy of full disclosure: Supported by the Federal Ministry of

Research and Education (‘‘Forschungsnetz fur psychische

Erkrankungen’’, German Center for Brain Stimulation-GCBS-WP5).

F.P. has received speaker’s honorarium from Mag&More GmbH and

the neuroCare Group as well as support with equipment from neu-

roConn GmbH, Ilmenau, Germany, Mag&More GmbH and

Brainsway Inc., Jerusalem, Israel. D.K. does not have disclosures to

report.

S-4a-04Towards causality: combining non-invasive brain stimulationand neuroimaging to understand neuroplasticity

C. Stagg1

1Wellcome Centre for Integrative Neuroimaging (WIN), University of

Oxford, Oxford, UK

Neuroplasticity is of vital importance to how we compensate for, and

recover from, a wide variety of neurological and psychiatric condi-

tions. However, studying these processes in humans is complex and

necessarily indirect. One potentially useful model system for under-

standing the physiological changes that underpin plasticity is the

motor system.

Here, therefore, I will discuss recent studies from our group using

NIBS to study the physiological basis of motor plasticity in vivo, in

combination with MR Imaging, MR Spectroscopy and Magnetoen-

cephalography. These studies provide increasing convergent evidence

that changes in local and network-level inhibitory processing is a key

component in plasticity.


report.

SOP-01 Effects of non-invasive neurostimulation

on brain activity

Chairs: Aleman and Herrmann

SOP-01-01Modulation of spontaneous and task-related alpha-bandoscillations using transcranial alternating current stimulation(tACS)

F. H. Kasten1, C. S. Herrmann1

1Experimental Psychology Lab, Department of Psychology, European

Medical School, Cluster for Excellence ‘‘Hearing for all’’, Carl von

Ossietzky University, Oldenburg, Germany

Oscillatory activity in the brain has been associated with a variety of

cognitive functions. Likewise, dysfunctional neural oscillations have

been implicated in neurological and psychiatric disorders such as

depression, schizophrenia, Parkinson’s disease, Epilepsy or ADHD.

Traditionally, correlational approaches such as Magneto- or Elec-

troencephalography (M/EEG) have been employed to study these

relationships. In recent years, non-invasive techniques to modulate

brain oscillations receive growing popularity in the scientific com-

munity. These methods now allow to directly probe the causal role of

neural oscillations for cognition and offer potential new treatments for

mental disorders involving dysfunctional oscillations. Especially the

application of alternating currents through the scalp by means of

transcranial alternating current stimulation (tACS) offers a


123

http://doi.org/10.1016/j.neuroimage.2017.04.052

comparatively cheap and easy to apply way to modulate endogenous

brain oscillations, while causing little discomfort for participants.

Here we present recent work from our group showing effects of

single-session tACS applied for 20 min on spontaneous and event-

related alpha oscillations. Increased alpha power after tACS was

observed for up to 70 min after stimulation during resting-state EEG.

Similar effects were elicited when tACS was administered while

participants performed a cognitive task involving frequent event-re-

lated power modulations in the alpha band. In that study, the overall

power increase in the alpha band was accompanied by enhanced

event-related alpha-desynchronization as well as facilitated perfor-

mance in the cognitive task. Subsequent utilization of concurrent

tACS-MEG revealed a similar facilitation of event-related desyn-

chronization in the alpha band already during the continuous

application of tACS. Our results demonstrate that tACS is capable of

eliciting long-lasting, frequency specific effects, which were directly

related to changes in behavioral performance. Further, the continuous

application of tACS during a cognitive task facilitated pre-existed

task-related power modulations in the stimulated frequency band,

rather than overwriting them.

Policy of full disclosure: CSH has filed a patent application on brain

stimulation and received honoraria as editor from Elsevier Publishers,

Amsterdam. FHK declares no competing interests.

SOP-01-02The effects of frontal tACS on reversal learning

M. Wischnewski1, D. Schutter1

1Donders Institute, Donders Centre for Cognition, Radboud

University, Nijmegen, The Netherlands

Reward and punishment learning is associated with increased activity

in the fronto-cortical network1. This frontal network is accompanied

by oscillatory activity in the theta and beta range2. In a previous study

we showed that frontal transcranial alternating current stimulation

(tACS) at the theta range can improve reversal learning performance3.

Here we investigated whether beta tACS has similar effects. Fur-

thermore, we investigated frontal coherence to speculate on the

neurophysiological mechanisms underlying any behavioural effects.

In the present study 108 healthy right-handed volunteers received

1 mA tACS at 20 Hz by applying four electrodes over the frontal

cortex for 12 min. Volunteers were divided into three groups

(n = 36). In the two experimental groups intra-hemispheric tACS was

either in-phase or anti-phase. The third group received sham stimu-

lation. During stimulation a learning task was performed in which

participants had to reverse strategy from a high-risk to a low-risk

option. Before and after the task and stimulation a 4-min resting state

EEG was recorded. Reversal learning performance was investigated

and was correlated to coherence measurements in the beta and theta

range.

Results showed that reversal learning performance was improved

after in-phase tACS compared to sham. Coherence in the theta range

was increased after in-phase stimulation in the left, but not right

frontal cortex. The pretest to posttest change in coherence was posi-

tively correlated with reversal learning performance. Furthermore,

coherence measurements did not depend on the EEG reference

position.

In accordance with previous studies, we here show that frontal

tACS can improve reversal learning performance3. Furthermore, we

show that frontal beta oscillations may affect theta coherence sug-

gesting a relationship between frontal theta and beta oscillatory

activity.

References:

1. Haber SN, Knutson B (2010) The reward circuit: linking primate

anatomy and human imaging. Neuropsychopharmacology 35(1):4–26

2. Fries P (2015) Rhythms for cognition: communication through

coherence. Neuron 88(1):220–235

3. Wischnewski M, Zerr P, Schutter DJLG (2016) Effects of theta

transcranial alternating current stimulation over the frontal cortex on

reversal learning. Brain Stimul 9(5):705–711


report.

SOP-01-03The effects of rTMS treatment for auditory verbal hallucinationson inner speech related brain networks

L. Bais1,2, E. Liemburg1,2,4, A. Vercammen6, Richard Bruggeman4,5,

R. Knegtering1,2,4, A. Aleman1,3

1Department of Neuroscience, and BCN NeuroImaging Center,

University of Groningen, University Medical Hospital Groningen,

Groningen, The Netherlands; 2Lentis, Psychiatric Institute,

Groningen, The Netherlands; 3Department of Psychology, University

of Groningen, Groningen, The Netherlands; 4University of

Groningen, University Medical Center Groningen, Rob Giel Research

Center, Groningen, The Netherlands; 5Department of Psychiatry,

University of Groningen, University Medical Center Groningen,

Groningen, The Netherlands; 6Independent researcher:

[email protected]



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SOP-01-04Antidepressant effects and change in brain activationof transcranial pulsed electromagnetic fields for treatmentresistant depression

S. M. van Belkum1,2, E. M. Opmeer2, M. K. de Boer1,

R. A. Schoevers1, A. Aleman2

1Department of Psychiatry, Research School of Behavioral and

Cognitive Neurosciences (BCN), Interdisciplinary Center

Psychopathology of Emotion regulation (ICPE), University of

Groningen, University Medical Center Groningen, Groningen, The

Netherlands; 2Department of Neuroscience, University of Groningen,

University Medical Center Groningen, Groningen, The Netherlands

Noninvasive neurostimulation with transcranial Pulsed Electromag-

netic Fields (tPEMF) is a promising method for the treatment of

treatment resistant depression (TRD). One study has shown remission

of depressive symptoms in patients with TRD but this has not been

replicated yet. We investigated the short- and long-term efficacy of

tPEMF and its effect on brain activation in participants with TRD, as

no evidence on this is available.

We included 55 participants with TRD in a sham-controlled

double-blind multicenter trial. Eligible participants were randomly

assigned to either daily 30 min active tPEMF stimulation or daily

sham stimulation, during 5 weeks. Severity of depression was

assessed directly pre- and post-treatment, and 5 and 15 weeks post-

treatment. We performed a functional MR-scan directly pre- and post-

treatment. Clinical outcome was defined as change on the 17-item

Hamilton depression rating scale (HAMD-17) directly post-treatment.

Participants performed two fMRI-tasks: an emotional processing task

and a reward task.

Of the 55 included participants, 50 completed the treatment pro-

tocol. There was no difference in outcome between the active (pre–

post HAMD-17: 22–16) and the sham group (pre–post HAMD-17:

22–17) on change in depression post-treatment. A small improvement

was observed over time independent of treatment that continued after

the 5-week treatment period until the last follow-up measure. Fur-

thermore, the active treatment group showed decreased activation

during reward processing in the left inferior frontal gyrus and in a

cluster comprising the right lingual gyrus and the posterior part of the

middle temporal gyrus. We did not find an effect of tPEMF on

emotional processing.

In contrast to a previous study using a similar design, our study

showed that treatment with active tPEMF was not superior to sham

treatment in patients with TRD. However, we did observe a small

difference in brain activation during reward processing.

Policy of full disclosure: The authors do not have disclosures to report.

SOP-01-05Quadri-pulse theta burst stimulation using ultra-high frequencybursts at I-wave periodicity induces direction dependent bi-directional plasticity in human motor cortex

N. H. Jung1, B. Gleich2, N. Gattinger2, H. R. Siebner3,4, V. Mall1

1School of Medicine, Technical University of Munich, Social

Pediatrics, Heiglhoftstr. 65, 81377 Munich, Germany; 2Munich

School of BioEngineering (MSB), Technische Universitat Munchen,

Boltzmannstraße 11, 85748 Garching, Germany; 3Danish Research

Center for Magnetic Resonance (DRCMR), Hvidovre Hospital,

Kettegaard Alle 30, 2650 Hvidovre, Denmark; 4Department of

Neurology, Copenhagen University Hospital, Bispebjerg,

Copenhagen, Denmark

Introduction: Patterned transcranial magnetic stimulation (TMS) such

as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS)

can induce long-term potentiation (LTP)-like and long-term depres-

sion (LTD)-like effects in human primary motor cortex (M1). These

mechanisms are considered to be synaptic processes underlying

learning and memory. Impairments are thought to play a pivotal role

in the phenotype of various medical conditions (e.g. bipolar disor-

ders). Here, we aimed to test the plasticity-inducing capabilities of a

novel protocol that merged TBS and QPS at interstimulus intervals

(ISI) that mimic I-wave periodicity (i.e. 1.5 ms/666 Hz) with an

anterior–posterior (AP) and posterior–anterior (PA) directed current

flow in M1.

Methods: We investigated healthy volunteers (n = 12 per protocol)

with 360 bursts of quadri-pulse TBS (qTBS) that was continuously

given to M1 (1440 full-sine pulses). QTBS consisted of repeated

bursts of four biphasic TMS pulses (duration: 160 ls) separated by

ISI of 1.5 ms (666 Hz) and inter-burst intervals of 200 ms. (5 Hz)

TMS was applied by a custom-made magnetic stimulator (MSB,

Munich). Resting motor threshold (rMT), and motor evoked poten-

tials (MEP) with stimulus intensities to target amplitudes of 1mv

(SI1 mV) were measured before (Pre) qTBS, directly after (Post1),

after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4).

Results: PA-qTBS at 666 Hz caused a LTD-like reduction, whereas

AP-qTBS at 666 Hz induced LTP-like increase in mean MEP

amplitude outlasting for approximately 60 min. As expected, baseline

data of rMT prior to qTBS differed significantly, with higher

thresholds in AP direction.

Discussion: Continuous qTBS at 666 Hz can induce lasting changes

in corticospinal excitability. Induced current direction in the brain

appears to be relevant when qTBS targets I-wave periodicity, cor-

roborating that high-fidelity spike timing mechanisms are critical for

inducing bi-directional plasticity in human M1 supporting the need of

individualized non-invasive brain stimulation techniques.


report.

SOP-02 Clinical applications

Chairs: Schonfeldt-Lecuona and Cordes

SOP-02-01The bipolar depression electrical treatment trial (BETTER):results from a randomized clinical trial

B. de Sampaio Pereira


SOP-02-02Attitudes and educational work regarding rTMS

C. Engelke1

1Department of Psychiatry and Psychotherapy, Medical Faculty,

Heinrich Heine University, Dusseldorf, Germany

Brain stimulation has been shown to be safe and effective, but the use

of brain stimulation techniques still underlies public criticism1,2.

There are several public stigma associated with brain stimulation

techniques for the treatment of depression, but patients who have

received brain stimulation are more favourable to it2. This also affects

the intention of a therapy and treatment compliance3. In this talk, we


123

will present the results of a study examining the attitude towards

rTMS treatment among 122 depressive in-patients and draw conclu-

sions on factors influencing educational work and the handling of

patients.

References:

1. Chakrabarti S, Grover S, Rajagopal R (2010) Electroconvulsive

therapy: a review of knowledge, experience and attitudes of patients

concerning the treatment. World J Biol Psychiatry 11:525–537

2. Walter G, Martin J, Kirkby K, Pridmore S (2001) Transcranial

magnetic stimulation: experience, knowledge and attitudes of recip-

ients. Aust N Z J Psychiatry 35:58–61

3. Vermeire E, Hearnshaw H, Van Royen P, Denekens J (2001)

Patient adherence to treatment: three decades of research. A com-

prehensive review. J Clin Pharm Ther 26:331–342

Robert Ostroff (USA): Creating an interventional psychiatry service.


SOP-02-03Creating an interventional psychiatry service

R. Ostroff1, R. Katz1, S. Wilkinson1, G. Sanacora1

1Yale Department of Psychiatry, Yale Psychiatric Hospital, New

Haven, CT, USA

Interventional psychiatry is an emerging subspecialty that uses vari-

ous procedural neuromodulation techniques to treat mental

dysfunction that views disruption of the normal chemo-electric

functioning of the brain as its proximal cause. Unlike traditional

pharmacologic interventions, the interventions that comprise inter-

ventional psychiatry involve the administration of electrical energy in

a controlled and monitored setting to induce a grand mal seizure, the

use of neurostimulation to increase neuroplasticity through direct

cortical stimulation or vagal nerve stimulation and the use of rapid

acting neuromodulators that can be administered intravenously or

intranasally. The uses of these techniques require special competen-

cies in both administering and monitoring that are beyond those

needed to prescribe a medication. These interventions require special

competency beyond the role of typical psychiatric training. We pre-

sent the Yale Interventional Psychiatry Service as a model for clinical

care, research and training. We will present the necessary steps to

organizing an interventional psychiatry service including required

competencies, staff training, the education of residents, the develop-

ment of a standardized database, research opportunities and ongoing

quality improvement through the use of a tumor board model.


S-5a Individualizing treatment

Chairs: Plewnia and Keeser

S-5a-01Understanding and predicting rTMS effect for the treatmentof negative symptoms in schizophrenia

Alkomiet Hasan, Berthold Langguth, Joachim Cordes, Birgit Kunze,

Nikolaos Koutsouleris, Thomas Wobrock and RESIS Study team


S-5a-02Stimulation genetics: new perspectives for an individualized brainstimulation

C. Plewnia1

1Department of Psychiatry and Psychotherapy, Neurophysiology and

Interventional Neuropsychiatry, University of Tubingen, Tubingen,

Germany


S-5a-03Individualized treatment of positive symptoms in schizophrenia:potentials and pitfalls

S. Winkelbeiner1, Philipp Homan1,2

1Translational Research Center, University Hospital of Psychiatry and

Psychotherapy, University of Bern, Bern, Switzerland; 2Center for

Psychiatric Neuroscience, The Feinstein Institute for Medical

Research, Hofstra Northwell School of Medicine, New York, USA

Individualized treatment of positive symptoms in schizophrenia requires

an understanding of the underlying neurobiological mechanisms of the

specific symptom.We investigated two of the major positive symptoms:

formal thought disorder (FTD) and auditory verbal hallucinations

(AVH). Regarding FTD, we found alterations in white matter integrity,

gray matter thickness, subcortical volume, and perfusion in language-

related areas to be associated with the severity of FTD. These findings

may contribute to a better understanding of involved neurobiological

processes and to the development of specific treatments.

With regard to AVH, we focused on cerebral blood flow (CBF) in

the left superior temporal gyrus (STG) and other language areas

before and after treatment with transcranial magnetic stimulation

(TMS). Treatment-augmentation with brain stimulation techniques is

increasing and has shown promising if mixed results, possibly due to

variability in treatment response. CBF measured with arterial spin

labelling might be a potential predictor of treatment response. Indeed,

we found evidence for higher pre-treatment CBF in the STG in TMS

responders compared to non-responders. This suggests that TMS

might be appropriate only for a clinical sub-population with a high

enough CBF in the left STG.

However, interpreting treatment response is not without pitfalls.

Depending on the study design, factors such as random within-subject

variability and regression to the mean need to be considered. For valid

classification, the difference in variation between treatment and

control have to be calculated, and only if this difference is clinically

meaningful, are subsequent responder analyses indicated.

Taken together, the detection of potential biomarkers of treatment

response has the potential to individualize treatment, but critically

depends on sound statistical modelling.


S-5a-04Computational modelling studies for non-invasive brainstimulation

M. Parazzini1, E. Chiaramello1, S. Fiocchi1, P. Ravazzani1

1Consiglio Nazionale delle Ricerche, Istituto di Elettronica e di

Ingegneria dell’Informazione e delle Telecomunicazioni, IEIIT CNR,

Milan, Italy

Brain neuronal activity can be modulated by non-invasive brain

stimulation (NIBS) techniques, via electric currents induced by an


123

externally generated electric or magnetic field. The possible appli-

cations of NIBS in clinics as a potential non-pharmacologic, non-

invasive, painless and reversible approach to different neurological

disorders, has attracted the interest of many researchers. NIBS is now

considered an elective tool as a treatment option for pain, psychiatric,

neurodegenerative and cognitive disorders, for the neurorehabilitation

from brain injuries and the diagnosis of central motor pathway

damages. One crucial aspect in the development and optimization of

NIBS treatment is the knowledge about the actual distributions of the

electric fields and the current densities induced in the target brain

areas.

Numerical modelling of the interaction between the electromag-

netic fields and the dielectrically inhomogeneous human body

provides a unique way of assessing the resulting spatial distributions

of internal electric fields and currents density. Knowledge of these

parameters is of crucial importance in understanding such interactions

and is a prerequisite when assessing, designing, or optimizing ther-

apeutic or diagnostic medical applications that employ

electromagnetic fields, such as NIBS.

This paper, therefore, aims to address how the use of electro-

magnetic computational techniques can support the development and

optimization of NIBS applications, boosting the translation of com-

putational bio-electromagnetics approaches into valuable information

for therapy and diagnosis.


report.

S-5b Cognition and psychotherapy, state dependency

Chairs: Brem and Wolkenstein

S-5b-01Trait rumination moderates the effects of anodal tDCSover the right dorsolateral prefrontal cortex on cognitiveprocessing of emotional information

M.-A. Vanderhasselt1,2,3, A. Sanchez 3, H. Josephy 4, C. Baeken1,5,

A. R Brunoni 6, R. De Raedt3

1Department of Psychiatry and Medical Psychology, Ghent

University, Ghent, Belgium; 2Faculty of Medicine and Pharmacy,

Free University Brussels, Brussels, Belgium; 3Department of

Experimental-Clinical and Health Psychology, Ghent University,

Ghent, Belgium; 4Department of Data Analysis, Ghent University,

Ghent, Belgium; 5Department of Psychiatry, Free University

Brussels, Brussels, Belgium; 6Service of Interdisciplinary

Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27),

Department and Institute of Psychiatry, University of Sao Paulo, Sao

Paulo, Brazil

Healthy individuals reporting higher (as compared to lower) levels of

trait rumination recruit more neural activity in dorso-cortical regions

when inhibiting negative information. In the present study, we

investigated whether these latter neural correlates are causally

implicated in cognitive control in these ruminating individuals. We

included a sample of thirty-five healthy volunteers reporting a broad

range of trait rumination levels and the Cued Emotional Control Task,

a measure of cognitive control indexed by cognitive costs for

inhibiting versus providing a habitual response for emotional infor-

mation, was administered. Participants completed the task after

receiving both real and sham-placebo (counterbalanced order) anodal

transcranial Direct Current Stimulation (tDCS) over the right dorso-

lateral prefrontal cortex (DLPFC). Results reveal that the tDCS

induced effects on cognitive costs for emotional information were

associated with individual differences in trait rumination: the higher

the trait rumination level, the less cognitive costs following real

neuromodulation of the right DLPFC. Interestingly, these effects were

observed for both positive and negative stimuli. Overall, the data

suggest that the right DLPFC is causally involved in the alteration of

Fig. 1 S-5b-01: Effect of rumination on the compound scores for cognitive control.


123

cognitive control in healthy individuals who tend to ruminate, pos-

sibly by helping them to disengage from emotional material.


report.

S-5b-02The psychomotor retardation may be a marker of responseto rTMS treatment in patients with major depressive disorder

A. Sauvaget1, S. Bulteau1,2, T. Deschamps3, V. Thomas-Ollivier3

1CHU de Nantes, Addictology and Liaison Psychiatry Department,

Nantes, France; 2University of Nantes-University of Tours, INSERM,

SPHERE U1246-‘‘methodS for Patients-centered outcomes & HEalth

REsearch’’, Nantes, France; 3Laboratory ‘Movement, Interactions,

Performance’ (EA 4334), Faculty of Sport Sciences, University of

Nantes, Nantes, France

Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic

option often used in routine care plans for patients with major

depressive disorder (MDD).

Cognitive state and state-dependency influence the effectiveness

of rTMS. Based on our recent studies, we therefore assume that

psychomotor retardation (PMR), a core symptom of depression, can

be a marker of response to rTMS. Thus, we aimed at better under-

standing the interaction between the cognitive component of the PMR

and the rTMS in patients with MDD.

First, we investigated the feasibility of a comprehensive battery of

tests assessing PMR in MDD patients after a 3-week protocol of

rTMS. All these measures not only were feasible, free of adverse

effects, and well tolerated by the MDD patients in naturalistic con-

ditions before or after the rTMS protocol. Interestingly, preliminary

insights emerged from improvements in some psychomotor assess-

ments following the intervention, especially in balance performance.

We then examined whether postural control variables, coming from

the analysis of center-of-pressure trajectories recorded by a force

platform, could be a relevant hallmark of depression-related PMR.

We found that the initial postural instability while backward counting

is likely a sound moderator of positive outcomes in MDD patients

after rTMS intervention. The improved dual task performance might

be indicative of improvement in cognitive efficiency. Accordingly,

we explored the cognitive component of PMR through the analysis of

verbal fluency (VF) performance in unipolar and bipolar depression.

We also examined whether rTMS could improve concomitantly the

PMR and VF capacities. Correlations between the Retardation Rating

Scale for Depression and VF performances were found after treat-

ment, showing the cognitive role of psychomotor functioning in

depression. Overall, all these promising results arise the issues of how

to characterize and measure objectively the PMR, and to better

understand the mechanisms of rTMS in depressive disorders.

References:

1. Thomas-Ollivier V, Foyer E, Bulteau S, Pichot A, Valriviere P,

Sauvaget A, Deschamps T (2017) Cognitive component of psy-

chomotor retardation in unipolar and bipolar depression: is verbal

fluency a relevant marker? Impact of repetitive transcranial stimula-

tion. Psychiatry Clin Neurosci 71(9):612–623

2. Deschamps T, Sauvaget A, Pichot A, Valriviere P, Maroulides M,

Bois A, Bulteau S, Thomas-Ollivier V (2016) Posture-cognitive dual-

tasking: a relevant marker of depression-related psychomotor retar-

dation. An illustration of the positive impact of repetitive transcranial

magnetic stimulation in patients with major depressive disorder.

J Psychiatr Res 83:86–93

3. Thomas-Ollivier V, Deschamps T, Bulteau S, Le Gall F, Pichot A,

Valriviere P, Vachon H, Sauvaget A. Effect of Repetitive Transcra-

nial Magnetic Stimulation on Psychomotor Retardation in Major

Depression: A Pilot Feasibility Study. J Neuropsychiatry Clin Neu-

rosci. 2016 Winter;28(1):62-5.

4. Miniussi C, Harris JA, Ruzzoli M (2013) Modelling non-invasive

brain stimulation in cognitive neuroscience. Neurosci Biobehav Rev

37(8):1702–1712

5. Silvanto J, Pascual-Leone A (2008) State-dependency of tran-

scranial magnetic stimulation. Brain Topogr 21(1):1–10


S-5b-03Challenging control over emotions in borderline personalitydisorder with tDCS

L. Wolkenstein1

1LMU, Munich, Germany


S-5b-04Cognitive and electrophysiological mechanisms of enhancing fluidintelligence

A.-K. Brem1,2 on behalf of the Honeywell SHARP Team1Max-Planck Institute of Psychiatry, Munich, Germany; 2Berenson-

Allen Center for Noninvasive Brain Stimulation, Department of

Neurology, Beth Israel Deaconess Medical Center, Harvard Medical

School, Boston, USA

To date, it is unclear whether fluid intelligence (Gf), an important pre-

dictor for professional success, wealth and health, can be enhanced, and

what the involved mechanisms might be. We investigated this question

in a randomized, controlled, double-blind, multicenter study. 392 par-

ticipants were assigned to receive executive function training combined

with either transcranial electrical stimulation or sham stimulation, or

active control training combined with sham stimulation. The results

show that changes in Gf are achievable as a function of training progress

and subsequent improvement in working memory performance, but not

other executive functions. At the neurophysiological level, the efficacy of

neurostimulation on cognitive training and Gf improvement depended on

frontal midline theta power. We further replicated this effect in an

independent within-subject design study. Understanding the effects of

physiological traits will help us to optimise and individualise interven-

tions using brain stimulation and cognitive training.

Policy of full disclosure: This research is based upon work supported

by the Office of the Director of National Intelligence (ODNI), Intel-

ligence Advanced Research Projects Activity (IARPA), via

2014-13121700007. The views and conclusions contained herein are

those of the authors and should not be interpreted as necessarily

representing the official policies or endorsements, either expressed or

implied, of the ODNI, IARPA, or the U.S. Government. The U.S.

Government is authorized to reproduce and distribute reprints for

Government purposes notwithstanding any copyright annotation

thereon. The speaker has no conflicts of interest.

S-5b-05Towards neurocognitive stimulation to treat affective disorders

J. O’Shea1

1Wellcome Centre for Integrative Neuroimaging, Oxford Centre for

Functional MRI of the Brain (FMRIB), Nuffield Department of

Clinical Neurosciences, University of Oxford, Oxford, UK


123

Cognitive neuropsychological models emphasize a causal role for

negative cognitive biases in susceptibility to anxiety and depression.

Acute administration of antidepressant drugs has been shown to shift

cognitive biases from negative to positive, with variation across

individuals predicting clinical response heterogeneity weeks later.

Thus brain circuits that encode cognitive biases are rational targets for

therapeutic brain stimulation.

While prefrontal TMS is an approved clinical treatment for

depression, tDCS is in development, with growing evidence for its

clinical efficacy. Relatively little is known about the mechanisms by

which prefrontal tDCS could drive affective change. We investigated

this is in a series of experiments.

We found that a single session of bifrontal tDCS reduced threat

vigilance, mimicking the acute cognitive impact of antidepressant

drugs. Next we tested whether this arises by tDCS changing aberrant

fronto-limbic signalling. In a high trait anxious sample, fMRI during

an attentional control task revealed that tDCS suppressed (hyperac-

tive) amygdala threat reactivity, and reduced the behavioural

influence of threatening face distractors. Thus, bifrontal tDCS causes

acute neuro-cognitive changes relevant to anxiety.

Next we asked whether bifrontal tDCS could augment positive

cognitive change induced by training. With attention bias modifica-

tion training in healthy volunteers we found null results. A follow-up

study in a high trait anxious sample also yielded a null effect. In both

studies, there was a null effect of the cognitive training itself. How-

ever, the combination of positive training and tDCS did reduce a

salivary cortisol marker of stress.

Using a reward-guided decision making task, we asked whether

bifrontal tDCS could change healthy volunteers’ learning rates from

probabilistic positive or negative outcomes. Stimulation increased the

influence of positive outcomes on participants’ subsequent instru-

mental choices, increasing approach behaviour. Ongoing research

aims to clarify the neural mediators of this tDCS-induced cognitive

change.

Policy of full disclosure: This work was supported by research

funding from the UK Medical Research Council. The authors have no

conflicts of interest.

S-6a Clinical applications: other

Chairs: Brunoni and Baeken

S-6a-01A multimodal investigation on the biological markers associatedwith the antidepressant effects of transcranial direct currentstimulation

A. Brunoni1,2

1Service of Interdisciplinary Neuromodulation, Department and

Institute of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil;2Department of Psychiatry and Psychotherapy, LMU Munich,

Munich, Germany

Transcranial direct current stimulation (tDCS) has been investigated

as a treatment for major depressive disorder, although results have

been heterogeneous: although some patients improve significantly

after tDCS, others show low response. Investigating predictors of

tDCS antidepressant response can identify patients that would

potentially benefit from tDCS and contribute to a better understanding

on the mechanisms of action of tDCS. In the Escitalopram vs. Electric

Current Therapy for Treating Depression Clinical Study (ELECT-

TDCS) trial, we evaluated the clinical efficacy of tDCS compared to

placebo and escitalopram, finding superiority of escitalopram vs.

tDCS and placebo and superiority of tDCS vs. placebo. In ELECT-

TDCS, we collected potential biomarkers of tDCS antidepressant

response. In this presentation data regarding clinical and neuropsy-

chological variables, heart rate variability, motor cortical excitability,

serum neurotrophin levels and voxel-based morphometry of the brain

in the context of antidepressant prediction will be shown and

discussed.

Policy of full disclosure: ARB receives a CAPES-Humboldt fellow-

ship for experienced researchers and is a consultant of the Neurocare

(Munich, Germany) group.

S-6a-02The impact of accelerated HF-rTMS on neurochemicals in majordepression: insights from 1H MR spectroscopy

C. Baeken1,2,3


University, Ghent, Belgium; 2Department of Psychiatry, Universitair

Ziekenhuis Brussel (UZBrussel), Vrije Universiteit Brussel (VUB),

Brussels, Belgium; 3Ghent Experimental Psychiatry (GHEP) Lab,

Ghent University, Ghent, Belgium

Accelerated repetitive transcranial magnetic stimulation (rTMS)

paradigms are currently used to improve treatment in major depres-

sive disorder (MDD). Although these new treatment algorithms seem

to be able to alleviate mood over a relatively short period of time, no

studies yet examined its cellular effects with regard to clinical out-

come, safety and neural integrity. We recruited eighteen right-handed

antidepressant-free unipolar treatment resistant depressed (TRD)

patients who participated in a 2-week randomized sham-controlled

accelerated high frequency (aHF)-rTMS crossover treatment study,

applied to the left dorsolateral prefrontal cortex (DLPFC). All

underwent 1H MR spectroscopy before and after each week of aHF-

rTMS treatment. We explicitly focused on neurochemical concen-

trations in the bilateral DLPFC and rostral anterior cingulate cortex

(rACC). At baseline, compared to healthy individuals, TRD patients

displayed significant lower glutaminergic concentrations in the left

DLPFC only. Clinical improvement was related to significant GABA

increases also in the left DLPFC only. No influences on neuronal

integrity were observed in any of the predefined regions of interest.

Besides that left DLPFC aHF-rTMS treatment resulted in immediate

GABA increases in the targeted area, this supposed excitatory neu-

rophysiologic stimulation paradigm seems to recruit primarily

inhibitory neurons, without affecting neuronal integrity.


report.

S-6a-03Transcranial direct current stimulation (tDCS) for obsessive–compulsive disorder

G. D’Urso1, A. R. Brunoni2,3, M. P. Mazzaferro4, A. Anastasia4,

A. de Bartolomeis5, A. Mantovani6,7

1Department of Clinical Neurosciences, Anesthesiology and

Pharmachoutilization, University Hospital of Naples Federico II,

Naples, Italy; 2Service of Interdisciplinary Neuromodulation,

Department and Institute of Psychiatry, University of Sao Paulo, Sao

Paulo, Brazil; 3Department of Psychiatry and Psychotherapy, LMU

Munich, Munich, Germany; 4Department of Public Health, University

of Naples Federico II, Naples, Italy; 5Department of Neurosciences,

Reproductive and Odontostomatological Sciences, University of


123

Naples Federico II, Naples, Italy; 6Department of Physiology,

Pharmacology and Neuroscience, Sophie Davis School of Biomedical

Education, City University of New York, New York, NY, USA;7Division of Experimental Therapeutics, Department of Psychiatry,

Columbia University/New York State Psychiatric Institute, New

York, NY, USA

Introduction: Presupplementary motor area (pre-SMA) hyperactivity

has been detected in obsessive–compulsive disorder (OCD) patients,

but it is not clear whether this is a putative primary cause or a

compensatory mechanism in this disorder pathophysiology. Consid-

ering the polarity-dependent effects on cortical excitability of

transcranial direct current stimulation (tDCS), we applied cathodal

and/or anodal tDCS to the pre-SMA of OCD patients to test which

current polarity might better improve symptoms.

Methods: Twelve treatment resistant OCD patients received in the

first phase of the study either 10 anodal (n = 6) or 10 cathodal

(n = 6) daily consecutive 2 mA/20 min tDCS sessions with the

active electrode placed bilaterally over the pre-SMA. In case of

improvement or no change in symptoms severity, the subjects

underwent 10 more sessions using the same current polarity. In case

of symptoms worsening after the first 10 sessions they were switched

to the other polarity for 10 more sessions to test the hypothesis of a

polarity-dependent effect. Therefore, each subject received 20 tDCS

sessions. The Yale–Brown Obsessive–Compulsive Scale (Y-BOCS)

and the Sheehan Disability Scale (SDS) were administered biweekly

to assess changes in symptoms severity.

Results: After 10 sessions, 50% of patients who initially received

anodal stimulation were switched to cathodal, while 100% of patients

initially assigned to cathodal stimulation continued on the same

polarity. At the end of the study, a statistically significant decrease

was observed in the mean Y-BOCS scores of those patients who

underwent cathodal tDCS, while no pre–post difference was found in

the scores of patients following anodal tDCS.

Discussion: Our results suggest that cathodal but not anodal tDCS

over the pre-SMA might be of help when dealing with treatment

resistant OCD patients.

Fig. 1 S-6a-03

References:

1. D’Urso G, Brunoni A, Mazzaferro M, Anastasia A, de Bartolomeis

A, Mantovani A (2016) Transcranial direct current stimulation for

obsessive–compulsive disorder: a randomized, controlled, partial

crossover trial. Depression Anxiety 33(12):1132–1140

2. Senco N, Huang Y, D’Urso G, Parra L, Bikson M, Mantovani A

et al (2015) Transcranial direct current stimulation in obsessive–

compulsive disorder: emerging clinical evidence and considerations

for optimal montage of electrodes. Expert Rev Med Devices

12(4):381–391

3. D’Urso G, Brunoni A, Anastasia A, Micillo M, de Bartolomeis A,

Mantovani A (2015) Polarity-dependent effects of transcranial direct

current stimulation in obsessive–compulsive disorder. Neurocase

22(1):60–64.


report.

S-6a-04Cognitive brain stimulation

A. T. Sack1

1Faculty of Psychology and Neuroscience and Maastricht Brain

Imaging Centre, Maastricht University, Maastricht, The Netherlands

Human cognition requires, and is to a large extent based on, our

ability of selectively focusing on certain aspects of our surroundings.

This ability of spatial attention control is often severely impaired after

stroke and in brain diseases including depression or dementia.

Investigating the neurobiological mechanism underlying these cog-

nitive abilities is paramount for understanding the relationship

between brain and cognition as a prerequisite to develop new means

to initiate, guide, and support cognitive enhancement and rehabilita-

tion. Magneto-/electroencephalography research demonstrated that

attention control is related to oscillatory mechanisms in specific lower

frequency-bands (4–20 Hz), especially the alpha frequency (10 Hz).

Directing attention to one visual hemifield lateralizes alpha power in

parietal cortices. We applied transcranial alternating current stimu-

lation (tACS) to modulate alpha lateralization as measured by EEG

and then assessed how such a tACS-induced change in alpha power

lateralization leads to respective changes in behavioral task perfor-

mances in healthy volunteers. Based on these studies, we then applied

this tACS alpha lateralization protocol also in patients suffering from

lateralized spatial attention deficits (hemineglect) in an attempt to

specifically support their cognitive rehabilitation.


report.

S-6b NIBS in cells and animals

Chairs: Reis and Nitsche

S-6b-01Testing neuromodulation avenues in model rats

R. Hadar1, C. Winter1

1Department of Psychiatry and Psychotherapy, Charite

Universitatsmedizin Berlin, Charite Campus Mitte, Berlin, Germany

The current challenge in the realm of psychiatry afflictions is to

progress from conventional treatments to individualized ones, how-

ever for this the underlying neurobiological mechanisms should be

thoroughly studied in an effort to identify biomarkers used to asso-

ciate symptoms with the underlying neurobiological deficits. To this

end, neuromodulation not only constitutes a promising novel inter-

vention technique, but also provides an excellent investigative tool

into the underlying neuropathologies. Using two different animal

models of psychopathology, a genetic rat model mimicking repetitive

symptoms as in Tourette Syndrome (TS) and the maternal immune

activation (MIA) rodent model of schizophrenia, we were able to

study the potential effects of targeted neuromodulation on disease

progression and manifestation, i.e. as an intervention technique as

well as a prevention measure. More specifically, we were able to

show that invasive deep brain stimulation (DBS) was successful in


123

reducing repetitive behavior and that these therapeutic effects are

mediated via the motor loop of basal ganglia thalamo-cortical circuit.

Further we revealed that non-invasive frontal anodal transcranial

direct current stimulation (tDCS) also yielded beneficial effects on

repetitive behavior, probably via the regulation of striatal parvalbu-

min interneurons. Using the MIA model we were able to show that a

continuous early DBS to the medial prefrontal cortex (mPFC) pre-

vented behavioral, brain structural and neurobiological manifestation

of schizophrenia. The identification of the involvement of the frontal

cortex in disease progression calls for the investigation of non-inva-

sive neuromodulation strategies such as frontal tDCS at an early, non-

symptomatic stage. Altogether our preclinical studies encourage the

testing of tDCS application as an intervention technique for TS

patients. The possibility of preventing or at least delaying symp-

tomatology in schizophrenia via early neuromodulation should be

further elaborated.

Policy of full disclosure: Supported by BMBF 01EW1409 (EraNet

Neuron RD_aDBS) and 01EE1403A (GCBS). The authors do not

have disclosures to report.

S-6b-02Cellular effects of low-dose tDCS: implications for neuroplasticity

B. Fritsch1

1Neuroplasticity and Neuromodulation Lab, Department of

Neurology, University Medical Center Freiburg, Freiburg, Germany


S-6b-03rTMS restores alterations in synaptic excitation/inhibition-balance

A. Vlachos1

1Department of Neuroanatomy, Institute of Anatomy and Cell Biol-

ogy, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Alterations in excitation/inhibition (E/I)-balance and disturbed

cortical homeostasis have been suggested to cause behavioral and

cognitive dysfunction in many brain diseases, such as schizophrenia,

autism and panic disorders. In these disease contexts, the diagnostic

and therapeutic potentials of non-invasive brain stimulation tech-

niques have been extensively studied. Yet, the cellular and molecular

mechanisms of rTMS-mediated neural plasticity and hence rTMS-

based therapies remain incompletely understood. We here tested

whether repetitive magnetic stimulation restores alterations in

synaptic E/I-balance in a preclinical model of maternal immune

activation (MIA). In entorhino-hippocampal slice cultures prepared

from the offspring of the well-established polyinosinic–polycytidylic

acid [Poly(I:C)] MIA model of schizophrenia, whole cell patch-clamp

recordings disclose alterations in E/I-balance of CA1 pyramidal

neurons. Specifically, an increase in inhibitory synaptic strength is

observed, while excitatory neurotransmission is not affected. Indeed,

a 10 Hz stimulation protocol reverses increased inhibitory synaptic

strength in MIA-slice cultures without affecting excitatory synaptic

strength. These results demonstrate that repetitive magnetic stimula-

tion influences the synaptic phenotype in MIA-slice cultures. Thus,

rTMS may assert its positive effects by reversing alterations in

synaptic E/I-balance under pathological conditions.

Policy of full disclosure: Supported by Federal Ministry of Education

and Research, Germany; GCBS-WP1: 01EE1403B.

S-7a Optimizing NIBS treatment: biomarkers

and RDoC approaches

Chairs: Poulet and Arns

S-7a-01Matching patient subtypes to neural circuits for novel brainstimulation treatments in affective disorders

D. Oathes1

1University of Pennsylvania, Philadelphia, USA

The utility of neuroimaging for defining targets in neuromodulation is

becoming increasingly apparent. We have gathered recent evidence

that TMS affects prototypical brain networks even when applied to

only a single brain area1. In our ongoing work, we show evidence that

TMS accessible regions in prefrontal cortex are effective in influ-

encing downstream subcortical brain regions as evidenced by

interleaved single pulse TMS with fMRI recordings. Additionally, our

broader research team has found robust evidence for subtypes of

major depressive disorder patients based on combined symptom and

resting fMRI data (‘biotypes’) that are confirmed in out of sample

cross validation and also predict clinical outcome from TMS2. We

argue that aggregating information from brain network representa-

tions with symptom profiles in patients will generate better, more

individualized targets for neuromodulation.

References:

1. Chen AC, Oathes DJ, Chang C, Bradley T, Zhou ZW, Williams

LM et al (2013) Causal interactions between fronto-parietal central

executive and default-mode networks in humans. Proc Natl Acad Sci

USA 110(49):19944–19949

2. Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F,

Meng Y et al (2017) Resting-state connectivity biomarkers define

neurophysiological subtypes of depression. Nat Med 23(1):28–38


report.

S-7a-02Optimizing TMS treatment for depression using neuro-cardiacguided TMS (NCG TMS)

T. Iseger1,2, M. Arns1,2,3

1Research Institute Brainclinics, Nijmegen, The Netherlands;2Department of Experimental Psychology, Utrecht University,

Utrecht, The Netherlands; 3neuroCare group, Munich, Germany

The efficacy of rTMS in the treatment of major depressive disorder

(MDD) has been well established in recent years. Most studies to date

have employed the ‘5-cm’ rule for targeting stimulation of the Dor-

solateral Prefrontal Cortex (DLPFC). New variations and

improvements of this targeting technique include the Beam-F3

method or neuronavigated rTMS. Furthermore, it has been proposed

that the efficacy of rTMS in MDD is more related to stimulating the

area that is functionally connected to the subgenual anterior cingulate

cortex (sgACC) rather than to specific cortical anatomical areas.

Therefore, we set-out to develop and test a new method that employs

knowledge about the functional role of the sgACC in parasympathetic

regulation such as heart rate control, to establish in real-time the

cortical area that is functionally connected to the sgACC. Previous

studies have shown that stimulation of both the DLPFC as well as the

sgACC, leads to heart rate deceleration, most likely through down-

stream connectivity with the vagal nerve. In a pilot study, we used


123

electrocardiogram (ECG) R-peak triggered single pulse TMS to

various frontal locations to investigate the location that most con-

sistently resulted in a heart rate deceleration. On group level, F3 and

F4 expressed the largest heart rate deceleration, in line with studies

suggesting these are the best 10–20 sites to target the DLPFC. On the

individual level, 20–40% subjects expressed the largest heart rate

deceleration at FC3 or FC4, indicating individual differences as to the

‘optimal site for stimulation’. The potential implications of this

Neuro-Cardiac-Guided TMS is that this could be the equivalent of the

‘motor threshold’ for the DLPFC, and thereby would be a cost-ef-

fective and reliable method for localizing the most efficient

stimulation target in the treatment of MDD.

Policy of full disclosure: TI has no disclosures to report. MA reports

options from Brain Resource (Sydney, Australia), is director and

owner of Research Institute Brainclinics, a minority shareholder in

neuroCare Group (Munich, Germany); TAI and MA are co-inventor

on a patent application covering NCG-TMS, but do not own the

patent nor receive any proceeds related to this patent; Research

Institute Brainclinics received research funding from Brain Resource

(Sydney, Australia) and neuroCare Group (Munich, Germany);

equipment support from Deymed, neuroConn and Mag-venture,

however data analyses and writing of this manuscript were

unconstrained.

S-7a-03Central and plasmatic plasticity markers and response to NIBS

M. Psomiades1

1Equipe de recherche PsyR2/CRNL/INSERM U1028/CNRS

UMR5292/CH Le Vinatier/UCBL1, Bron, France

Background: Fronto-temporal transcranial direct-current stimulation

(tDCS) with the anode placed over the left prefrontal cortex (PFC)

and the cathode over the left temporoparietal junction (TPJ) has been

proposed as a treatment for auditory verbal hallucinations (AVH) in

patients with schizophrenia1. However the neurophysiological effects

induced by tDCS that might underpin beneficial improvements

remain unclear. In this study, we used proton magnetic resonance

spectroscopy (MRS) to investigate N-acetyl-aspartate (NAA) con-

centration, a marker of brain metabolism, after and before patients

with AVH received ten tDCS sessions. We used ELISA assay to

investigate Brain-Derived Neurotrophic factor (BDNF) levels, a

peripheral marker of neuronal plasticity, after and before one tDCS

session.

We hypothesized that (1) tDCS decreases severity of AVH; (2) tDCS

decreases NAA concentration under the cathode and increases NAA

concentration under the anode; (3) one tDCS session modulates

peripheral BDNF levels.

Methods: In a double blind sham controlled study, 60 patients were

randomly allocated to receive either 10 sessions of real or sham tDCS

(2 sessions/day, 2 mA, 20 min). The severity of AVH was evaluated

by the Auditory Hallucination Rating Scale. 29 patients underwent 2

MRS acquisitions, one before and one after the 10 tDCS sessions.

Voxels were placed in the left TPJ and in the left DLPFC. The

neurotrophic effects of tDCS were evaluated in 27 patients after and

before one tDCS session.

Results: Real tDCS significantly reduced AVH in patients with

schizophrenia [Active group (n = 30): - 26%; sham group (n = 26):

- 12%; F(1,54) = 4.172; p = 0.046; g2 = 0.072]. Active tDCS

significantly decreased NAA concentration in the left TPJ [(n = 14;

- 1.05 ± 1.30; F(1,27) = 4.902; p = 0.035; g2 = 0.154]. One

session of active tDCS significantly decrease peripheral mature

BDNF levels (n = 14; - 24.5 ± 20%; F(1,25) = 5.166; p = 0.032;

g2 = 0.171).

Conclusion: In patients with schizophrenia, tDCS may reduce AVH

and decrease neuronal metabolism in the left TPJ. Also, one tDCS

session may reduce peripheral mature BDNF levels.


report.

S-7a-04Personalizing and enhancing rTMS treatment response: EEGpredictors, biomarkers and role of combining interventions

M. Arns1,2,3

1Department of Experimental Psychology, Utrecht University,

Utrecht, The Netherlands; 2Research Institute Brainclinics, Nijmegen,

The Netherlands; 3neuroCare group, Munich, Germany

Background: Repetitive transcranial magnetic stimulation (rTMS) is

considered an efficacious non-invasive neuromodulation treatment for

major depressive disorder (MDD). However, little is known about the

clinical outcome of combined rTMS and psychotherapy (rTMS + PT)

and biomarkers to predict treatment response. Through common

neurobiological brain mechanisms, rTMS + PT may exert enhanced

antidepressant effects compared to the respective monotherapies.

Objective: The current naturalistic study aimed to evaluate feasibility

and clinical outcome of rTMS + PT in a large group of MDD

patients. The second aim was to identify predictors of response and

remission.

Methods: A total of 196 patients with MDD were treated with at least

10 sessions of simultaneous rTMS and PT. rTMS was applied over

the DLPFC, either 10 Hz left or 1 Hz right. Psychotherapy was based

on principles of cognitive behavioural therapy (CBT). Symptoms

were measured using the BDI each fifth session until end of treatment

and at 6-month follow-up. Comparisons were made between

responders and non-responders, as well as between the 10 and 1 Hz

protocol. Additionally, baseline variables and early BDI change were

evaluated as predictors of response/remission.

Major findings and conclusions: (1) combining rTMS and PT resulted

in a 66% response and a 56% remission rate at the end of treatment

with 60% sustained remission at follow-up. Compared to previous

findings in RCTs, these rates are relatively high; (2) no differences

were found between the 10 and 1 Hz TMS regarding clinical out-

come; (3) clinical baseline variables were not predictive of treatment

outcomes; (4) early symptom improvement (at session 10) was highly

predictive of response, and may therefore be used to guide

rTMS + PT continuation.

Policy of full disclosure: MA reports options from Brain Resource

(Sydney, Australia); he is director and owner of Research Institute

Brainclinics, a minority shareholder in neuroCare Group (Munich,

Germany), and a co-inventor on 4 patent applications (A61B5/0402;

US2007/0299323, A1; WO2010/139361 A1) related to EEG, neuro-

modulation and psychophysiology, but does not own these nor

receives any proceeds related to these patents; Research Insitute

Brainclinics received funding from Brain Resource (Sydney, Aus-

tralia) and neuroCare Group (Munich, Germany), and equipment

support from Deymed, neuroConn and Magventure, however data

analyses and writing of this manuscript were unconstrained.


123

GCBS-1

Chairs: Nitsche and Winter

GCBS-1-01Neuromodulation in model rats

R. Hadar1, C. Winter1

1Department of Psychiatry and Psychotherapy, Charite

Universitatsmedizin Berlin, Charite Campus Mitte, Berlin, Germany

Non-invasive transcranial direct current stimulation (tDCS) and

invasive deep brain stimulation (DBS) of the prefrontal cortex (PFC)

constitute two stimulation approaches that affect dysfunctional PFC-

associated neural networks, i.e. specific neurobiological states that

underlie the behavioural manifestation of psychiatric syndromes. The

clinical efficacy of the stimulation approach is determined by its

ability to affect the underlying neurobiological states. We here pre-

sent an animal experimental approach that uses two different

previously characterized animal models of psychopathology, a

genetic rat model mimicking repetitive symptoms as in Tourette

Syndrome (TS) and the maternal immune activation (MIA) rodent

model of schizophrenia to study the behavioral and neurobiological

effects of DBS and tDCS on disease progression and manifestation,

i.e. as an intervention technique as well as a prevention measure. DBS

is first used in an effort to normalize pathological behaviors and

further in combination with neurobiological assessments, imaging

techniques and computational modeling such that brain regions for

the application of tDCS are identified. Using the genetic rat model of

TS, we were able to show that DBS was successful in reducing

repetitive behavior and that these therapeutic effects are mediated via

the motor loop of basal ganglia thalamo-cortical circuit. Further we

revealed that frontal anodal tDCS also yielded beneficial effects on

repetitive behavior, probably via the regulation of striatal parvalbu-

min interneurons. Using the MIA model we were able to show that a

continuous early DBS to the medial prefrontal cortex (mPFC) pre-

vented behavioral, brain structural and neurobiological manifestation

of schizophrenia. The identification of the involvement of the frontal

cortex in disease progression also calls for the investigation of non-

invasive frontal neuromodulation at an early, non-symptomatic stage.

In summary we found that non-invasive tDCS and invasive DBS of

the PFC were proven to be effective in normalising aberrant beha-

vioural manifestations along with its underlying neurobiological

states using different pathology models. Altogether, our preclinical

studies encourage the application of tDCS as an intervention tech-

nique and its investigation as a possible preventive strategy in

psychiatry.

Policy of full disclosure: Supported by BMBF 01EW1409 (EraNet

Neuron RD_aDBS) and 01EE1403A (GCBS). The authors do not

have disclosures to report.

GCBS-1-02rTMS animals (WP1B)

K. Funke1

1Department of Neurophysiology, Ruhr-University Bochum, 44780

Bochum, Germany

Project WP1B of the German Center for Brain Stimulation (GCBS)

utilizes rat models to investigate the neural effects of repetitive

transcranial magnetic stimulation (rTMS) at the cellular and beha-

vioural level. Maternal immune stimulation (MIS) is used as a model

system to find cellular counterparts of changes in behavioural phe-

notypes associated with psychiatric states and to test rTMS as a

potential therapeutic intervention. Directly referring is the question if

pathological as well as physiological changes of the status of the

stimulated neuronal network will affect the outcome of rTMS.

Previous studies have shown that high-frequency stimulation

protocols—in particular the intermittent theta-burst stimulation

(iTBS)—induce effects indicative of a disinhibitory actions, evident

as reduced parvalbumin (PV) expression in fast-spiking inhibitory

interneurons (FSI)1, enhanced cortical sensory responses2 and

improved learning performance3. The iTBS effect, however, varies

with the history of exploratory behaviour, age and strain of the rats,

the latter obviously as a consequence of differences in number and

activity of inhibitory elements4.

First results obtained with the MIS model indicate not only altered

sensory gating (pre-pulse inhibition) but also altered expression of PV

and calbindin (another calcium-binding protein expressed in non-FSI)

in subregions of prefrontal cortex (PFC), and altered activity patterns

within the PFC-hippocampal network as verified by the temporal

correlation of theta and gamma rhythms. While effects of iTBS were

not evident at the behavioural level when applied in adulthood, PFC-

hippocampal theta/gamma coupling tended to improve after iTBS.

In vitro studies on CA1 region of the hippocampus showed increased

inhibition and less excitability of pyramidal cells in the MIS model

which could be almost normalized via both acute rTMS treatment

(10 Hz) of hippocampal cultures but also with iTBS of rats prior to

subsequent ex vivo–in vitro analysis. These other findings indicate

possible interventions prior to or during adolescent development.

References:

1. Benali A, Trippe J, Weiler E, Mix A, Petrasch-Parwez E, Girzalsky

W, Eysel UT, Erdmann R, Funke K (2011) Theta-burst transcranial

magnetic stimulation alters cortical inhibition. J Neurosci

31(4):1193–1203. https://doi.org/10.1523/JNEUROSCI.1379-10.2011

2. Thimm A, Funke K (2015) Multiple blocks of intermittent and

continuous theta-burst stimulation applied via transcranial magnetic

stimulation differently affect sensory responses in rat barrel cortex.

J Physiol 593(4):967–985. https://doi.org/10.1113/jphysiol.2014.

282467

3. Mix A, Benali A, Eysel UT, Funke K (2010) Continuous and

intermittent transcranial magnetic theta burst stimulation modify

tactile learning performance and cortical protein expression in the rat

differently. Eur J Neurosci 32(9):1575–1586. https://doi.org/10.1111/

j.1460-9568.2010.07425.x

4. Mix A, Benali A, Funke K (2014) Strain differences in the effect of

rTMS on cortical expression of calcium-binding proteins in rats. Exp

Brain Res 232(2):435–442. https://doi.org/10.1007/s00221-

013-3751-6


report.

GCBS-1-03Optimizing physiological tDCS effects

M. A. Nitsche1, D. Agboada1, M. Mosayebi1, M.-F. Kuo1

1Department of Psychology and Neurosciences, Leibniz Research

Centre for Working Environment and Human Factors, Leibniz,

Germany

Transcranial direct current stimulation (tDCS) induces neuroplastic

alterations of cortical excitability, which are stimulation-polarity

dependent regarding classical stimulation protocols, where anodal

tDCS enhances, while cathodal tDCS reduces cortical excitability.

For clinical application, stimulation protocols which result in opti-

mized strength of effects are required. Here, the impact of


123

http://dx.doi.org/10.1523/JNEUROSCI.1379-10.2011

http://dx.doi.org/10.1113/jphysiol.2014.282467

http://dx.doi.org/10.1113/jphysiol.2014.282467

http://dx.doi.org/10.1111/j.1460-9568.2010.07425.x

http://dx.doi.org/10.1111/j.1460-9568.2010.07425.x

http://dx.doi.org/10.1007/s00221-013-3751-6

http://dx.doi.org/10.1007/s00221-013-3751-6

pharmacological interventions as well as specific stimulation dura-

tion, and intensity effects, which have shown to result in non-

linearities of the impact of tDCS on cortical excitability, have to be

taken into account. In two project lines, we (1) explored the impact of

chronic antidepressant application on tDCS effects, and (2) investi-

gated the effects of variation of stimulation duration (15, 20, 30 min),

and intensity (1, 2, and 3 mA) on neuroplastic after-effects of tDCS.

The results show that the SSRI citalopram and the SNRI reboxetine

enhanced the long-term potentiation-like effects of anodal tDCS,

while these pharmacological interventions converted long-term

depression-like effects of cathodal tDCS into facilitation. Moreover,

dependent on stimulation intensity and duration, anodal and cathodal

tDCS exerted complex non-linear effects on cortical excitability. We

thus conclude that combination of tDCS with SSRI and SNRI might

be able to potentiate therapeutic effects of tDCS, if LTP-like plasticity

is warranted, and that furthermore specification of stimulation

intensity and duration might be crucial to obtain optimal effects.

Policy of full disclosure: Member of the Advisory board of

Neuroelectrics.

GCBS-1-04Lasting amelioration of deficient cognitive control in depressionby transcranial direct current stimulation (tDCS)-enhancedtraining

C. Plewnia1


Interventional Neuropsychiatry, University of Tubingen, Tubingen,

Germany


S-8a Reproducibility of NIBS

Chairs: Kuo and Kammer

S-8a-01Effects of prefrontal tDCS on resting-state functionalconnectivity: variability, non-linearity and state-dependency

J. Worsching1

1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-

University, Munich, Germany

Transcranial Direct Current Stimulation (tDCS) is a non-invasive

brain stimulation technique with the potential to modify cortical

excitability. Especially, tDCS over the dorsolateral prefrontal cortex

(DLPFC) may be a promising stimulation target for clinical appli-

cation and in combination with neuroimaging may advance

investigations into plasticity of cognitively relevant neural systems

and circuits. Recently, both the test–retest (TRT) reliability of tDCS

effects as well as the classical anodal-increase and cathodal-decrease

assumptions have been questioned. In addition, inter-individual

variations in and state-dependency of tDCS responses have been

found. Yet, none of these issues have been systematically evaluated

for tDCS-induced modulations in functional magnetic resonance

imaging (fMRI). Therefore, prior to a more extensive use, it is

important to understand the interplay between neural systems and

stimulation protocols requiring basic methodological work. In a first

study, we investigated the TRT reliability of prefrontal tDCS-effects

on functional resting-state (RS) connectivity and found a shift in the

distribution of voxel-wise intra-class-correlations (ICC) towards

lower values in the active tDCS-group as compared to the sham

group. In a second study, we investigated whether tDCS effects are

electrode-montage specific by systematically reversing and changing

the prefrontal electrode-placement within the same subjects. Because

findings, including our TRT results, may be state-dependent, tDCS

effects were monitored using both RS-fMRI and a cognitive task.

Results indicated both montage- and monitoring-level-specific

effects. Altogether, these results support the notion of active tDCS

modulating RS-fMRI connectivity, however point towards a high

intra-individual variability, state-dependency and non-dichotomous

and even non-linear, montage-specific dose–response relations.

Policy of full disclosure: This work was supported by the German

Center for Brain Stimulation (GCBS) research consortium (Work

Package 5, grant number: 01EE1403E), funded by the Federal Min-

istry of Education and Research (BMBF).

S-8a-02Efficacy and interindividual variability following LTP-likeplasticity inducing PAS and anodal tDCS

W. Strube1, T. Bunse1, B. Malchow1, A. Hasan1


University (LMU), Munich, Germany

Interindividual response variability to various motor-cortex stimula-

tion protocols has been recently reported. Comparative data of

stimulation protocols with different modes of action is lacking. We

aimed to compare the efficacy and response variability of two LTP-

inducing stimulation protocols in the human motor cortex: anodal

transcranial direct current stimulation (a-tDCS) and paired-associative

stimulation (PAS25). In two experiments 30 subjects received 1 mA

a-tDCS and PAS25. Data analysis focused on motor-cortex

excitability change and response defined as increase in MEP applying

different cut-offs. Furthermore, the predictive pattern of baseline

characteristics was explored. Both protocols induced a significant

increase in motor-cortical excitability. In the PAS25 experiments the

likelihood to develop a MEP response was higher compared to

a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for

a response was higher in the a-tDCS experiments. Baseline ICF

(12 ms) correlated positively with an increase in MEPs only follow-

ing a-tDCS and responders had significantly higher ICF baseline

values. Contrary to recent studies, we showed significant group-level

efficacy following both stimulation protocols confirming older stud-

ies. However, we also observed a remarkable amount of

nonresponders. Our findings highlight the need to define sufficient

physiological read-outs for a given plasticity protocol and to develop

predictive markers for targeted stimulation.

Policy of full disclosure: W.S. has received speaker’s honorarium

from Mag&More GmbH.

S-8a-03What does it tell you when your transcranial electric stimulationexperiment failed?

P. Sauseng1, A. L. Biel1, E. V. C. Friedrich1

1Department of Psychology, LMU Munich, Munich, Germany

Empirical research on electrical brain stimulation in cognition has

been a field where traditionally many experiments are statistically

underpowered. Sample sizes of a couple of participants to approxi-

mately 20 volunteers are common. At the same time it has been

shown that transcranial electrical stimulation leads to fairly small


123

effects on cognition (particularly in young, healthy participants). This

makes it likely that a lot of experiments fail to provide evidence for

the tested alternative hypothesis. But does this mean that these

experiments support the null hypothesis? Here we will discuss what

parameters need to be addressed when planning a transcranial electric

stimulation study, so that the results might be more likely to be

conclusive. And we will propose that under certain circumstances

frequentist statistics (p-statistics) are not suitable for concluding that a

particular effect is not present (i.e. that the null hypothesis is true).


report.

S-8a-04Reproducibility of tDCS

M.-F. Kuo1, M. A. Nitsche1

1Department of Psychology and Neurosciences, Leibniz Research

Centre for Working Environment and Human Factors, Leibniz,

Germany

Transcranial direct current stimulation has been applied as a tool for

basic neurophysiological research and clinical studies over the past

decades. Despite encouraging results, variability was also observed in

some studies. This presentation will introduce possible sources of

variability, including methodological issues and clinical aspects.

Future directions of research will also be briefly discussed.


report.

GCBS-2

Chairs: Padberg and Bajbouj

GCBS-2-01Disorder-tailored transcranial direct current stimulation (tDCS)of the prefrontal cortex: goals and achievements

D. Keeser1,2, J. Worsching1, E. Mezger2, F. Padberg1


University Munich, Munich, Germany; 2Department of Radiology,

Ludwig Maximilian University Munich, Munich, Germany

The GCBS consortium aims to better understand non-invasive brain

stimulation methods such as tDCS of the prefrontal brain. In work

package 5 and work package 7, electrical stimulation in healthy

subjects and patients with major depression is investigated using

multimodal Magnetic Resonance Imaging (MRI) techniques. The

overall goal is a better understanding of the effects of transcranial

electrical stimulation in the brain. Are these effects reproducible?

What is the neurophysiological effect of specific prefrontal electrode

montages? Do we need to individually apply imaging to better predict

tDCS outcome? On the basis of finalized studies our approach of

these work packages will be presented and an outlook on (1) basic

research, (2) translation to the clinical application and (3) general-

ization of prefrontal tDCS will be presented and discussed.



Package 5, Grant number 01EE1403E), funded by the Federal Min-

istry of Education and Research (BMBF).

GCBS-2-02PsychotherapyPlus: augmentation of cognitive behavioraltherapy (CBT) with prefrontal transcranial direct currentstimulation (tDCS) in major depressive disorder: study designand methodology of a multicenter double-blind randomizedplacebo controlled trial

M. Bajbouj1, S. Aust1

1Department of Psychiatry, Charite-Universitatsmedizin Berlin,

Berlin, Germany

Background: Major Depressive Disorder (MDD) is one of the most

prevalent psychiatric disorders worldwide. About 20–30% of patients

do not respond to standard psychopharmacological and/or psy-

chotherapeutic treatment interventions. Mounting evidence from

neuroimaging studies in MDD patients revealed altered activation

patterns in lateral prefrontal brain areas showing that successful

cognitive behavioral therapy (CBT) is associated with a recovery of

these neural alterations. Moreover, it has been demonstrated that

transcranial direct current stimulation (tDCS) is capable of influenc-

ing prefrontal cortex activity and cognitive functions such as working

memory and emotion regulation. Thus, a clinical trial investigating

the effects of an antidepressant intervention combining CBT with

tDCS seems promising. The present study investigates the antide-

pressant efficacy of a combined CBT-tDCS intervention as compared

to CBT with sham-tDCS or CBT alone.

Methods: A total of 192 patients (20–65 years) with MDD (HDRS-

21 C 15) will be recruited at four study sites across Germany (Berlin,

Munich, Tuebingen, Freiburg) and randomly assigned to one of the

following three treatment arms: (1) CBT + active tDCS, (2)

CBT + sham-tDCS, and (3) CBT alone. All participants will attend a

6-week psychotherapeutic intervention comprising twelve sessions of

CBT each lasting 100 min in a closed group setting. tDCS will be

applied during each CBT session with active tDCS including stimu-

lation with an intensity of 2 mA for 30 min with the anode placed

over F3 and the cathode over F4 according to the EEG 10–20 system,

if assigned. The primary outcome measure is the change in Mont-

gomery-Asberg Depression Rating Scale scores from baseline to 6,

18, and 30 weeks after the first session. Participants also undergo pre

and post treatment neuropsychological testing and functional mag-

netic resonance imaging (fMRI) to assess changes in prefrontal

functioning and connectivity.

Discussion: The study investigates whether CBT can be augmented

by non-invasive brain stimulation techniques such as tDCS in the

treatment of MDD. It is designed as a proof-of-principle trial for the

combined tDCS-CBT treatment, but also allows the investigation of

the neurobiological underpinnings of the interaction between both

interventions in MDD.


report.

GCBS-2-03Design and methods of an ongoing randomized controlled studyof tDCS in major depression: the DepressionDC trial

F. Padberg1, T. Matt1, N. Behler1, L. Wulf1, U. Kumpf1, U. Palm1, S.

Egert2, U. Mansmann3, D. Keeser1, C. Plewnia4, B. Langguth5, J.

Cordes6, C. Normann7, P. Zwanzger8, A. Hasan1, M. Bajbouj9


University Munich, Munich, Germany; 2Munchner Studienzentrum,

Technical University of Munich, Germany; 3Institute for Medical

Information Processing, Biometry and Epidemiology (IBE), Ludwig

Maximilian University Munich, Munich, Germany; 4Department of

Psychiatry and Psychotherapy, University of Tubingen, Tubingen,


123

Germany; 5Department of Psychiatry and Psychotherapy, University

of Regensburg, Regensburg, Germany; 6Department of Psychiatry

and Psychotherapy, Medical Faculty, Heinrich-Heine University,

Dusseldorf, Germany; 7Department of Psychiatry and Psychotherapy,

University Medical Center Freiburg, Freiburg, Germany; 8kbo-Inn-

Salzach-Hospital, Wasserburg am Inn, Germany; 9Department of

Psychiatry and Psychotherapy, Charite-Campus Benjamin Franklin,

Berlin, Germany

The DepressionDC trial is a triple-blind, randomized, placebo-con-

trolled multicenter trial investigating the efficacy and safety of

prefrontal tDCS used as additive treatment in MDD patients who have

not responded to selective serotonin reuptake inhibitors (SSRI). At 7

German sites 152 patients with MDD receive a 6-weeks treatment

with active tDCS (anode F3 and cathode F4, 2 mA intensity,

30 min/day) or sham tDCS add-on to a stable antidepressant medi-

cation with an SSRI. Follow-up visits are at 3 and 6 months after the

last tDCS.

The primary outcome measure is the change of the Montgomery-

Asberg Depression Rating Scale (MADRS) scores at week 6 post-

randomisation compared to baseline. Secondary endpoints also cover

other psychopathological domains, and a comprehensive safety

assessment includes measures of cognition. The study uses an

advanced tDCS technology including recording of technical param-

eters (current, impedance, voltage) in each tDCS session. Here, we

present this novel approach for monitoring technical parameters of

tDCS and further methodological requirements (i.e. current density

modelling, standardized electrode positioning). The DepressionDC

trial aims at answering the clinical question whether prefrontal tDCS

is a safe and effective add-on intervention in patients who have not

sufficiently responded to SSRIs.

Policy of full disclosure: F.P. has received speaker’s honorarium from

Mag&More GmbH and the neuroCare Group as well as support with

equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More

GmbH and Brainsway Inc., Jerusalem, Israel. The other authors do

not have disclosures to report.

Poster abstracts

P-01Exploring the parameter space of physiological effects of cathodaltranscranial direct current stimulation over the primary motorcortex

M. M. Samani1,2, D. Agboada1,3, M.-F. Kuo1, M. A. Nitsche1,4

1Leibniz Research Centre for Working Environment and Human

Factors, Dortmund, Germany; 2Institute of Biomedical Engineering

and Informatics, Ilmenau University of Technology, Ilmenau,

Germany; 3International Graduate School of Neuroscience, IGSN,

Ruhr University Bochum, Bochum, Germany; 4Department of

Neurology, University Hospital Bergmannsheil, Bochum, Germany

Transcranial direct current stimulation (tDCS) can non-invasively

induce polarity-dependent excitability alterations in the human

motor cortex lasting more than an hour after stimulation [1, 2].

Clinical application with encouraging results have been reported in

several pilot studies, but the optimal stimulation protocols remain

to be determined. Recently, it was shown that there is a nonlinear

modulatory effect of stimulation intensity/duration on neuroplas-

ticity [3–5]. In this study, we systemically explored the association

between tDCS parameters (intensity, duration) and induced after-

effects on motor cortex excitability. Cathodal tDCS was applied in

three different intensities (1, 2 and 3 mA) and durations (15, 20

and 30 min) on 16 young healthy subjects and the after-effects

were monitored with TMS-induced motor evoked potentials (MEP)

until the evening after stimulation. The results revealed nonlinear

after-effects, which might be caused by calcium dynamics relevant

for long term depression and potentiation induction. 1 mA (for all

stimulation durations) and 3 mA -20 min induced LTD-like plas-

ticity, while LTP-like plasticity was observed after 2 mA

stimulation for 20 min. Our study thus provides further insights on

the dependency of tDCS-induced neuroplasticity on the stimulation

parameters, and therefore delivers crucial information for future

clinical applications.

References:

1. Nitsche MA, Paulus W (2001) Sustained excitability elevations

induced by transcranial DC motor cortex stimulation in humans.

Neurology 57:1899–1901

2. Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus

W (2003) Level of action of cathodal DC polarisation induced inhi-

bition of the human motor cortex. Clin Neurophysiol 114:600–604

3. Jamil A, Batsikadze G, Kuo HI, Labruna L, Hasan A, Paulus W

et al (2016) Systematic evaluation of the impact of stimulation

intensity on neuroplastic after-effects induced by transcranial direct

current stimulation. J Physiol 10:1e16

4. Batsikadze G, Moliadze V, Paulus W, Kuo MF, Nitsche MA (2013)

Partially non-linear stimulation intensity-dependent effects of direct

current stimulation on motor cortex excitability in humans. J Physiol

591:1987–2000

5. Monte-Silva K, Kuo M-F, Hessenthaler S, Fresnoza S, Liebetanz

D, Paulus W, Nitsche MA (2013) Induction of late LTP-like plasticity

in the human motor cortex by repeated non-invasive brain stimula-

tion. Brain Stimul 6:424–432


report.

P-02Electrode montage dependent effects of transcranial directcurrent stimulation on working memory

M. Splittgerber1*, M. Maack1*, H. Brauer2, C. Breitling3,

A. Prehn-Kristensen2, K. Krauel3, P. Miranda4, R. Nowak5,

M. Siniatchkin1*, V. Moliadze1*1Department of Medical Psychology and Medical Sociology,

Schleswig-Holstein University Hospital (UK-SH), Christian-

Albrechts-University, Kiel, Germany; 2Department of Child and

Adolescent Psychiatry, Center for Integrative Psychiatry, Kiel,

Germany; 3Department of Child and Adolescent Psychiatry and

Psychotherapy, Otto-von-Guericke University Magdeburg,

Magdeburg, Germany; 4Fundacao da Faculdade de Ciencias da

Universidade de Lisboa, Lisbon, Portugal; 5Neuroelectrics,

Barcelona, Spain

* These authors have equally contributed to the work

Introduction: Recent studies show that tDCS applied over the left

dorsolateral prefrontal cortex (lDLPFC) can successfully affect

working memory (WM) performance1. The present study investigates

the influences of a classical bipolar and more focal multichannel

tDCS over the lDLPFC on WM performance (2-back task) and con-

tinuous performance task (CPT) as non-target task.

Methods: The study was approved by the Ethic Committee of the

Faculty of Medicine Christian-Albrechts University Kiel. Eighteen

healthy young adults (18–30 years) participated in the study. Partic-

ipants were stimulated 3 times (bipolar, multichannel, sham

stimulation in randomized order) over the lDLPFC for 20 min, min-

imum period between sessions was 7 days. For bipolar stimulation

1 mA was applied by two circular saline-soaked surface sponge

electrodes (25 cm2), with anode positioned over F3 and reference


123

over FP2. For multichannel tDCS we used five 3.14 cm2 circular

PiStim electrodes (Neuroelectrics, Barcelona, Spain), positioned at

AF3 (897uA), AF7 (284uA), F3 (819uA), FP2 (-1000uA) and T7 (-

1000uA). After stimulation EEG at rest (2 min eyes closed, 2 min

eyes open) and during 2-back and CPT performance was recorded.

Results: Preliminary behavioral results show significant improvement

of accuracy in the 2-back task after multichannel and bipolar tDCS

compared to sham stimulation but not for CPT performance. Inci-

dence and intensity of aversive side effects did not differ between

multichannel, bipolar or sham tDCS.

Conclusion: Our behavioral results show that multichannel and

bipolar tDCS over the lDLPFC have the potential of modulating WM

performance, with multifocal stimulation not eliciting greater effects,

which is in contrary to results of motor cortex area stimulation2. Our

results on aversive side effect underline the tolerability of both

multichannel and bipolar tDCS.

References

1. Coffman B; Clark V, Parasuraman R (2014) Battery powered

thought. Enhancement of attention, learning, and memory in healthy

adults using transcranial direct current stimulation. NeuroImage 85(Pt

3):895–908

2. Fischer DB, Fried PJ, Ruffini G, Ripolles O, Salvador R, Banus J

et al (2017) Multifocal tDCS targeting the resting state motor network

increases cortical excitability beyond traditional tDCS targeting uni-

lateral motor cortex. NeuroImage 157:34–44

Policy of full disclosure: This study was conducted as part of the

STIPED program. STIPED has received funding from European

Union’s Horizon 2020 research and innovation programme under

Grant Agreement No. 731827. The authors do not have disclosures to

report.

P-03Exploring the effects of transcranial direct current stimulationon cognitive control training

S. Weller1, C. Plewnia1

1Department of Psychiatry and Psychotherapy Neurophysiology and

Interventional Neuropsychiatry, University Hospital Tubingen,

Tubingen, Germany

The dorsolateral prefrontal cortex (dlPFC) is a brain structure

responsible for working memory performance and cognitive control

(CC) [1]. CC, critically underlying goal-directed behaviour, has been

shown to be impaired in depression and to be associated with reduced

activity of the dlPFC [2]. Transcranial direct current stimulation

(tDCS) of this brain area can modify CC and has already shown to

enable amelioration as well as the impairment of CC [3–5]. Within

this study series we systematically investigate the effects of tDCS on

a CC training in healthy participants by varying stimulation param-

eters regarding intensity, polarity and laterality. Over the course of 8

sessions within 4 weeks participants perform a modified adaptive

paced auditory serial addition task (PASAT) during which they hear a

series of single digit numbers and are instructed to add the most recent

digit to the third to last digit (n + n - 2). Digit presentation speed is

adapted to performance with the goal to challenge CC by inducing

stress and frustration during the experiment. TDCS is applied for

19 min during each training session. The first two test groups receive

stimulation of the left dlPFC with 1 and 2 mA respectively, the third

and fourth group are treated likewise except that stimulation is shifted

to the right dlPFC. Each group is furthermore divided into subjects

receiving either anodal, cathodal or sham tDCS. Within the first study

group, subjects who received anodal stimulation (1 mA) to the left

dlPFC showed significant performance gains in the PASAT compared

to cathodal (1 mA) and sham stimulation, suggesting that

improvement was aided by plasticity enhancement of CC induced by

tDCS. Results for the second group (2 mA, left dlPFC) are currently

being processed, while the third and fourth group (1 and 2 mA, right

dlPFC) will be finished by end of this year.

References

1. Miller EK (2000) The prefrontal cortex and cognitive control. Nat

Rev Neurosci 1(1):59–65

2. Fitzgerald P, Laird A (2008) A meta-analytic study of changes in

brain activation in depression. Hum Brain Mapp [Internet]

29(6):683–695

3. Wolkenstein L, Plewnia C (2013) Amelioration of cognitive con-

trol in depression by transcranial direct current stimulation [Internet].

Biol Psychiatry 73

4. Plewnia C, Schroeder PA, Kunze R, Faehling F, Wolkenstein L

(2015) Keep calm and carry on: Improved frustration tolerance and

processing speed by transcranial direct current stimulation (tDCS).

PLoS One [Internet] 10(4):1–12

5. Plewnia C, Schroeder PA, Wolkenstein L (2015) Targeting the

biased brain: non-invasive brain stimulation to ameliorate cognitive

control. Lancet Psychiatry 2(4):351–356


report.

P-04The effect of transcranial direct current stimulation on cognitivecontrol and emotion regulation in depressed patients

A. Sommer, S. Max, L. Wolkenstein, C. Plewnia

Department for Neurophysiology and interventional Neuropsychiatry,

University Hospital Tuebingen, Clinic for Psychiatry and

Psychotherapy, Tubingen, Germany

Background: Deficient cognitive control (CC) and the use of dys-

functional emotion regulation strategies (ERS) are both central

characteristics of major depression. Both are associated with reduced

activity of the dorsolateral prefrontal cortex (dlPFC). Transcranial

direct current stimulation (tDCS) is a safe, simple and effective non-

invasive method to modulate the cortical excitability. The goal of our

study is to examine the effect of transcranial direct current stimulation

(tDCS) on the CC and ERS in depressed patients compared to healthy

subjects.

Methods: Overall, this randomized, sham-controlled, double blind

clinical trial will include 44 participants (22 depressed patients and 22

healthy subjects). Each participant will complete a CC task while

receiving sham tDCS in one session and anodal tDCS in the other

session (counterbalanced). Afterwards the ERS ‘rumination’ will be

measured during a 7-min resting phase by means of a questionnaire

and psychophysiological measures (heart rate variability). Overall,

this experiment will provide additional data for the development of

new treatment methods.

Results: As the study is still in preparation preliminary results will be

presented and discussed at the conference. We hypothesize (1) an

amelioration of CC by anodal tDCS and (2) a reduced use of the

dysfunctional emotion regulation strategy ‘rumination’ after anodal

tDCS.

Future prospects: The effect tDCS can outlast the stimulation time

when combined with a training. The next step towards a new treat-

ment method for major depression and also other psychiatric diseases

will be to conduct a tDCS supported CC-training study.


report.


123

P-05General effects of cathodal tDCS on implicit associations

P. A. Schroeder1, C. Plewnia1

1Department of Psychiatry and Psychotherapy, University of

Tubingen, Tubingen, Germany

In contrast to deliberate decisions, spontaneous human behaviour can

be influenced by implicit cognitive biases. Without direct intention,

and convergent to explicit self-reports, implicit associations are

thought to predict particularly non-reflective behaviours. Neverthe-

less, activation of implicit associations could draw on prefrontal

cortex regions. For example, the implicit spatial association of

number magnitude was reduced during stimulation with cathodal

tDCS to the left prefrontal cortex [1]. In the present study, we tested

the general effect of prefrontal cathodal tDCS on the standardized

insect-flower implicit associations task (IAT). In the task, participants

use two keys to classify four target categories (insects, flowers, pos-

itive, negative). The blocked combinations of insects + negative and

flowers + positive in the compatible IAT condition produced faster

response times than the opposite combinations of insects + positive

and flowers + negative in the incompatible IAT condition. Most

critically, this IAT effect was reduced during cathodal tDCS, as

compared to sham tDCS (see Figure 1). These results indicate gen-

eralizability of our previous findings and exemplify another

potentially beneficial effect of cathodal tDCS [1–3]. Future studies on

modulations of implicit biases with cathodal tDCS are needed to

examine longevity, transfer, and stability in other biases and/or set-

tings. Clinical effectivity should be examined in patient populations

as well.

References:

1. Schroeder PA, Pfister R, Kunde W, Nuerk H-C, Plewnia C (2016)

Counteracting implicit conflicts by electrical inhibition of the pre-

frontal cortex. J Cogn Neurosci 28(11):1737–1748

2. Schroeder PA, Plewnia C (2016) Beneficial effects of cathodal

transcranial direct current stimulation (tDCS) on cognitive perfor-

mance. J Cogn Enhanc 1(1):5–9

3. Zwissler B, Sperber C, Aigeldinger S, Schindler S, Kissler J,

Plewnia C (2014) Shaping memory accuracy by left prefrontal tran-

scranial direct current stimulation. J Neurosci 34(11):4022–4026


report.

P-06Brain stimulation over frontopolar cortex enhances motivationto exert effort for reward

A. Soutschek1,2, P. Kang1, C. C. Ruff1,2, T. A. Hare1,2,*,

P. N. Tobler1,2,*

1Laboratory for Social and Neural Systems Research, Department of

Economics, University of Zurich, Zurich, Switzerland; 2Neuroscience

Center Zurich, University of Zurich, Swiss Federal Institute of

Technology Zurich, Zurich, Switzerland

*Shared senior authors

Loss of motivation is a characteristic feature of several psychiatric

and neurological disorders. However, the neural mechanisms under-

lying human motivation are far from being understood. Here, we

show that frontopolar cortex (FPC) plays a crucial role in motivating

cognitive and physical effort exertion by computing subjective effort

equivalents. We manipulated neural processing with transcranial

direct current stimulation targeting FPC while participants decided

whether or not to engage in cognitive or physical effort to obtain

rewards. We found that brain stimulation targeting FPC increased the

amount of both types of effort participants were willing to exert for

rewards, while leaving the subjective strain of the required effort

unaffected. Our findings provide important insights into the neural

mechanisms involved in motivating effortful behaviour and suggest

that further exploration of FPC function could facilitate the devel-

opment of treatments for the loss of motivation commonly seen in

psychiatric and other neurological disorders.


report.

P-07The influence of tDCS on prosocial behaviour when being sociallyexcluded: experimental design

L. Wulf1, J. Dewald-Kaufmann1,2, T. Wustenberg3, B. Barton1, N.

Behler1, J. Worsching1, F. Padberg1

1Department of Psychiatry and Psychotherapy, University Hospital

LMU Munich, Munich, Germany; 2Hochschule Fresenius, University

of Applied Sciences, Munich, Germany; 3Charite-

Universitatsmedizin Berlin, Charite Campus Mitte, Klinik fur

Psychiatrie & Psychotherapie, Berlin, Germany

Background: The Cyberball-Paradigm represents an elegant tool to

investigate psychosocial phenomena such as ostracism, discrimina-

tion and prejudices [1, 2]. A considerable amount of Cyberball-studies

could show that the experience of social exclusion leads to an increase

of negative feelings, aggressive behaviour and the inclination of anti-

social behaviour [3–7]. A new modified version of the Cyberball-

Paradigm allows the simulation of a partial exclusion [8]. The par-

ticipant is excluded by only one player (one includer, one excluder)

which enables a more differentiated data collection regarding beha-

vioural tendencies and cognitions towards the including and

excluding person. For instance, a recent, unpublished study by

Dewald-Kaufmann and colleagues [8] provides evidence that

depressive and borderline patients behave significantly less prosocial

towards the excluder than healthy participants. On this background

the goal of this pilot study is to examine the effect of a brain stim-

ulation targeting emotion regulations areas (rVLPFC, F6) with anodal

tDCS on prosocial behaviour and cognition. In addition, we want to

shed light on potential moderating trait factors like neuroticism val-

ues, self-esteem and resilience. An electrocardiogram (ECG) is

integrated as objective stress measurement to figure out if excluded

participants show a higher stress response than in the inclusion

condition.

Study-design: Double-blind, randomized placebo-controlled 2 9 2

within-subject and between-groups design with 36 healthy partici-

pants. Each participant will play both conditions (inclusion and

exclusion) of the new Cyberball-Paradigm for 12 min. 15 min before

Cyberball starts each participant receives brain stimulation (sham vs.

verum tDCS) of the right ventrolateral prefrontal cortex (F6). The

ECG will record the heart rate in the 12 min period of playing. All

participants will be screened regarding psychological abnormalities in

advance to the first study visit.

Conclusion:With this pilot study we want to gain more insights about

the effects of rVLPFC tDCS on interpersonal behavior and cognition

as well as to figure out potential application areas of tDCS on emotion

regulation and coping with stressful social situations.

References:

1. Williams KD, Jarvis B (2006) Cyberball: a program for use in

research on interpersonal ostracism and acceptance. Behav Res

Methods 38(1):174–180

2. Williams KD, Williams KD, Cheung CK, Choi W (2000)

Cyberostracism: effects of being ignored over the Internet. J Person-

ality Soc Psychol 79(5):748–762


123

3. Riva P, Lauro LJR, DeWall CN, Bushman BJ (2012) Buffer the

pain away stimulating the right ventrolateral prefrontal cortex reduces

pain following social exclusion. Psychol Sci 23(12):1473–1475

4. Riva P, Lauro LJR, DeWall CN, Chester DS, Bushman BJ

(2014) Reducing aggressive responses to social exclusion using

transcranial direct current stimulation (tDCS). Soc Cogn Affect

Neurosci nsu053

5. Riva P, Romero Lauro LJ, Vergallito A, DeWall CN, Bushman BJ

(2015) Electrified emotions: modulatory effects of transcranial direct

stimulation on negative emotional reactions to social exclusion. Soc

Neurosci 10(1):46–54

6. Dambacher F, Schuhmann T, Lobbestael J, Arntz A, Brugman S,

Sack AT (2015) Reducing proactive aggression through non-invasive

brain stimulation. Soc Cogn Affect Neurosci nsv018

7. Eisenberger NI, Lieberman MD, Williams KD (2003) Does

rejection hurt? An fMRI study of social exclusion. Science

302(5643):290–292

8. Dewald-Kaufmann et al., in preparation




GmbH and Brainsway Inc., Jerusalem, Israel. Linda Wulf is part-time

employee at the neurocare Group.

P-08Prefrontal MRI-compatible tDCS reduces ventromedial corticalperfusion after being criticized

J. Dedoncker1,2, M.-A. Vanderhasselt1,2,3, J. Remue1,3, S. De Witte1,2,

G.-R. Wu4, R. De Raedt3, C. Baeken1,2,5

1Department of Psychiatry and Medical Psychology, University

Hospital (UZ) Ghent, Ghent University, Ghent, Belgium; 2Ghent

Experimental Psychiatry (GHEP) Lab, Ghent, Belgium; 3Department

of Experimental Clinical and Health Psychology, Ghent University,

Ghent, Belgium; 4Key Laboratory of Cognition and Personality,

Faculty of Psychology, Southwest University, Chongqing, China;5Department of Psychiatry, University Hospital (UZ) Brussels,

Brussels, Belgium

Being sensitive to self-referential criticism might be a vulnerability

factor for the development and/or recurrence of mood disorders. We

aimed to explore whether one prefrontal tDCS session is capable of

modulating frontolimbic cortical perfusion in response to criticism,

depending on criticism-sensitivity (low vs. high). In a randomized,

sham-controlled crossover study, 30 healthy females were adminis-

tered one session of left prefrontal MRI-compatible active tDCS (vs.

sham), followed by exposure to verbal criticism recordings in the

scanner. Individual criticism-sensitivity (low vs. high) was evaluated

at baseline. Momentary mood and frontolimbic perfusion (by means

of arterial spin labeling) were assessed in the MRI scanner at three

time points: baseline, directly following tDCS, and after hearing

criticism. Regardless of being sensitive to criticism, and independent

from having had sham or active tDCS, after being criticized young

healthy females felt angrier. Criticism-sensitivity did however influ-

ence tDCS-induced brain perfusion: being criticized following active,

but not sham tDCS was related to a decrease in right ventromedial

prefrontal (pgACC/mPFC) perfusion only in highly criticism-sensi-

tive individuals. Momentary changes in mood following hearing

criticism, specifically increased angriness, were not modulated by

tDCS. Given that active tDCS decreased ventromedial prefrontal

perfusion after being criticized, tDCS may be able to reduce

responsiveness to negative self-referential information in highly

criticism-sensitive young females.


report.

P-09Does electrode localization in tDCS research matter?A comparison between 10–20 EEG system and MRI-guidedneuronavigation

S. De Witte1,2, D. Klooster3,4,5, J. Dedonckera,b, R. Duprat1,2,

J. Remue1,6, C. Baeken1,2,7


University Hospital, Ghent University, Ghent, Belgium; 2Ghent

Experimental Psychiatry (GHEP) Lab, Ghent, Belgium;3Kempenhaeghe Academic Center for Epileptology, P.O. Box 61,

5590 AB Heeze, The Netherlands; 4Department of Electrical

Engineering, University of Technology Eindhoven, P.O. Box 513,

5600 MB Eindhoven, The Netherlands; 5Department of Neurology,

Ghent University Hospital, Ghent, Belgium; 6Department of

Experimental Clinical and Health Psychology, Ghent University,

Ghent, Belgium; 7Department of Psychiatry, University Hospital

UZBrussel, Brussels, Belgium

Although the 10–20 EEG system is frequently used to locate the

dorsolateral prefrontal cortex (DLPFC) in tDCS research, due to inter-

subject brain variability, this method may have limited target accu-

racy and may result in suboptimal stimulation. To address this issue,

we compared left DLPFC-localization via the 10–20 EEG system to

MRI-guided neuronavigation in forty healthy female participants

within the same age range. Compared to the 10–20 EEG system,

MRI-guided neuronavigation localizes the DLPFC-targeting anode

more latero-posteriorly. Furthermore, tDCS-induced electric fields

(derived from one subject) suggest that these different localization

methods induce different electric fields in distinct brain regions. Our

findings indicate that prefrontal tDCS targeting methods result in

distinct electrode localizations, each of which suggested being asso-

ciated to unique underlying electric field distributions. Considering

the frequent use of tDCS in research, an evaluation and direct com-

parison of the outcome of both targeting methods is therefore

warranted.


report.

P-10Effects of different prefrontal-tDCS electrode-montageson resting-state connectivity and cognitive control

J. Worsching1*, F.Padberg1*, S. Goerigk1,2, I. Heinz1, C.Bauer1,

C. Plewnia3, A. Hasan1, B. Ertl-Wagner4, Da. Keeser1,4


University, Munich, Germany; 2Department of Psychological

Methodology and Assessment, Ludwig-Maximilians-University,

Munich, Germany; 3Department of Psychiatry and Psychotherapy,

Neurophysiology and Interventional Neuropsychiatry and Werner

Reichardt Centre for Integrative Neuroscience (CIN), University of

Tubingen, Tubingen, Germany; 4Department of Radiology, Ludwig-

Maximilians-University, Munich, Germany

*Both authors contributed equally to this work.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex

has been advocated as an experimental and therapeutic intervention in

various neuropsychiatric disorders. Although computational models

of tDCS induced current density distribution in the brain are avail-

able, there is need for empirical studies investigating


123

neurophysiological effects of prefrontal tDCS and its methodological

underpinnings. We therefore aimed to investigate the influence of

different electrode montages on tDCS-induced neuromodulation.

Within a cross-over design, 32 right-handed healthy male subjects

underwent three active tDCS conditions and sham tDCS in a pseudo-

randomized order. Before and after tDCS a resting-state fMRI (RS

fMRI) was recorded, which was then followed by a cognitive-control

task. RS-fMRI connectivity measures indicated reduced connectivity

within the right frontal gyrus after cathodal tDCS of the left and

concurrent anodal tDCS of the right DLPFC. On a behavioural level,

the expected slowing in reaction times after negative vs. neutral

pictures reversed under anodal tDCS of the left DLPFC with the

cathode placed above the right DLPFC, yet, was intensified when the

cathode was shifted to a more supraorbital position. The current study

provides evidence for electrode-montage specific tDCS-effects and a

complex interaction between passive neurophysiological and active

behavioural outcome measures.



Package 5, Grant Number 01EE1403E), funded by the Federal Min-

istry of Education and Research (BMBF). F.P. has received speaker’s

honorarium from Mag&More GmbH and the neuroCare Group as

well as support with equipment from neuroConn GmbH, Ilmenau,

Germany, Mag&More GmbH and Brainsway Inc., Jerusalem, Israel.

P-11Neurophysiological impact of a fronto-temporal transcranialdirect current stimulation in healthy subjects: a multimodal PET-MR imaging approach

C. Fonteneau1,2, I. Merida3, J. Redoute3, F. Haesebaert1,2, N. Costesc,

J. Brunelin1,2, M.-F. Suaud-Chagny1,2

1Centre de Recherche en Neurosciences de Lyon, Equipe PSYR2

(INSERM U1028, CNRS UMR5292, UCBL, Universite de Lyon),

Lyon, France; 2Centre Hospitalier Le Vinatier, 69000 Bron, France;3CERMEP-Imagerie du vivant, Lyon, France

Fronto-temporal transcranial direct current stimulation (tDCS), with

anodal stimulation over the left dorsolateral prefrontal cortex and

cathodal stimulation over the left temporo-parietal junction, has been

reported to reduce treatment-resistant symptoms in patients with

schizophrenia. Despite an increasing use in clinical settings, acute and

subsequent effects of fronto-temporal tDCS are far from being

completely understood. The few offline imaging and computational

reports available suggest that fronto-temporal tDCS effects are not

restricted to the brain areas located under the electrodes, but spread

through distributed cortical networks functionally connected with the

targets and reach subcortical areas, such as dopaminergic areas.

However, these effects are currently described at different levels

depending on the imaging technique used and online effects are rarely

inspected. Objectives: The aim of this study is to reveal the combined

acute and subsequent neurobiological effects of a single session of

fronto-temporal tDCS in a unique experiment by developing a

simultaneous multimodal imaging approach (PET-MR).

Methods: 30 healthy subjects randomly received a single-session of

either active (30 min, 1 mA; n = 15) or sham (n = 15) fronto-tem-

poral tDCS during a simultaneous PET-MR scan. The distributed

changes are explored at rest through:

• Specific and localized dopaminergic transmission evaluated by

PET using dopaminergic D2 subtype receptor availability via

[11C]raclopride binding. The tracer was administered intravenous,

using a bolus-plus-continuous-infusion method.

• Brain activity assessed by cerebral blood flow quantitatively and

directly measured by pseudo-continuous arterial spin labelling

(pCASL, three 6 min-scans before, during and after tDCS).

• Spontaneous functional connectivity assessed by resting state

functional MRI (rs-fMRI, three 13 min-scans before, during and

after tDCS).

• Structural connectivity assessed by diffusion tensor imaging (DTI,

two 10 min scans before and after tDCS).

• Perspectives: Our unique combined approach will create a

coherent ensemble, which is a mandatory and critical step to

understand the mechanisms of action of fronto-temporal tDCS.


report.

P-12Modulation of brain metabolites and resting state functional MRIconnectivity by transcranial direct current stimulation (tDCS)over the left dorsolateral prefrontal cortex in healthy subjects

E. Mezger1, B. Rauchmann1, J. Worsching1, M. Mortazavi1,

A. Brunoni1, B.Ertl-Wagner2, F. Padberg1, D. Keeser1,2

1Department of Psychiatry and Psychotherapy, University Hospital

LMU Munich, Munich, Germany; 2Department of Radiology,

University Hospital LMU Munich, Munich, Germany

Introduction: Magnetic Resonance Spectroscopy (MRS) studies have

shown that transcranial direct current stimulation (tDCS) modulates

the metabolite concentration of GABA in the motor cortex (M1). In a

recent study, Hone-Blanchet et al. (2016) have not observed such

effects for tDCS applied over the dorsolateral prefrontal cortex

(DLPFC), but observed changes in glutamate in the striatum. To

clarify these results, we investigated the effects of tDCS on DLPFC

GABA, N-acetyl-aspartate (NAA), glutamate/glutamine (Glx) and

glutamate concentrations using an online protocol in conjunction with

pre and post fMRI resting state connectivity (fcMRI) measurements.

Methods: Thirty healthy subjects (18 women, mean age 23) were

assigned to active (20 min, 2 mA) and sham tDCS using a double-

blind cross-over design. The anode was positioned over F3 (left

DLPFC), the cathode over F4 (right DLPFC). A MRS MEGA-PRESS

sequence (TE = 68), currently the most widely used technique for

GABA quantification, was acquired before, during and after stimu-

lation. GABA concentrations were quantified using Gannet 2.0.

Repeated measures ANOVA was conducted comparing active and

sham tDCS. Result: Preliminary data of 19 healthy subjects (11

women, mean age 23) showed a statistical significant reduction of

DLPFC glutamate concentrations comparing during to after anodal

tDCS. However, this difference was not significant compared to sham

tDCS. We could not find any effects of anodal tDCS on GABA, NAA

and Glx values. Conclusion: This is the first study reporting a

reduction of glutamate in the left DLPFC due to anodal tDCS stim-

ulation. To our knowledge only the study of Hone-Blanchet and

colleagues (2016) already investigated the change of glutamate con-

centrations in this brain region together with tDCS stimulation. Other

metabolite changes may be also small and only detectable with

increased participant numbers. The effect of tDCS on functional

connectivity will be further analysed.









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P-13Effects of transcranial direct current stimulation (tDCS)on working memory performance in patients with schizophrenia

T. Schwippel1, I. Papazova2, W. Strube2, A. Fallgatter1, A. Hasan2, C.

Plewnia1


Interventional Neuropsychiatry, University of Tubingen, Calwerstr.

14, 72076 Tubingen, Germany; 2Department of Psychiatry and

Psychotherapy, Klinikum der Universitat Munchen, Ludwig-

Maximilians University Munich, Nußbaumstraße 7, 80336 Munich,

Germany

Introduction: Cognitive impairment is a core symptom of

schizophrenia and is in a large part responsible for the poor psy-

chosocial outcome of the disorder. The use of non-invasive brain

stimulations techniques as a therapeutic option is just commencing

and showed a few promising results to ameliorate specific cognitive

domains in impaired patients. In healthy subjects, we have previously

shown that anodal tDCS of the right DLPFC parallel to working

memory training can sustainably enhance performance in a spatial

n-back task (Ruf et al. 2017). As a first translational step, we now

assessed the efficacy of anodal tDCS to the right DLPFC on spatial

working memory performance in patients with schizophrenia.

Methods: 32 patients with the DSM-V diagnosis of schizophrenia

were enrolled in this double-blind, sham controlled cross-over study.

The first experiment was conducted with 1 mA and the second with

2 mA current strength. Both otherwise identical experiments con-

sisted of three experimental sessions, in which a spatial n-back task

was administered. The anode was placed over the right dorsolateral

prefrontal cortex and the cathode over the contralateral deltoid mus-

cle. Calculated baseline corrected d prime was defined as primary

outcome variable.

Results: In experiment 1, no difference between sham and anodal

stimulation was found for corrected d prime. In our preliminary

analysis of experiment 2, the use of 2 mA did result in a significant

difference between sham and anodal tDCS in the most challenging

working memory condition (3-back). With concurrent 2 mA tDCS,

the patients performed better in the 3-back than during sham stimu-

lation. This result is in line with the notion that higher current

intensities are necessary in a patient population and that effects of

stimulation only occur when patients work at their cognitive limit.


report.

P-14Transcranial direct current stimulation in three patientswith Gilles de la Tourette syndrome

N. Behler1, B. Leitner1, E.Weidinger1, R. Musil1, B. Blum1,2,

B. Kirsch1, L. Wulf1,3, L.Lohrs1, F. Padberg1, U. Palm1,3

1Department of Psychiatry and Psychotherapy, Ludwig-Maximilian

University, Klinikum der Universitat Munchen, 80336 Munich,

Germany; 2Department of Neurology, Ludwig-Maximilian

University, Klinikum der Universitat Munchen, 81377 Munich,

Germany; 3NeuroCare Group, 80331 Munich, Germany

Background: In the treatment of Gilles de la Tourette Syndrome

(GTS) interesting pharmacological options are limited by a lack of

FDA approval, partly unsatisfactory treatment outcomes and often-

times considerable side effects (1). Manualised psychotherapeutic

options are hindered by poor compliance and availability as well as

long application-times (2). In this neuropsychiatric disorder, tics are

caused by alterations in the activity of cortico-striatao-thalamo-

cortical networks with an upregulation of motor-networks and a

downregulation of superordinate control-systems (3). By modifying

cortical activity, non-invasive brain-stimulation appears a viable new

treatment option in GTS. This technique is considered safe, with very

limited side effects. Previous findings suggested high therapeutic

effects of cathodal transcranial direct current stimulation (tDCS) to

pre-SMA both via bilateral or unilateral treatment of the most affected

side (4, 5).

Methods: Hypothesizing that bilateral treatment as well as higher

frequency of treatment and higher current intensity might yield more

pronounced therapeutic effects, we administered 5 days of twice daily

sessions of bilateral cathodal tDCS (30 min, 2 mA) over the pre-SMA

in three patients with severe GTS. Tic severity as well as obsessive–

compulsive disorder (OCD) symptoms and affective scales were rated

before and after 5 days of stimulation.

Result: Only one out of three patients showed any reduction in tic

severity. The two other patients showed an increase in tic severity. All

patients showed a mild increase in positive affect and a reduction in

negative affect.

Conclusion: Our results contradict earlier findings of extensive ther-

apeutic effects of cathodal tDCS on tics in patients with GTS and

show that prediction of stimulation effects on a targeted brain area

remains inaccurate. Thus, we propose a follow-up study to determine

most effective stimulation site, intensity and polarity of tDCS, using a

crossover design in 20 Tourette patients.




GmbH and Brainsway Inc., Jerusalem, Israel. Linda Wulf is part-time

employee at the neurocare Group. Ulrich Palm has a private practice

with neurocare Group.

P-15tDCS-enhanced working memory training in subjective cognitivedecline

N. Stoynova1, C. Laske1, C. Plewnia1

1University Hospital Tuebingen, Tubingen, Germany

Subjective cognitive decline (SCD) is defined as self-reported cog-

nitive decline before the deficits could be detected by cognitive tests

[1]. SCD increasingly acknowledged as a risk factor for the devel-

opment of Alzheimer’s disease [2] and is therefore considered a stage

particularly accessible for interventional strategies [3]. However,

studies evaluating the efficacy of therapeutic interventions in this

condition are scarce. SCD has been particularly linked with deficient

cognitive control (CC) functions [4]. Anodal transcranial direct cur-

rent stimulation (tDCS) to the left dorsolateral prefrontal cortex

(dlPFC) can significantly enhance CC. Specifically, this has been

demonstrated by means of a challenging and frustrating continuous

performance task (Paced Serial Addition Task; PASAT).

This 2-armed, randomized, sham-controlled study aims at pro-

viding evidence for the efficacy of a tDCS-enhanced cognitive control

training (PASAT) in participants with SCD. 30 participants will take

part in a 4 week training (12 sessions); 50% of them will receive

2 mA anodal tDCS for 20 min applied to the left dlPFC, the other half

will receive sham stimulation. Event-related potentials (ERPs) evoked

by the feedback on the correctness of the response at baseline and

after training will be measured with EEG as neurophysiological sig-

natures of cognitive control. Near and far transfer will be assessed by

a verbal 2-back task and the Trail Making Test A and B. The amount

of worrying regarding the memory impairment will be quantified by

means of a 10-point Likert scale and will serve as the primary mea-

sure outcome. Together with changes of PASAT performance these


123

measures will be obtained before and after the tDCS-enhanced

training. Follow-up assessments 3, 12 and 24 months after training

will investigate the sustainability of the training effects.

This study is designed to provide first proof of principle and

effect-size estimates for larger clinical studies. First results will be

presented at the conference.

References:

1. Molinuevo JL, Rabin LA, Amariglio R et al, Subjective Cognitive

Decline Initiative (SCD-I) Working Group (2016) Implementation of

subjective cognitive decline criteria in research studies. Alzheimers

Dement S1552-5260:33019–9

2. Jessen F, Amariglio RE, Van Boxtel M et al (2014) A conceptual

framework for research on subjective cognitive decline in preclinical

Alzheimer’s disease. Alzheimers Dement 10:844–852

3. Fernandez-Blazquez MA, Avila-Villanueva M, Maestu F, Medina

M (2016) Specific features of subjective cognitive decline predict

faster conversion to mild cognitive impairment. J Alzheimers Dis

52(1):271–281

4. Stogmann E, Moser D, Klug S, Gleiss A, Auff E, Dal-Bianco P,

Pusswald G, Lehrner J (2016) Activities of daily living and depressive

symptoms in patients with subjective cognitive decline, mild cogni-

tive impairment, and Alzheimer’s disease. J Alzheimers Dis

49:1043–1050


report.

P-16Transcranial direct current stimulation (tDCS) as treatmentfor major depression: a prospective multicenter double blindrandomized placebo controlled trial (DepressionDC)—earlyquality control of technical data from a blind selection of activetDCS sessions

U. Kumpf 1*, T. Nenov-Matt1*, N. Behler1, J. Nolden1, U. Palm1, L.

Wulf1, Be. Kirsch1, J.Worsching1, D. Keeser1, T. Gorlitz1, U.

Mansmann2, M. Bajbouj3, C. Plewnia4, B. Langguth5, P. Zwanzger6,

F. Padberg7

1Department of Psychiatry and Psychotherapy, Ludwig-Maximilian

University, Munich, Germany; 2IBE University of Munich, Munich,

Germany; 3Department of Psychiatry, Charite, Berlin, Germany;4Department of Psychiatry, University Tubingen, Tubingen,

Germany; 5Department of Psychiatry, University Regensburg,

Regensburg, Germany; 6Inn-Salzach-Klinikum, Wasserburg,

Germany

*Both authors equally contributed to this work.

Background: The DepressionDC study investigates efficacy and tol-

erability of prefrontal tDCS used as an additive therapy to an

antidepressant medication (SSRI) as treatment for major depression in

a double-blinded, placebo-controlled multicenter trial. There is a

consensus on parameters like electrical current (1–2 mA) and the

critical impedance values are known from safety-studies, but the

in vivo stability of these technical parameters over the stimulation

period has not been investigated yet. For this study a novel system for

recording and monitoring of technical data has been established.

Here, we present a blind analysis of the technical data of 120 active

tDCS sessions from a single center.

Methods: Patients with MDD receive a 6-weeks treatment with pre-

frontal tDCS (anode: F3, cathode: F4, 5 sessions/week for 4 weeks

followed by 2 sessions/week for 2 weeks, 30 min/day, 2 mA inten-

sity) or sham tDCS (parameters correspondent active tDCS, ramp in

and ramp out periods only without intermittent stimulation) as

adjunctive treatment to a SSRI. Impedance, current and voltage, are

continuously recorded (1800 time points over 30 min). After the

stimulation, data is automatically transferred to a cloud where the data

are stored under the randomization code with maintaining integrity of

blinding.

Results: The descriptive analysis showed a high homogeneity and

stability of the technical parameters over the time of the tDCS session

in 120 active stimulations. Considering only the stimulation time

without ramp in and ramp out periods direct current is stabile between

2008 and 1970 lA, impedance between 6053 and 1454 kX and

voltage between 12,093 and 2902 V. Using a window function the

standard deviation of the measures was analysed. A steady state of

voltage was reached between 46 and 55 measurements, i.e. after

46–55 s, and the impedance reached a steady state after 15–20

measurements i.e. after 15–20 s of stimulation.



Package 7, Grant Number 01EE1403G), funded by the Federal

Ministry of Education and Research (BMBF).F.P. has received

speaker’s honorarium from Mag&More GmbH and the neuroCare

Group as well as support with equipment from neuroConn GmbH,

Ilmenau, Germany, Mag&More GmbH and Brainsway Inc., Jer-

usalem, Israel. Linda Wulf is part-time employee at the neurocare

Group. Ulrich Palm has a private practice with neurocare Group.

P-17Targeting fatigue, mood and cognition in multiple sclerosis usingtDCS

M. A. Chalah1,2*, J.-P. Lefaucheur1,2, A. Creange1,3, S. S. Ayache1,2,4

1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-



de Paris, Creteil, France; 3Service de Neurologie, Hopital Henri

Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France;4Neurology Division, Lebanese American University Medical Center

Rizk Hospital, Beirut, Lebanon

*Corresponding author: Moussa A. Chalah, Service de Physiologie–

Explorations Fonctionnelles, Hopital Henri Mondor, Assistance

Publique–Hopitaux de Paris, 94010 Creteil, France.

Background: Multiple Sclerosis (MS) is a chronic inflammatory and

neurodegenerative disease of the central nervous system, through

which the patients may experience various symptoms such as fatigue,

psychiatric complaints, cognitive deficits, to cite a few [1, 2]. The

current pharmacological treatments are majorly limited by their side

effects profile and modest efficacy. Recently, non-invasive brain

stimulation techniques, particularly transcranial direct current stimu-

lation (tDCS) have proved some benefits in the context of

neurological and psychiatric diseases [2, 3]. The purpose of this work

was to evaluate tDCS effects on fatigue, anxiety and depression

symptoms, and attentional abilities.

Methods: The study adapted a double-blind, sham-controlled and

cross-over design. Each of the 10 MS patients randomly received

three anodal tDCS blocks made each of 5 consecutive daily sessions:

active stimulation over the right posterior parietal cortex (PPC),

active stimulation over the left dorsolateral prefrontal cortex

(DLPFC) or sham stimulation over either site. Each block was made

of 5 consecutive daily sessions. A washout interval of 3 weeks sep-

arated them.

Results: Only right PPC tDCS improved the anxiety and depression

scores. Only left DLPFC tDCS improved fatigue. Neither condition

improved the attentional capacities.

Conclusion: The results of this work highlight the effects of tDCS on

fatigue, anxiety and depression symptoms in the context of MS. This

could be explained by the fact that DLPFC plays a key role in the


123

cortico-striato-thalamo-cortical fatigue loop. In addition, the PPC per

se was previously found to be implicated in the pathophysiology of

anxiety and depressive disorders. Although both cortical sites are

implicated in attentional networks, the lack of tDCS effects on

attention could be partially attributed to the small sample size or the

protocol duration. The current findings merits to be replicated in

large-scale studies aiming to improve MS patients’ quality of life.

References:

1. Chalah MA, Ayache SS (2017) Psychiatric event in multiple

sclerosis: could it be the tip of the iceberg? Rev Bras Psiquiatr.

pii:S1516-44462017005007105.

https://doi.org/10.1590/1516-4446-2016-2105 [Epub ahead of print]

2. Chalah MA, Riachi N, Ahdab R, Creange A, Lefaucheur JP,

Ayache SS (2015) Fatigue in multiple sclerosis: neural correlates and

the role of non-invasive brain stimulation. Front Cell Neurosci 9:460

3. Ayache SS, Chalah MA (2017) Fatigue in multiple sclerosis—

insights into evaluation and management. Neurophysiol Clin

47:139–171

Policy of full disclosure: SSA declares having received travel grants

or compensation from Genzyme, Biogen, Novartis and Roche. AC

gave expert testimony for CSL Behring, Novartis, received grants

from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and

gave lectures for Genzyme. JPL and MAC: Nothing to disclose.

P-18Frontal EEG coherence after beta-tACS during reversal learning

M. Wischnewski, D. Schutter

Donders Institute, Donders Centre for Cognition, Radboud

University, Nijmegen, The Netherlands


P-19Online effects of transcranial alternating current stimulationon event-related alpha power modulations: a concurrent tACS-MEG study

F. H. Kasten1,2, B. Maess3, C. S. Herrmann1,2,4

1Experimental Psychology Lab, Department of Psychology, European

Medical School, Cluster for Excellence ‘‘Hearing for All’’, Carl von

Ossietzky University, Oldenburg, Germany; 2Neuroimaging Center,

European Medical School, Carl von Ossietzky University, Oldenburg,

Germany; 3MEG and Cortical Networks Group, Max Planck Institute

for Human Cognitive and Brain Sciences, Leipzig, Germany;4Research Center Neurosensory Science, Carl von Ossietzky

University, Oldenburg, Germany

Transcranial alternating current stimulation (tACS) is receiving

increasing popularity as a non-invasive approach to modulate oscil-

latory activity in the brain. Besides allowing to study causal

relationships between brain oscillations and cognition, tACS might

offer promising new therapeutic applications for a variety of neuro-

logical and psychiatric conditions in which dysfunctional brain

oscillations are implied. However, so far, only little is known about

effects of tACS during stimulation, due to a massive stimulation

artifact at the targeted frequency. Especially, it is not clear how

continuous tACS application during a cognitive task changes event-

related oscillatory activity. TACS might either enhance event-related

changes in oscillatory activity or overwrite the existing pattern of

perturbations. Knowledge about the direction of tACS effects on

event-related oscillations is crucial to understand and predict the

outcome of solely behavioral experiments or clinical trials.

Here, a recently proposed procedure to suppress tACS artifacts by

projecting MEG data into source space using a linearly constrained

minimum variance beamformer was utilized to reveal the effect of tACS

on event-related power modulations in the alpha band during a cognitive

task. Twenty volunteers performed a mental rotation task, while MEG

was continuously recorded. After 10 min of baseline measurement, they

received either 20 min of tACS at individual alpha frequency or sham

stimulation. Another 40 min of MEG were acquired thereafter.

Results revealed a strong facilitation of event-related power

modulations in the alpha band during tACS. Data provide first direct

evidence that tACS does not counteract top–down suppression of

intrinsic oscillations, but rather enhances pre-existent power modu-

lations within the range of the individual alpha (=stimulation)

frequency. Furthermore, the study provides a framework to analyze

event-related oscillatory dynamics during tACS in the presence of

residual artefacts. Thus, it contributes to further understand mecha-

nisms of tACS, paving the way for future therapeutic applications.

Policy of full disclosure: CSH has filed a patent application on brain

stimulation and received honoraria as an editor from Elsevier Pub-

lishers, Amsterdam. FHK and BM declare no competing interests.

P-20Long-term effect of 3 daily sessions of transcranial random noisestimulation (tRNS) on inhibitory control

C. Brevet-Aeby1,2,3, M. Mondino1,2, E. Poulet1,2,3,4, J. Brunelin1,2,4

1Inserm, U1028; Cnrs, Umr5292; Lyon Neuroscience Research

Center, WR2 Team, 69000 Lyon, France; 2University Lyon 1, 69000

Villeurbanne, France; 3Emergency Psychiatry, Edouard Herriot

Hospital, Hospices Civils de Lyon, Lyon, France; 4Centre Hospitalier

Le Vinatier, 69678 Bron, France

Introduction: Deficits in inhibitory control, a key feature of impul-

sivity, was reported in numerous neuropsychiatric conditions. These

deficits may lead to inappropriate behaviours such as suicidal attempt.

Noninvasive brain stimulation technique applied over the dorsolateral

prefrontal cortex (DLPFC) may enhance inhibitory control but little is

known regarding the duration of these beneficial effects.

Objective: To investigate the duration of the effect of 1 and of 3

sessions of transcranial random noise stimulation (tRNS) applied over

the DLPFC on inhibitory control as compared with sham. The effect

of stimulation was measured immediately after tRNS, 1 day (D1) and

1 week (D8) after the end of the sessions.

Method: In a double blind sham-controlled study, 32 healthy subjects

were randomly allocated to receive 1 active and 2 placebo (1A2P,

n = 10), 3 active (3A, n = 11) or 3 placebo (3P, n = 11) tRNS

sessions. One session lasted 20 min at 2 mA and each tRNS sessions

were separated by 30 min. The anode was placed over the right

DLPFC and the cathode over the left. Inhibitory control was measured

by reaction time at the Go/No Go test.

Results: Repeated measures ANOVA revealed a significant interac-

tion between time and group (p = 0.03, g2 = 0.14). After tRNS,

there was a significant difference between 3P (0.00 ± 0.03%) and 3A

(- 8.51 ± 0.03%; p = 0.04), 3P and 1A2P (- 8.75 ± 0.02%;

p = 0.01) but no difference between 3A and 1A2P groups. At D1,

there was a significant difference between 3P (- 3.33 ± 0.03%) and

3A (- 14.2 ± 0.02%; p\ 0.01), 3P and 1A2P (- 10.55 ± 0.02%;

p = 0.04) groups but no difference between 3A and 1A2P groups. At

D8, only the 3P (- 4.42 ± 0.03%) and 3A (- 13.54 ± 0.02%)

groups were significantly different (p = 0.03).

Conclusion: Compared with sham and with 1 session of tRNS, 3

sessions of tRNS over the DLPFC have a longer beneficial duration

on inhibitory control.


123

http://dx.doi.org/10.1590/1516-4446-2016-2105


report.

P-21Effects of transcranial direct current stimulation appliedto the prefrontal cortex on TMS evoked potentials

P. C. Gordon1,2, C. Zrenner1, D. Desideri1, P. Belardinelli1,

B. Zrenner1, A. Brunoni2, U. Ziemann1


Clinical Brain Research, University of Tubingen, Tubingen,

Germany; 2Department of Psychiatry, University of Sao Paulo, Sao

Paulo, Brazil

Transcranial direct current stimulation (tDCS) of prefrontal cortex

(PFC) is considered a possible therapy for various psychiatric con-

ditions1. However, current models of tDCS mechanism of action are

largely based on studies targeting human motor cortex, where

excitability can be quantified through motor evoked potentials, but

where reported effects are also variable, partially due to differences in

stimulation parameters2. A recent study has shown a significant

change in TMS evoked potentials (TEPs) over PFC following tDCS3.

In the present study, we further investigate the effects of tDCS on

TEPs over PFC in response to different tDCS parameters.

22 healthy subjects underwent 5 different tDCS interventions in a

randomized double-blind study design with the following parameters:

(1) 1.5 mA, anode left-PFC, cathode right-PFC, (2) 1.5 mA, cathode

left-PFC, anode right-PFC, (3) 0.5 mA, anode left-PFC, cathode

right-PFC, (4) 1.5 mA, anode left-PFC, cathode deltoid muscle, (5)

sham. Stimulation was delivered by tDCS electrodes integrated

between the EEG sensors of a standard 64 channel EEG cap, centred

around the dorsolateral PFC and having a total area of 3 cm2 over

each hemisphere. 160 TEPs were recorded before and after the tDCS

intervention. A cluster based analysis was performed as well as an

analysis of TEP peaks in a predefined region of interest (ROI) con-

sisting of 10 EEG channels over left PFC and within the following

times of interest (TOI): 25–55 ms (N40), 45–75 ms (P60), 85–145 ms

(N100) and 170–230 ms (P200).

Cluster based statistics revealed a negative cluster over the pari-

eto-occipital region (p = 0.003) at the N100 in condition 1 only. No

other cluster was shown to be statistically significant in any other

condition. A repeated measures ANOVA failed to identify any sta-

tistically significant effect of time (pre and post tDCS) or condition in

the TEPs amplitude of the ROI.


report.

P-22Changes in firing properties and synaptic plasticity in differentbrain regions of schizophrenia model and control ratsafter transcranial magnetic stimulation

G. Barmashenko1, K. Funke1

1Department of Neurophysiology, Medical Faculty University

Bochum, Bochum, Germany

In former experiments repetitive transcranial magnetic stimulation

(rTMS) seems to change functional properties of brain inhibitory

systems. In our study we compare rats with schizophrenia model

resulting from maternal immune activation (MIA) and control rats

after rTMS and sham rTMS treatment. Firing properties in four brain

regions (prefrontal cortex (PrL), nucleus accumbens (NAc), ventral

tegmental area (VTA) and ventral hippocampus) in vivo show the

significantly different changes between the animal groups after high

frequency stimulation (130 Hz) and after theta burst stimulation.

In vitro experiments in prefrontal cortex and hippocampal slices show

the alteration in short term (paired pulse facilitation) and long term

(LTP) synaptic plasticity.


report.

P-23Advances in TMS technology: from flexible pulse shape designto high speed individualized biphasic quadri-pulse stimulation

N. Gattinger1, A. Heidsieck1, N. Jung2, V. Mall2, B. Gleich1

1Technische Universitat Munchen, Munich School of BioEngineering

(MSB), Boltzmannstraße 11, 85748 Garching, Germany; 2Technical

University of Munich, School of Medicine, Social Pediatrics,

Heiglhoftstr. 65, 81377 Munich, Germany

Transcranial magnetic stimulation (TMS) is able to noninvasively

excite neuronal populations due to brief magnetic field pulses. The

efficiency and the characteristics of stimulation pulse shapes, repeti-

tion rate and pulse length influence the physiological effect of TMS.

However, commercial devices mostly allow only a minimum of

control of different pulse shapes. Basically, only sinusoidal and

monophasic pulse shapes with fixed pulse widths are available. Only

few research groups are working on TMS devices with controllable

pulse parameters such as pulse shape or pulse width. We describe

three novel TMS devices based on our IGBT technology. The flexible

flexTMS device can generate magnetic pulses, which can be adjusted

with respect to pulse shape, pulse width, polarity, and intensity with

repetition rates up to 30 pulses per second (pps), or, respectively, up

to 100 pps in theta burst mode. The QPS device allows the application

of quadri-pulses with biphasic and polyphasic pulse currents,

respectively. ISI as short as 1.5 ms with a repetition rate of up to 100

pulses per second are possible. The experiment also shows that both,

biphasic as well as polyphasic, QPS given at a sub-threshold level

were able to modulate brain activity. The IQPS device is an

enhancement of the QPS stimulator. It allows the user to individualize

the ISI with respect to the subjects I-wave latency even within in a

quadri-pulse burst. The device can be fully controlled by a computer

and is usable for closed-loop applications with the possibility of

triggering each individual stimulus within the protocol.

References:

1. Jung NH, Gleich B, Gattinger N, Hoess C, Haug C, Siebner HR,

Mall V (2016) Quadri-pulse theta burst stimulation using ultra-high

frequency bursts—a new protocol to induce changes in cortico spinal

excitability in human motor cortex. PLoS One 11:e0168410

2. Gattinger N, Moessnang G, Gleich B (2012) flexTMS—a novel

repetitive transcranial magnetic stimulation device with freely pro-

grammable stimulus currents. IEEE Trans Biomed Eng 59:1962–1970


report.

P-24The role of the parietal cortex in memory confidence

S. C. Wynn1, M. P. H. Hendriks1,2, S. M. Daselaar1, R. P. C. Kessels1,

D. J. L. G. Schutter1

1Donders Institute for Brain, Cognition and Behaviour, Radboud

University, Nijmegen, The Netherlands; 2Academic Centre of

Epileptology, Kempenhaeghe, Heeze, The Netherlands



123

P-25Time lapse of individualized rTMS effects on resting statefunctional connectivity of healthy brains

A. Singh1*, T. Erwin-Grabner1*, G. Sutcliffe1, S. Wolter1, R. Goya

Maldonado1

1Systems Neuroscience and Imaging in Psychiatry, Clinic for

Psychiatry and Psychotherapy, University Medical Center, Gottingen,

Germany

*Equal contribution

Numerous studies have suggested that a single session of repetitive

transcranial magnetic stimulation (rTMS) is effective at manipulating

the brain’s functional connectivity [1]. While it is possible to

manipulate functional connectivity by stimulating at several acces-

sible cortical targets, the DLPFC as an rTMS target is of particular

importance due to its therapeutic use in the alleviation of depressive

symptoms. To detect differences in rTMS induced effects related to

time lapsed after stimulation targeted at the left DLPFC in healthy

brains, we recruited healthy volunteers for three experimental ses-

sions. In the initial session, the resting state (rs)-fMRI scan is utilized

to select the strongest node within the overlap of two components, one

spanning the DLPFC (positive correlation), and the other the anterior

cingulate cortex (negative correlation), which then becomes the target

for individualized rTMS intervention [2]. The next two sessions, at

least a week apart, involve either real or sham rTMS intervention

delivered using real time neuronavigation. A pre-rTMS rs-fMRI

session and three subsequent post-rTMS sessions are acquired upon

completion of rTMS. The data is analyzed for differences in func-

tional connectivity during resting state, both within the three rs-fMRI

scans acquired post-rTMS and between the pre-rTMS and post-rTMS

resting state scans, to answer how long the rTMS effects are sustained

and which resting state networks are involved over time, also com-

plimenting the work by Tik et al. 2017 [3]. Additionally, we also aim

to utilize the rs-fMRI scan from the first session and the two pre-

rTMS rs-fMRI scans from next two sessions to test the stationarity of

target selection across sessions [4].

References:

1. Fox M, Halko M, Eldaief M, Pascual-Leone A (2012) Measuring

and manipulating brain connectivity with resting state functional

connectivity magnetic resonance imaging (fcMRI) and transcranial

magnetic stimulation (TMS). NeuroImage 62(4):2232–2243

2. Fox M, Buckner R, White M, Greicius M, Pascual-Leone A (2012)

Efficacy of transcranial magnetic stimulation targets for depression is

related to intrinsic functional connectivity with the subgenual cin-

gulate. Biol Psychiatry 72(7):595–603

3. Tik M (2017) Towards understanding rTMS mechanism of action:

stimulation of the DLPFC causes network-specific increase in func-

tional connectivity. NeuroImage 162:289–596

4. Fox M, Liu H, Pascual-Leone A (2013) Identification of repro-

ducible individualized targets for treatment of depression with TMS

based on intrinsic connectivity. NeuroImage 66:151–160


report.

P-26The effect of seed determination on functional connectivityanalyses to study the effect of transcranial magnetic stimulation

D. C. W. Klooster1,2,3, R. M. H. Besseling1,2,3, A. P. Aldenkamp1,2,3,4,

M. D. Fox5,6, C. Baeken3,7

1Academic Center for Epileptology Kempenhaeghe, Heeze, The

Netherlands; 2Eindhoven University of Technology, Eindhoven, The

Netherlands; 3Ghent University Hospital, Ghent, Belgium;

4Maastricht University Hospital, Maastricht, The Netherlands;5Berenson-Allen Center for Noninvasive Brain Stimulation, Boston,

USA; 6Harvard Medical School, Boston, USA; 7University Hospital

Brussel, Brussels, Belgium

Functional connectivity (FC) studies have shown insight into the

mechanism of action of transcranial magnetic stimulation (TMS).

However, the choice of the seed, representing the stimulated area, is

ambiguous. The aim of this study is to investigate the effect of the

choice of the seed region.

Baseline anatomical and resting-state functional MRI (rs-fMRI)

data were collected from 50 depression patients who were stimulated

at the left DLPFC. The rs-fMRI scans were realigned, motion- and

slice-time-corrected, smoothed and normalized. Motion parameters,

including their first derivatives, white matter signal, cerebrospinal

fluid signal, and a linear and quadratic trend were used as con-

founders. Time-series were bandpass filtered between 0.01 and 0.1 Hz

[1].

Three different seeding methods were implemented. The first two

seeds were derived from electric field simulations (Simnibs [2]). A

weighted regressor (RegEfield_bin-weighted) was calculated as a weighted

average of time-series within the gray matter voxels, using the electric

field strengths as weights. A binary-weighted regressor (RegEfield_bin-

weighted) was defined as the weighted time-series of the gray matter

voxels where the electric field exceeds a patient-specific threshold

(50% of the maximum field strength in gray matter [3]). Third, a

simpler cone model [4] was implemented (RegCone).

Regressors resulting from the different seeding methods were

correlated with each other. High correlations were found:

mean = 0.84, std = 0.14 for RegEfield_bin-weighted versus RegEfield_bin-

weighted, mean = 0.79, std = 0.22 for RegCone versus RegEfield_bin-

weighted, and mean = 0.81, std = 0.13 for RegCone versus RegEfield_bin-

weighted. Zooming in on the effects of stimulation on the specific

connection between the left DLPFC and the sgACC did not show any

effect, for either type of regressor. This indicates that the relatively

simple cone model can be used to derive a representative TMS

regressor for FC analyses.

References:

1. Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F,

Meng Y, Fetcho RN, Zebley B, Oathes D, Etkin A, Schatzberg AF,

Sudheimer K, Keller J, Mayberg HS, Gunning FM, Alexopoulos GS,

Fox MD, Pascual-Leone A, Voss HU, Casey BJ, Dubin MJ, Liston C

(2016) Resting-state connectivity biomarkers define neurophysiolog-

ical subtypes of depression. Nat Med 23(1):28–38

2. Thielscher A, Antunes A, Saturnino GB (2015) Field modeling

for transcranial magnetic stimulation: a useful tool to understand

the physiological effects of TMS? IEEE EMBS 2015, Milano,

Italy

3. Opitz A, Fox MD, Craddock CR, Colcombe S, Milham MP (2016)

An integrated framework for targeting functional networks via tran-

scranial magnetic stimulation. NeuroImage 127:86–96

4. Fox MD, Liu H, Pascual-Leone A (2013) Identification of repro-


based intrinsic connectivity. NeuroImage 1:151–160


report.

P-27The relation between brain morphological factors and efficacyof rTMS treatment in patients with schizophrenia and auditoryverbal hallucinations

L. Bais1, C. Kos1, J.-B. Marsman1, S. Koops2,3, J. Dlabac-de Lange1,5,

He. Knegtering4,5, I. E. Sommer2,3, M.-J. van Tol1, A. Aleman1,5,6


123

1Department of Neuroscience, University Medical Center Groningen,

University of Groningen, Antonius Deusinglaan 2, 9713 AW

Groningen, The Netherlands; 2Department of Psychiatry, University

Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The

Netherlands; 3UMC Utrecht Brain Center Rudolf Magnus,

Universiteitsweg 100 Utrecht, 3584 CG Utrecht, The Netherlands;4Lentis Research, Lentis Center for Mental Health Care, Hereweg 80,

9725 AG Groningen, The Netherlands; 5Rob Giel Research Center,

University Medical Center Groningen, University of Groningen,

Hanzeplein 1, 9713 GZ Groningen, The Netherlands; 6Department of

Psychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS

Groningen, The Netherlands

Background: Repetitive Transcranial Magnetic Stimulation (rTMS)

has been studied as a treatment option for auditory verbal halluci-

nations in patients with schizophrenia. However, meta-analyses on the

efficacy of rTMS treatment are inconclusive [4]. Inter-individual

differences in response to treatment have been observed, which

indicates that patient-specific characteristics might play a role [1]. In

this study, it was assessed whether morphological factors, including

scalp-to-cortex distance (SCD) and gray matter density (GMD) of the

stimulated brain region could predict response to rTMS treatment in

patients suffering from auditory verbal hallucinations (AVH).

Methods: Data from four clinical trials were combined, leading to the

inclusion of 54 patients. All patients received inhibitory rTMS of the

temporo-parietal junction (TPJ), and underwent Magnetic Resonance

Imaging before the start of the treatment. Correlation coefficient

calculations and hierarchical linear regression models were applied to

investigate the relationship between treatment efficacy and SCD and

GMD of the stimulated brain region.

Results: Shorter SCD and higher GMD of the TPJ were associated

with greater AVH improvement after rTMS treatment.

Conclusion: SCD and GMD possibly predict the efficacy of rTMS

treatment for AVH. When these associations are proved to be robust

in future studies, rTMS treatment efficacy might benefit from indi-

vidual-specific protocols.

References:

1. Bais L, Vercammen A, Stewart R, van Es F, Visser B, Aleman A

(2014) Short and long term effects of left and bilateral repetitive

transcranial magnetic stimulation in schizophrenia patients with

auditory verbal hallucinations: a randomized controlled trial. PLoS

One 9:e108828

2. Dlabac-de Lange JJ, Knegtering R, Aleman A (2010) Repetitive

transcranial magnetic stimulation for negative symptoms of

schizophrenia: review and meta-analysis. J Clin Psychiatry

71:411–418

3. Freitas C, Fregni F, Pascual-Leone A (2009) Meta-analysis of the

effects of repetitive transcranial magnetic stimulation (rTMS) on

negative and positive symptoms in schizophrenia. Schizophr Res

108:11–24

4. Slotema CW, Aleman A, Daskalakis ZJ, Sommer IE (2012) Meta-

analysis of repetitive transcranial magnetic stimulation in the treat-

ment of auditory verbal hallucinations: update and effects after

1 month. Schizophr Res 142:40–45


report.

P-28Abnormal brain asymmetry and behavior in ADHD: a TMS-EEGstudy

A. Avnit1, U. Alyagon1, S. Zibman1, A. Zangen1

1Department of Life Sciences and Zlotowski Center for Neuroscience,

Ben-Gurion University of the Negev, Beersheba, Israel

Background: ADHD is characterized by abnormal hemispheric

asymmetry, which may result from compromised inter-hemispheric

connectivity, and by deficient response inhibition. Here, we investi-

gated the relations between these factors in ADHD and their

relevance to its symptomology. For this purpose, we examined the

hemispheric asymmetry of the stop-signal N200 event-related

potential (ERP) component, which is related to response inhibition,

TMS-evoked potential (TEP) in the right frontal hemisphere, and

frontal right-to-left interhemispheric signal propagation (ISP).

Methods: ERPs of 52 ADHD and 43 non-clinical adult participants

were measured during performance of a visual stop-signal task. N200

right-asymmetry was calculated for each group in posterior and

anterior regions of interest (ROIs). Concurrent TMS and EEG were

used to measure TEP and ISP during rest.

Results: The ADHD group demonstrated greater N200 right-asym-

metry in the posterior ROI specifically for successful stop trials. In the

anterior ROI, this group exhibited reduced N200 right-asymmetry,

which was positively correlated with response inhibition performance

(for successful stop trials) and with symptoms severity (for unsuc-

cessful stop trials). ISP was stronger in the ADHD group, while TEP

was reduced and positively correlated with anterior N200 asymmetry

(for successful stop trials) in this group only.

Discussion: Compromised anterior asymmetry is related to sympto-

mology, as well as to cognitive and neurophysiological deficits in

ADHD, and may constitute an endophenotype of this disorder. The

observation that TEP, but not ISP, correlated with anterior N200

asymmetry suggests that this abnormal asymmetry is not the resultant

of compromised inter-hemispheric connectivity, but of reduced ability

of the right hemisphere to activate inhibitory interneurons in the left

hemisphere.


report.

P-29Anxiety symptoms correlates with transcallosal inhibitionin patients with multiple sclerosis

M. A. Chalah1,2, J.-P. Lefaucheur1,2, A. Creange1,3,

S. S. Ayache1,2,4,*1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-



de Paris, Creteil, France; 3Service de Neurologie, Hopital Henri

Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France;4Neurology Division, Lebanese American University Medical Center

Rizk Hospital, Beirut, Lebanon

*Corresponding author: Samar S. Ayache, Service de Physiologie-

Explorations Fonctionnelles, Hopital Henri Mondor, Assistance

Publique-Hopitaux de Paris, 94010 Creteil, France.

Objectives: Psychiatric symptoms, particularly anxiety and depres-

sion, are commonly reported during the course of multiple sclerosis

(MS) [1]. Despite their drastic impact on the patients’ quality of life,

their neurophysiological correlates were not previously assessed. This

work addresses the relationship between cortical excitability measures

and each of anxiety and depression.

Methods: Patients were included if they were aged between 18 and

75 years, with a confirmed diagnosis of MS according to the 2010

revised McDonald criteria, and not taking any medication that might

alter cortical excitability measures. The Hospital Anxiety and

Depression Scale was employed. Socio-demographic and clinical data

were obtained. Transcranial magnetic stimulation was used to assess

the following cortical excitability measures: resting motor threshold,

motor evoked potentials amplitudes and latencies, contralateral silent


123

period, short-interval intracortical inhibition, intracortical facilitation

and interhemispheric inhibition [2]. Correlation analysis was per-

formed to evaluate the association between psychiatric scores

(HADS) and cortical excitability measures.

Results: Fifty consecutive MS patients completed the protocol (24

women; mean age: 51.82 ± 12.72 years; mean expanded disability

status score: 5.52 ± 1.64; mean duration of illness:

11.88 ± 6.03 years). Their mean depression and anxiety scores were

respectively 6.08 ± 3.66 (range 0–14) and 5.82 ± 3.42 (range 1–15).

Correlation analysis revealed a significant positive correlation

between anxiety scores and interhemispheric inhibition mean

(r = 0.43, p = 0.003) and maximal values (r = 0.35, 0.017).

Depression did not correlate with any neurophysiological measure.

Conclusion: A direct relationship between anxiety and callosal

transfer was previously reported in one study [3]. Our results could be

interpreted in the light of the latter findings, in a way that MS patients

with higher anxiety scores may have relatively more efficient callosal

transfer compared to those with low anxiety scores.

References:

1. Chalah MA, Ayache SS (2017) Psychiatric event in multiple

sclerosis: could it be the tip of the iceberg? Rev Bras Psiquiatr.

pii:S1516-44462017005007105.

https://doi.org/10.1590/1516-4446-2016-2105 [Epub ahead of print]

2. Ayache SS, Creange A, Farhat WH, Zouari HG, Mylius V, Ahdab

R et al (2014) Relapses in multiple sclerosis: effects of high-dose

steroids on cortical excitability. Eur J Neurol 21:630–636

3. Leavengood A, Weekes NY (2000) The association between stress,

hemispheric specialization, and callosal interactions. Brain Cogn

43:306–310

Policy of full disclosure: SSA declares having received travel grants

or compensation from Genzyme, Biogen, Novartis and Roche. AC

gave expert testimony for CSL Behring, Novartis, received grants

from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and

gave lectures for Genzyme. JPL and MAC: Nothing to disclose.

P-30Impaired corticospinal excitability revealed by transcranialmagnetic stimulation in patients with major depressive disorder

P. Vignaud1, E. Poulet1,2, M.-F. Suaud-Chagny1, J. Brunelin 1

1INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research

Center, PsyR2 Team, Centre Hospitalier Le Vinatier, University

Lyon, 69000 Lyon, France; University Lyon 1, 69000 Villeurbanne,

France; 2Department of Psychiatric Emergency, Hopital Edouard

Herriot, Lyon, France

Background: Growing evidence suggests that neuroplasticity is

impaired in patients with Major Depressive Disorder (MDD). The

modulation of corticospinal excitability induced by Transcranial

Magnetic Stimulation (TMS) might be an index of neuroplasticity

measured in the living Human. In the last years, several studies

reported impaired neuroplasticity induced by TMS protocol in

patients with psychiatric disorders such as autism spectrum disorder.

We hypothesized that TMS would revealed impaired neuroplasticity

in patients with MDD.

Methods: Eight right-handed patients with DSM 5 unipolar MDD free

for any other axis I disorder and 6 matched healthy controls were

included. Participants were free for any psychotropic drugs.

In a crossover study, participants received 2 sessions of theta-burst

stimulation (TBS) protocols separated by a least 2 days: one session

of intermittent TBS (iTBS) and one sessions of continuous TBS

(cTBS). TBS was applied over the left primary motor cortex (M1).

Motor evoked potentials (MEPs) were recorded before TBS ses-

sions and each 10 min during 2 hs after the TBS sessions.

Results: Effect of iTBS induced a significant increase of MEPs

amplitude in both patients with MDD and healthy controls. iTBS

induced a significant lower effect (p = 0.003) in depressed patients

(+ 537.4 mV ± 329.3) as compared with healthy volunteers

(+ 1581.4 mV ± 728.9) Effect of cTBS induced a significant

decrease of MEPs amplitude in both depressed patients and controls.

There was no difference (p = 0.2) between the cTBS induced

decrease of MEPs amplitude in healthy volunteers (- 389.2 ± 308.8)

and in depressed patients (- 811.8 ± 513.4; p = 0.2).

Conclusion: iTBS revealed impaired corticospinal excitability in

patients with MDD. Response to cTBS seems preserved in patients as

compared to controls. These results suggest that LTP-like plasticity is

impaired in MDD but not LTD-like plasticity.


report.

P-31Individualized connectivity between rTMS targetsand the subgenual cingulate is unrelated to antidepressantresponse

S. H. Siddiqi1,2,3, A. T. Weigand4,5, A. Pascual-Leone5, M. D. Fox2,5

1Department of Neurology, McLean Hospital, Belmont, MA, USA;2Department of Neurology, Massachusetts General Hospital, Boston,

MA, USA; 3Department of Psychiatry, Washington University School

of Medicine, St. Louis, MO, USA; 4Berlin School of Mind and Brain,

Humboldt-Universitat zu Berlin, Berlin, Germany; 5Berenson-Allen

Center for Noninvasive Brain Stimulation, Beth Israel Deaconess

Medical Center, Boston, MA, USA

Background: Antidepressant efficacy of rTMS targets for depression

has been related to resting-state functional connectivity (FC) between

each target and the subgenual anterior cingulate cortex (sgACC) [1,

2]. However, this prior work utilized connectome data from a large

group of normal subjects, ignoring individual differences in func-

tional connectivity that may better predict antidepressant response [3].

Methods: 25 patients with medication-refractory depression under-

went resting-state fMRI scans (3T GE scanner, 28 min of FC data per

patient) before a course of clinical rTMS. Functional data were pro-

cessed following Power et al. 2014 [4]. Each patient’s stimulation site

was identified using the standard 5.5 cm approach and recorded using

neuronavigation. Individualized FC between this site and an a priori

region of interest (ROI) in the sgACC was computed and compared to

antidepressant response (percent change in Beck Depression Inven-

tory). Given known problems with signal to noise ratio (SNR) in the

sgACC, several approaches were used to optimize this ROI: (1) a

‘‘seed map’’ approach previously shown to improve reproducibility of

sgACC connectivity estimates [3], (2) a sgACC ROI weighted by

individualized SNR maps, (3) an individualized subgenual ROI based

on connectivity to the above seed map, and (4) an individualized

subgenual ROI based on an individualized cortical parcellation

algorithm [5].

Results: Antidepressant response was unrelated to individualized FC

between the stimulation site and the sgACC (r = 0.04). All patients

showed extremely poor SNR in the area of the sgACC. Approaches

for optimizing the subgenual ROI improved the reproducibility of

individualized FC estimates, but did not improve the association with

antidepressant response (- 0.06\ r\0.20).

Conclusions: Antidepressant efficacy of rTMS is unrelated to indi-

vidualized connectivity between the stimulation site and the sgACC.

Our results do not support the use of subject-specific FC with the

sgACC for selecting individualized rTMS targets for depression.


123

http://dx.doi.org/10.1590/1516-4446-2016-2105

References:

1. Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A

(2012) Efficacy of transcranial magnetic stimulation targets for

depression is related to intrinsic functional connectivity with the

subgenual cingulate. Biol Psychiatry 72(7):595–603

2. Fox MD, Buckner RL, Liu H, Chakravarty MM, Lozano AM,

Pascual-Leone A (2014) Resting-state networks link invasive and

noninvasive brain stimulation across diverse psychiatric and neuro-

logical diseases. Proc Natl Acad Sci USA 111(41):E4367–E4375

3. Fox MD, Liu H, Pascual-Leone A (2013) Identification of repro-


based on intrinsic connectivity. Neuroimage 66:151–160

4. Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL,

Petersen SE (2014) Methods to detect, characterize, and remove

motion artifact in resting state fMRI. Neuroimage 84:320–341

5. Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ,

Leuthardt EC et al (2013) Resting state network estimation in indi-

vidual subjects. Neuroimage. 82:616–633


report.

P-32Imagery guided personalized robotic rTMS in depression:preliminary results of a feasibility study

J. R. Foucher*1,2, O. A. Mainberger1,2, S. Weibel3,4, G. Bertschy3,4

1ICube-CNRS UMR 7357, Neurophysiology, FMTS, University of

Strasbourg, Strasbourg, France; 2CEMNIS-Noninvasive

Neuromodulation Center, University Hospital Strasbourg, Strasbourg,

France; 3Physiopathologie et Psychopathologie Cognitive de la

Schizophrenie-INSERM 1114, FMTS, University of Strasbourg,

Strasbourg, France; 4Pole de Psychiatrie, Sante Mentale et

Addictologie, University Hospital Strasbourg, Strasbourg, France

Introduction: The iADAPT study - Imagery guided Anti-Depressive

Adaptive Personalized TMS (Clinicaltrials NCT02863380)—is a

double-blind randomized cross-over study designed to assess the

feasibility and efficiency of personalizing rTMS protocol, based on

the functional imaging of single subjects, relative to classical HF-

rTMS and tDCS. Each patient undergone two sessions per day for

10 days.

Method: Brain imaging included two kinds of ASL sequences, con-

verted in rCBF, repeated in three different sessions, using different

functional paradigms and contrasted to thirty-six normal controls. The

tDCS protocol used an F3 anodal positioning, cathode upon the right

upper arm, 20 min sessions at 2 mA DC. Classical HF-rTMS on F3,

delivering 3000 pulses per session (120%, 10 Hz, 4 s trains, 26 ISI).

Last personalized rTMS was designed to correct the rCBF anomalies.

Thirty targets were planned to cover at best reachable parts of the

complex regions with abnormal perfusion. Coil positioning used a

robotic neuronavigated device.

Results: We report on the first 11 patients. All patients had significant

rCBF changes with two main patterns: one with a bilateral fronto-

parietal hypo-perfusion (n = 9, figure 1a), and one with a bilateral

frontal hyper-perfusion (n = 2, figure 1b). The classical target, the

L-DLPFC, was hypo-perfused in only half of the patients, hyper-

perfused in one case. Three patients improved under tDCS, six under

classical rTMS and seven under personalized rTMS. Patient’s rating

showed an average of 10, 30 and 40% symptomatic improvement

respectively for tDCS (blue), classical rTMS (green) and personalized

rTMS (red, figure 1c).

Conclusion: Getting reliable single subject functional results to guide

rTMS treatment was possible. The robotic settings allowed to design

and execute complex personalized protocols which permitted a good

coverage of perfusion anomalies. More subjects are needed to draw

conclusion on the therapeutic efficacy of each arm.

Fig. 1 P-32


report.

P-33A nationwide questionnaire survey on attitudes of Japanesepsychiatric specialists toward repetitive transcranial magneticstimulation therapy for depression

S. Takahashi1,2, S. Kito3,4, M. Nakamura5,6, K. Shinosaki2,7

1Clinic for Psychiatry and Psychotherapy, Ludwig-Maximilians

University Munchen, Munich, Germany; 2Department of

Neuropsychiatry, Wakayama Medical University, Wakayama, Japan;3Department of Psychiatry and Advanced Medical Technology,

National Center Hospital, National Center of Neurology and

Psychiatry, Tokyo, Japan; 4Department of Neuropsychiatry, Kyorin

University School of Medicine, Tokyo, Japan; 5Kanagawa Psychiatric

Center, Yokohama, Japan; 6 Medical Institute of Developmental

Disabilities Research, Showa University, Tokyo, Japan; 7Asakayama

General Hospital, Sakai, Japan

Introduction: Repetitive transcranial magnetic stimulation (rTMS)

was developed as a non-invasive neuromodulation therapy for treat-

ment-resistant depression, but it has not been approved in the clinical

use in Japan. The aim of this study was to reveal the opinions of

psychiatric specialists on the introduction of rTMS therapy for

depression to the clinical setting in Japan.

Methods: This questionnaire survey was designed by the ECT and

rTMS Review Committee of the Japanese Society of Psychiatry and

Neurology (JSPN). Questionnaires were distributed nationwide to

1318 Japanese psychiatric specialist training facilities, and data from

711 facilities were analysed in 2015. The questionnaire inquired about

agreement with the introduction of rTMS therapy for depression to

the clinical setting and recognized problems with its introduction.

Results: In Japan, 60.3% of the responding facilities needed the

introduction of rTMS therapy for depression to the clinical setting.

Conversely, over half of the responding facilities reported insufficient

evidence for the therapeutic benefit of rTMS, uncertainty of the


123

differences in indications between rTMS and other existing therapies,

and insufficient information about rTMS therapy systems. Addition-

ally, 90.0% of the responding facilities indicated that academic

societies should issue treatment guidelines for rTMS; 63.2% of the

responding facilities wanted a training seminar on rTMS operation.

Conclusion: This questionnaire survey suggested that the majority of

psychiatric specialists needed the introduction of rTMS therapy for

depression to the clinical setting in Japan; they also recognized sev-

eral problems with its introduction. Additionally, treatment guidelines

and training seminars for rTMS therapy were deemed necessary.

After this survey, on July 2017, Ministry of Health, Labor and

Welfare in Japan commissioned academic working group to formu-

late guideline for clinical application of rTMS in treatment of

depression.

Policy of full disclosure: This survey was conducted and sponsored by

the Japanese Society of Psychiatry and Neurology. All authors have

no conflict of interest in relation to this survey.

P-34Clinical application of deep transcranial magnetic stimulation(DTMS) in neuropsychiatric disorders: a systematic literaturereview and meta-analysis

K. K. Kedzior1, H. M. Gellersen2

1Institute of Psychology and Transfer, University of Bremen, Bremen,

Germany; 2Department of Psychology, University of Cambridge,

Cambridge, UK

Introduction: Deep transcranial magnetic stimulation (DTMS) with

the H-coil is a non-invasive method of stimulating the entire cortex

and presumably deeper neural structures. The aim of the current study

was to evaluate the acute clinical outcomes of daily DTMS treatment

in neuropsychiatric disorders using a systematic review and meta-

analysis.

Methods: Following a systematic literature search of PsycInfo and

Medline (up to 28.04.2017), k = 35 studies (k = 24 open-label and

k = 11 double-blind randomised controlled trials, RCT, with inactive

sham groups) were included in the current study. The clinical out-

comes were assessed with standardised scales at baseline and after

daily DTMS and expressed as standardised change scores (Hedges’

g). Effect sizes were pooled using a random-effects meta-analysis

with inverse-variance weights.

Results: Symptom severity significantly decreased after DTMS rela-

tive to baseline (large pooled g = 1.23, 95% confidence interval CI

0.97–1.49; k = 35 studies with 560 patients who received active

treatment). The largest reductions in symptom severity were observed

in studies with unipolar major depression (MDD; k = 11), bipolar

MDD (k = 4), neuropathy (k = 2), and substance use disorders

(SUD; k = 6). High-frequency (18–20 Hz) and high-intensity (120%

of the resting motor threshold, %RMT) protocols produced signifi-

cantly better outcomes relative to lower frequency/intensity (\ 18 Hz/

\ 120% RMT) protocols. DTMS also produced significant reductions

in symptom severity relative to sham (moderate pooled g = 0.53,

95% CI 0.24–0.82; k = 11 RCTs with 383 patients).

Discussion: DTMS produces acceptable clinical outcomes in various

neuropsychiatric disorders, especially in MDD and SUD. Future

research is required to understand the influence of stimulation pro-

tocols on the clinical outcomes.


report.

P-35Acute efficacy of deep transcranial magnetic stimulation (DTMS)in unipolar vs. bipolar major depressive disorder (MDD):a systematic literature review and meta-analysis

H. M Gellersen1, K. K Kedzior2

1Department of Psychology, University of Cambridge, Cambridge,

UK; 2Institute of Psychology and Transfer, University of Bremen,

Bremen, Germany

Introduction: Deep transcranial magnetic stimulation (DTMS) with

the H-coil is a non-invasive treatment alternative for pharmaco-re-

sistant major depression (MDD) as it stimulates widespread cortical

and presumably subcortical regions to normalise brain activity. The

method has been FDA-approved for unipolar MDD. The aim of the

current study was to determine the efficacy of DTMS for bipolar

compared to unipolar MDD using a systematic review and meta-

analysis.

Methods: A systematic literature search of PubMed and PsycInfo

identified k = 4 studies that used the H-coil to treat bipolar MDD

(one randomised-controlled trial [RCT], three open-label) and k = 11

studies with unipolar MDD (one RCT, ten open-label). Clinical out-

comes were the standardised change in depression severity

(baseline—after last daily DTMS session) according to standardised

scales and expressed as Hedges’ g (effect size), and response and

remission rates. A random-effects meta-analysis with inverse-vari-

ance weights was carried out to pool the effects.

Results: The meta-analysis revealed a large acute antidepressant

effect in k = 4 studies with n = 65 bipolar patients (g = 1.81, 95%

confidence interval CI 0.90–2.72). Pooled response and remission

rates were 62 and 29%, respectively. The antidepressant effect in

n = 282 unipolar patients was similarly large (g = 1.51, 95% CI

1.23–1.79), with pooled response and remission rates of 51 and 29%,

respectively. Most of k = 15 studies used stimulation parameters of

18–20 Hz frequency at 120% motor threshold with 1680 or 1980

stimuli (42 or 55 trains per session) across 20 daily sessions. The

majority of patients in both groups were on concurrent

stable antidepressants.

Discussion: The acute antidepressant outcomes for unipolar and

bipolar MDD are of similar magnitude and suggest acceptable clinical

relevance of DTMS. However, effects in bipolar patients were more

variable. Results are limited by the use of mostly open-label studies

with medicated patients. Nonetheless, they show that DTMS is a

promising acute treatment for bipolar MDD.


report.

P-36Predicting deep transcranial magnetic stimulation (dTMS)efficiency in depressed using brain network activation (BNA)analysis

C. Baumeister1, R. Shani-Hershkovich1, A. Amit1, Z. Peremen1, Y.

Levkovitz2,3, A. Geva1,4

1ElmindA Ltd, Hertsliya, Israel; 2Tel Aviv University, Tel Aviv,

Israel; 3Beer Yaakov-Ness Ziona Mental Health Center, Be’er

Ya’akov, Israel; 4Ben Gurion University, Beersheba, Israel



123

P-37Cognitive effects of high-frequency-rTMS in chronicschizophrenic patients

S. J. Kim1, E. Meuthen1, J.Cordes1

1Department of Psychiatry and Psychotherapy, LVR-Klinikum

Dusseldorf, University Hospital HHU Dusseldorf, Dusseldorf,

Germany

Introduction: To assess positive as well as negative cognitive effects

of high-frequency-rTMS we examined cognitive changes in n = 32

chronic schizophrenic in-patients with predominant negative symp-

toms. Furthermore we explored both whether cognitive rTMS-effects

were correlated with baseline psychopathology and whether rTMS-

effects on psychopathology were associated with baseline cognitive

performance.

Methods: Patients on stable antipsychotic treatment were randomly

assigned to verum- or sham-condition. In the verum-group patients

received ten sessions of 10 Hz-rTMS over the left dorsolateral pre-

frontal cortex (DLPFC) at 110%-motor-threshold over 2 weeks. The

sham-group received sham-stimulation. RTMS-effects on cognitive

performance were assessed with a neurocognitive test-battery con-

sisting of the trail making test A and B (TMT), Wisconsin card sorting

test (WCST), D2 attention task and the ‘‘shortest for general intelli-

gence’’ (KAI). Psychopathology and global-functioning were

measured by the Clinical Global Impression scale (CGI), Global

Assessment of Functioning Scale (GAF) and Positive and Negative

Symptom Scale (PANSS).

Results: No statistically significant differences in cognitive rTMS-

effects between groups with small to moderate effect sizes were

shown, the effects were partly contradictory. In the verum-group a

poor performance in executive-functions at baseline was associated

with an improvement in psychopathology, especially in negative

symptoms, after rTMS-treatment. Whereas in the sham-group a

favourable status in executive-functions at baseline was associated

with an improvement in clinical global impression after sham-

stimulation.

Discussion: Our results show no significant change in cognitive

performance after 10 Hz-rTMS-treatment. Thus they indicate good

tolerability in regard to negative cognitive side-effects, but they also

failed to show consistent favourable effects on cognitive performance.

Moreover they suggest, that the effects of high-frequency-rTMS on

psychopathology and cognitive performance could be associated with

baseline cognitive performance or baseline psychopathology respec-

tively. The absence of significant effects might be due to low

stimulation-parameters, short stimulation-periods and a small sample-

size (n = 32).


report.

P-38Transcranial magnetic stimulation has different short-termefficacy on different major depressive disorder symptoms:a nested prospective cohort study in Croatia

T. Gajsak1, I. Filipcic1,2,3, Z. Milovac1, S. Sucic1, S. Zecevic Penic1,

E. Ivezic1, Z. Bajic4

1Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb, Croatia; 2Faculty of

Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,

Croatia; 3School of Medicine, University of Zagreb, Zagreb, Croatia;4Biometrika Healthcare Research, Zagreb, Croatia

Introduction: This presentation will describe the protocol and interim

analysis of 12-month study with rTMS/dTMS and standard therapy

control in patients with moderate/severe MDD. The study objective is

to explore the short and long-term efficacy/tolerability, and to create

and validate the treatment outcomes multivariate prediction model.

Methods: In this, randomized, active-controlled, prospective study

4-weeks sessions are conducted with rTMS, five times weekly, at

10 pulses/s, 120% of motor threshold, 3000 pulses/session, and with

dTMS by Brainsway protocol. Primary outcomes are the changes in

HAM-D17, PSQ9, MADRS, BDI-II results and remission rates.

Secondary outcomes are changes in WHOQOL, EQ-5D-5L, GAF.

Sleep quality is evaluated with EPWORTH and Pittsburgh scales.

Tolerability assessment included all adverse events (AEs). Personality

traits measured by IPIP, plasma serotonin, BDNF and other clinical

variables will be used in the derivation of a prediction model.

Results: By May 2017, 162 patients were enrolled (54 randomized in

each group). After adjustment for baseline HAM-D17 and con-

founders, TMS groups were significantly different from the control

group (p\ 0.001). Mean HAM-D17 score was lowered for 69% in

dTMS, 59% in rTMS and 28% in control group. The difference

between dTMS and rTMS was not significant (p = 0.070). After

4-weeks, 63% of patients treated with dTMS achieved remission, 52%

in rTMS and 19% in control group. The difference between TMS and

control was significant (p\ 0.001), but not between the two TMS

groups (p = 0.243). We did not observe significant changes in quality

of life. TMS was well tolerated with a no dropout for AEs.

Conclusion: Preliminary data indicate that augmentative rTMS or

dTMS are more effective in MDD treatment than standard therapy.

dTMS with H1-coil is more effective than rTMS, but not statistically

significant. Both treatments are well tolerated.


report.

P-39Efficacy and tolerability of repetitive transcranial magneticstimulation with and without the Brainsway H1-coil in treatmentof major depressive disorder: presentation of the protocoland interim analysis

I. Filipcic1,2,3, I. S. Filipcic4, T. Gajsak1, S. Sucic1, Z. Milovac1,

S. Zecevic Penic1, E. Ivezic1, I. Orgulan1, N. Tunjic Vukadinovic1,

Z. Bajic5

1Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb, Croatia; 2Faculty of

Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,

Croatia; 3School of Medicine, University of Zagreb, Zagreb, Croatia;4Department of Psychological Medicine, University Hospital Center

Zagreb, Zagreb, Croatia; 5Biometrika Healthcare Research, Zagreb,

Croatia

Introduction: This presentation will describe the protocol and interim

analysis of 12-month study with rTMS/dTMS and standard therapy

control in patients with moderate/severe MDD. The study objective is

to explore the short and long-term efficacy/tolerability, and to create

and validate the treatment outcomes multivariate prediction model.

Methods: In this, randomized, active-controlled, prospective study

4-weeks sessions are conducted with rTMS, five times weekly, at

10 pulses/s, 120% of motor threshold, 3000 pulses/session, and with

dTMS by Brainsway protocol. Primary outcomes are the changes in

HAM-D17, PSQ9, MADRS, BDI-II results and remission rates.

Secondary outcomes are changes in WHOQOL, EQ-5D-5L, GAF.

Sleep quality is evaluated with EPWORTH and Pittsburgh scales.

Tolerability assessment included all adverse events (AEs). Personality

traits measured by IPIP, plasma serotonin, BDNF and other clinical

variables will be used in the derivation of a prediction model.

Results: By May 2017, 162 patients were enrolled (54 randomized in

each group). After adjustment for baseline HAM-D17 and


123

confounders, TMS groups were significantly different from the con-

trol group (p\ 0.001). Mean HAM-D17 score was lowered for 69%

in dTMS, 59% in rTMS and 28% in control group. The difference

between dTMS and rTMS was not significant (p = 0.070). After

4-weeks, 63% of patients treated with dTMS achieved remission, 52%

in rTMS and 19% in control group. The difference between TMS and

control was significant (p\ 0.001), but not between the two TMS

groups (p = 0.243). We did not observe significant changes in quality

of life. TMS was well tolerated with a no dropout for AEs.

Conclusion: Preliminary data indicate that augmentative rTMS or

dTMS are more effective in MDD treatment than standard therapy.

dTMS with H1-coil is more effective than rTMS, but not statistically

significant. Both treatments are well tolerated.


report.

P-40Interaction of serotonin and age is significant predictorof transcranial magnetic stimulation effect on major depressivedisorder: a prospective cohort study in Croatia

I. Simunovic Filipcic1, T. Gajsak2, S. Sucic2, Z. Milovac2, S. Zecevic

Penic2, E. Ivezic2, N.Ruljancic2, Z. Bajic3, I.Filipcic2,4,5

1Department of psychological medicine, University Hospital Center

Zagreb, Zagreb, Croatia; 2Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb,

Croatia; 3Biometrika Healthcare Research, Zagreb, Croatia; 4Faculty

of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,

Croatia; 5School of Medicine, University of Zagreb, Zagreb, Croatia

Introduction: Serotonin plays an important role in mood control. It is

one of the two primary antidepressants’ targets. However, previous

studies have not found the baseline serotonin level to be a significant

predictor of TMS effects on major depressive disorder (MDD). One

of the explanations was that plasma concentrations may have limited

validity for the brain serotonin levels.

Objective: We hypothesized that previous studies failed to detect

serotonin predictive value because they missed to analyze some

important moderators or control the effect of some important con-

founders. We hypothesized that such moderators may be: age, sex,

duration and severity of MDD.

Methods: This cohort study was conducted at Psychiatric Hospital

Sveti Ivan, Zagreb, Croatia during 2016/2017, on the sample of

patients diagnosed with MDD. The outcome was Beck Depression

Inventory-II (BDI-II) result after 4-week treatment with TMS,

adjusted for BDI-II baseline result. Moderators values defining

Johnson–Neyman significance regions were analyzed in PROCESS

Release 1.16.2, written by Andrew F. Hayes.

Results: We enrolled the sample of 37 patients. The overall model

including age, serotonin, and their interaction significantly predicted

BDI-II change (R2 = 0.52; p = 0.006). Interaction of baseline sero-

tonin concentration and age was significant predictor by itself

(R2 = 0.29; p = 0.003). Serotonin was a significant predictor of TMS

effects in patients younger than 35, and older than 51. In younger

patients, higher baseline serotonin levels were associated with higher

BDI-II results at fourth week indicating lower efficacy of TMS

treatment. In older patients, this effect was reversed. Interactions of

serotonin and other hypothesized moderators were not significant

predictors of BDI-II change.

Conclusion: Baseline serotonin level prediction value for TMS effects

on MDD is moderated by patients’ age. If serotonin is analyzed alone,

it is not significantly associated with TMS treatment outcome, as its

effects in lower and higher age groups are reversed and they mutter.


report.

P-41Treatment of pediatric catatonia with ECT: a case seriesand review

R. Katz1, M. Toprak1, Z. Qayyum1, C. Wilson1, R. Ostroff1

1Yale Psychiatric Hospital, Yale Department of Psychiatry, New

Haven, CT, USA

Catatonia is an under-recognized illness commonly associated with

mood disorders, psychotic disorders and medical illness, for which the

gold standard curative treatment is Electroconvulsive Therapy (ECT).

Morbidity and mortality in this state are significant, especially in

malignant catatonic states with autonomic instability, and warrants

urgent and aggressive care. We discuss six cases of pediatric patients

presenting with catatonia, all of whom were successfully treated with

ECT on our Interventional Psychiatry Service. Notably, two of these

patients had no history of psychiatric illness. We will review the

literature on pediatric catatonic states and the history of and evidence

for treating this condition. We will also address the legal issues sur-

rounding consent for ECT in a pediatric population.


report.

P-42Adjustment of pulse wave parameters to optimize effective ECTtreatment

R. Ostroff1, R. Katz1, J. Cahill1

1Yale Psychiatric Hospital, Yale Department of Psychiatry, New

Haven, CT, USA

The sine qua non for a therapeutic effect of ECT is the induction of a

generalized grand mal seizure achieved by administering a dose of

energy above the patient’s seizure threshold (ST). The seizure

threshold (ST) at any given ECT treatment may vary depending on

both patient characteristics and treatment specific factors. Conven-

tionally, ST is estimated as the total energy (in Joules, J) or charge (in

milliCoulombs, mC) required to induce a seizure at titration. At times

patients with exceptionally high STs exceed the maximum allowed

stimulus energy that can be administered with a pulse wave apparatus

particularly on subsequent treatments which call for a five- to sixfold

increase in right ultra brief pulse unilateral treatment and 50%

increase in bilateral treatment courses. Recent evidence however,

points to a complex interaction between the pulse wave parameters

and ST. This may result in an apparent ‘super-saturation’ of the sei-

zure threshold in patients requiring high-energy stimulations. This

case series presents examples where an excessively high stimulus

frequency appears to negate seizure initiation at a comparatively high

energy (an example of ‘stimulus-crowding’). A reduction in fre-

quency and the overall energy produced a seizure. Focus only on the

total quantity of energy delivered during a pulse wave stimulation, in

lieu of adjusting other pulse wave parameters, may result in sub-

threshold stimulations, unnecessary side effects and a non-therapeutic

treatment session. An extension in the range of available stimulus

parameters, specifically duration, should result in the practitioner’s

ability to keep the frequency setting within physiological parameters

and still obtain an adequate energy level to induce a seizure.


report.


123

P-43Transcranial direct current stimulation (tDCS) replaceselectroconvulsive therapy (ECT) in a patient with corpuscallosum agenesis and catatonic schizophrenia: a longitudinalnetwork-metric approach

D. Keeser 1,2, O. Pogarell1, U. Palm1, E.Weidinger1, V. Kirsch3, A.

Hasan1, B. Kirsch1, T. Karali1,2, J. Worsching1, S. Karch1, Ma.

Paolini2, B. Ertl-Wagner2, F. Padberg1


University, Munich, Germany; 2Institute of Clinical Radiology,

Ludwig Maximilian University, Munich, Germany; 3Department of

Neurology, Ludwig Maximilian University, Munich, Germany

Introduction: Here, we report about a single case of catatonic

schizophrenia, which has been treated with prefrontal tDCS for

almost 4 years. Based on excessive stimulation sessions, clinical

ratings, multimodal MRI measurements, and EEG recordings, we

show the relationship between clinical improvement and macroscale

brain activity changes.

Methods: The 44-year-old male patient with known complete corpus

callosum agenesis CCA had shown severe catatonic symptoms since

adolescence and been treated with weekly electroconvulsive therapy

(ECT) for almost 6 years, because drug treatment was ineffective.

After obtaining approval from the local ethics committee and

informed consent from the patient and his relatives, tDCS was started

with the following stimulation settings: Anode over the left dorso-

lateral prefrontal cortex (F3) and cathode over the right (F4); 2 mA

for 2 9 20 min/day (90-min interval), 39/week for 2 weeks, once to

twice weekly thereafter with the same parameter settings. Concomi-

tant medication (clozapine 600 mg/day, aripiprazole 10 mg/day,

pirenzepine 50 mg/day, lorazepam 3 mg/day) was continued. A

weekly clinical assessment was conducted that included the Bush-

Francis Catatonia Rating Scale. Functional magnetic resonance

imaging was performed at baseline and after 70, and 140 tDCS ses-

sions to assess resting-state functional connectivity (rs-FC), structural

brain volumes (T1-MPRAGE, T2-FLAIR) and Diffusion Tensor

Imaging (DTI). EEG was recorded at baseline and after 70, 140 and

300 tDCS sessions. To obtain a reference to healthy age-matched

male subjects, 26 volunteers were measured at the same time with a

rehearsal session using resting state EEG and fMRI.

Results: The patient overall received about 330 tDCS sessions

between August 2013 and June 2017. ECT was needed only once

after a 10-day hospitalization for pneumonia in September 2013,

during which time tDCS had been suspended. The patient showed

fewer catatonic symptoms ([ 50% of BCRS reduction in average)

during tDCS treatment than during ECT treatment (BCRS scores:

20–27/69 during ECT, 4–12/69 during tDCS with one outlier of a

BCRS score of 18 at September 9, 2015. His speech fluency, personal

hygiene, and attendance at a sheltered workshop improved. Seed-

based functional connectivity in the right insula and the frontal brain

showed increased connectivity after 140 tDCS sessions compared to

baseline. Low-frequency EEG activity (1–12 Hz) decreased over the

course of the tES sessions in the frontal and insula cortex, whereas

high-frequency EEG activity (12–50 Hz) increased. The BCRS scores

were negatively correlated with left frontal (- 0.74, p = 0.002), right

frontal (r = - 0.62, p = 0.01) and right insular cortex (r = - 0.867,

p\ 0.001) rs-FC. There was no correlation to the left insular cortex

(r = - 0.09, p = 0.75). The BCRS scores were positively correlated

to the low-frequency in right frontal (r = r = 0.63, p = 0.03) and left

insular cortex (r = r = 0.78, p = 0.003) and negatively correlated

with the right insular cortex (r = - 0.87, p\ 0.001). EEG and rs-FC

changes developed in the direction of the healthy cohort, but still

remained deviated after over 300 tDCS sessions.

Discussion: The findings of this study increase our knowledge of

longitudinal non-invasive brain stimulation in a case of catatonic

schizophrenia with CCA. We show that network activity changes in

the frontal brain are associated with clinical improvement, which

might have been induced by tES. The results illustrate the utility of

high temporal resolution and high spatial resolution to monitor

experimental therapy intervention. The negative correlation between

BCRS scores and the number of activated seed-based left, right

frontal, and right insular cortices in the resting fMRI and the positive

correlation between BCRS scores in the left, right frontal, and left

insular cortices (negative correlation in the right insular cortex) and

low-frequency EEG indicate network based mechanism of clinical

improvement. Finally, by providing repeated assessments of network

metrics, this approach could help to track individual patients longi-

tudinally, and also assess their neural responses to therapeutic

interventions.








P-44Individualized thresholds: calibrating brain stimulation throughconcurrent TMS/fMRI

M. Tik1, M. Woletz1, A. Hummer1, N. Geissberger1,

C. Windischberger1

1fMRI.at, Center for Medical Physics and Biomedical Engineering,

Medical University of Vienna, Vienna, Austria

Introduction: Current TMS applications are adjusted in relation to

individual motor thresholds (MT), however there is no consensus on

how to define this threshold (1) and if determined MT is applicable to

other cortical targets (2). We have developed a setup for high-reso-

lution image acquisition and unimpeded simultaneous TMS based on

a dedicated TMS/fMRI multi-channel receive (RF) array. This has

been shown to allow mapping of intensity-dependent TMS effects in

the primary motor cortex, m1(3). Here we go beyond m1 to exploit

this high sensitivity setup combined with advanced imaging and

neuronavigation methods to map intensity-related TMS effects over

left DLPFC.

Methods: The study was performed on a 3T Prisma (Siemens,

Erlangen, Germany). TMS/fMRI setup included a MagProX100

stimulator (Magventure, Farum, Denmark), MRi-B91 MR-compatible

TMS coil mounted on dedicated RF-coil, MR-compatible neuronav-

igation and MR-visible fiducial markers installed in the RF-coil to

allow coil-localisation during imaging. Five right-handed female

subjects (age 24.9 ± 3.2 years) participated in the experiment.

Functional images were acquired using EPI sequence with TR/

TE = 1000/33 ms, 28 slices, 1.5 9 1.5 9 3 mm3. FMRI data anal-

yses were performed using SPM12. The design matrix comprised four

regressors representing different stimulation amplitudes of 10 Hz

rTMS over left DLPFC.

Results: 10 Hz TMS led to intensity-dependent local and remote

activation changes. The stimulated target (left DLPFC) and its con-

tralateral homologue (right DLPFC) showed proportional direct

intensity related changes, while ACC manifested a more complex

response pattern. Tracking of fiducial markers unraveled subject-

drifts of more than 4 mm to render stimulation ineffective.

Discussion: We demonstrate acute local and network effects of TMS

over the left DLPFC on an individual level, i.e. intensity-dependent

BOLD increase at the stimulation site and in interconnected network

nodes. This allows setting a framework for optimal individualized


123

stimulation, based on parameters that evoke exactly the desired local

or network effect/response, without having to rely on MT.


report.

P-45Is hippocampal neurogenesis mediating clinical efficacyand memory outcome after electroconvulsive therapyin depression?

D. Attali1,2, A. Cachia3, P. Abdel-Ahad1,2, C. Oppenheim3, P. Gori3,

M. O. Krebs1,2, R. Gaillard1,2, M. Plaze1,2

1Pathophysiology of Psychiatric Disorders: Development and

Vulnerability, Center of Psychiatry and Neurosciences, INSERM

UMR 894, University Paris Descartes, Sorbonne Paris Cite, Paris,

France; 2Centre Hospitalier Sainte-Anne, Service Hospitalo-

Universitaire, Paris, France; 3Biomarkers of Brain Development and

Disorders, Center of Psychiatry and Neurosciences, INSERM

UMR894, University Paris Descartes, Sorbonne Paris Cite, Paris,

France

Background: Electroconvulsive therapy (ECT) is the most effective

treatment for treatment-resistant depression (TRD) but its use is partly

restricted due to its cognitive side effects (1). Animal models have

linked hippocampal neurogenesis to both ECT response (2) and

memory function, suggesting that increasing hippocampal neurogen-

esis weakens existing memories (3, 4). The aim of this study was to

investigate the effect of ECT on hippocampal volume and its relation

to clinical and memory outcome in depression.

Method: 10 patients with TRD, referred for ECT by their psychiatrist,

were recruited at Sainte-Anne Hospital in Paris. Patients were treated

twice weekly with bi-temporal ECT until remission on the MADRS

was achieved. Clinical and cognitive outcomes were investigated with

a neuropsychological test battery focused on retrograde amnesia for

autobiographical information (CUAMI-SF) and retrograde episodic

memory loss (mWMS-IV). Patients underwent 1.5 T structural MRI

at both time points. We used the CAT12 toolbox in SPM12 to study

whole brain voxel-wise longitudinal grey matter changes and FSL 5.0

to measure hippocampal volumes.

Results: Both left and right hippocampal volumes increased signifi-

cantly following ECT (5.06 ± 0.85%, p\ 0.001). Retrograde

memory was altered with significant autobiographical and pre-exist-

ing episodic memory loss (p\ 0.01). Positive correlations were

observed between increase in total hippocampal volume and (1)

treatment efficacy (p = 0.008) and (2) retrograde episodic memory

loss (p = 0.002).

Conclusion: Patients with TRD showed specific bilateral hippocampal

volume increases following ECT. Total hippocampal volume increase

was associated with (1) treatment efficacy and (2) retrograde episodic

memory loss. These findings suggest that ECT clinical efficacy and its

cognitive side-effects could be underpinned by common neurobio-

logical mechanisms, such as neurogenesis, gliogenesis,

synaptogenesis or angiogenesis. Larger sample sizes, control groups,

functional imaging and peripheral biomarkers could provide a better

coverage of biological substrates that contribute to ECT-induced

clinical improvement and cognitive side-effects.

References:

1. UK ECT Review Group (2003) Efficacy and safety of electro-

convulsive therapy in depressive disorders: a systematic review and

meta-analysis. Lancet Lond Engl 361(9360):799–808

2. Schloesser RJ, Orvoen S, Jimenez DV, Hardy NF, Maynard KR,

Sukumar M et al (2015) Antidepressant-like effects of electrocon-

vulsive seizures require adult neurogenesis in a neuroendocrine model

of depression. Brain Stimul 8(5):862–867

3. Epp JR, Silva Mera R, Kohler S, Josselyn SA, Frankland PW

(2016) Neurogenesis-mediated forgetting minimizes proactive inter-

ference. Nat Commun 7:10838

4. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro

A, Hsiang H-LL et al (2014) Hippocampal neurogenesis regulates

forgetting during adulthood and infancy. Science 344(6184):598–602

Policy of full disclosure: This study was supported by the Fondation

Pierre Deniker. The authors declare no conflict of interest.

P-46Real-time fMRI neurofeedback in patients with alcohol usedisorder: craving-related modulations

K. Lehnert1, J. Konrad1, D. Haller1, S. Gschwendtner1, H. Jeanty1,

A. Reckenfelderbaumer1, O. Yaseen1, M. Paolini2, D. Keeser1,2,

G. Koller1, B. Ertl-Wagner2, O. Pogarell1, S. Karch1


University Munich, Munich, Germany; 2Institute of Clinical

Radiology; Ludwig-Maximilians-University Munich, Munich,

Germany

Background: About 1.7 million persons in Germany suffer from

alcohol use disorder, 10.4 million persons show a risky alcohol

consumption [2]. Hartwell and colleagues [1] demonstrated that the

modulation of neuronal activity using real-time fMRI neurofeedback

(rtfMRI NF) is a promising therapeutic approach for patients with

alcohol use disorder.

Aim: Aim of the present study was to examine if patients with alcohol

use disorder are able to learn the modulation of craving-related

neuronal responses using rtfMRI NF and to reduce craving.

Methods: 52 patients with alcohol use disorder participated in the

study. All patients were recruited in a ward specialised for the

treatment of alcohol use disorders. The rtfMRI NF training was an

add-on to the standard treatment. Patients were randomised to a real

and sham condition. During the fMRI session, alcohol-associated and

neutral pictures were presented. Subjects were instructed to reduce

their neuronal responses during the presentation of alcohol cues in the

individual region of interest (ROI: anterior cingulate cortex, insula or

dorsolateral prefrontal cortex). Directly before and after the rtfMRI

session individual craving (Obsessive Compulsive Drinking Scale;

Mann & Ackermann, 2000) as well as emotional responses (Beck

Depression Inventory [BDI]; Barrett Impulsiveness Scale [BIS]) were

assessed.

Results and discussion: The relapse rate was lower in the real group

compared to the sham group. A significant reduction auf neuronal

responses in the target regions (especially frontal areas/prefrontal

cortex, insula) was demonstrated. In addition, BOLD responses in

brain regions which are associated with emotion processing (e.g.

limbic regions) decreased.

The comparison of BOLD responses of patients that remained

abstinent 3 months after the rtfMRI NF training and patients with a

relapse 3 month after the fMRI measurements revealed a pronounced

reduction of frontal responses during NF training in patients that

remained abstinent. Overall, the rtfMRI NF training may be useful as

an add-on to the standard treatment. Further studies should address

questions about subgroups as well as rtfMRI parameters to enhance

the effect of the training.

References:

1. Hartwell KJ et al (2013) Real-time fMRI in the treatment of

nicotine dependence: a conceptual review and pilot studies. Psychol

Addict Behav US 27:501–509


123

2. Singer MV, Teyssen S, Schneider A (2005) Alkohol und Alko-

holfolgekrankheiten: Grundlagen-Diagnostik-Therapie. Springer,

Berlin


report.

P-47LMU scripts • ready-made HPC-applicable pipelinefor structural and functional data analyses

T. Karali1, V. Kirsch2, F. Padberg3, B. Ertl-Wagner4, D. Keeser1

1Department of Psychiatry, Institute of Clinical Radiology, Ludwig-

Maximilians University, Munich, Germany; 2Department of

Neurology, Ludwig-Maximilians University, Munich, Germany;3Department of Psychiatry and Psychotherapy, Ludwig-Maximilians

University, Munich, Germany; 4Institute of Clinical Radiology,

Ludwig-Maximilians University, Munich, Germany

Introduction: Basic requirements in imaging research are changing

rapidly due to the growing size of datasets and multimodal approa-

ches with increasingly complex, time consuming, diverse, and fast-

altering standards. LMU Scripts offers a ready-made, free and open-

source (FOSS) high-performance-computing (HPC) applicable pipe-

line for state-of-the-art structural and functional data analyses that

utilize parallel processing.

Methods: LMU Scripts depends on the software libraries listed below.

FSL [1], AFNI [2], R [3], including the packages car [4], gplots [5],

grDevices [3], graphics [3], nlme [6], multcomp [7], Python [8],

including the package rpy2.

LMU Scripts is compatible with Linux-based operating systems. For a

dataset with n[ 1, parallel processing is supported using SLURM on

a HPC cluster, and using a Python multiprocessing pool on a local

computer. This procedure is elaborated below.

Results: LMU Scripts follows a three-step workflow, as illustrated

below.

The starter script checks whether all required files are available and

valid, sets up the folder structure for output files, and spawns sub-

processes in an efficient way. Multiple instances of the pre-processing

script(s) calculate and permanently store the ‘‘subject-level’’ data

(voxel counts, T1/T2 anatomical data, connectivity matrices, etc.).

Finally, the post-processing script accesses the data that was created

by the instances of the pre-processing script(s), and processes it into

the ‘‘group-and-study-level’’ data (overviews, plots, statistical calcu-

lations, etc.).

Examples to output data—as mentioned—are illustrated below.

• Structural preprocessing (FLTR: skull strip, CSF/WM/GM seg-

mentation, brain mask, individual brain parcellation).

• Functional preprocessing (time series, registration, motion cor-

rection, z-scores).

• Quality control (FoV, motion, SNR)

• Anatomical region finding using autoaq and automatic generation

of publication-ready tables.

Conclusion: In future, HPC applicable pipelines will be a requirement

for any imaging lab. LMU Scripts offers a ready-made, cost-free, and

open source alternative. A publication, along with a release of the

source code tree, is currently in preparation.

References:

1. Jenkinson M et al (2012) FSL. NeuroImage 62:782–790

2. Cox R (1996) AFNI: software for analysis and visualization of

functional magnetic resonance neuroimages. Comput Biomed Res

29:162–173

3. R Core Team (2016) R: a language and environment for statistical

computing. R Foundation for Statistical Computing, Vienna, Austria.

https://www.R-project.org/

4. Fox J et al (2011) An R companion to applied regression, 2nd edn.

Sage, Thousand Oaks

5. Warnes G et al (2016) gplots: Various R programming tools for

plotting data. R package version 3.0.1. https://CRAN.R-project.

org/package=gplots

6. Pinheiro J et al (2016) nlme: Linear and nonlinear mixed effects

models. R package version 3.1-128. http://CRAN.R-project.org/

package=nlme

7. Hothorn T et al (2008) Simultaneous inference in general para-

metric models. Biom J 50(3):346–363

8. Van Rossum G (1995) Python tutorial. Technical Report CS-

R9526, Centrum voor Wiskunde en Informatica (CWI), Amsterdam




GmbH and Brainsway Inc., Jerusalem, Israel.


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https://www.R-project.org/

https://CRAN.R-project.org/package%3dgplots

https://CRAN.R-project.org/package%3dgplots

http://CRAN.R-project.org/package%3dnlme

http://CRAN.R-project.org/package%3dnlme

2nd european conference on brain stimulation in psychiatry...

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