the effects of two different repetitive tms stimulation protocols on muscle fatigue associated...

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Movement Disorders Poster Only 206 Joint coordination studied by TMS in focal hand dystonia Boyadjian A, Tyc F, Allam N, Brasil-Neto JP, Laboratoire plasticite ´& physio-patholog (Marseille Cedex, FR) Writer’s cramp belongs to a group of focal task-specific dystonias affecting fine manual skills and is characterized by excessive muscular activation during writing. Different TMS protocols have shown that the functional characteristics of cortical networks in motor areas were different in dystonic patients than control subjects. Furthermore, cortical activity during the movement preparation is different in dystonic patients, which could be responsible for a modification of the response of cells to afferent inputs and then the production of movement. The properties of neural excitability have to be considered in the context of muscle coordination. Our work focused on the integrated neural networks linking proximal and distal muscles that move the shoulder, the wrist and the finger. Such networks linking shoulder and wrist were observed in control subjects. We wanted to observe in dystonic patients the properties of response in different coordination condition to know how muscles are linked. Motor evoked potentials (MEPs) were recorded from medial deltoid (MD), extensor carpi radialis (ECR) and the first dorsal interosseus (FDI) muscles in 10 patients with focal hand dystonia and six healthy subjects. The subjects had to maintain a ring in order to do not touch a wire passing through this ring. The first condition was to maintain the ring using only the arm (ECR Alone), the elbow rested on an armrest. The second condition was to maintain the ring using the whole upper limb (ECR and MD co-activated). The TMS was done on the hot spot of the ECR with seven increasing intensities of stimulation, determined as percentages of the ECR active motor threshold (aMT). At each intensity, four stimulations were done and the corresponding MEPs averaged to compute excitability curves for the three muscles. Each group exhibited MEPs facilitation of ECR during the voluntary activation of MD as showed by plateau and slope of sigmoid regression. Interestingly only the patient group showed facilitation of FDI when MD was activated. Then, in dystonic patients, even the ‘‘most’’ distal part of muscle chain could be facilitated by the ‘‘most’’ proximal part of the upper limb. The generalization of neural pathways though to allow the coordi- nation between each joint could be responsible of an excess in tonic activity resulting in an inadequate pattern of coordination observed in dystonic patients during writing. Clinical Studies Poster Only 207 Cortico-cortical properties in Parsonage-Turner Syndrome: a TMS case study Rossi-Durand C, Boyadjian A, Devanne H, Tyc F, Laboratoire plasticite ´ & physio-patholog (Marseille Cedex, FR) We report the long-term effects of one unilateral Parsonage-Turner Syndrome case (PTS) on motor cortex representation of a proximal upper limb muscle. The subject suffered from a sporadic painful episode of weakness of the shoulder girdle muscles seven years earlier. At this time, needle EMG recordings showed only few MUs in the left anterior deltoid muscle (AD), while nerve conduction was found normal. Arthroscanner examination was unremarkable confirming the absence of joint lesion. The episode lasted for one year. Currently, the PTS-subject uses his left arm without any limitation in strength and accuracy. Bilateral transcranial magnetic stimulation mapping of proximal AD and distal First Dorsal Interosseus muscles (FDI) during low-level voluntary contraction showed that cortical representation of both the left AD and FDI muscles were smaller than the right ones and than those obtained in control subjects. Single motor unit potential analysis of AD muscle have shown a decrease in the probability of response to the single pulse TMS. Macro motor-unit potential analysis did not show any difference between right and left AD, suggesting an absence of motoneu- ron death. A decrease of single MU excitability associated with the absence of macro-MUP size variation has been considered as an index of dysfunction in cortico-spinal pathways in neurodegenerative pathology like amyotrophic lateral sclerosis. We hypothesized that seven years later, despite complete motor recovery, a functional modification of cortico- spinal pathway still persists. To test whether long-term modifications of cortico-cortical properties have occurred, we applied intermittent and continuous thetaburst stimulation (iTBS and cTBS) on each hemisphere. We have tested ECR and FDI. The data obtained with iTBS and cTBS showed that cortical mechanisms were different between pathological and non-pathological side. This suggests altered plasticity processes, which could explain the absence of recovery in muscle representation size. Finally, we have tested the influence of AD activity on ECR excitability to understand the normal coordination observed in the patient. ECR excitability curves were similar in both hemispheres showing that the cortical interaction between the AD and the ECR muscles. These results showed that cortical networks underlying muscle coordinations were preserved, which could explain the normal coordination observed in the PTS-subject, despite the small AD representation. Physiology Poster Only 208 The effects of two different repetitive TMS stimulation protocols on muscle fatigue associated changes in excitability of motor cortex in man Ljubisavljevic M 1 , Dhanasekaran S 1 , Maric J 2 , Blesic S 2 , Filipovic S 3 , 1 FMHS, UAE University (Al Ain, AE); 2 Institute for Medical research (Belgrade, RS); 3 Institute of Neurology CCS (Belgrade, RS) Objective: Muscle fatigue involves processes at all levels of the motor pathway between the brain and the muscle. Central fatigue represents the failure of the nervous system to drive the muscle optimally. When measured by transcranial magnetic stimulation (TMS) central fatigue appear as a decrease in corticospinal excitability after exercise. Repetitive transcranial magnetic stimulation (rTMS) can produce effects on cortico- spinal excitability that outlast the duration of the stimulation. The direction, magnitude and duration of effects critically depend on stimu- lation variables. We applied two rTMS protocols over M1 to test their influence on fatigue associated behavioral correlates (endurance time) and cortical excitability. Method: Low frequency [LF] (1 Hz for 20 min) and High frequency rTMS stimulation [HF] (5 Hz for 20 min) were applied in order to induce lasting decrease and increase in cortical excitability before fatigue, respectively. In the LF the TMS intensity was set to 95% of the first dorsal interosseous muscle (FDI) resting motor threshold (RMT) and in the HF protocol the TMS intensity was set to 110% of the RMT. Changes in cortical excitability after fatigue induced by continuous isometric abduction of the index finger against elastic resistance maintained at 50% of maximal voluntary contraction until endurance point were examined in 6 men. Result: Fatigue induced lasting decrease in cortical excitability. HF applied alone evoked lasting increase in MI excitability, while when applied before fatiguing contraction it reversed fatigue induced reduction in cortical excitability but had no effects on endurance time. LF applied alone decreased cortical excitability but when applied before fatigue it did not further influence fatigue related decrease in excitability. However, in 4 subjects the endurance time decreased by approximately 10%. Abstracts 305

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Page 1: The effects of two different repetitive TMS stimulation protocols on muscle fatigue associated changes in excitability of motor cortex in man

Abstracts 305

Movement DisordersPoster Only

206 Joint coordination studied by TMS in focal hand dystonia

Boyadjian A, Tyc F, Allam N, Brasil-Neto JP, Laboratoire plasticite &physio-patholog (Marseille Cedex, FR)

Writer’s cramp belongs to a group of focal task-specific dystonias affecting

fine manual skills and is characterized by excessive muscular activation

during writing.

Different TMS protocols have shown that the functional characteristics of

cortical networks in motor areas were different in dystonic patients than

control subjects. Furthermore, cortical activity during the movement

preparation is different in dystonic patients, which could be responsible

for a modification of the response of cells to afferent inputs and then the

production of movement.

The properties of neural excitability have to be considered in the context of

muscle coordination. Our work focused on the integrated neural networks

linking proximal and distal muscles that move the shoulder, the wrist and

the finger. Such networks linking shoulder and wrist were observed in

control subjects. We wanted to observe in dystonic patients the properties

of response in different coordination condition to know how muscles are

linked.

Motor evoked potentials (MEPs) were recorded from medial deltoid (MD),

extensor carpi radialis (ECR) and the first dorsal interosseus (FDI) muscles

in 10 patients with focal hand dystonia and six healthy subjects. The

subjects had to maintain a ring in order to do not touch a wire passing

through this ring. The first condition was to maintain the ring using only

the arm (ECR Alone), the elbow rested on an armrest. The second

condition was to maintain the ring using the whole upper limb (ECR and

MD co-activated). The TMS was done on the hot spot of the ECR with

seven increasing intensities of stimulation, determined as percentages of

the ECR active motor threshold (aMT). At each intensity, four stimulations

were done and the corresponding MEPs averaged to compute excitability

curves for the three muscles.

Each group exhibited MEPs facilitation of ECR during the voluntary

activation of MD as showed by plateau and slope of sigmoid regression.

Interestingly only the patient group showed facilitation of FDI when MD

was activated. Then, in dystonic patients, even the ‘‘most’’ distal part of

muscle chain could be facilitated by the ‘‘most’’ proximal part of the upper

limb. The generalization of neural pathways though to allow the coordi-

nation between each joint could be responsible of an excess in tonic

activity resulting in an inadequate pattern of coordination observed in

dystonic patients during writing.

Clinical StudiesPoster Only

207 Cortico-cortical properties in Parsonage-Turner Syndrome: a

TMS case study

Rossi-Durand C, Boyadjian A, Devanne H, Tyc F, Laboratoire plasticite& physio-patholog (Marseille Cedex, FR)

We report the long-term effects of one unilateral Parsonage-Turner

Syndrome case (PTS) on motor cortex representation of a proximal upper

limb muscle. The subject suffered from a sporadic painful episode of

weakness of the shoulder girdle muscles seven years earlier. At this time,

needle EMG recordings showed only few MUs in the left anterior deltoid

muscle (AD), while nerve conduction was found normal. Arthroscanner

examination was unremarkable confirming the absence of joint lesion. The

episode lasted for one year.

Currently, the PTS-subject uses his left arm without any limitation in

strength and accuracy. Bilateral transcranial magnetic stimulation mapping

of proximal AD and distal First Dorsal Interosseus muscles (FDI) during

low-level voluntary contraction showed that cortical representation of both

the left AD and FDI muscles were smaller than the right ones and than

those obtained in control subjects. Single motor unit potential analysis of

AD muscle have shown a decrease in the probability of response to the

single pulse TMS. Macro motor-unit potential analysis did not show any

difference between right and left AD, suggesting an absence of motoneu-

ron death. A decrease of single MU excitability associated with the

absence of macro-MUP size variation has been considered as an index of

dysfunction in cortico-spinal pathways in neurodegenerative pathology

like amyotrophic lateral sclerosis. We hypothesized that seven years later,

despite complete motor recovery, a functional modification of cortico-

spinal pathway still persists.

To test whether long-term modifications of cortico-cortical properties have

occurred, we applied intermittent and continuous thetaburst stimulation

(iTBS and cTBS) on each hemisphere. We have tested ECR and FDI. The

data obtained with iTBS and cTBS showed that cortical mechanisms were

different between pathological and non-pathological side. This suggests

altered plasticity processes, which could explain the absence of recovery in

muscle representation size. Finally, we have tested the influence of AD

activity on ECR excitability to understand the normal coordination

observed in the patient. ECR excitability curves were similar in both

hemispheres showing that the cortical interaction between the AD and the

ECR muscles. These results showed that cortical networks underlying

muscle coordinations were preserved, which could explain the normal

coordination observed in the PTS-subject, despite the small AD

representation.

PhysiologyPoster Only

208 The effects of two different repetitive TMS stimulation

protocols on muscle fatigue associated changes in excitabilityof motor cortex in man

Ljubisavljevic M1, Dhanasekaran S1, Maric J2, Blesic S2, Filipovic S3,1FMHS, UAE University (Al Ain, AE); 2Institute for Medical research

(Belgrade, RS); 3Institute of Neurology CCS (Belgrade, RS)

Objective: Muscle fatigue involves processes at all levels of the motor

pathway between the brain and the muscle. Central fatigue represents the

failure of the nervous system to drive the muscle optimally. When

measured by transcranial magnetic stimulation (TMS) central fatigue

appear as a decrease in corticospinal excitability after exercise. Repetitive

transcranial magnetic stimulation (rTMS) can produce effects on cortico-

spinal excitability that outlast the duration of the stimulation. The

direction, magnitude and duration of effects critically depend on stimu-

lation variables. We applied two rTMS protocols over M1 to test their

influence on fatigue associated behavioral correlates (endurance time) and

cortical excitability.

Method: Low frequency [LF] (1 Hz for 20 min) and High frequency rTMS

stimulation [HF] (5 Hz for 20 min) were applied in order to induce lasting

decrease and increase in cortical excitability before fatigue, respectively. In

the LF the TMS intensity was set to 95% of the first dorsal interosseous

muscle (FDI) resting motor threshold (RMT) and in the HF protocol the

TMS intensity was set to 110% of the RMT. Changes in cortical

excitability after fatigue induced by continuous isometric abduction of

the index finger against elastic resistance maintained at 50% of maximal

voluntary contraction until endurance point were examined in 6 men.

Result: Fatigue induced lasting decrease in cortical excitability. HF

applied alone evoked lasting increase in MI excitability, while when

applied before fatiguing contraction it reversed fatigue induced reduction

in cortical excitability but had no effects on endurance time. LF applied

alone decreased cortical excitability but when applied before fatigue it did

not further influence fatigue related decrease in excitability. However, in 4

subjects the endurance time decreased by approximately 10%.

Page 2: The effects of two different repetitive TMS stimulation protocols on muscle fatigue associated changes in excitability of motor cortex in man

306 Abstracts

Conclusion: Our results suggest complex interactions between rTMS

induced and fatigue related changes of cortical network excitability. The

observed changes in behavioral output which are not accompanied by

changes in cortical excitability may reflect dynamic modulation of

different subset of cortical neurons by muscle fatigue and rTMS. However,

their importance in control of the fatigued muscle remains unclear.

tDCSPoster Only

209 Polarity-specific cortical plasticity induced by tDCS in the

awake rhesus monkey

Amaya F, Liebetanz D, Department of Clinical Neurophysiology,

Georg-August University (Gottingen, DE)

Transcranial direct current stimulation (tDCS) may be of therapeutic value

in several neuro-psychiatric disorders. It application in the awake rhesus

monkey could be useful to develop more potent stimulation paradigms.

Therefore we aimed at determining the effective stimulation intensity and

electrode arrangement of tDCS in the awake rhesus monkey.

Two male rhesus monkeys were trained to relax their hand muscles. tDCS

was applied 7 min using 2 non-polarizable rubber electrodes (10 cm2).

Three different tDCS-electrode positions were tested: a) ipsilateral

motorcortex-contralateral motocortex, b) ipsilateral motorcortex-ipsilateral

occipital cortex, c) ipsilateral motorcortex-contralateral arm. For each

electrode montage, anodal and cathodal stimulation was applied with

following stimulation intensities: 21, 24, 27 and 40mA/cm2. These were

chosen in relation to the effective current density used in human research,

e.g. 27,7mA/cm2. Every experimental condition was tested twice over each

hemisphere of both monkeys leading to 8 measurements per condition. To

monitor tDCS after-affects TMS was applied at 0.2 Hz. MEPs were

measured from the contralateral abductor pollicis brevis (APB) for 10

minutes before and after tDCS.

When both stimulating electrodes were positioned over the scalp, no tDCS

induced after-effects were observed, irrespective of the stimulation inten-

sity used. Using a current density of 27 or 40 mA/cm2, tDCS induced

polarity specific after-effects on the size of MEPs, when applied over the

motor cortex and contralateral arm. At 27 mA/cm2 anodal tDCS increased

MEP-Size about 20% and cathodal stimulation decreased it about 40% of

baseline. Increasing the current density to 40 mA/cm2 led to stronger after-

effects e.g. an increase of 100% or a decrease of 60%.

The lack of effects observed when both electrodes were placed over the

scalp may be due to the short distance between the them, resulting in a

shunting of the current flow at the scalp surface, without effective current

flowing through the brain. Therefore, in the rhesus monkey, the scalp-arm

montage is more effective to induce similar polarity-specific changes of

cortical excitability as in human tDCS. These results set the basis for future

tDCS-studies offering the possibility to develop intensified and effective

stimulation paradigms, without the safety restrains of human research.

TMSPoster Only

210 Chronometry of functional relevance within the effective

connectivity network underlying visual-spatial judgment.

de Graaf TA, Roebroeck A, Sack AT, Maastricht University

(Maastricht, NL)

Objective: Visual-spatial judgment activates a bilateral frontal-parietal

network in the brain. TMS over right PPC suggested functional relevance

of this region (1). However, a recent simultaneous fMRI and TMS study

showed that the behavioral visual-spatial impairments induced by right

parietal TMS were mirrored by neural deactivations within a network of

regions in the right hemisphere, including the stimulated PPC but also

MFG (2). The current study examined the dynamics within this right-

lateralized frontal-parietal network and investigated the chronometry of the

functional relevance of PPC and MFG for visual-spatial judgment.

Method: Ten participants took part in the fMRI study and subsequent

offline TMS experiment using a visual-spatial and visual-color paradigm

(for details see 2). Granger Causality Mapping (GCM: 3) was used to

investigate effective connectivity in the frontal-parietal network. Neuro-

navigated triple-pulse TMS was applied over PPC and MFG as identified

by the effective connectivity analysis in the same subjects testing six time

windows ranging from stimulus presentation to response time.

Results: GCM analysis revealed visual-spatial task-specific directed

influence from MFG to PPC. However, within these larger regions, small

neighboring clusters could be identified which either received or projected

directed influence from or to other clusters within the entire network.

Preliminary TMS results based on this subject sample suggest a time- and

task-specific effect of TMS over both PPC and MFG. TMS-induced

behavioral impairments seem to be earlier for PPC than for MFG.

Conclusion: At this point our data suggest that TMS over PPC and MFG

leads to behavioral impairment on a visual-spatial judgment task. Our

previous study (2) showed that TMS can have state-dependent local and

remote effects. Now it seems these remote effects may also be functionally

relevant for the task being investigated. It is thus possible that in our task

TMS deactivates a frontal-parietal network which, as a whole, is func-

tionally relevant. This notion is perhaps supported by the finding that

interactions within the frontal-parietal network are complex, evidenced by

the proximity of both projecting and receiving clusters within the larger

regions PPC and MFG.

1. Ellison & Cowey, Experimental Brain Research, 2006.

2. Sack et al., Cerebral Cortex, 2007.

3. Roebroeck et al., Neuroimage, 2005.

TMSPoster Only

211 The role of posterior parietal cortex in the simon effect: A TMS

study

Schiff S, Bardi L, Massironi M, Basso D, Mapelli D, University of Padua

(Padua, IT)

In a two-choice visual task, reaction times (RTs) are faster when spatial

position of a stimulus corresponds to the response hand, with respect to

when they do not correspond. This effect (namely the Simon effect) is

detectable even if spatial information of the stimulus is task-irrelevant. The

Simon effect seems to depend on the interference between the represen-

tation of a stimulus and the positions of the response hand. Given the huge

amount of literature supporting the posterior parietal cortex (PPC) as the

cerebral substrate of attentional processes, it has been also indicated to be

crucial in the generation of the Simon Effect.

The aim of the study was to investigate the role of the PPC in the

representation of spatial information during the execution of a Simon task.

Thus, a single-pulse Transcranial Magnetic Stimulation (TMS) experiment

has been run: stimulation has been applied 100 ms after the stimulus onset

at 110% of the motor threshold. The four sites of stimulation were: right

and left angular gyrus (lANG, rANG), left supramarginal gyrus and the

Vertex (Cz: control site). Stimulation sites was defined using an hunting

procedure (using a visual search task), while their stereotaxic coordinates

have been calculated co-registering anatomical MRI images with the

subjects’ heads (using the Brainsight neuronavigator).

Reaction times analysis revealed a reduction of the Simon effect when

stimulation was delivered to the PPC (mainly to the right hemisphere), as

compared to the control site Cz. The stimulation appeared to be more

effective when applied to the right angular girus, while an effect on the

motor response has been interpreted as a possible explanation for the

consequences of stimulation on the left supramarginal gyrus.