evoked motor response following deep transcranial magnetic stimulation in a cynomolgus monkey

1
TMS Poster Only 191 Evoked motor response following deep transcranial magnetic stimulation in a cynomolgus monkey Ishii K 1 , Matsuzaka Y 2 , Izumi S 1 , Abe T 3 , Nakazato N 4 , Okita T 5 , Yashima Y 3 , Takagi T 5 , Nagatomi R 1 , 1 Tohoku university Graduate School of Biomedical Engineering (Sendai, JP); 2 Dept. of Physiol., Graduate Scool of Medical Sciences, Tohoku University (Sendai, JP); 3 IFG Co., Ltd. (Sendai, JP); 4 Kohnan Hospital (Sendai, JP); 5 Institute of Fluid Science, Tohoku University (Sendai, JP) Objective: Transcranial magnetic stimulation (TMS) is a noninvasive technique in which magnetic pulses of the current loops are applied to the brain cortex. It is difficult to stimulate deeper regions of the brain with current TMS techniques, since the magnetic field strength decays in inverse proportion to the square of the distance from the current sources. We have recently developed a new TMS coil to overcome this limitation. The purpose of this study is, therefore, to show the new TMS coil is capable of stimulating deeper regions of the brain by monitoring the evoked motor responses and the silent periods following magnetic pulses delivered to the brain of a cynomolgus monkey. Method: A 5-year-old male cynomolgus monkey weighing 3.8kg was fixed on a primate chair, anesthetized with ketamine. Magnetic stimulus was delivered using a circular coil of 10 turns with internal diameters of 110 mm. The coil was set so that the head was inserted into the coil. The surface of the coil was set either at 0, 10, 20 or 30 mm below a plane including bilateral porus acusticus externus and supraorbital tori. A single electric pulse was applied to the coil at voltages ranging from 500 to 1000 V. The distribution of the pulsed magnetic flux density generated by the coil was numerically calculated with the use of RC integration circuit. Motor evoked potentials were recorded from the right triceps brachii muscle via intramuscular electrodes. The experiment was recorded with a video camera. Result: Fig.1 shows the distribution of the pulsed magnetic flux density generated by the coil. Fig.2. shows a representative electromyogram recording from the triceps brachii muscle, in which a silent period and a secondary response induced by the magnetic stimuli were recorded. Not only upper limb but also lower limb and trunk muscle contractions were elicited by the magnetic pulse. No acute adverse events such as hypoten- sive shock, epileptic seizure, visual and auditory impairment, and abnor- mal behaviors were observed. Conclusion: Using a newly designed TMS coil, we could successfully deliver magnetic stimuli to the brain of a cynomolgus monkey that evoked motor responses and silent periods. The fact that our TMS coil did not only elicit contraction of arm muscles, but also of lower limb muscles and trunk muscles, suggests that the new TMS technique is capable of efficiently stimulating deeper regions of the brain for the 1st time in the world. Movement Disorders Poster Only 192 Cortical contribution to subthalamic activity during chronic electrical stimulation Modolo J, Beuter A, IMS, UMR CNRS 5218 (Talence, FR) Objective: In Parkinson’s disease (PD), the motor cortex appears to play an important role in the generation of abnormal activity in the motor loop network involving basal ganglia, thalamus and cortex. When activity in this network is disrupted, motor symptoms appear but are alleviated by deep brain stimulation (DBS). We use a computational model to examine cortical contribution during DBS. Exploring brain mechanims underlying the effect of DBS may help us propose less invasive but efficient (cortical) stimulation protocols. Method: We used a multi-scale, population based, mathematical model of the subthalamic nucleus (STN) -the main excitatory structure of the basal ganglia- and the external globus pallidus, which receive cortical and striatal input. The model simulates healthy (stable, low-amplitude) and pathological (5 Hz oscillatory synchronized) activity within these two nuclei. In the pathological state, constant or oscillatory (low-frequency) cortical inputs to the STN are simulated and the ability of DBS to suppress abnormal oscillations (bursts) is explored. Results: In the presence of 10 Hz cortical inputs to the STN, DBS does not suppress abnormal bursts present in the STN and correlated with tremor generation (Figure 1). On the contrary DBS suppresses abnormal bursts when cortical input is constant (not shown). Conclusion: Results support the view that a functional decoupling takes place between resonant cortical input and STN during DBS in PD. Indeed cortical input to the STN has a frequency similar to that of the STN, enhancing STN abnormal oscillatory behavior. This decoupling may originate from the descending cortical spikes colliding with the antidromic depolarization rising from the STN and induced by DBS. This mechanism could be responsible for clinical improvements. In principle such a 300 Abstracts

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Page 1: Evoked motor response following deep transcranial magnetic stimulation in a cynomolgus monkey

300 Abstracts

TMSPoster Only

191 Evoked motor response following deep transcranial magnetic

stimulation in a cynomolgus monkey

Ishii K1, Matsuzaka Y2, Izumi S1, Abe T3, Nakazato N4, Okita T5,

Yashima Y3, Takagi T5, Nagatomi R1, 1Tohoku university

Graduate School of Biomedical Engineering (Sendai, JP);2Dept. of Physiol., Graduate Scool of Medical Sciences, Tohoku

University (Sendai, JP); 3IFG Co., Ltd. (Sendai, JP); 4Kohnan

Hospital (Sendai, JP); 5Institute of Fluid Science, Tohoku University

(Sendai, JP)

Objective: Transcranial magnetic stimulation (TMS) is a noninvasive

technique in which magnetic pulses of the current loops are applied to the

brain cortex. It is difficult to stimulate deeper regions of the brain with

current TMS techniques, since the magnetic field strength decays in

inverse proportion to the square of the distance from the current sources.

We have recently developed a new TMS coil to overcome this limitation.

The purpose of this study is, therefore, to show the new TMS coil is

capable of stimulating deeper regions of the brain by monitoring the

evoked motor responses and the silent periods following magnetic pulses

delivered to the brain of a cynomolgus monkey.

Method: A 5-year-old male cynomolgus monkey weighing 3.8kg was fixed

on a primate chair, anesthetized with ketamine. Magnetic stimulus was

delivered using a circular coil of 10 turns with internal diameters of 110

mm. The coil was set so that the head was inserted into the coil. The

surface of the coil was set either at 0, 10, 20 or 30 mm below a plane

including bilateral porus acusticus externus and supraorbital tori. A single

electric pulse was applied to the coil at voltages ranging from 500 to 1000

V. The distribution of the pulsed magnetic flux density generated by the

coil was numerically calculated with the use of RC integration circuit.

Motor evoked potentials were recorded from the right triceps brachii

muscle via intramuscular electrodes. The experiment was recorded with a

video camera.

Result: Fig.1 shows the distribution of the pulsed magnetic flux density

generated by the coil. Fig.2. shows a representative electromyogram

recording from the triceps brachii muscle, in which a silent period and a

secondary response induced by the magnetic stimuli were recorded. Not

only upper limb but also lower limb and trunk muscle contractions were

elicited by the magnetic pulse. No acute adverse events such as hypoten-

sive shock, epileptic seizure, visual and auditory impairment, and abnor-

mal behaviors were observed.

Conclusion: Using a newly designed TMS coil, we could successfully

deliver magnetic stimuli to the brain of a cynomolgus monkey that

evoked motor responses and silent periods. The fact that our TMS coil

did not only elicit contraction of arm muscles, but also of lower limb

muscles and trunk muscles, suggests that the new TMS technique is

capable of efficiently stimulating deeper regions of the brain for the 1st

time in the world.

Movement DisordersPoster Only

192 Cortical contribution to subthalamic activity during chronic

electrical stimulation

Modolo J, Beuter A, IMS, UMR CNRS 5218 (Talence, FR)

Objective: In Parkinson’s disease (PD), the motor cortex appears to play

an important role in the generation of abnormal activity in the motor loop

network involving basal ganglia, thalamus and cortex. When activity in

this network is disrupted, motor symptoms appear but are alleviated by

deep brain stimulation (DBS). We use a computational model to examine

cortical contribution during DBS. Exploring brain mechanims underlying

the effect of DBS may help us propose less invasive but efficient (cortical)

stimulation protocols.

Method: We used a multi-scale, population based, mathematical model of

the subthalamic nucleus (STN) -the main excitatory structure of the basal

ganglia- and the external globus pallidus, which receive cortical and

striatal input. The model simulates healthy (stable, low-amplitude) and

pathological (5 Hz oscillatory synchronized) activity within these two

nuclei. In the pathological state, constant or oscillatory (low-frequency)

cortical inputs to the STN are simulated and the ability of DBS to suppress

abnormal oscillations (bursts) is explored.

Results: In the presence of 10 Hz cortical inputs to the STN, DBS does not

suppress abnormal bursts present in the STN and correlated with tremor

generation (Figure 1). On the contrary DBS suppresses abnormal bursts

when cortical input is constant (not shown).

Conclusion: Results support the view that a functional decoupling takes

place between resonant cortical input and STN during DBS in PD. Indeed

cortical input to the STN has a frequency similar to that of the STN,

enhancing STN abnormal oscillatory behavior. This decoupling may

originate from the descending cortical spikes colliding with the antidromic

depolarization rising from the STN and induced by DBS. This mechanism

could be responsible for clinical improvements. In principle such a