Brain Connections for Arm Movement After Stroke

Study Overview
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Brief Summary
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The purpose of this study is to use Transcranial Magnetic Stimulation (TMS) while subjects are making reaching movements in a robotic arm device in order to discover how different brain areas control movement before and after stroke and when these brain areas are most sensitive to TMS.

Detailed Description
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The general objective of this application is to study reorganization of network interactions following a common type of subcortical stroke (i.e. internal capsule) with mechanistic studies using noninvasive neurophysiology in humans. The goal is to obtain pilot data and to demonstrate the feasibility of the approach that combines transcranial magnetic stimulation (TMS) with reaching in an advanced exoskeleton robot. As reaching is an essential part of many daily activities, this approach will have beneficial impacts on the quality of life of these stroke patients. The central hypothesis is that bilateral premotor cortical areas, dorsal (PMd) more so than ventral (PMv,) develops greater connectivity with primary motor cortex (M1) after stroke and thus better ability to produce motor outputs that support reaching with the paretic arm. When there is more damage to the corticospinal tract, contralesional areas will take on a greater role. The relationship between connectivity, behavioral effects of stimulation and motor performance will be established. These findings will allow the investigators to formulate clear hypotheses about which premotor area should be modulated with TMS, depending on stroke extent and deficits in motor control, when reaching the stage of proposing a treatment trial. Increased knowledge of the dynamic changes of physiological interactions during various phases of reaching movements will allow a more defined study regarding the role of premotor areas in recovery of motor function after stroke, and a novel treatment protocol that delivers precisely timed stimulations during practice of reaching movements. Ultimately, the investigators can test these novel treatments in clinical trials and compare their impact to other, less specific, neuromodulatory methods such as transcranial direct current stimulation. This study will also lay the groundwork for collaboration in brain computer interface and non-human primate investigations in the mechanisms and treatment of motor deficits after stroke.

Official Title
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Brain Areas That Control Reaching Movements After Stroke: Task-relevant Connectivity and Movement-synchronized Brain Stimulation

Conditions
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Stroke, Brain Disease, Central Nervous System Diseases, Nervous System Diseases, Cardiovascular Diseases

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria (control participants): Be 45-90 years of age Have adequate language and neurocognitive function to participate in training and testing Be medically stable to participate in the study Be English speaking Inclusion Criteria (participants with stroke): Be 45-90 years of age Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible diagnosis Stroke onset at least 6 months before enrollment Subcortical stroke (ex: internal capsule, deep white matter of posterior frontal lobe) Present with mild to moderate arm dysfunction Be medically stable to participate in the study Be English speaking Exclusion Criteria: (for both groups) Unable to give informed consent Have a serious complicating medical illness that would preclude participation Contractures or orthopedic problems limiting range of joint motion in the potential study arm or other impairments that would interfere with the study activities Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor Unable to comply with requirements of the study Enrollment in another greater-than-minimal risk study Presence of medical condition or implant that prevents safe administration of TMS or MRI Pregnancy

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Pilot project
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reaching with TMS<br>All participants enrolled in this group will receive TMS while performing reaching movements in a robotic system. | Device: Transcranial Magnetic Stimulation<br>* Paired pulse transcranial magnetic stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Path length | Movement path length in centimeters from KINARM system during the one second reaching period. (units: cm) | Immediate (within 2 s after stimulation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Times | Specific kinematic data from KINARM system: reaction time, movement time to reach target (units: ms) | Immediate (within 2 s after stimulation) | 
| Velocities | maximum velocity reached during reach (units: cm/s) | Immediate (within 2 s after stimulation) | 
| Accuracy | specific position data from KINARM system: target accuracy, distance from manipulandum position at end of one second reaching period to target center. (units: cm.) | Immediate (within 2 s after stimulation) | 
| EMG | Electromyographic data from surface electrodes on biceps, triceps, anterior deltoid, and posterior deltoid muscles - These signals will be rectified and normalized to the maximum values during practice reaches. (units: mV/mV - dimensionless). | Immediate (within 2 s after stimulation) |