Influence of Brain Oscillation-Dependent TMS on Motor Function

Study Overview
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Brief Summary
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Background: When people have a stroke, they often have difficulty moving their arms and hands. Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke can move their arms and hands. But the effects of TMS are minor, and it doesn t work for everyone. Researchers want to study how to time brain stimulation so that the effects are more consistent. Objective: To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved. Eligibility: Adults ages 18 and older who had a stroke at least 6 months ago Healthy volunteers ages 50 and older Design: Participants will have up to 5 visits. At visit 1, participants will be screened with medical history and physical exam. Participants with stroke will also have TMS and surface electromyography (sEMG). For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple movements during TMS. For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded. At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the loud noise. At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG, small electrodes on the scalp will record brainwaves. Participants will sit still, watch a movie, or do TMS. Participants may be asked to have 2 extra visits to redo procedures.

Detailed Description
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Study Description: We will study if corticospinal excitability (primary outcome measure) varies across different sensorimotor alpha electroencephalography (EEG) wave form oscillation phases in healthy older adults and chronic stroke patients. Sensorimotor cortical neuronal spiking is highest at sensorimotor alpha oscillation troughs and lowest at sensorimotor alpha oscillation peaks, suggesting that cortical excitability is higher at sensorimotor alpha oscillation troughs relative to peaks. We will address these questions using closed-loop transcranial magnetic stimulation (TMS). Objectives: TMS is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been customarily applied uncoupled from brain oscillatory activity (as measured using EEG waveforms), resulting in variability in the biological response to each stimulus, small effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e., EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical inhibition, motor function and cognitive processing, and therefore influences brain function. Limitations in open-loop systems the rely on post-hoc trial sorting based on EEG state have shown mixed results. For example, corticospinal excitability (as measured with TMS) in healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity). One prior closed-loop study showed only an effect of power but not phase angle on cortical excitability, but using a similar setup, but we have replicated the finding of increased cortical excitability during sensorimotor alpha troughs in young healthy adults. We therefore aim to extend these findings to two new populations: healthy older adults (Experiment 1) and patients with chronic stroke (Experiment 2). Previous studies have demonstrated that older adults exhibit significant differences in motor cortical physiology compared to young adults, so Experiment 1 will be performed to determine whether an association between sensorimotor alpha oscillatory phase and corticospinal excitability is present in healthy aging. Additionally, Experiment 2 will be performed to determine if the expected association between sensorimotor alpha oscillatory phase and corticospinal excitability is also present after chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing more effective TMS-based (i.e., closed-loop) interventions. In both experiments, TMS delivery will be timed to specific sensorimotor alpha oscillation phases. We expect the results of this work to provide new insights into how corticospinal excitability is affected by sensorimotor alpha oscillation phase in the aged and post-stroke brain, which could lead to more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols in the future. Endpoints: For both experiments, the primary outcome measure is corticospinal excitability. Exploratory outcome measures include MEP amplitude variability, and TMS-induced oscillations.

Official Title
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Influence of Brain Oscillation-Dependent TMS on Motor Function

Conditions
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Healthy, Stroke, Normal Physiology, Aging

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Healthy older adults: Age 50 and over Willingness/ability to provide informed consent In good general health as evidenced by ability to induce a motor evoked potential in the muscle target of the upper extremity, as evaluated during the TMS Screening Stroke patients: Age 18 and over Unilateral or bilateral upper limb hemiparesis with the ability to voluntarily contract a finger, hand, wrist, or elbow muscle in the affected arm(s) Stroke onset > 6 months prior to participation Intact M1 sufficient to induce motor evoked potentials in the affected upper extremity following ipsilesional TMS, as evaluated during the TMS Screening. Willingness/ability to provide informed consent If the investigator feels the individual s capacity to provide informed consent is questionable, the NIH Human Subjects Protection Unit (HSPU) will be requested to determine the individual s ability to consent. EXCLUSION CRITERIA: Healthy older adults: Presence of severe neurological or medical disorder (e.g. Parkinson s disease or multiple sclerosis) History of seizures Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), tri-cyclic or other anti-depressants, benzodiazepines, or prescription stimulants TMS contraindications, such as: Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull Diagnosed severe hearing loss Current pregnancy Staff from our section Stroke patients: Presence of severe neurological or medical disorder, other than stroke (e.g. Parkinson s disease or multiple sclerosis) History of brainstem stroke History of seizures Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), benzodiazepines, or prescription stimulants TMS contraindications, such as: Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull Diagnosed severe hearing loss Current pregnancy Staff from our section

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br>Healthy volunteers age 50 and older | |
| Stroke patients<br>Stroke patients aged 18 and older | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| We will study if corticospinal excitability varies across different sensorimotor alpha EEG waveform oscillation phases in healthy older adults and chronic stroke patients. | For both experiments, the primary outcome measure is corticospinal excitability. Exploratory outcome measures include MEP amplitude variability, and TMS-induced oscillations | 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Natural History