Influence of Brain Oscillation-Dependent TMS on Motor Function


Phase Results N/A

Trial Description

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.
To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved.
Adults ages 18 and older who had a stroke at least 6 months ago
Healthy volunteers ages 18 and older
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

OBJECTIVE: Transcranial magnetic stimulation (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. 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). Here, we will first attempt replication of this result using closed-loop TMS in young healthy adults (Experiment 1). Subsequently, we aim to extend these findings to two new populations: healthy older adults (Experiment 2), and patients with chronic stroke (Experiment 3). Previous studies have demonstrated that older adults exhibit significant differences in motor cortical physiology compared to young adults, so Experiment 2 will be performed to determine whether a similar association between sensorimotor alpha oscillatory phase and corticospinal excitability is present in healthy aging. Finally, Experiment 3 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 all 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, which could lead to more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols in the future.
STUDY POPULATION: Up to 24 young healthy volunteers (ages 18-59), up to 24 older healthy volunteers (ages 60 and older), and up to 26 stroke patients (age 18 and older).
DESIGN: Each experiment will begin with MRI to allow for co-registration with a frameless stereotactic device for the precise targeting of TMS. In Experiment 1, healthy young adults will receive single-pulse, closed-loop TMS to the motor cortex hand area (M1-hand) during sensorimotor alpha oscillation (a) troughs (i.e., maximum surface negativity), (b) peaks (i.e., maximum surface positivity), and (c) uncoupled from sensorimotor alpha oscillation phase (as measured with EEG) using a within-subject design. In Experiment 2, healthy older adults will complete the same procedures described for Experiment 1. In Experiment 3, chronic stroke patients will also complete the same procedures described for Experiment 1, except that TMS will be delivered to the ipsilesional M1-hand. For each experiment, up to 700 single-pulse TMS pulses will be delivered (excluding pulses used to identify scalp hotspot and resting motor threshold), and all subjects will be given rest breaks as needed.
OUTCOME MEASURES: For all experiments, the primary outcome measure is corticospinal excitability. The secondary outcome measure is effective intracortical connectivity between M1 and the rest of the brain. Exploratory outcome measures include MEP amplitude variability, TMS-induced oscillations, and resting state EEG brain connectivity.


Trial Population

Healthy young adults -Age 18-59; -Healthy older adults -Age 60 and over; Stroke patients


Type Measure Time Frame Safety Issue
Primary Corticospinal Excitability Ongoing
Secondary Effective Intracortical Connectivity Ongoing