Modulation of Beta Oscillatory Rhythms in Stroke to Promote Corticomuscular Circuit Function - ABSTRACT The goal of this proposal is to generate an enriched mechanistic understanding of post-stroke motor recovery by examining corticomuscular circuit function in adults with stroke. The study of specific neural circuits in stroke aligns with our long-term goal of developing targeted and personalized stroke treatments based on an individual’s neural circuitry. Towards this precision rehabilitation approach, we have previously assessed neural oscillatory activity in 30 persons with stroke using electroencephalography to measure functional connectivity between brain and muscle (corticomuscular coherence, CMC). Findings from this work suggest that CMC in a motor-relevant frequency band (beta, 13-30 Hz) is both a marker of post-stroke motor function and recovery. The cortical and muscular sources that comprise this corticomuscular circuit may thus serve as a potential therapeutic target for neuromodulation. This proposal will determine the modulatory effects of beta-burst repetitive transcranial magnetic stimulation (rTMS) on corticomuscular circuit function as measured by CMC. We hypothesize that the enhancement of neural oscillatory rhythms that are consistent with corticomuscular circuit function using beta - burst rTMS with strengthen the corticomuscular circuit. We will test this hypothesis in 20 persons with chronic (≥ 6 months) stroke during a single research visit using a randomized cross-over study design. During this visit, participants will receive brief bouts of stimulation just prior to the execution of a precision grip task performed with their affected upper extremity. Aim 1a focuses on target specificity by comparing CMC change following beta-burst stimulation to an active site within the corticomuscular circuit vs. a control/decoy site outside of the immediate circuit. Aim 1b responsibly addresses stroke-related injury by determining how downstream damage to the ipsilesional corticomuscular circuit, based on corticospinal excitability evaluation with TMS, impacts beta-burst rTMS efficacy. This aim was informed by our prior work along with others showing that injury to the corticospinal tract significantly predicts participants’ response to treatment. Aim 1b will begin to identify neurophysiological characteristics of potential responders and non-responders to beta-burst rTMS. Independent of Aims 1a and 1b, Aim 2 will determine if beta-burst rTMS impacts motor task performance (reaction time and grip precision). This aim will provide preliminary evidence that corticomuscular circuit enhancement has motor behavioral relevance. This proposal introduces an innovative strategy by evaluating corticomuscular circuit function during goal- directed movement in stroke using a frequency-specific probe (rTMS). Findings generated from this work will provide proof-of-concept and causal support that dysregulated coupling between brain and muscle represents a treatable target for enhancing post-stroke function.
