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.

Grant Number: 1R21HD117319-01A1
NIH Institute/Center: NIH
Principal Investigator: Jessica Cassidy