Parneet Grewal1, Michael Seidman4, Colin Bowyer3, Ivy Dickens2, Carol Joseph3, Kevin Caulfield2, Lisa McTeague2
1Department of Neurology, 2Department of Psychiatry, Medical University of South Carolina, 3Medical University of South Carolina, 4Department of Neurology, University of Colorado
Objective:
To evaluate the safety, feasibility, tolerability, and preliminary efficacy of accelerated high-dose repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex (dmPFC) to reduce apathy in adults with chronic stroke.
Background:
Apathy, diminished motivation for goal-directed behavior, is a common and disabling neuropsychiatric consequence of stroke, contributing to poorer rehabilitation outcomes, reduced quality of life, and increased caregiver burden. While rTMS targeting the dorsolateral prefrontal cortex is effective for depression, apathy involves distinct neural circuits including the dorsal medial prefrontal and anterior cingulate cortices. This pilot study tested a novel accelerated, high-dose rTMS protocol targeting the dmPFC in post-stroke apathy (PSA).
Design/Methods:
Fourteen adults with chronic stroke and clinically significant apathy completed baseline structural and resting-state MRI for individualized targeting, along with validated assessments of apathy, cognition, and neuropsychiatric symptoms. Participants received open-label intermittent theta burst stimulation (iTBS)-rTMS to the left dmPFC: 600 pulses per session, 12 sessions per day over three treatment days within one week (36 sessions total; 21,600 pulses). Assessments were repeated immediately post-treatment and weekly for one month. All procedures were approved by the MUSC Institutional Review Board, and written informed consent was obtained (ClinicalTrials.gov NCT05878457).
Results:
All 14 participants completed treatment. The protocol was well tolerated, with no adverse neurocognitive, neuropsychiatric, or neuroradiological effects and >80% retention. Significant improvements from baseline to one month were observed in apathy measures: Apathy Evaluation Scale (AES; Cohen’s d = 0.70, p = 0.024), AES-informant (d = 0.63, p = 0.037), and Lille Apathy Rating Scale (d = 0.78, p = 0.012). Secondary outcomes showed gains in cognitive performance (NIH toolbox, d = 0.62, p = 0.050), improved stroke-specific quality of life (p = 0.037), and reduced caregiver burden (Zarit, p = 0.027).
Conclusions:
Accelerated high-dose iTBS-rTMS targeting the dmPFC appears safe, feasible, and well tolerated in PSA, with promising preliminary efficacy.
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