Improving Motivation in Post-stroke Apathy with Repetitive Transcranial Magnetic Stimulation (IMPART): A Phase-I Pilot Trial

ABSTRACT Background Post-stroke apathy (PSA) is a common, disabling syndrome with few evidence-based treatment options. We evaluated the safety, feasibility, acceptability, and evidence of effects of a three-day accelerated intermittent theta burst stimulation-repetitive transcranial magnetic stimulation (iTBS-rTMS) protocol targeting the left dorsomedial prefrontal cortex (dmPFC) in chronic stroke survivors with apathy. Methods Stroke survivors with symptomatic apathy received open-label iTBS-rTMS at the left dmPFC (21,600 pulses across 36 sessions; 3 treatment days; 12 sessions/day within one week). Safety endpoints included adverse events, neuroradiological findings, and objective cognitive performance. Secondary outcomes included measures of apathy and other neuropsychiatric symptoms, as well as psychosocial functioning, including quality of life and caregiver burden. Participants were followed up for one month. Results Fourteen participants (mean age = 61.8 ± 14.0 years; mean time since stroke = 55.6 ± 31.6 months) completed the iTBS-rTMS treatment course. No serious adverse events occurred. Participants rated the treatment as highly acceptable, and cognitive performance was stable from pre- to post-rTMS, with no treatment-related changes on structural MRI. Regarding apathy, participants had significant improvements with moderate to large effect sizes on the Lille Apathy Rating Scale (LARS), on both self ( d = 0.78) and caregiver-rated versions ( d = 1.28), p