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

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<0.05 pretreatment-to-one-month follow-up. In addition, secondary measures of psychosocial function also showed improvement with moderate to large effect sizes (Stroke Specific Quality of Life Scale: d = 0.62; Zarit Burden Interview: d = 0.72), and the Brief Inventory of Psychosocial Function: d = 0.89).

CONCLUSIONS

In chronic stroke survivors with PSA, accelerated iTBS-rTMS targeting the left dmPFC appears to be safe, feasible, tolerable, and highly acceptable, with preliminary evidence suggesting a potential role in reducing apathy and secondarily promoting improvements in quality of life, caregiver burden, and broader psychosocial function. Clinical Trial Registration ID: NCT05878457 , listing: https://clinicaltrials.gov/study/NCT05878457.

NONSTANDARD ABBREVIATIONS AND ACRONYMS: none.

CLINICAL PERSPECTIVE: What Is New?: Dorsomedial prefrontal cortex (dmPFC) holds promise as a network-informed target capable of stimulation with transcranial magnetic stimulation for reducing apathy.High dose of intermittent theta burst (iTBS) stimulation administered to date in a chronic stroke population to dmPFC appears safe, well-tolerated, and feasible with a novel accelerated protocol.What Are the Clinical Implications?: Accelerated iTBS at the left dmPFC appears to be a feasible and potentially efficacious target for apathy in chronic stroke-a patient group with limited evidence-based intervention options.