To treat or not to treat? A point of view on the clinical translation of non-invasive neuromodulation therapy for post-stroke upper limb recovery

Abstract

Background and Purpose: This Point of View paper offers a commentary on challenges and opportunities discussed during the 6th International Brain Stimulation Conference held in February 2025 in Kobe, Japan, with a focus on the clinical application of repetitive transcranial magnetic stimulation (rTMS) in post-stroke rehabilitation. We argue that the major barrier lies in the field’s overreliance on standardized, one-size-fits-all protocols and its reluctance to embrace personalization in the pursuit of precision. Results: During the conference, 2 research cultures were evident: the “Systematicists,” who rely on conventional clinical trials, and the “Personalizers,” who tailor non-invasive brain stimulation (NIBS) protocols to individual patient characteristics. This dichotomy reflects a broader challenge: how can we reconcile the need for standardization with the demand for personalization in translational research? The future of NIBS may lie in patient-specific, biomarker-driven neuromodulatory protocols that incorporate deep phenotyping and brain state-dependent stimulation, such as closed-loop TMS guided by Hebbian plasticity principles. This approach recognizes that post-stroke recovering brain is a 4-dimensional structure, shaped by space and time, which contributes to substantial intra- and inter-individual variability. Conclusion: Understanding how NIBS interacts with each uniquely recovering brain is essential. Addressing this complexity remains a challenge for designing rigorous clinical trials and moving the field closer to effective, personalized integration in stroke rehabilitation. By delineating key components of personalization, we aim to reframe the discussion from “if” NIBS works to “for whom, for what and why, for where and when, and how” it can facilitate clinically meaningful recovery.