State-dependent repetitive transcranial magnetic stimulation in disorders of consciousness

Disorders of consciousness (DOCs), including coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS), remain among the most difficult conditions to manage in neurorehabilitation. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising neuromodulatory approach, yet its clinical effects appear to vary substantially across DOC subtypes, and the basis of this response gradient remains incompletely understood. In this narrative review, we used a structured literature-search approach and prioritized randomized or sham-controlled clinical studies, controlled observational studies, and mechanistic studies integrating rTMS with neuroimaging and/or electrophysiological measures to synthesize current evidence on therapeutic efficacy and putative mechanisms across DOC subtypes. Available data, interpreted in light of unequal evidence strength across subtypes, indicate that rTMS most consistently improves Coma Recovery Scale-Revised (CRS-R) scores in patients with MCS, shows heterogeneous effects in VS/UWS, and lacks sufficient therapeutic evidence in coma. Converging neurophysiological findings, although not equivalent to therapeutic efficacy, further suggest that coma and VS/UWS are often characterized by reduced thalamo-cortical reactivity and limited plastic/metaplastic capacity, whereas MCS more commonly retains partially preserved frontoparietal networks that may provide a plausible substrate for therapeutic rTMS testing. Taken together, these heterogeneous findings may be organized through a state-dependent, hypothesis-generating perspective on rTMS application in DOC, while the uneven evidence base remains the primary interpretive constraint. Within this secondary conceptual heuristic, rTMS in MCS may be better understood as a form of network fine-tuning, VS/UWS as an experimental network rebooting hypothesis, and coma primarily as an evidence gap in which TMS-EEG probing may inform future therapeutic studies rather than current treatment guidance. Rather than serving as a validated treatment algorithm, this subtype-, population-, and biomarker-informed framework is intended to organize current evidence, clarify evidence gaps, identify candidate readiness-related biomarkers, and inform future hypothesis-driven studies of biomarker-informed neuromodulation and residual consciousness-related stratification in DOC.