EEG hemispheric asymmetry and behavioral responsiveness following rTMS in unresponsive wakefulness syndrome: an exploratory study

BACKGROUND: Hemispheric asymmetry is a fundamental feature of large-scale brain organization, yet its relevance to disorders of consciousness (DOC) and its modulation following repetitive transcranial magnetic stimulation (rTMS) remain insufficiently studied. This study investigated pre-to-post rTMS changes in EEG hemispheric asymmetry, particularly differences between responders and non-responders and examined how these changes relate to long-term functional outcomes. METHODS: This exploratory single-arm pre–post study enrolled 20 patients with unresponsive wakefulness syndrome (UWS) who received 10-Hz rTMS for 10 consecutive days. Resting-state EEG was acquired before (T0) and after stimulation (T1) to quantify alpha-band hemispheric asymmetry indices, including frontal alpha asymmetry (FAA), parietal alpha asymmetry (PAA), frontal alpha synchrony asymmetry (FASA) and parietal alpha synchrony asymmetry (PASA). Clinical outcomes were tracked for 12 months by Disability Rating Scale. RESULTS: Clinical improvement after rTMS was observed in a subset of patients, accompanied by changes in EEG asymmetry from pre- to post-stimulation. Changes in frontal alpha asymmetry (FAA) were associated with responder status, with responders exhibiting a greater leftward shift in FAA after stimulation. In addition, baseline frontal alpha synchrony asymmetry (FASA) and parietal alpha asymmetry (PAA) were associated with functional disability at the 12-month follow-up. CONCLUSIONS: In this single-arm cohort, rTMS was associated with clinical improvement in a subset of patients with DOC, accompanied by changes in EEG hemispheric asymmetry, particularly FAA. FAA may serve as an exploratory marker for identifying DOC patients who respond to rTMS. Moreover, asymmetry indices were associated with long-term functional outcomes.