Temporal Interference Stimulation of Centromedian‐Parafascicular Complex in Disorders of Consciousness: A Pilot Study

OBJECTIVE: Treatment of disorders of consciousness (DoC) remains a major clinical challenge, and noninvasive, targeted modulation of deep brain structures has emerged as a promising therapeutic strategy. We aimed to evaluate the feasibility/safety and preliminary effects of thalamic temporal interference stimulation (TIS) targeting centromedian-parafascicular (CM-PF) complex in patients with DoC. METHODS: We conducted a single-arm, self-controlled trial in nine patients with DoC. All patients received TIS targeting the bilateral CM-PF complex once daily for 10 consecutive days. Stimulation targets were guided by patient-specific electric field modeling to ensure precise neuromodulation. Outcome measures included adverse events, the change in Coma Recovery Scale-Revised (CRS-R) total and subscale scores from baseline to after five and 10 stimulation sessions, and alterations in EEG "ABCD" patterns and power spectral density (PSD) following the tenth session. RESULTS: No serious adverse events were reported. After 10 stimulation sessions, CRS-R total scores increased significantly, with improvements primarily observed in the auditory, visual, and motor subscales. No significant changes in CRS-R scores were detected after five stimulation sessions. EEG analyses demonstrated an increased prevalence of patterns C and D, disappearance of pattern A, and elevated global PSD in the alpha and beta frequency bands after 10 stimulation sessions. INTERPRETATION: This pilot study demonstrates that thalamic TIS is a safe and feasible noninvasive deep brain stimulation technology that may facilitate consciousness recovery in patients with DoC. Larger randomized controlled trials with longer follow-up are needed to confirm these preliminary observations.