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

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.

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.

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.

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.