Disruption of the claustrum-ACC pathway contributes to human mind blanking.

The claustrum is a highly connected structure hypothesized to orchestrate conscious experience, yet its role in humans remains enigmatic. To address this question, we prospectively investigated patients with drug-resistant epilepsy who underwent stereoelectroencephalography (SEEG) implantation driven by clinical indications, with electrode trajectories optimized to target the claustrum. Across the eight participants, the stimulated claustrum was left-sided in six and right-sided in two. Focal stimulation of the left claustrum reproducibly induced a transient arrest of ongoing thought and a reduced behavioral responsiveness in one of eight patients, consistent with mind blanking (MB). Simultaneous intracranial recordings revealed site-specific suppression of neural activity within the anterior cingulate cortex (ACC). Machine learning-based analysis further confirmed that spectral attenuation across frequency bands in the ACC served as reliable electrophysiological fingerprints of this stimulation-induced mind blanking. Finally, 1 Hz claustrum-cortical evoked potentials identified a robust claustrum-ACC pathway. Together, these findings suggest that the claustrum-ACC pathway is critically involved in ongoing conscious thought, and its disruption offers a circuit-level mechanism for MB. (ClinicalTrials.gov identifier: NCT06575413).