Local and interregional thalamocortical dynamics show temporally dissociable changes during propofol induced loss of consciousness.

Whether propofol-induced loss of consciousness (LOC) reflects a single thalamocortical transition or involves temporally dissociable local and interregional dynamics remains unclear. Using stereo-electroencephalography recordings from the anterior nucleus of the thalamus, prefrontal cortex, and temporal cortex during anesthesia induction, we quantified permutation entropy, spectral power, directional connectivity, and phase-amplitude coupling (PAC) to determine the relative onset timing of significant changes across metrics, regions, and frequency bands. Here, we show that complexity in the anterior nucleus of the thalamus decreased before LOC and did so significantly earlier than in the prefrontal and temporal cortices. Spectral power changes likewise emerged earlier in the anterior nucleus of the thalamus than in the prefrontal cortex. Across brain regions, power changes at lower frequencies generally emerged earlier than those at higher frequencies, with the specific timing differences varying across regions. The temporal pattern of PAC was primarily frequency-dependent rather than region-specific. Changes in local directed connectivity were observed earlier in cortical regions than in the anterior nucleus of the thalamus, while thalamo-prefrontal connectivity showed earlier significant modulation than other interregional connections. Furthermore, local directed connectivity changes preceded interregional alterations; spectral, complexity, and connectivity shifts preceded local PAC. Propofol-induced LOC involves a reorganization of neural dynamics both within local regions and across directed interregional pathways. Rather than reflecting a single focal event or uniform global suppression, this transition unfolds as an ordered spatiotemporal cascade, characterized by temporally dissociable changes across neural markers and hierarchical network levels.