Increased Global and Regional Connectivity in Propofol-induced Unconsciousness: Human Intracranial Electroencephalography Study

BACKGROUND: The conscious state is maintained through intact communication between brain regions. However, studies on global and regional connectivity changes in unconscious state have been inconsistent. These inconsistencies could arise from unclear definition of unconsciousness, spatial and temporal limitations of neuroimaging modalities, and estimating only single connectivity measure. This study investigated global and regional changes in amplitude and phase-based functional connectivity in propofol-induced unconsciousness, which is widely recognized as unconsciousness. METHODS: Amplitude and phase-based functional connectivity was calculated using amplitude envelope correlation, weighted phase lag index, and magnitude squared coherence from intracranial electroencephalography data of 73 patients. Global changes in connectivity, complexity, and network efficiency were estimated. Regional connectivity changes between Brodmann areas, between seven cortical lobes, and between resting state networks were assessed across all frequency bands. Additionally, machine learning analysis was employed to identify specific regions in classifying conscious and unconscious states. RESULTS: In the unconscious state, global connectivity increased across all frequency bands, while global complexity and efficiency decreased, accompanied by increased delta and decreased high gamma power spectral density. Regional connectivity increased between entire cortical regions across all frequency bands. Machine learning analysis revealed that posterior connectivity was the most influential in classifying consciousness. Amplitude-based connectivity predominantly increased in the delta and theta bands, while phase-based connectivity predominantly increased from the beta to high gamma bands. CONCLUSIONS: Propofol anesthesia suppresses cortical activity and induces oscillatory changes characterized by increased delta power and decreased high gamma power. These changes are accompanied by increased functional connectivity and reduced network complexity and efficiency. These changes limit the brain's ability to generate a diverse repertoire of activity, ultimately leading to unconsciousness. Posterior connectivity, which showed high accuracy in predicting conscious states, would be crucial for sustaining consciousness.