Propofol-induced general anesthesia was associated with a selective breakdown of alpha-band functional connectivity linking parietal, occipital, and subcortical regions, a change that reliably distinguishes unconsciousness from wakefulness, according to a prospective observational study published in Cell Reports Medicine.
Investigators primarily based in China analyzed high-density electroencephalogram recordings from 31 adult surgical patients during induction of propofol anesthesia to identify network-level signatures of consciousness. Using 128-channel recordings with source localization, the team reconstructed time-varying functional connectivity across nine cortical and subcortical regions implicated in consciousness, spanning 242 network nodes. Connectivity was quantified across delta, theta, alpha, beta, and gamma frequency bands during wakefulness and after loss of consciousness.
Compared with wakefulness, unconsciousness was associated with increased delta- and theta-band connectivity and reduced alpha-, beta-, and gamma-band connectivity across distributed brain regions. The most pronounced reductions occurred in alpha-band connections between the parietal cortex and the occipital cortex, thalamus, cingulate gyrus, claustrum, and temporal cortex. Network topology analyses showed that, relative to wakefulness, alpha-, beta-, and gamma-band networks during unconsciousness exhibited longer characteristic path lengths and lower clustering coefficients, consistent with reduced global integration and altered local processing.
To evaluate whether these connectivity changes could discriminate states of consciousness, the researchers trained a support vector machine to identify interregional and intraregional connectivity features. Alpha-band connectivity showed the highest classification performance, with accuracy, sensitivity, and specificity all 87%, in distinguishing unconsciousness from wakefulness. Delta-band connectivity also performed well, with an accuracy of 82%. Feature-weight analyses identified parietal-related alpha connections as the dominant contributors to classification.
Dynamic analyses aligned to the clinical time point of loss of consciousness showed that parietal-centered alpha connectivity declined abruptly within approximately 20 seconds before and after loss of responsiveness, whereas less influential connections remained relatively stable. These temporal patterns suggested that disruption of parietal-subcortical and parietal-occipital alpha connectivity coincided with the transition into unconsciousness rather than reflecting gradual sedation effects.
The researchers independently tested the findings in a second cohort of 46 adult patients who received low-dose propofol for mild sedation. In this group, alpha-band connectivity was reduced compared with wakefulness, but changes were smaller than those observed during general anesthesia. Classification accuracy for distinguishing sedation from wakefulness fell to 62%, and parietal-related alpha connections no longer carried strong discriminative weight, supporting their specificity for the unconscious state.
The researchers acknowledged limitations of the analysis, including a focus on anesthesia induction rather than maintenance or recovery, uncertainty in subcortical source localization using surface EEG, extensive statistical testing, and small, relatively homogeneous patient cohorts. They emphasized that findings should be interpreted as exploratory and warrant confirmation with intracranial or multimodal approaches.
“Our results suggest the importance of functional networks in understanding the physiology underlying changes in consciousness induced by anesthesia,” the researchers wrote. “A classification model and dynamic analysis of consciousness loss suggest that alpha connectivity between the parietal cortex, occipital cortex, and subcortical areas is critical for consciousness and disruption of these connections signifies a key transition to loss of consciousness.”
This study was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Shanghai Jiao Tong University School of Medicine, and the Shanghai Eastern Talent Plan. The authors reported no competing interests.
Source: Cell Reports Medicine
