Propofol disrupts asynchronous functional connectivity...

The human brain under ecological conditions exhibits a preference for asynchronous functional connectivity, with a tendency for delays in the order of one minute from cortical inputs into primary sensorimotor and language-associated regions. Consistent with hierarchical neurocomputational models of consciousness, this may reflect predictive or reverberant signalling, where temporally complex information is utilised to resolve incoming stimuli at momentary timescales in consumer cortical modules, allowing rich experiences of contextually embedded phenomena. Herein, we test the hypothesis that during states of unconsciousness, there is a reduction in both the duration of delays, and number of afferent delayed connections, into unimodal cortices – reflecting a deflation of the brain’s capacity for distributed top-down anticipatory neural dynamics. Further, we test the hypothesis that delays depend on long-range parvalbumin GABAergic interneurons, who’s expression profile traces the cortical hierarchy and activity is necessary for maintaining detailed excitatory-inhibitory balance. Using fMRI data collected from individuals at ‘rest’ or listening to a story at several levels of propofol-induced anaesthesia, we show that auditory cortex and language-associated regions receive information from across the brain over long delays when consciously attending to an auditory narrative, an effect that is significantly attenuated during unconscious presentation of the same stimuli, or awake ‘resting’ conditions. Furthermore, we show that the cortical topography of delay indeed resembles transcriptomic maps for the parvalbumin gene. This work bridges micro and macroscales of biological organisation to gain insight into the processes underlying human consciousness, while advancing the study of asynchronous communication in the brain.

Significance Statement

Elucidating the mechanisms supporting conscious processing is perhaps the greatest task facing neuroscience. Here, we leverage a recently developed metric characterising whole-brain asynchronous functional connectivity architectures, to show that conscious processing of auditory stimuli is associated with pronounced delays, and number of afferent delayed functional connections, into auditory and language-associated regions. This work presents an alternative approach to investigating global brain dynamics, sheds light on the inadequacies of canonical static analyses of the brain, provides a novel mechanism for predictive or reverberant theories of consciousness, and potentially a means by which recovery from disorders of consciousness may be forecasted.