Differential Cortical Network Engagement During States of Un/Consciousness in Humans

Abstract

The neural basis of consciousness remains a major unresolved issue in human neuroscience, with theories of consciousness and experimental studies differing concerning which brain regions are necessary for consciousness. Direct experimental evidence to resolve this debate requires identifying the global, network, and regional involvement during different states of consciousness in humans. We utilized multi-region intracranial single-pulse direct electrical stimulation to examine circuit and network interactions during three canonical states of consciousness: wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (e.g., propofol-induced general anesthesia). Increased variability in cortical responses, reduced information transfer, and reduced complexity characterized states of diminished consciousness. Notably, however, these metrics differed in different brain regions and types of unconscious states.Anesthesia induced more overall changes in brain responses than sleep, but cortical network engagement depended on the kind of unconsciousness. Brain activity changes were largely anatomically uniform during sleep, contrasting with a substantial and selective disconnection of the prefrontal cortices during anesthesia. These results provide direct evidence from human intracranial recordings during the loss of consciousness, suggesting that the obliteration of consciousness during anesthesia results not from just altered overall physiology but from a disconnection between prefrontal areas and other brain areas. Significance What happens in the human brain when we are unconscious? Despite substantial work, we are still unsure which brain regions are involved and how they are impacted when consciousness is disrupted. Using intracranial recordings and direct electrical stimulation, we mapped global, network, and regional involvement during wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (propofol-induced general anesthesia). Information integration and complex processing were reduced, while variability increased during the loss of consciousness. These changes were more pronounced during anesthesia than sleep. They also involved different cortical engagement; During sleep, changes were mostly uniformly distributed across the brain while during anesthesia the prefrontal cortex was the most disrupted. These findings indicate different neural signatures for different types of unconsciousness. Highlights · Sleep and anesthesia showed decreased complexity, connectivity, and response amplitude with increased response variability compared to wake states in the human brain. · These changes in brain response to stimulation were more pronounced during propofol-induced general anesthesia than during natural sleep. · During sleep, changes were homogeneously distributed across the brain. · During anesthesia, there was a substantial disconnection of the frontal cortices.

Modular pipeline for reconstruction and localization of implanted intracranial ECoG and sEEG electrodes

“…This allows us to algorithmically determine the locations of electrode contacts in the brain. This brain region localization alone has been useful for following seizure activity, planning stimulation, and localizing neural activity relative to cognitive processes [5,6,[11][12][13][14][30][31][32][33][34][35][36][37][38]. Finally, this output data is easily converted into a universal format so that we can share our data with the greater scientific community (iEEG BIDS; [43]).…”

“…In addition, some co-registration pipelines require the pre-operative and post-operative scans to first be transformed into a standardized brain space (e.g., Montreal Neurological Institute (MNI) space) before identifying electrode locations [28,29]. There are various methods for a user to achieve their goal when attempting to localize implanted electrodes, but here we lay out a protocol involving multiple software packages that we have used in a large data set (>260 patients) and which we have used to address many neuroscientific and clinically-relevant goals [5,6,[11][12][13][14][30][31][32][33][34][35][36][37][38].…”

Theta-burst direct electrical stimulation remodels human brain networks

“…For a subset of participants (N=4), neural activity during single pulse electrical stimulation (SPES, Supplemental Table 1 ) has been presented in previous publications with different analyses 85,86 .…”

“…Stimulation was controlled via a custom CereStim API via MATLAB or a custom C++ code (https://github.com/Center-For-Neurotechnology/CereLAB). For both TBS and SPES, the same 233 µs duration waveforms were used: 90 µs charge-balanced biphasic symmetrical pulses with an interphase interval of 53 µsec at 7 mA between 10 and 25 trials (for SPES) 69,74,[85][86][87][88][89][90] and TBS at 1 mA and 2 mA. The interval of 53 µs within the biphasic waveform was required as a hardware-limited minimum interval between square pulses with the CereStim stimulator.…”

“…To examine effective connectivity of the stimulated network, we used responses to SPES to perform corticocortical evoked potential (CCEP) mapping 43,44,50,69,72,74,[85][86][87][88][89][90]95 . Since we were comparing the SPES-induced CCEP responses with the TBS responses, we applied SPES in the same or nearby contact pairs as the TBS stimulation.…”