A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans

During awake consciousness, the brain intrinsically maintains a dynamical state in which it can coordinate complex responses to sensory input. How the brain reaches this state spontaneously is not known. General anesthesia provides a unique opportunity to examine how the human brain recovers its functional capabilities after profound unconsciousness. We used intracranial electrocorticography and scalp EEG in humans to track neural dynamics during emergence from propofol general anesthesia. We identify a distinct transient brain state that occurs immediately prior to recovery of behavioral responsiveness. This state is characterized by large, spatially distributed, slow sensory-evoked potentials that resemble the K-complexes that are hallmarks of stage two sleep. However, the ongoing spontaneous dynamics in this transitional state differ from sleep. These results identify an asymmetry in the neurophysiology of induction and emergence, as the emerging brain can enter a state with a sleep-like sensory blockade before regaining responsivity to arousing stimuli.National Institutes of Health (U.S.) (Grant K99-MH111748)National Institutes of Health (U.S.) (Grant R00-NS080911)National Institutes of Health (U.S.) (Grant DP2-OD006454)National Institutes of Health (U.S.) (Grant S10-RR023401)National Institutes of Health (U.S.) (Grant R01- NS062092)National Institutes of Health (U.S.) (Grant R01AG056015)National Institutes of Health (U.S.) (Grant P01GM118269)National Institutes of Health (U.S.) (Grant R01-EB009282

The Characterization Of Visual Evoked Feedforward-Feedback Travelling Waves In Mice During Waking And Anesthetized States

A cardinal feature of consciousness is the maintenance of a stable perceptual world. To accomplish this, sensory information must be faithfully relayed and integrated within the brain. General anesthetic agents reliably and reversibly produce states of unconsciousness. However, despite their ubiquitous use in medicine and science, the mechanisms by which anesthetics induce loss of consciousness remains unknown. Over the past 170 years, researchers have searched for the universal targets that anesthetic agents use to ablate perception (Alkire et al., 2008; Kelz and Mashour, 2019). However, there is not yet a common structural motif, receptor target, or sleep/arousal circuit that all known anesthetics interact with (Alkire et al., 2008; Kelz and Mashour, 2019). It was once postulated that anesthetics may ablate perception by disconnecting the cortex from incoming thalamic signals (Alkire et al., 2000; Alkire and Miller, 2005; White and Alkire, 2003); yet under anesthesia, neurons within primary cortical areas are still able to encode features of sensory stimuli, thereby suggesting sensory information is effectively relayed to the cortex (Hubel and Wiesel, 1962). Thus, it has been recently theorized that anesthetics may hinder the ability for sensory responses to faithfully participate in hierarchal, feedback and integrative circuits at a network level (Lee et al., 2009; Mashour, 2006, 2014). In this dissertation, I investigate this theory by analyzing the spatiotemporal features of visual evoked oscillations over multiple hierarchical cortical areas in awake and anesthetized mice presented with simple visual stimuli and answering a series of motivating questions. Are there consistent neurophysiological substrates to coordinate visual evoked activity across the many cortical regions involved in visual processing in awake mice, who have the ability to perceive stimuli? If so, what is the spatiotemporal structure of this activity pattern, and does it coordinate neural firing in disparate cortical areas? Can we identify patterns that may be related to hierarchical visual processing vs feedback signaling? How do mechanistically distinct anesthetic agents disrupt visual evoked patterns seen in the awake brain? Are there agent specific effects? And finally, can we identify a common mechanism by which all tested anesthetic agents breakdown visual evoked activity? While my research does not test perception per se, findings herein will provide the neurophysiological basis for the integration of visual-evoked activity across cortices during wakefulness, and the breakdown of this coordinated pattern of activity during anesthetic induced states of unconsciousness