Disconnecting Consciousness: Is There a Common Anesthetic End Point?

Abstract

A quest for a systems-level neuroscientific basis of anesthetic-induced loss and return of consciousness has been in the forefront of research of the last two decades. Recent advances toward the discovery of underlying mechanisms have been achieved using experimental electrophysiology, multichannel electroencephalography, magnetoencephalography, and functional magnetic resonance imaging. By the careful dosing of various volatile and IV anesthetic agents to the level of behavioral unresponsiveness, both specific and common changes in functional and effective connectivity across large-scale brain networks have been discovered and interpreted in the context of how the synthesis of neural information might be affected during anesthesia. The results of most investigations to date converge toward the conclusion that a common neural correlate of anesthetic-induced unresponsiveness is a consistent depression or functional disconnection of lateral frontoparietal networks, which are thought to be critical for consciousness of the environment. A reduction in the repertoire of brain states may contribute to the anesthetic disruption of large-scale information integration leading to unconsciousness. In future investigations, a systematic delineation of connectivity changes with multiple anesthetics using the same experimental design and the same analytical method will be desirable. The critical neural events that account for the transition between responsive and unresponsive states should be assessed at similar anesthetic doses just below and above the loss or return of responsiveness. There will also be a need to identify a robust, sensitive, and reliable measure of information transfer. Ultimately, finding a behavior-independent measure of subjective experience that can track covert cognition in unresponsive subjects and a delineation of causal factors vs. correlated events will be essential to understand the neuronal basis of human consciousness and unconsciousness.

Isoflurane Impairs Low-Frequency Feedback but Leaves High-Frequency Feedforward Connectivity Intact in the Fly Brain

“…A number of studies have demonstrated that general anesthetics preferentially reduce FB from frontal to posterior areas as measured using human scalp level electroencephalography (EEG; Lee et al, 2009; Ku et al, 2011; Boly et al, 2012; Jordan et al, 2013; Lee et al, 2013; Ranft et al, 2016). Although a subset of studies show differing results (Barrett et al, 2012; Nicolaou et al, 2012; Maksimow et al, 2014), the disrupted frontal-parietal connectivity has also been demonstrated using functional magnetic resonance imaging (fMRI; Hudetz and Mashour, 2016). In addition, general anesthetic suppression of FB has also been reported in rodents (Imas et al, 2006; Pal et al, 2016), ferrets (Wollstadt et al, 2017), and monkeys (Lamme et al, 1998; Papadopoulou et al, 2015).…”

Accelerated Recovery of Consciousness after General Anesthesia Is Associated with Increased Functional Brain Connectivity in the High-Gamma Bandwidth

“…There is convergent evidence from multiple studies involving multiple species, multiple neuroimaging modalities, multiple analytic techniques, and diverse drug classes suggesting that anesthetic-induced unconsciousness is characterized by a functional fragmentation of cortical and thalamocortical networks (for review see Hudetz and Mashour, 2016). This reversible fragmentation is broadly supportive of the cognitive unbinding theory of anesthetic-induced unconsciousness (Mashour, 2013) as well as the integrated information theory of consciousness (Tononi et al, 2016) and other higher-order perspectives on the neurobiology of subjective experience.…”

Recreational use of GHB is associated with alterations of resting state functional connectivity of the central executive and default mode networks

“…This is however not exclusively related to these compounds since sleep induction without pharmacological agents is known to produce similar effects (De Havas, Parimal, Soon, & Chee, 2012;Hudetz & Mashour, 2016;Liang et al, 2015;Sämann et al, 2011;Stamatakis, Adapa, Absalom, & Menon, 2010a;Uhrig, Dehaene, & Jarraya, 2014). Contrary to normal rest, there is decreased intrinsic connectivity of the DMN and decreased anti-correlation between the CEN and the DMN during sedation and hypnotic states, and this is associated with a diminished capacity to integrate sensory stimuli (De Havas et al, 2012;Hudetz & Mashour, 2016;Liang et al, 2015;Stamatakis, Adapa, Absalom, & Menon, 2010b;Uhrig et al, 2014). Recent studies have started to investigate the acute effects of GHB-exposure on the DMN, the CEN and the SN (Bosch et al, 2017(Bosch et al, , 2018von Rotz et al, 2017).…”