Propofol disrupts functional interactions between sensory and high‐order processing of auditory verbal memory

Abstract

Current theories suggest that disrupting cortical information integration may account for the mechanism of general anesthesia in suppressing consciousness. Human cognitive operations take place in hierarchically structured neural organizations in the brain. The process of low-order neural representation of sensory stimuli becoming integrated in high-order cortices is also known as cognitive binding. Combining neuroimaging, cognitive neuroscience, and anesthetic manipulation, we examined how cognitive networks involved in auditory verbal memory are maintained in wakefulness, disrupted in propofol-induced deep sedation, and re-established in recovery. Inspired by the notion of cognitive binding, an fMRI-guided connectivity analysis was utilized to assess the integrity of functional interactions within and between different levels of the task-defined brain regions. Task-related responses persisted in the primary auditory cortex (PAC), but vanished in the inferior frontal gyrus (IFG) and premotor areas in deep sedation. For connectivity analysis, seed regions representing sensory and high-order processing of the memory task were identified in the PAC and IFG. Propofol disrupted connections from the PAC seed to the frontal regions and thalamus, but not the connections from the IFG seed to a set of widely distributed brain regions in the temporal, frontal, and parietal lobes (with exception of the PAC). These later regions have been implicated in mediating verbal comprehension and memory. These results suggest that propofol disrupts cognition by blocking the projection of sensory information to high-order processing networks and thus preventing information integration. Such findings contribute to our understanding of anesthetic mechanisms as related to information and integration in the brain.

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

“…During sedation with propofol, regionally diverse, dose-dependent changes in resting-state connectivity have been found (Hudetz, 2012;Liu et al, 2013d). In particular, a breakdown of functional or effective connectivity has been demonstrated with both fMRI and electrophysiological methods (Boveroux et al, 2010;Ferrarelli et al, 2010;Gomez et al, 2013;Lee et al, 2009a;Liu et al, 2012;Schrouff et al, 2011). Functional connectivity changes in both thalamocortical (Alkire et al, 2000;Liu et al, 2013c;White and Alkire, 2003) and corticocortical networks (Alkire and Miller, 2005;Boly et al, 2012;Boveroux et al, 2010;Ferrarelli et al, 2010;Hudetz, 2012;Schrouff et al, 2011;Soddu et al, 2012) have been detected.…”

Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats

“…Conversely, regaining consciousness may depend on the restoration of the brain's state repertoire and the interaction of its units. There is experimental evidence for reduced functional integration in large-scale systems under general anesthesia 32-35 but corresponding data in neuronal populations have not been obtained to-date.…”

General Anesthesia and Human Brain Connectivity

“…Deep sedation was defined as absent responsiveness to verbal commands. Data are from seven volunteers (Liu et al, 2012b). Note the substantial and reversible reduction of nonspecific thalamocortical connectivity during deep sedation (Figure by the courtesy of Dr. Xiaolin Liu).…”