Muting, not fragmentation, of functional brain networks under general anesthesia

Corson N Areshenkoff,Joseph Y Nashed,R Matthew Hutchison,Melina Hutchison,Ron Levy,Douglas J Cook,Ravi S Menon,Stefan Everling,Jason P Gallivan

doi:10.1016/j.neuroimage.2021.117830

Abstract

Changes in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and a disruption of the brain’s ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC. Specifically, by comparing the actual FC data to surrogate data sets that we derived to test competing hypotheses of how FC changes as a function of dose, we found that increases in whole-brain modularity and the number of network communities – considered hallmarks of fragmentation – are artifacts of constructing FC networks by thresholding based on correlation magnitude. Taken together, our findings suggest that deepening levels of unconsciousness are instead associated with the increasingly muted expression of functional networks, an observation that constrains current interpretations as to how anesthesia-induced FC changes map onto existing neurobiological theories of consciousness.

Highlights

While much work has focused on how different anesthetics affect ion channels and receptor function at the cellular level (Anis et al, 1983; Franks, 2006; Peduto et al, 1991), it remains poorly understood, by comparison, how anesthetics affect the coordinated activity of distributed whole-brain networks (Alkire et al, 2008; Brown et al, 2011)
We used common principal component analysis to derive a set of components that summarize the correlation structure across dose, and show that the expression of these components decreases in a near monotonic fashion as dose increases
Functional neuroimaging plays a central role in the testing of these predictions, as these techniques allow for the precise characterization of brain activity across various states of consciousness and unconsciousness

Summary

Introduction

While much work has focused on how different anesthetics affect ion channels and receptor function at the cellular level (Anis et al, 1983; Franks, 2006; Peduto et al, 1991), it remains poorly understood, by comparison, how anesthetics affect the coordinated activity of distributed whole-brain networks (Alkire et al, 2008; Brown et al, 2011). In recent years, resting-state functional MRI (rs-fMRI) has provided important glimpses into the large-scale, network-level effects of anesthesia This approach, which measures covariance structure in spontaneous low-frequency oscillations in neural activity (Biswal et al, 1995), has repeatedly revealed an apparent fragmentation of functional brain network structure during various states of unconsciousness (Boly et al, 2012b; Hudetz and Mashour, 2016; Hutchison et al, 2014).

Objectives

Methods

Results

Discussion

Conclusion