Thalamus, Brainstem and Salience Network Connectivity Changes During Propofol-Induced Sedation and Unconsciousness

Abstract

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness.

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

“…A reduction in the coherence and information transfer among select frontal, parietal, and occipital cortical regions has been found using electrophysiological techniques (Ku et al, 2011;Lee et al, 2009bLee et al, , 2013. More generally, anesthetics have been thought to target subcortical mechanisms (Brown et al, 2010;Guldenmund et al, 2013;Mhuircheartaigh et al, 2010) including the natural sleep promoting circuits (Franks and Zecharia, 2011;Zecharia and Franks, 2009), and the neocortex itself (Hentschke et al, 2005;Hudetz, 2006;Seth et al, 2005;Velly et al, 2007).…”

“…Subcortical ROIs were as follows: hippocampus (Hipp), caudate-putamen (CPu), nucleus basalis of Meynert (NBM), medial thalamus (mTh), hypothalamus (Hypo), and nucleus pontis oralis (PnO). The ROIs were chosen to cover the most extensive cortical regions and important subcortical centers suggested to be involved in the anesthetic modulation of the ascending arousal system (Alkire et al, 2007;Brown et al, 2010;Devor and Zalkind, 2001;Guldenmund et al, 2013;Mhuircheartaigh et al, 2010;Sukhotinsky et al, 2007;Zecharia and Franks, 2009). Group analysis for 12 ROIs involved the calculation of CTC temporal variance at each propofol dose and the relative contribution of each ROI to the dose-dependent change in global variance.…”

“…Recently, a rapidly expanding group of investigators began to approach the problem by applying anesthetic agents to reversibly modulate the state of consciousness in search of unique neuronal correlates of state transitions in the brain in both humans and animals Boly et al, 2013;Bonhomme et al, 2012;Brown et al, 2010;Hudetz, 2012;Mashour and Alkire, 2013). Tentative findings have suggested a role for large-scale thalamocortical and corticocortical networks, subcortical modulatory and higher cortical integration centers in the orchestration of the reversible transitions between conscious and unconscious states (Alkire, 2008;Bonhomme et al, 2011;Boveroux et al, 2010;Ferrarelli et al, 2010;Guldenmund et al, 2013;Hudetz, 2012;Langsjo et al, 2012;Lee et al, 2009aLee et al, , 2009bLee et al, , 2013Mhuircheartaigh et al, 2010;Nallasamy and Tsao, 2011;Peltier et al, 2005;Schrouff et al, 2011;White and Alkire, 2003). However, a final common pathway or unitary theory for losing and regaining consciousness has not emerged.…”

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

“…With task-free neuroimaging, an examiner is not dependent on patient co-operation and a patient's possibility to exhibit body movement. In resting state fMRI, examination of intactness of the default mode network (DMN) might improve diagnosis in DOC, as it is known to be important for internally-oriented consciousness [5,[7][8][9][10][11][12]. In recent years, interest has also increased for other brain regions associated with specific higher-order networks [13].…”

Propofol-Induced Frontal Cortex Disconnection: A Study of Resting-State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies

“…Indeed, the DMN connectivity has been shown to be decreased in deep sleep (Horovitz et al, 2009), general anesthesia (Boveroux et al, 2010;Guldenmund et al, 2013), and in patients in coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) , and minimally conscious state (MCS) (Vanhaudenhuyse et al, 2010). Anesthesia studies have also specifically focused on the posterior cingulate cortex (PCC)/precuneus, showing propofol-induced alterations of the connectivity pattern (Amico et al, 2014;Liu et al, 2014;Stamatakis et al, 2010), while others indicated the involvement of a wide range of higher-order RSNs in the loss of responsiveness (expected to be a state of unconsciousness), like the external control network (ECN; left and right ECN components are frequently mentioned separately), important for externally oriented awareness (Boveroux et al, 2010;Liu et al, 2012), and the salience network, which is implicated in the detection of salient stimuli (Guldenmund et al, 2013). Furthermore, disconnection between higherorder RSNs and the thalamus has been found to be associated with propofol-induced loss of responsiveness (Boveroux et al, 2010;Guldenmund et al, 2013;Liu et al, 2013).…”