Preferential Inhibition of Frontal-to-Parietal Feedback Connectivity Is a Neurophysiologic Correlate of General Anesthesia in Surgical Patients

University of British Columbia, Canada
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e25155. DOI: 10.1371/journal.pone.0025155
Source: PubMed


The precise mechanism and optimal measure of anesthetic-induced unconsciousness has yet to be elucidated. Preferential inhibition of feedback connectivity from frontal to parietal brain networks is one potential neurophysiologic correlate, but has only been demonstrated in animals or under limited conditions in healthy volunteers.
We recruited eighteen patients presenting for surgery under general anesthesia; electroencephalography of the frontal and parietal regions was acquired during (i) baseline consciousness, (ii) anesthetic induction with propofol or sevoflurane, (iii) general anesthesia, (iv) recovery of consciousness, and (v) post-recovery states. We used two measures of effective connectivity, evolutional map approach and symbolic transfer entropy, to analyze causal interactions of the frontal and parietal regions. The dominant feedback connectivity of the baseline conscious state was inhibited after anesthetic induction and during general anesthesia, resulting in reduced asymmetry of feedback and feedforward connections in the frontoparietal network. Dominant feedback connectivity returned when patients recovered from anesthesia. Both analytic techniques and both classes of anesthetics demonstrated similar results in this heterogeneous population of surgical patients.
The disruption of dominant feedback connectivity in the frontoparietal network is a common neurophysiologic correlate of general anesthesia across two anesthetic classes and two analytic measures. This study represents a key translational step from the underlying cognitive neuroscience of consciousness to more sophisticated monitoring of anesthetic effects in human surgical patients.

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    • "Prior preclinical studies of anterior-posterior connectivity in rat brain identified a selective inhibition of frontal-to-posterior transfer entropy in the gamma bandwidth in association with isoflurane-induced unconsciousness (Imas et al., 2005). Our laboratory first demonstrated anesthetic inhibition of frontal-to-parietal connectivity in human volunteers (Lee et al., 2009) and surgical patients (Ku et al., 2011); inhibition of functional, directional, and effective connectivity in frontal-parietal networks in association with propofol-induced unconsciousness has been identified by studies from multiple research groups using multiple analytic methods (Boveroux et al., 2010; Schrouff et al., 2011; Boly et al., 2012; Jordan et al., 2013). Of note, the recent study of Jordan et al used combined electroencephalography and functional magnetic resonance imaging with no a priori assumptions regarding connectivity and found that the selective loss of frontal-to-parietal connectivity (as measured by symbolic transfer entropy) was the best discriminator between consciousness and propofol-induced unconsciousness (Jordan et al., 2013). "
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    ABSTRACT: Recent studies of propofol-induced unconsciousness have identified characteristic properties of electroencephalographic alpha rhythms that may be mediated by drug activity at γ-aminobutyric acid (GABA) receptors in the thalamus. However, the effect of ketamine (a primarily non-GABAergic anesthetic drug) on alpha oscillations has not been systematically evaluated. We analyzed the electroencephalogram of 28 surgical patients during consciousness and ketamine-induced unconsciousness with a focus on frontal power, frontal cross-frequency coupling, frontal-parietal functional connectivity (measured by coherence and phase lag index), and frontal-to-parietal directional connectivity (measured by directed phase lag index) in the alpha bandwidth. Unlike past studies of propofol, ketamine-induced unconsciousness was not associated with increases in the power of frontal alpha rhythms, characteristic cross-frequency coupling patterns of frontal alpha power and slow-oscillation phase, or decreases in coherence in the alpha bandwidth. Like past studies of propofol using undirected and directed phase lag index, ketamine reduced frontal-parietal (functional) and frontal-to-parietal (directional) connectivity in the alpha bandwidth. These results suggest that directional connectivity changes in the alpha bandwidth may be state-related markers of unconsciousness induced by both GABAergic and non-GABAergic anesthetics.
    Frontiers in Systems Neuroscience 07/2014; 8:114. DOI:10.3389/fnsys.2014.00114
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    • "By contrast, the top-down approach to ketamine-induced unconsciousness has successfully identified a common neural correlate of unconsciousness induced by propofol, ketamine, and sevoflurane that could have been predicted based on the neurobiology of consciousness (Lee et al., 2013) (Figure 6). Loss of effective connectivity from the frontal cortex to more posterior cortices has been consistently observed with all three drugs, suggesting inhibition of reentrant processing as a candidate for the common mediator of anesthetic effects on consciousness (Ku et al., 2011; Jordan et al., 2013). Furthermore, this loss of top-down information processing was selective, because feedforward processing (from posterior parietal to frontal area) appeared preserved. "
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    ABSTRACT: The question of how structurally and pharmacologically diverse general anesthetics disrupt consciousness has persisted since the nineteenth century. There has traditionally been a significant focus on "bottom-up" mechanisms of anesthetic action, in terms of sensory processing, arousal systems, and structural scales. However, recent evidence suggests that the neural mechanisms of anesthetic-induced unconsciousness may involve a "top-down" process, which parallels current perspectives on the neurobiology of conscious experience itself. This article considers various arguments for top-down mechanisms of anesthetic-induced unconsciousness, with a focus on sensory processing and sleep-wake networks. Furthermore, recent theoretical work is discussed to highlight the possibility that top-down explanations may be causally sufficient, even assuming critical bottom-up events.
    Frontiers in Systems Neuroscience 06/2014; 8:115. DOI:10.3389/fnsys.2014.00115
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    • "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. 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., 2009b, 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). "
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    ABSTRACT: The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, iv. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78±20% and 76±20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in twelve anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness.
    Brain Connectivity 04/2014; 5(1). DOI:10.1089/brain.2014.0230
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