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: 3.53). 10/2011; 6(10):e25155. DOI: 10.1371/journal.pone.0025155
Source: PubMed

ABSTRACT 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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    • "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.
    04/2014; 5(1). DOI:10.1089/brain.2014.0230
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    • "The utility of our model lies first and foremost in its simplicity—in both practical application and interpretation. While electroencephalographic studies may require application of complex statistical methods to resolve the underlying dynamics (Ku et al., 2011), the cortical slice strips away much of this complexity to give a more intuitive visualisation of the results. The source localisation procedure described in this study was potentially confounded by three matters. "
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    ABSTRACT: How general anaesthetic drugs cause unconsciousness is a topic of ongoing clinical and scientific interest. It's becoming increasingly apparent that they disrupt cortical information processing, but the effects appear to depend on the spatial scale under investigation. In this study we investigated whether the intravenous anaesthetic etomidate synchronises neuronal activity on a sub-millimetre scale in mouse neocortical slices. In slices generating no-magnesium seizure-like event (SLE) activity, we analysed the morphology of field potential activity recorded with 50µm extracellular electrodes. The analysis was based on the understanding that the amplitude and sheerness of field potential oscillations correlates with the synchrony of the underlying neural activity. When recorded from the region of the slice initiating SLE activity, etomidate consistently increased both population event amplitude (median(range) 85(24-350) to 101(30-427) µV) and slope 16.6(1.5-106.2) to 20.2(1.7-111.1) µV/msec (p=0.016 and p=0.0013, respectively). The results are consistent with an increase in neuronal synchrony within the receptive field of the recording electrode, estimated to be a circle diameter of 300µm. In conclusion, the neocortical slice preparation supports in vivo data showing that general anaesthetics increase neuronal synchrony on a local scale and provides an ideal model for investigating underlying mechanisms.
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