Dexmedetomidine Disrupts the Local and Global Efficiencies of Large-scale Brain Networks

Abstract

Background A clear understanding of the neural basis of consciousness is fundamental to research in clinical and basic neuroscience disciplines and anesthesia. Recently, decreased efficiency of information integration was suggested as a core network feature of propofol-induced unconsciousness. However, it is unclear whether this finding can be generalized to dexmedetomidine, which has a different molecular target. Methods Dexmedetomidine was administered as a 1-μg/kg bolus over 10 min, followed by a 0.7-μg · kg−1 · h−1 infusion to healthy human volunteers (age range, 18 to 36 yr; n = 15). Resting-state functional magnetic resonance imaging data were acquired during baseline, dexmedetomidine-induced altered arousal, and recovery states. Zero-lag correlations between resting-state functional magnetic resonance imaging signals extracted from 131 brain parcellations were used to construct weighted brain networks. Network efficiency, degree distribution, and node strength were computed using graph analysis. Parcellated brain regions were also mapped to known resting-state networks to study functional connectivity changes. Results Dexmedetomidine significantly reduced the local and global efficiencies of graph theory–derived networks. Dexmedetomidine also reduced the average brain connectivity strength without impairing the degree distribution. Functional connectivity within and between all resting-state networks was modulated by dexmedetomidine. Conclusions Dexmedetomidine is associated with a significant drop in the capacity for efficient information transmission at both the local and global levels. These changes result from reductions in the strength of connectivity and also manifest as reduced within and between resting-state network connectivity. These findings strengthen the hypothesis that conscious processing relies on an efficient system of information transfer in the brain.

Neural Signatures of α2 Adrenergic Agonist-Induced Unconsciousness and Awakening by Antagonist

“…Dexmedetomidine is a highly selective a2 adrenergic agonist and is unique among currently 52 available anesthetics, most of which are known to act at multiple receptors in the central nervous 53 system. A recent neuroimaging study suggests that dexmedetomidine significantly reduces 54 information transfer in the local and global brain networks in humans (Hashmi et al, 2017), 55 consistent with the effect of propofol (Monti et al, 2013). Functional disconnection between brain 56 regions is a possible mechanism suggested for dexmedetomidine-induced unconsciousness (Akeju 57 et al, 2014a;Song et al, 2017).…”

Degrees of functional connectome abnormality in disorders of consciousness

“…The regression analysis of the effects of the covariates was limited in power by the sample size and by the presence of correlated predictors: (a) etiology and DOC duration, (b) sedation and diagnosis. It has been reported that dexmedetomidine reduces average brain connectivity strength in healthy individuals (Hashmi et al, ), although its effect on some aspects of brain connectivity was found to be smaller than that of propofol and non‐rapid‐eye‐movement sleep (Guldenmund et al, ). These results suggest that the effect of sedation may be significant in our context.…”

Brain network motifs are markers of loss and recovery of consciousness

“…All epochs and channels with noise or non-physiological artifacts were visually identified and removed. We then band-pass filtered the cleaned EEG data into delta (1-4 Hz), theta (4-8Hz), alpha , and beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) frequency bands. Analysis of the alpha band were presented in the main body of the paper, while analyses of other frequency bands are included in the supplementary material.…”

“…Both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies have shown that propofol-, sevoflurane-, and ketamine-induced unconsciousness induce a functional disconnection of anterior and posterior regions of the cortex [3][4][5][6][7][8], while propofol and sevoflurane also induce an anteriorization of alpha power from the occipital to the frontal cortex [9][10][11]. Graph theoretical analysis has demonstrated that global and topographic properties of brain networks are altered during anesthetic-induced unconsciousness [12][13][14][15][16]. While these advances have led to a clearer understanding of how anesthetic-induced unconsciousness creates inhospitable conditions for information processing and transfer [17], these measures describe whole-brain network processes rather than region-specific changes in brain functioning.…”

“…Nine healthy subjects underwent a 3-hour anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8)(9)(10)(11)(12)(13) band, five-minute epochs of EEG were extracted for: baseline; induction; unconsciousness; 30-, 10-and 5-minutes pre-recovery of consciousness; 30-and 180-minutes post-recovery of consciousness. We constructed a functional brain network using both the weighted and the directed phase lag index, on which we calculated graph theoretical network properties, and the frequency and topography of 3-node motifs.…”