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 level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. 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 12 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.

No abstract

Consciousness is thought to scale with brain complexity, and it may be diminished in anesthesia. Lempel-Ziv complexity (LZC) of field potentials has been shown to be a promising measure of the level of consciousness in anesthetized human subjects, neurological patients, and across the sleep-wake states in rats. Whether this relationship holds for intrinsic networks obtained by functional brain imaging has not been tested. To fill this gap of knowledge, we estimated LZC from large-scale dynamic analysis of functional magnetic resonance images (fMRI) in conscious sedated and unconscious anesthetized rats. Blood oxygen dependent (BOLD) signals were obtained from 30-min whole-brain resting-state scans while the anesthetic propofol was infused intravenously at constant infusion rates of 20 mg/kg/h (conscious sedated) and 40 mg/kg/h (unconscious). Dynamic brain networks were defined at voxel level by sliding window analysis of regional homogeneity (ReHo) of the BOLD signal. From scans performed at low to high propofol dose, the LZC was significantly reduced by 110%. The results suggest that the difference in LZC between conscious sedated and anesthetized unconscious subjects is conserved in rats and this effect is detectable in large-scale brain network obtained from fMRI.

The balance between excitation and inhibition is considered to be of significant importance for neural computation and cognitive function. Excitatory and inhibitory functional connectivity in intact cortical neuronal networks in wakefulness and graded levels of anesthesia has not been systematically investigated. We compared monosynaptic excitatory and inhibitory spike transmission probabilities using pairwise cross-correlogram (CCG) analysis. Spikes were measured at 64 sites in the visual cortex of rats with chronically implanted microelectrode arrays during wakefulness and three levels of anesthesia produced by desflurane. Anesthesia decreased the number of active units, the number of functional connections, and the strength of excitatory connections. Connection probability (number of connections per number of active unit pairs) was unaffected until the deepest anesthesia level, at which a significant increase in the excitatory to inhibitory ratio of connection probabilities was observed. The results suggest that the excitatory–inhibitory balance is altered at an anesthetic depth associated with unconsciousness.

State-dependent neuronal firing patterns reflect changes in ongoing information processing and cortical function. A disruption of neuronal coordination has been suggested as the neural correlate of anesthesia. Here, we studied the temporal correlation patterns of ongoing spike activity, during a stepwise reduction of the volatile anesthetic desflurane, in the cerebral cortex of freely moving rats. We hypothesized that the recovery of consciousness from general anesthesia is accompanied by specific changes in the spatiotemporal pattern and correlation of neuronal activity. Sixty-four contact microelectrode arrays were chronically implanted in primary visual cortex (contacts spanning 1.4 mm depth and 1.4 mm width) for recording of extracellular unit activity at four steady-state levels of anesthesia (8%–2% desflurane) and wakefulness. Recovery of consciousness was defined as the regaining of the righting reflex (near 4%). High-intensity firing (HI) periods were segmented using a threshold (200 ms) representing the minimum in the neurons’ bimodal interspike interval histogram under anesthesia. We found that the HI periods were highly fragmented in deep anesthesia and gradually transformed to a near-continuous firing pattern at wakefulness. As the anesthetic was withdrawn, HI periods became longer and increasingly correlated among the units both locally and across remote recording sites. Paradoxically, in 4 of 8 animals, HI correlation was also high at the deepest level of anesthesia (8%) when local field potentials (LFP) were burst-suppressed. We conclude that recovery from desflurane anesthesia is accompanied by a graded defragmentation of neuronal activity in the cerebral cortex. Hypersynchrony during deep anesthesia is an exception that occurs only with LFP burst suppression.

Background Cortical γ oscillations are thought to play a role in conscious cognitive functions. Suppression of 40 Hz γ activity was implicated in the loss of consciousness during general anesthesia. However, several experimental studies found that γ oscillations were preserved in anesthesia. We investigated the concentration-dependent effect of isoflurane on spontaneous γ oscillations in two frequency bands and three distinct brain regions in the rat. Methods Adult Sprague-Dawley rats were chronically implanted with epidural and coaxial depth electrodes to record cortical field potentials in frontal cortex, visual cortex and hippocampus in waking and at steady-state isoflurane concentrations of 0.4, 0.8 and 1.2 percent. The γ power was calculated for the frequency bands 30-50 and 70-140 Hz. Temporal variation and interregional synchrony of γ activity were analyzed using wavelet transform. Loss of consciousness was indexed by the loss of righting reflex. Results Rats lost their righting reflex at 0.8±0.1% isoflurane. High-frequency γ power was decreased by isoflurane in a concentration-dependent manner (p<0.001, 50% decrease at 0.8% isoflurane) in all brain regions. Low-frequency γ power was unaffected by isoflurane. The duration and interregional synchrony of high-frequency γ bursts was also reduced (p<0.001, 40% decrease at 0.8% isoflurane). Conclusions Distinction between high and low γ frequency bands is important when evaluating the effect of general anesthetics on brain electrical activity. Spontaneous 40 Hz γ power does not indicate the state of consciousness. The attenuation and interregional desynchronization of high-frequency γ oscillations appear to correlate with the loss of consciousness.

Background The nucleus Basalis of Meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. Here we investigated its role in the modulation of general anesthesia. Methods Rats were chronically implanted with bilateral infusion cannulae in the nucleus Basalis of Meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices. Animals were anesthetized with desflurane at a concentration required for the loss of righting reflex (4.6 ± 0.5%). Norepinephrine (17.8 nmol), or artificial cerebrospinal fluid was infused at 0.2 µl/min (1 µl total). Behavioral response to infusion was measured by scoring the orofacial, limb and head movements, and postural changes. Results Behavioral responses were higher after norepinephrine (2.1 ± 1) than artificial cerebrospinal fluid (0.63 ± 0.8) infusion (p < 0.01, t-test). Responses were brief (1–2 minutes), repetitive and more frequent after norepinephrine infusion (p < 0.0001, chi-square test). Electroencephalogram δ power decreased after norepinephrine in frontal (70 ± 7%) but not in visual cortex (p < 0.05, t-test). Simultaneously, electroencephalogram cross-approximate entropy between frontal and visual cortices increased from 3.17 ± 0.56 to 3.85 ± 0.29 after norepinephrine infusion (p < 0.01, t-test). Behavioral activation was predictable by the decrease in frontal δ power (logistic regression, p < 0.05). Conclusions Norepinephrine infusion into the nucleus Basalis of Meynert can modulate anesthetic depth presumably by ascending activation of the cortex. The transient nature of the responses suggests a similarity with micro-arousals normally observed during natural sleep, and may imply a mechanism for transient awareness under light anesthesia.

States of consciousness have been associated with information integration in the brain as modulated by anesthesia and the ascending arousal system. The present study was designed to test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) can augment information integration in the cerebral cortex of anesthetized rats. Extracellular unit activity and local field potentials were recorded in freely moving animals from parietal association (PtA) and secondary visual (V2) cortices via chronically implanted microwire arrays at three levels of anesthesia produced by desflurane: 3.5, 4.5, and 6.0% (where 4.5% corresponds to that critical for the loss of consciousness). Information integration was characterized by integration (multiinformation) and interaction entropy, estimated from the statistical distribution of coincident spike patterns. PnO stimulation elicited electrocortical activation as indicated by the reductions in δ- and θ-band powers at the intermediate level of anesthesia. PnO stimulation augmented integration from 1.13 ± 0.03 to 6.12 ± 1.98 × 103 bits and interaction entropy from 0.44 ± 0.11 to 2.18 ± 0.72 × 103 bits; these changes were most consistent in the PtA at all desflurane concentrations. Stimulation of the retina with discrete light flashes after PnO stimulation elicited an additional 166 ± 25 and 92 ± 12% increase in interaction entropy in V2 during light and intermediate levels. The results suggest that the PnO may modulate spontaneous ongoing and sensory stimulus-related cortical information integration under anesthesia.