Functional integration in the cortical neuronal network of conscious and anesthetized animals

General anesthesia consists of amnesia, analgesia, areflexia and unconsciousness. How anesthetics suppress consciousness has been a mystery for more than one and a half centuries. The overall goal of my research has been to determine the neural correlates of anesthetic-induced loss of consciousness. I hypothesized that anesthetics induce unconsciousness by interfering with the functional connectivity of neuronal networks of the brain and consequently, reducing the brain\u27s capacity for information processing. To test this hypothesis, I performed experiments in which neuronal spiking activity was measured with chronically implanted microelectrode arrays in the visual cortex of freely-moving rats during wakefulness and at graded levels of anesthesia produced by the inhalational anesthetic agent desflurane. I then applied linear and non-parametric information-theoretic analyses to quantify the concentration-dependent effect of general anesthetics on spontaneous and visually evoked spike firing activity in rat primary visual cortex. Results suggest that desflurane anesthesia disrupts cortical neuronal integration as measured by monosynaptic connectivity, spike burst coherence and information capacity. This research furthers our understanding of the mechanisms involved with the anesthetic-induced LOC which may facilitate in the development of better anesthetic monitoring devices and the creation of effective anesthetic agents that will be free of unwanted side effects

Desflurane Selectively Suppresses Long-latency Cortical Neuronal Response to Flash in the Rat

Background—The effect of inhalational anesthetics on sensory-evoked unit activity in the cerebral cortex has been controversial. Desflurane has desirable properties for in vivo neurophysiologic studies but its effect on cortical neuronal activity and neuronal responsiveness is not known. We studied the effect of desflurane on resting and visual evoked unit activity in rat visual cortex in vivo. Methods—Desflurane was administered to adult albino rats at steady-state concentrations at 2%, 4%, 6% and 8%. Flashes from a light emitting diode were delivered to the left eye at 5-second intervals. Extracellular unit activity within the right visual cortex was recorded using a 49-electrode array. Individual units were identified using principal components analysis. Results—At 2% desflurane 578 active units were found. Of these, 75% increased their firing rate in response to flash. Most responses contained early (0–100ms) and late (150–1000ms) components. With increasing desflurane concentration, the number of units active at baseline decreased (−13%), the number of early responding units increased (+31%), and number of late responding units decreased (−15%). Simultaneously, baseline firing rate decreased (−77%), the early response was unchanged, and the late response decreased (−60%). Conclusions—The results indicate that visual cortex neurons remain responsive to flash stimulation under desflurane anesthesia but the long-latency component of their response is attenuated in a concentration-dependent manner. Suppression of the long-latency response may be related to a loss of cortico-cortical feedback and loss of consciousness

Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake Rats

Background: Neuronal interactions are fundamental for information processing, cognition and consciousness. Anesthetics reduce spontaneous cortical activity; however, neuronal reactivity to sensory stimuli is often preserved or augmented. How sensory stimulus-related neuronal interactions change under anesthesia has not been elucidated. Here we investigated visual stimulus-related cortical neuronal interactions during stepwise emergence from desflurane anesthesia. Methods: Parallel spike trains were recorded with 64-contact extracellular microelectrode arrays from the primary visual cortex of chronically instrumented, unrestrained rats (N=6) at 8%, 6%, 4%, 2% desflurane anesthesia and wakefulness. Light flashes were delivered to the retina by transcranial illumination at 5-15s randomized intervals. Information theoretical indices, integration and interaction complexity, were calculated from the probability distribution of coincident spike patterns and used to quantify neuronal interactions before and after flash stimulation. Results: Integration and complexity showed significant negative associations with desflurane concentration (N=60). Flash stimulation increased integration and complexity at all anesthetic levels (N=60); the effect on complexity was reduced in wakefulness. During stepwise withdrawal of desflurane, the largest increase in integration (74%) and post-stimulus complexity (35%) occurred prior to reaching 4% desflurane concentration – a level associated with the recovery of consciousness according to the rats\u27 righting reflex. Conclusions: Neuronal interactions in the cerebral cortex are augmented during emergence from anesthesia. Visual flash stimuli enhance neuronal interactions in both wakefulness and anesthesia; the increase in interaction complexity is attenuated as post-stimulus complexity reaches plateau. The critical changes in cortical neuronal interactions occur during transition to consciousness

Monosynaptic Functional Connectivity in Cerebral Cortex During Wakefulness and Under Graded Levels of Anesthesia

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