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. The authors 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-s 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 (0-100 ms) and late (150-1000 ms) 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 corticocortical feedback and loss of consciousness.

Burst activation of the cerebral cortex by flash stimuli during isoflurane anesthesia in rats.

BACKGROUND: The degree of suppression of sensory functions during general anesthesia is controversial. Here, the authors investigated whether discrete flash stimuli induced cortical field potential responses at an isoflurane concentration producing burst suppression and compared the spatiotemporal properties and frequency spectra of flash-induced burst responses with those occurring spontaneously. METHODS: Rats were equipped with multiple epidural and intracortical electrodes to record cortical field potentials in the right hemisphere at several locations along the anterior-posterior axis. At isoflurane concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to the left eye while cortical field potentials were continuously recorded. RESULTS: Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual evoked potential in the primary visual cortex followed by secondary bursting activity in more anterior regions. The average latency and duration of these bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced bursts were similar in frequency, duration, and spatial distribution. They had maximum power in the frontal (primary motor) cortex with a dominant frequency of 10 Hz. CONCLUSIONS: The results suggest that discrete flash stimuli activate the motor regions of the cerebral cortex during isoflurane anesthesia and that these activations are analogous with those that occur spontaneously during burst suppression. Electrocortical suppression of the cortex during anesthesia does not prevent its response to visual stimuli.

Isoflurane disrupts anterio-posterior phase synchronization of flash-induced field potentials in the rat.

Consciousness presumes a set of integrated functions such as sensory processing, attention, and interpretation, and may depend upon both local and long-range phase synchronization of neuronal activity in cerebral cortex. Here we investigated whether volatile anesthetic isoflurane at concentrations that produce loss of consciousness (LOC) disrupts long-range anterio-posterior and local anterior synchronization of neuronal activity in the rat. In six rats, deep electrodes were chronically implanted in the primary visual cortex (V1) and in two areas of the motor cortex (M1 and M2) for recording of intracortical event-related potentials (ERP). Thirty discrete flashes were presented at random interstimulus intervals of 15-45 s, and ERPs were recorded at stepwise increasing isoflurane concentrations of 0-1.1%. Neuronal synchronization was estimated using wavelet coherence computed from the ERP data band-pass filtered at 5-50 Hz. We found that (1) in the waking state, long-range anterio-posterior coherence in 5-25 Hz and 25-50 Hz frequency bands was significantly higher than local anterior coherence; (2) anterio-posterior coherence in both 5-25 Hz and 26-50 Hz bands was significantly reduced by isoflurane in a concentration-dependent manner; (3) local anterior coherence was not affected by isoflurane at any of the concentrations studied. These findings suggest that a disruption of long-range anterio-posterior rather than local anterior synchronization of neuronal activity precedes the anesthetic-induced loss of consciousness.

Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat.

We seek to understand neural correlates of anesthetic-induced unconsciousness. We hypothesize that cortical integration of sensory information may underlie conscious perception and may be disrupted by anesthetics. A critical role in frontal-posterior interactions has been proposed, and gamma (20-60 Hz) oscillations have also been assigned an essential role in consciousness. Here we investigated whether general anesthetics may interfere with the exchange of information encoded in gamma oscillations between frontal and posterior cortices. Bipolar electrodes for recording of event-related potentials (ERP) were chronically implanted in the primary visual cortex, parietal association and frontal association cortices of six rats. Sixty light flashes were presented every 5s, and ERPs were recorded at increasing concentrations of halothane or isoflurane (0-2%). Information exchange was estimated by transfer entropy, a novel measure of directional information transfer. Transfer entropy was calculated from 1-s wavelet-transformed ERPs. We found that (1) feedforward transfer entropy (FF-TE) and feedback transfer entropy (FB-TE) were balanced in conscious-sedated state; (2) anesthetics at concentrations producing unconsciousness augmented both FF-TE and FB-TE at 30 Hz but reduced them at 50 Hz; (3) reduction at 50 Hz was more pronounced for FB-TE, especially between frontal and posterior regions; (4) at high concentrations, both FF-TE and FB-TE at all frequencies were at or below conscious-sedated baseline. Our findings suggest that inhalational anesthetics preferentially impair frontal-posterior FB information transfer at high gamma frequencies consistent with the postulated role of frontal-posterior interactions in consciousness.

Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex.

BACKGROUND: The authors sought to understand neural correlates of anesthetic-induced unconsciousness. Cortical gamma oscillations have been associated with neural processes supporting conscious perception, but the effect of general anesthesia on these oscillations is controversial. In this study, the authors examined three volatile anesthetics, halothane, isoflurane, and desflurane, and compared their effects on flash-induced gamma oscillations in terms of equivalent concentrations producing the loss of righting reflex (1 minimum alveolar concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were presented every 5 s for 5 min, and event-related potentials were recorded from primary visual cortex of 15 rats with a chronically implanted bipolar electrode at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper power spectral technique. Wavelet decomposition was used to determine spectral and temporal distributions of gamma power. RESULTS: The authors found that (1) halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical response in a concentration-dependent manner; (2) the effective concentration for this enhancement was the lowest for isoflurane, intermediate for halothane, and the highest for desflurane when compared at equal fractions of the concentration that led to a loss of righting; (3) the power of flash-induced late (> 100 ms) gamma oscillations was augmented at intermediate concentrations of all three anesthetic agents; and (4) flash-induced gamma power was not reduced below waking baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a reduction in flash-induced gamma oscillations in rat visual cortex is not a unitary correlate of anesthetic-induced unconsciousness.