Reduced neural feedback signaling despite robust neuron and gamma auditory responses during human sleep.

During sleep, sensory stimuli rarely trigger a behavioral response or conscious perception. However, it remains unclear whether sleep inhibits specific aspects of sensory processing, such as feedforward or feedback signaling. Here, we presented auditory stimuli (for example, click-trains, words, music) during wakefulness and sleep in patients with epilepsy, while recording neuronal spiking, microwire local field potentials, intracranial electroencephalogram and polysomnography. Auditory stimuli induced robust and selective spiking and high-gamma (80-200 Hz) power responses across the lateral temporal lobe during both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Sleep only moderately attenuated response magnitudes, mainly affecting late responses beyond early auditory cortex and entrainment to rapid click-trains in NREM sleep. By contrast, auditory-induced alpha-beta (10-30 Hz) desynchronization (that is, decreased power), prevalent in wakefulness, was strongly reduced in sleep. Thus, extensive auditory responses persist during sleep whereas alpha-beta power decrease, likely reflecting neural feedback processes, is deficient. More broadly, our findings suggest that feedback signaling is key to conscious sensory processing.

Propofol anesthesia concentration rather than abrupt behavioral unresponsiveness linearly degrades responses in the rat primary auditory cortex.

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration versus behavioral unresponsiveness, which are typically confounded. Here, we used slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural electroencephalogram, and neuronal spiking activity in primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, postonset neuronal silence duration, late-locking to 40 Hz click-trains, and offset responses, gradually changed in a dose-dependent manner with increasing anesthesia levels without showing abrupt shifts around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Locus coeruleus norepinephrine activity mediates sensory-evoked awakenings from sleep.

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.

Evaluation of image enhancement software as a method of performing half-count bone scans.

Reducing the radiation dose and scanning time of diagnostic tests is often desirable. One method uses image enhancement software such as Pixon, which processes lower-count scans and aims to produce high-quality images. However, it is essential that diagnostic accuracy is not compromised. We compared the level of agreement between clinicians using standard scans, with half-count and Pixon-enhanced half-count scans. Bone scans from 150 patients referred to diagnose metastatic disease were degraded by a process of Poisson-preserving binomial resampling to generate equivalent half-count scans and then processed by Pixon software to recreate 'original' high-quality scans. Two experienced clinicians reported the scans in a randomized, blinded manner for metastatic disease (yes/no) and assigned a confidence level to this diagnosis. Levels of agreement between clinicians were calculated for the full-count, half-count, and Pixon-enhanced half-count scans and between scanning methods for each clinician. Agreement between clinicians for standard full-count scans was 92% (±4%, κ=0.80), compared with 92% (±4%, κ=0.79) for half-count scans and 87% (±5%, κ=0.70) for Pixon-processed half-count scans. Agreement for a single clinician viewing full-count versus half-count scans was 95% (±2%, κ=0.88), similar to the agreement for a single clinician viewing full-count versus Pixon-processed half-count scans (95%, ±2%, κ=0.88). With respect to confidence in diagnosis, 127 full-count scans were scored in the highest category, compared with 98 half-count and 88 Pixon-processed half-count scans. Switching to half-count scanning does not introduce more diagnostic disagreement than is already present between clinicians. However, clinicians feel less confident reporting half-count scans. The Pixon enhancement step improved neither objective diagnostic agreement nor clinician confidence.