Conscious perception is greatly diminished during sleep, but the underlying circuit mechanism is poorly understood. We show that cortical ignition-a brain process shown to be associated with conscious awareness in humans and non-human primates-is strongly suppressed during non-rapid-eye-movement (NREM) sleep in mice due to reduced cholinergic modulation and rapid inhibition of cortical responses. Brain-wide functional ultrasound imaging and cell-type-specific calcium imaging combined with optogenetics showed that activity propagation from visual to frontal cortex is markedly reduced during NREM sleep due to strong inhibition of frontal pyramidal neurons. Chemogenetic activation and inactivation of basal forebrain cholinergic neurons powerfully increased and decreased visual-to-frontal activity propagation, respectively. Furthermore, although multiple subtypes of dendrite-targeting GABAergic interneurons in the frontal cortex are more active during wakefulness, soma-targeting parvalbumin-expressing interneurons are more active during sleep. Chemogenetic manipulation of parvalbumin interneurons showed that sleep/wake-dependent cortical ignition is strongly modulated by perisomatic inhibition of pyramidal neurons.
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http://dx.doi.org/10.1016/j.cell.2023.11.012 | DOI Listing |
J Neurosci Methods
January 2025
School of Electrical and Computer Engineering, Gallogly College of Engineering, University of Oklahoma, Norman, OK 73019, USA.
Background: Recent advances in multimodal signal analysis enable the identification of subtle drug-induced anomalies in sleep that traditional methods often miss.
New Method: We develop and introduce the Dynamic Representation of Multimodal Activity and Markov States (DREAMS) framework, which embeds explainable artificial intelligence (XAI) techniques to model hidden state transitions during sleep using tensorized EEG, EMG, and EOG signals from 22 subjects across three age groups (18-29, 30-49, and 50-66 years). By combining Tucker decomposition with probabilistic Hidden Markov Modeling, we quantified age-specific, temazepam-induced hidden states and significant differences in transition probabilities.
Eur J Neurol
February 2025
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Objective: Disorders of arousal (DoA) are characterized by an intermediate state between wakefulness and deep sleep, leading to incomplete awakenings from NREM sleep. Multimodal studies have shown subtle neurophysiologic alterations even during wakefulness in DoA. The aim of this study was to explore the brain functional connectivity in DoA and the metabolic profile of the anterior and posterior cingulate cortex, given its pivotal role in cognitive and emotional processing.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
Introduction: Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.
Methods: We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.
Sleep entails significant changes in cerebral hemodynamics and metabolism. Yet, the way these processes evolve throughout wakefulness and sleep and their spatiotemporal dependence remain largely unknown. Here, by integrating a novel functional PET technique with simultaneous EEG-fMRI, we reveal a tightly coupled temporal progression of global hemodynamics and metabolism during the descent into NREM sleep, with large hemodynamic fluctuations emerging as global glucose metabolism declines, both of which track EEG arousal dynamics.
View Article and Find Full Text PDFbioRxiv
January 2025
Yale School of Medicine, New Haven, CT, U.S.A.
Study Objectives: Sleep deficiency is associated with Alzheimer's disease (AD) pathogenesis. We examined the association of sleep architecture with anatomical features observed in AD: (1) atrophy of hippocampus, entorhinal, inferior parietal, parahippocampal, precuneus, and cuneus regions ("AD-vulnerable regions") and (2) cerebral microbleeds.
Methods: In 271 participants of the Atherosclerosis Risk in the Communities Study, we examined the association of baseline sleep architecture with anatomical features identified on brain MRI 13~17 years later.
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