Non-rapid eye movement sleep determines resilience to social stress normal
Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience. To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience-demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that plays a determinative role in promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.
Data generated in this study are deposited in Dryad.
Non-rapid eye movement sleep determines resilience to social stressDryad Digital Repository, doi:10.5061/dryad.x0k6djhn4.
Article and author information
National Institute of General Medical Sciences (GM127260)
- J Christopher Ehlen
National Institute on Minority Health and Health Disparities (Pilot funding,MD007602)
- J Christopher Ehlen
National Institute of Neurological Disorders and Stroke (NS078410)
- Ketema N Paul
National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL103104)
- Brittany J Bush
National Heart, Lung, and Blood Institute (Graduate Student Fellowship,HL007901)
- Eva-Jeneé A Andrews
National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL117929)
- Cloe L Gray
National Heart, Lung, and Blood Institute (Postdoctoral Fellowship,HL116077)
- Allison J Brager
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to a protocol (21-02) approved by the Morehouse School of Medicine institutional animal care and use committee (IACUC). All surgery was performed under isoflurane anesthesia, and analgesia was provided. Every effort was made to minimize pain and suffering.
- Matthew N Hill, University of Calgary, Canada
- Received: May 12, 2022
- Preprint posted: June 1, 2022 (view preprint)
- Accepted: September 21, 2022
- Accepted Manuscript published: September 23, 2022 (version 1)
- Accepted Manuscript updated: September 26, 2022 (version 2)
- Version of Record published: October 21, 2022 (version 3)
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
- Page views
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local parameters, revealing increased stability of hippocampal and insular dynamics as signatures of brain atrophy in AD and bvFTD, respectively. Using variational autoencoders, we visualized different pathologies and their severity as the evolution of trajectories in a low-dimensional latent space. Finally, we perturbed the model to reveal key AD- and bvFTD-specific regions to induce transitions from pathological to healthy brain states. Overall, we obtained novel insights on disease progression and control by means of external stimulation, while identifying dynamical mechanisms that underlie functional alterations in neurodegeneration.
Previous research has associated alpha-band [8–12 Hz] oscillations with inhibitory functions: for instance, several studies showed that visual attention increases alpha-band power in the hemisphere ipsilateral to the attended location. However, other studies demonstrated that alpha oscillations positively correlate with visual perception, hinting at different processes underlying their dynamics. Here, using an approach based on traveling waves, we demonstrate that there are two functionally distinct alpha-band oscillations propagating in different directions. We analyzed EEG recordings from three datasets of human participants performing a covert visual attention task (one new dataset with N = 16, two previously published datasets with N = 16 and N = 31). Participants were instructed to detect a brief target by covertly attending to the screen’s left or right side. Our analysis reveals two distinct processes: allocating attention to one hemifield increases top-down alpha-band waves propagating from frontal to occipital regions ipsilateral to the attended location, both with and without visual stimulation. These top-down oscillatory waves correlate positively with alpha-band power in frontal and occipital regions. Yet, different alpha-band waves propagate from occipital to frontal regions and contralateral to the attended location. Crucially, these forward waves were present only during visual stimulation, suggesting a separate mechanism related to visual processing. Together, these results reveal two distinct processes reflected by different propagation directions, demonstrating the importance of considering oscillations as traveling waves when characterizing their functional role.