Research Reveals Brain Changes During Sleep Transition

Brigham and Women's Hospital

Findings from Mass General Brigham investigators highlight the intricate interplay of diverse physiological processes as the brain shifts from wakefulness to sleep

A new study by investigators from Mass General Brigham used next-generation imaging technology to discover that when the brain is falling asleep, it shows a coordinated shift in activity. They found that during NREM (non-rapid eye movement) sleep, parts of the brain that handle movement and sensory input stay active and keep using energy, while areas involved in thinking, memory and daydreaming quiet down and use less energy. Their results are published in Nature Communications.

"This research helps explain how the brain stays responsive to the outside world even as awareness fades during sleep," said corresponding author Jingyuan Chen, PhD, an assistant investigator at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system. "By revealing how brain activity, energy use, and blood flow interact during sleep, these findings, and the imaging tools we used to uncover them, offer new insights into the mechanisms of neurological and sleep-related diseases."

The body cycles through two types of sleep several times each night: NREM and REM (rapid eye movement). NREM is the deep, restorative stage of sleep that plays a key role in physical health, brain function and disease prevention. Yet, many of its underlying processes and impacts on long-term health remain poorly understood. Previous studies have suggested that NREM helps clear waste from the brain.

Using a new tri-modal EEG-PET-MRI technique that combines EEG to study brain activity, fMRI to analyze blood flow, and functional PET (fPET)-FDG to monitor glucose metabolic dynamics, researchers examined the brains of 23 healthy adults during brief afternoon sleep sessions.

The researchers found that energy use and metabolism decrease as sleep deepens, while blood flow becomes more dynamic, especially in sensory areas that stay relatively active. At the same time, higher-order cognitive networks quiet down, and cerebrospinal fluid flow increases. Together, these findings support the idea that sleep helps clear waste from the brain while maintaining sensitivity to sensory cues that can trigger awakening.

The authors note future studies should include larger, more diverse groups and collect longer, deeper sleep recordings. The researchers also plan to use more precise methods to measure brain metabolism and better distinguish between sleep stages.

Authorship: In addition to Chen, Mass General Brigham authors include Laura D. Lewis, Sean E. Coursey, Ciprian Catana, Jonathan R. Polimeni, Jiawen Fan, Kyle S. Droppa, Rudra Patel, Hsiao-Ying Wey, Dara S. Manoach, Julie C. Price, Christin Y. Sander, and Bruce R. Rosen. Additional authors include Catie Chang from Vanderbilt University.

Disclosures: The authors declare no competing interests

Funding: This work was supported in part by the National Institutes of Health (grants K99/R00-NS118120, R01-MH111438, P41-EB030006, R01-MH092638, U19-NS123717, U19-NS128613, and R21-MH135201), by the Harvard Mind Brain Behavior Faculty Research Award, by the Brain & Behavior Research Foundation Young Investigator Grant, by the BrightFocus Foundation Research Grant, and by the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging; and was made possible by the resources provided by NIH Shared Instrumentation grants (S10-RR022976, S10-RR019933, S10-OD010759). Computational resources were generously provided by the Massachusetts Life Sciences Center.

Paper cited: Chen JE et al. "Simultaneous EEG-PET-MRI identifies temporally coupled and spatially structured brain dynamics across wakefulness and NREM sleep" Nature Communications DOI: 10.1038/s41467-025-64414-x

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