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October 09, 2022 4 min read

Sleep promotes physical and mental health. It is absolutely essential for both high-level cognitive processing and also basic maintenance and restoration of physiological function.

Good sleep is characterized by a rhythmic cycle of entering shallow non-rapid eye movement sleep (NREM), moving into deep NREM sleep, moving back to shallow NREM sleep, and finally into rapid eye movement (REM) sleep before the cycle repeats.

Deep NREM sleep is essentially a resting state of brain neurons characterized by slow rhythmic waves of electrical activity quite different from the more complex neural activity observed during various physical and mental tasks.  

Neurophysiology of sleep: How things unfold?

During human NREM sleep, the electroencephalogram (EEG), which measures the electrical activity of the brain, exhibits low-frequency (<4 Hz) oscillatory dynamics that support memory and neural computation(1).

In addition, functional magnetic resonance imaging (fMRI) studies measuring blood-oxygenation-level-dependent signals have demonstrated widespread hemodynamic alterations during non-rapid eye movement sleep(2).

Sleep is also associated with increased interstitial fluid volume and clearance of metabolic waste products into the cerebrospinal fluid (CSF)(3), and clearance is stronger in sleep with more low-frequency EEG oscillations(4).

Why these diverse physiological processes co-occur within this state of low arousal is not known. In particular, it remains unclear how CSF dynamics change during sleep, and how they relate to the major changes in neural activity and hemodynamics.

Based on the known correlation between good sleep and good health, researchers at Boston University set out to investigate physiological mechanisms that might explain this phenomenon.

Thirteen volunteers ages 23-33 were EEG caps while lying motionless in a noisy MRI machine trying to sleep. This experimental set-up allowed the researchers to simultaneously monitor the brain’s electrical activity and the movement of CSF and the blood in the brain during NREM sleep(5).  

The unique combination of EEG, which measures the electrical activity of the brain, with fMRI, which monitors changes in blood flow were used to identify a mechanism that could explain how sleep promotes rest and renewal of the brain and how neurodegenerative disease may be tied to disruption of that process.

Brain washing during sleep may clear toxic substances

Researchers demonstrated that when the volunteers entered NREM sleep and their brain neurons switched to a slow rhythmic pattern, the volume of blood in the brain decreased, leaving open spaces in the brain that then filled with CSF.

The movement of the CSF into those spaces was far larger and faster than the CSF flow that normally occurs during the day. The researchers believe this movement of cerebral spinal fluid could contribute to a rinsing of the brain, which is likely to remove toxic waste products that build up during the day.

 

The results are particularly exciting because it is known that NREM sleep declines as people age, and even more dramatically in those with neurogenerative diseases such as Alzheimer’s.

The research team plans to look in older adults, who have reduced sleep quality, to see if they have reduced periods of NREM sleep as well as reduced pulsing of CSF into and out of the brain during NREM sleep.

Ultimately, the protocol might someday become a diagnostic test that identifies individuals with higher risk of neurodegenerative diseases including Alzheimer’s.

Summary

Sleep is associated with large coupled low-frequency oscillations in neuronal activity, blood oxygenation, and CSF flow. While electrophysiological slow waves are known to play important roles in cognition, these results indicate that they may also be linked to the physiologically restorative effects of sleep, as slow neural activity is followed by brainwide pulsations in blood volume and CSF flow.

Results of this study address a key missing link in the neurophysiology of sleep.

The macroscopic changes in CSF flow identified are expected to alter waste clearance. The identification of sleep-associated CSF dynamics also proposes a new biomarker to be explored in clinical conditions associated with sleep disturbance.

Memory impairment in aging is associated with suppressed slow waves, and this model suggests this slow wave loss would in turn be associated with decreased CSF flow.

This research provides further evidence of just how important getting quality sleep every night is.

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References:
1.    Watson, B.O., et al., Network Homeostasis and State Dynamics of Neocortical Sleep. Neuron, 2016. 90(4): p. 839-52.
2.    Larson-Prior, L.J., et al., Cortical network functional connectivity in the descent to sleep. Proc Natl Acad Sci U S A, 2009. 106(11): p. 4489-94.
3.    Xie, L., et al., Sleep drives metabolite clearance from the adult brain. Science, 2013. 342(6156): p. 373-7.
4.    Hablitz, L.M., et al., Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv, 2019. 5(2): p. eaav5447.
5.    Fultz, N.E., et al., Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science, 2019. 366(6465): p. 628-631.

Dr. Paul Henning

About Dr. Paul

I'm currently an Army officer on active duty with over 15 years of experience and also run my own health and wellness business. The majority of my career in the military has focused on enhancing Warfighter health and performance. I am passionate about helping people enhance all aspects of their lives through health and wellness. Learn more about me