By Rohan Sharma

Receiving an adequate amount of good quality sleep is essential in general healthy brain function as well as cognition. Nearly 50% of United States adults fail to achieve their needed amount with an average of less than 7 hours of sleep per weeknight.1 For many who do get enough sleep, the poor quality results in continued fatigue. A mechanism not previously studied involving the effects of brain waves and blood flow volume on clearance of brain waste products through cerebrospinal fluid was examined. The results elucidate the multifactorial mechanism involved in waking properly rested and allow for further future studies on the possible clinical correlates associated with a defect in any one of the factors.2

It is well established that cerebrospinal fluid (CSF) clears metabolic waste from the brain, and low frequency brain waves during non-rapid eye movement (NREM) sleep are linked to brain function and memory. Additionally, it has been seen that this clearance of metabolic waste is more efficient in low oscillation NREM sleep and occurs with increased interstitial fluid volume. A study titled “Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep” by Fultz et al. was performed to determine whether these phenomena are linked. A sample size of thirteen was tested for blood oxygen level dependent signals (BOLD) using fMRI, EEG oscillations, and CSF flow. Contrary to what is seen when awake, large oscillations were seen in CSF flow dynamics at the fourth ventricle when measured during NREM sleep. Interestingly, examining hemodynamic signals showed an anticorrelation between BOLD and CSF flow, as shown in figure B. EEG readings during NREM sleep revealed a peak in slow delta EEG consistently occurring 6.4 seconds before the CSF peak.2     

These results corroborate the existing hypothesis that electrophysiological slow waves play an important role in brain function; additionally, they point to evidence that these waves may also play a role in the important aspect of sleep that leads to us being well rested. Based on the anticorrelation between BOLD signals and CSF flow, it is hypothesized that during periods of lesser blood volume in the brain, there is a greater flow of CSF into the brain. The fact that slow delta EEG signals consistently occur before both BOLD signals and CSF flow allows us to hypothesize that EEG signals can be used to predict waste removal by CSF and therefore quality of sleep. The findings of the study by Fultz et al. reveal that different aspects are involved in CSF waste removal and can allow us to further study sleep disturbances and lack of quality sleep in patients.2 

Further experiments can still be performed to clarify the exact mechanisms involved and possible treatments to disruptions in any of the components involved.Clinical studies observing patients who report sleep disturbance or continued fatigue despite receiving adequate sleep can be impactful. Specifically, the methods utilized in this study can be repurposed to determine whether discrepancies are seen among individuals who report differing qualities of sleep. CSF oscillations may not be as significant, leading to less waste removal. Alternatively, inadequate blood clearance from the brain would not allow for the anticorrelated CSF oscillations, leading to the same result. The study by Fultz et al. nicely sets the stage for novel experiments in this area of health that is gaining evermore attention.  

1. L. Xing, G. Shi, Y. Mostovoy, N. W. Gentry, Z. Fan, T. B. Mcmahon, P.-Y. Kwok, C. R. Jones, L. J. Ptáček, Y.-H. Fu, Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation. Sci. Transl. Med. 11, eaax2014 (2019).
2. Fultz et al. Interactions between neural waves, hemodynamics, and cerebrospinal fluid oscillations in sleep , Science 366, 628–631 (2019)