Apparent diffusion coefficient changes in human brain during sleep – Does it inform on the existence of a glymphatic system?

&NA; The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume ‐ an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested‐wakefulness versus wakefulness following one night of sleep‐deprivation. Sleep compared to wakefulness was associated with increases in slow‐ADC in cerebellum and left temporal pole and with decreases in fast‐ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep‐induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested‐wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast‐ and slow‐ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep‐related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep‐induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.