This study investigates brain water dynamics across the sleep-wake cycle using near-infrared spectroscopy (NIRS) and linear mixed-effects modeling, motivated by prior observations that glymphatic activity increases during non-rapid eye movement (NREM) and decreases during REM sleep. Forty-one healthy volunteers underwent polysomnography with concurrent cerebral NIRS, with measurements taken 30 minutes before sleep, throughout the night, and for 60 minutes after waking. Brain water content (arbitrary unit, A.U.) was block-averaged for 5-minute epochs and analyzed across WAKE→NREM, NREM→WAKE, NREM→REM, and REM→NREM transitions. Water content significantly increased during WAKE→NREM (0.57 A.U., d= 0.77, p < 0.001) and decreased during NREM→WAKE (−0.93 A.U., d = −1.25, p < 0.001). Decreases during NREM→REM (−0.40 A.U., d= −0.53, p < 0.05) were followed by increases during REM→NREM (0.62 A.U., d = 1.10, p < 0.001). Brain water accumulation was significantly greater during the first compared to the last NREM cycle (0.70 A.U., d = 0.86, p < 0.01). These findings reveal robust, state-dependent fluctuations in brain water content that parallel established glymphatic physiology. Water-sensitive NIRS may offer a promising non-invasive approach to monitoring sleep-related brain fluid dynamics in humans, though further multimodal studies are needed to determine its specificity for glymphatic activity.
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