Sleep deprivation impairs molecular clearance from the human brain

Abstract

It remains an enigma why human beings spend one-third of their life asleep. Experimental data suggest that sleep is required for clearance of waste products from brain metabolism. This has, however, never been verified in humans. The primary aim of the present study was to examine in vivo whether one night of total sleep deprivation affects molecular clearance from the human brain. Secondarily, we examined whether clearance was affected by subsequent sleep. Multiphase MRI with standardized T1 sequences was performed up to 48 h after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml), which served as a tracer molecule. Using FreeSurfer software, we quantified tracer enrichment within 85 brain regions as percentage change from baseline of normalized T1 signals. The cerebral tracer enrichment was compared between two cohorts of individuals; one cohort (n = 7) underwent total sleep deprivation from Day 1 to Day 2 (sleep deprivation group) while an age and gender-matched control group (n = 17; sleep group) was allowed free sleep from Day 1 to Day 2. From Day 2 to 3 all individuals were allowed free sleep. The tracer enriched the brains of the two groups similarly. Sleep deprivation was the sole intervention. One night of sleep deprivation impaired clearance of the tracer substance from most brain regions, including the cerebral cortex, white matter and limbic structures, as demonstrated on the morning of Day 2 after intervention (sleep deprivation/sleep). Moreover, the impaired cerebral clearance in the sleep deprivation group was not compensated by subsequent sleep from Day 2 to 3. The present results provide in vivo evidence that one night of total sleep deprivation impairs molecular clearance from the human brain, and that humans do not catch up on lost sleep.

Keywords: brain metabolism; cerebrospinal fluid tracer; magnetic resonance imaging; sleep; sleep deprivation.