0208 No Improvement in Degraded Performance One Month After 7 Nights of Modest Sleep Restriction

Abstract Introduction Sleep restriction (SR), defined as regularly obtaining less than seven hours of sleep per day, is associated with significant performance deficits in humans. Preclinical studies suggest that SR induces widespread microglial activation and neuroinflammation, damage to arousal nuclei, white matter damage, and other neuropathophysiological changes. Here we examine whether similar neuropathophysiological effects occur in humans and whether such changes help explain SR-related performance deficits. Methods Seven healthy adults (ages 18-39) participated in a two-month study involving baseline, seven nights of SR (5h time-in-bed/night), and a one-month recovery period. Performance was assessed throughout the study. Magnetic Resonance Imaging (MRI) was conducted at baseline (T1), during middle and end of SR (T2-T3), following four nights of recovery sleep (T4), and after one month of recovery at home (T5). J-edited Magnetic Resonance Spectroscopy (MRS) indexed ten metabolites in a prefrontal cortex voxel serving as measures of neuroinflammation, glial activation, oxidative stress, and neuronal and axonal integrity. Positron Emission Tomography (PET) dynamic acquisitions with CT for attenuation correction were conducted at T1, T3, and T5. PET scans indexed translocator protein (TSPO), synaptic vesicular protein 2A (SV2A), and beta-amyloid as measures of microglial activation, synaptic density, and toxic protein aggregation, respectively. PET images were co-registered with MRI structural images. The study was approved by the Walter Reed Army Institute of Research Institutional Review Board. Results Psychomotor Vigilance Test (PVT) performance and self-reported vigor declined across SR and did not return to baseline levels one-month later (F≥3.40, p≤0.03). No significant changes were detected in MRS metabolites, TSPO and beta-amyloid measures, or self-reported sleepiness and mood. Conclusion One week of modest SR was associated with performance degradations that remarkably failed to improve at all from maximum impairment even one month later. Brain health indices did not explain the long-lasting deficits in performance. Preliminary results suggest: (a) SR is associated with behavioral effects that manifest before neurophysiological effects (in which case overt sleepiness may constitute an “early warning system”), and/or (b) the observed performance deficits are not driven by the brain health-related factors examined in this study. Data analyses are ongoing (e.g., SV2A, cortical thickness, etc.). Support (if any) MOMRP