Sleep fragmentation intensifies sleep architecture disruption and fatigue after traumatic brain injury

Sleep/wake disturbances (SWDs) are common following traumatic brain injury (TBI) and can have deleterious impacts on recovery. Regulation of the time spent in non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) is a complex process that is influenced by both biological and environmental factors. We hypothesize that extrinsic factors such as environmental stimuli amplify SWDs after brain injury. Here, we examine the acute, sub-acute, and chronic effects of TBI with and without mechanical sleep fragmentation (SF) on sleep/wake time-in-state and architecture in established mouse models. SF after TBI advances cage activity deficits compared to TBI alone. Additionally, cosinor analysis of activity revealed that TBI and SF independently induce fatigue, but when combined, fatigue was exacerbated and associated with dysfunctional control of rest-activity diurnal profiles. Overall, TBI decreased time spent in REMS acutely with only modest effects on time spent in wakefulness and NREMS chronically. SF persistently reduced REMS with reorganization of NREMS bouts. Shams compensated for decreased time spent in REMS following SF, but this did not occur in TBI SF mice. Spectral analysis was used to assess sleep microarchitecture. TBI blunted NREM delta power, and this was exacerbated by SF after TBI. Additionally, REM beta and gamma power spectra were further decreased due to the combination of TBI and SF. Together, these data highlight the vulnerability in NREMS and REMS following TBI as well as the critical role of environmental stimuli in exaggerating rest-activity impairments and SWDs over time. • Environmental stimuli that fragment sleep worsen sleep/wake behavior • Sleep fragmentation intensifies fatigue after traumatic brain injury • Post-injury sleep fragmentation disrupts vigilance state and sleep bout structure • Sleep fragmentation after brain injury decreases non rapid eye movement delta power • Detailed sleep metrics offer novel insight to recovery after brain injury