0260 Mapping the Brain Around the Clock: Spontaneous Neural Activity Is Influenced by Time Awake and Time of Day

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Abstract Introduction The timing and depth of sleep and wakefulness are influenced by a homeostatic process that reflects accumulating sleep pressure over time (Process S) and a circadian process (Process C) that produces an oscillating diurnal rhythm of alertness. Together, these two processes influence an individual’s propensity toward sleep or alertness throughout the day, but their neurobiological mechanisms remain to be fully elucidated. Here, we obtained repeated resting state fMRI scans every 6 hours during 39 hours of continuous sleep deprivation and mapped the changes in cerebral Amplitude of Low Frequency Fluctuations (ALFF), a measure of spontaneous neural activity. Methods Twenty healthy adults (9 female; age=23.6, SD=4.7 years) underwent a night of normal sleep in the lab followed by a 39-hour period of continuous wakefulness. Beginning at 0900, rsFMRI scans were collected at 3T every 6-hours. Data were preprocessed and analyzed using standard pipelines using CONN v22.v2407. Spontaneous neural activity was identified using ALFF at each timepoint. Two GLMs were calculated: 1) the linear change in ALFF across sessions, controlling for the circadian rhythm (based on a cosine function model), and 2) the circadian rhythm, controlling for the linear effects of time awake. Results There was a significant (p<.05, FDR corrected) linear effect of sleep deprivation (Process S), showing increasing ALFF within primary sensory and motor regions (e.g., precentral/postcentral gyri; superior temporal gyrus, occipital cortex) and thalamus, basal ganglia, amygdala, and medial orbitofrontal cortex). After removing the effect of sleep deprivation, ALFF showed significant (p<.05, FDR corrected) circadian modulation (Process C) primarily within higher order cortex including dorsolateral prefrontal, ventromedial prefrontal, lateral orbitofrontal, inferior parietal cortices, and the temporal poles. Conclusion This is the first study to demonstrate changes in spontaneous neural activity over the course of sleep deprivation. There was a linear increase in ALFF within frequently used regions of the sensorimotor cortex, consistent with the tenets of the synaptic homeostasis hypothesis (SHY), which posits a buildup of synaptic potentiation with increasing time awake. Higher order regions involved in executive functioning showed a circadian pattern of spontaneous neural activity. These findings provide a neurobiological basis for models of cognitive fatigue during sleep loss. Support (if any) W911NF2210223-SUBK00016417

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