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Introduction Sleep deprivation and circadian disruptions impair brain function and cognitive performance, but few studies have examined the effect of sleep inconsistency. Here we investigated how inconsistent sleep duration and sleep timing between weekend (WE) and weekdays (WD) affected behavior and brain function during task and at rest in 56 (30 female) healthy human subjects. Methods WE-WD differences in sleep duration and sleep midpoint were calculated using one-week actigraphy data. All subjects underwent 3Tesla BOLD-fMRI to measure brain activity during a visual attention task (VAT) and in resting-state condition. Results We found that WE-WD inconsistency of sleep duration and sleep midpoint were uncorrelated with each other (r=.08, p=.58) and influenced behavior and brain function differently. Our healthy subjects showed relatively small WE-WD differences (WE-WD: 0.59 hours) and benefited from longer WE catch-up sleep, which was associated with better attentional performance (3-ball: β=.30, t=2.35, p = .023; 4-ball: β=.30, t=2.21, p =.032) and greater deactivation of the default mode network (DMN) during VAT (p &amp;lt; .05, cluster-corrected) and greater resting-state functional connectivity (RSFC) between anterior DMN and occipital cortex (p &amp;lt; .01, cluster-corrected). In contrast, inconsistent WE-WD sleep midpoint (WE-WD: 1.11 hours) was associated with worse performance (4-ball: β=-.33, t=-2.42, p = .020) and with lower occipital activation during VAT and lower RSFC within the DMN. Conclusion Our results document the importance of consistent sleep timing for brain function in particular of the DMN, and provide evidence of the benefits of WE catch-up sleep in healthy adults. Support This work was supported by NIAAA IRP (Y01AA3009). R.Z. received research fellowship from German research foundation (DFG).

0166 Sleep Inconsistency Related Changes in Brain Function During Task and Rest