Abstract Introduction Light exposure, particularly blue wavelength light, has consistent positive effects on daytime sleepiness following mild traumatic brain injuries (mTBIs). While self-perceived improvements in daytime sleepiness are well-documented, the neurobiological underpinnings are not well understood. The purpose of this study was to localize changes in functional connectivity after daily morning blue light therapy (BLT) and to associate these changes with improvements in post-mTBI daytime sleepiness. Methods 29 individuals with a history of mTBI were randomized to receive either BLT (n=13) or placebo amber light (ALT; n=16). All participants self-reported daytime sleepiness (Epworth Sleepiness Scale (ESS); lower is better) and underwent resting-state functional magnetic resonance imaging at pre- and post-treatment. Whole-brain functional connectivity (FC) was estimated as the correlations between 400 cortical regions of interest (ROIs) assigned to 7 resting-state networks. A two-sample T-test for post-treatment ROI-to-ROI FC identified target connections (FDR corrected p<0.01). Post-treatment ESS scores and FC for these connections were correlated for treatment-related brain-behavior associations (uncorrected p<0.05). Results Lower FC after BLT in 4 ROI-to-ROI connections linking the default mode and visual networks was associated with lower ESS scores. Higher FC after BLT in 9 ROI-to-ROI connections linking attention, cognitive control, and visual networks was also associated with lower ESS scores. Conclusion BLT resulted in decreased self-reported daytime sleepiness, which was associated with decoupling of the default mode and visual networks as well as increased connectivity between and within attention and cognitive control networks, suggesting potentially improved attention to relevant stimuli and cognitive processes and less internal mentation. These associations may contribute to improved alertness, attention, and cognitive performance following a mTBI. Further work is needed to identify the optimal timing and dosage of BLT to maximize these outcomes. Support This study was funded by an award to Dr. Killgore from the US Army Medical Research and Materiel Command (USAMRMC; award number: W81XWH-14-1-0571).
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