Daily Morning Blue Light Therapy for Post-mTBI Sleep Disruption: Effects on Brain Structure and Function

Abstract

Background: Mild traumatic brain injuries (mTBIs) are associated with novel or worsened sleep disruption. Several studies indicate that daily morning blue light therapy (BLT) is effective for reducing post-mTBI daytime sleepiness and fatigue. Studies demonstrating changes in brain structure and function following BLT are limited. The present study's purpose is to identify the effect of daily morning BLT on brain structure and functional connectivity and the association between these changes and self-reported change in post-mTBI daytime sleepiness.Methods: A total of 62 individuals recovering from a mTBI were recruited from two US cities to participate in a double-blind placebo-controlled trial. Eligible individuals were randomly assigned to undergo 6 weeks of 30 min daily morning blue or placebo amber light therapy (ALT). Prior to and following treatment all individuals completed a comprehensive battery that included the Epworth Sleepiness Scale as a measure of self-reported daytime sleepiness. All individuals underwent a multimodal neuroimaging battery that included anatomical and resting-state functional magnetic resonance imaging. Atlas-based regional change in gray matter volume (GMV) and region-to-region functional connectivity from baseline to post-treatment were the primary endpoints for this study.Results: After adjusting for pre-treatment GMV, individuals receiving BLT had greater GMV than those receiving amber light in 15 regions of interest, including the right thalamus and bilateral prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with greater GMV in 74 ROIs, covering many of the same general regions. Likewise, BLT was associated with increased functional connectivity between the thalamus and both prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with increased functional connectivity between attention and cognitive control networks as well as decreased connectivity between visual, motor, and attention networks (all FDR corrected p < 0.05).Conclusions: Following daily morning BLT, moderate to large increases in both gray matter volume and functional connectivity were observed in areas and networks previously associated with both sleep regulation and daytime cognitive function, alertness, and attention. Additionally, these findings were associated with improvements in self-reported daytime sleepiness. Further work is needed to identify the personal characteristics that may selectively identify individuals recovering from a mTBI for whom BLT may be optimally beneficial.

Exposure to Blue Wavelength Light Is Associated With Increases in Bidirectional Amygdala-DLPFC Connectivity at Rest

“…Specifically, studies have shown that acute exposure to blue wavelength or bright broad-spectrum light leads to immediate increases in simple alertness and attention (6, 7) as well as more complex cognitive functions, such as improved working memory performance (8) and short-term verbal memory retention (9). Daily morning blue wavelength light exposure over several weeks has also been used as an effective treatment for seasonal and non-seasonal depression (10)(11)(12)(13), certain sleep disorders, such as delayed sleep phase syndrome (14), and to improve symptoms of fatigue in individuals with neurological conditions, such as acquired brain injury (15)(16)(17)(18). The exact mechanisms underlying these beneficial effects of blue light on emotion and cognition, however, are not well-understood.…”

Treatment with morning blue light increases left amygdala volume and sleep duration among individuals with posttraumatic stress disorder

“…In our prior studies of mTBI, we observed that BLT led to significant improvements in subjective sleep measures, such as daytime sleepiness ( Killgore et al, 2020 ; Raikes et al, 2020 , 2021 ) and subjective sleep quality ( Raikes et al, 2020 ). Overall, we did not find a significant improvement in total sleep quality or nightmare severity here among those who received BLT versus ALT.…”

“…Morning exposure to blue-wavelength light has the effect of phase advancing the rhythm (i.e., shifting the sleep period earlier in the evening), while light in the evening will produce a phase delay (i.e., shifting the sleep period later into the night). Accordingly, we have successfully applied morning blue light treatment (BLT) to improve the sleep and circadian functioning of individuals with mild traumatic brain injury (mTBI) ( Killgore et al, 2020 ; Raikes et al, 2021 ). Using a simple light-box device for 30-min each morning, we were able to shift the circadian rhythm of sleep/wake, improve cognitive performance, and influence brain structure and functional connectivity in these individuals ( Bajaj et al, 2017 , 2021 ; Killgore et al, 2020 ; Raikes et al, 2020 , 2021 ).…”

“…Accordingly, we have successfully applied morning blue light treatment (BLT) to improve the sleep and circadian functioning of individuals with mild traumatic brain injury (mTBI) ( Killgore et al, 2020 ; Raikes et al, 2021 ). Using a simple light-box device for 30-min each morning, we were able to shift the circadian rhythm of sleep/wake, improve cognitive performance, and influence brain structure and functional connectivity in these individuals ( Bajaj et al, 2017 , 2021 ; Killgore et al, 2020 ; Raikes et al, 2020 , 2021 ). Two recent studies have examined the potential for bright light exposure treatment in PTSD, with promising preliminary outcomes suggesting reductions in symptoms ( Zalta et al, 2019 ; Youngstedt et al, 2021 ).…”

Effects of docosahexaenoic acid and eicosapentaoic acid supplementation on white matter integrity after repetitive sub-concussive head impacts during American football: Exploratory neuroimaging findings from a pilot RCT

“…To minimize false positives, the list of edges was initially thresholded to exclude confidence intervals including 0 and then thresholded at an FDR-corrected p < 0.01. This approach has previously been used to identify edge-wise treatment effects on functional connectivity in other populations ( 89 ).…”