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

Adam C Raikes, Natalie S Dailey, Brittany Forbeck, Anna Alkozei, William D S Killgore, Adam C Raikes, Natalie S Dailey, Brittany Forbeck, Anna Alkozei, William D S Killgore

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.

Keywords: concussion; daytime sleepiness; fatigue; functional connectivity; gray matter volume; phototherapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Raikes, Dailey, Forbeck, Alkozei and Killgore.

Figures

Figure 1
Figure 1
Regions of interest (ROIs) exhibiting moderate-to-large baseline adjusted differences in gray matter volume (GMV). Greater GMV was observed following blue light treatment (ROIs in blue) in 15 cortical and subcortical ROIs. Greater GMV was observed following amber light (red ROIs) in two cerebellar regions. All ROIs were false discovery rate corrected p < 0.05. Top Left: Lateral left view, Top Middle: Superior view; Top Right, Lateral right view. Bottom Left, anterior view; Bottom Middle: Inferior view; Bottom Right: Posterior view.
Figure 2
Figure 2
Region-to-region functional connectivity differences following treatment. Blue light treatment was associated with greater functional connectivity in 14 ROI-to-ROI connections linking the visual, default mode, somatomotor, and dorsal attention networks (all FDR p < 0.01).
Figure 3
Figure 3
Regions of interest (ROIs) exhibiting moderate-to-large correlations (|r| > 0.4) between Epworth Sleepiness Scale scores and gray matter volume (GMV) at baseline (left) and at post-treatment (right). Treatment-related decreases in daytime sleepiness were associated with moderate-to-large increases in GMV in 74 ROIs. All ROIs were FDR corrected at p < 0.05.
Figure 4
Figure 4
Edges (region-to-region connections) exhibiting moderate-to-large correlations (|r| > 0.4) between Epworth Sleepiness Scale scores and gray matter volume (GMV) at post-treatment (right). Treatment-related decreases in daytime sleepiness were associated with moderate-to-large increases in functional connectivity in 82 edges and with decreases in functional connectivity in 39 edges. All edgewise correlations were FDR corrected at p < 0.05.

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