Blue-Light Therapy Strengthens Resting-State Effective Connectivity within Default-Mode Network after Mild TBI

Sahil Bajaj, Adam C Raikes, Adeel Razi, Michael A Miller, William Ds Killgore, Sahil Bajaj, Adam C Raikes, Adeel Razi, Michael A Miller, William Ds Killgore

Abstract

Background: Emerging evidence suggests that post concussive symptoms, including mood changes, may be improved through morning blue-wavelength light therapy (BLT). However, the neurobiological mechanisms underlying these effects remain unknown. We hypothesize that BLT may influence the effective brain connectivity (EC) patterns within the default-mode network (DMN), particularly involving the medial prefrontal cortex (MPFC), which may contribute to improvements in mood.

Methods: Resting-state functional MRI data were collected from 41 healthy-controls (HCs) and 28 individuals with mild traumatic brain injury (mTBI). Individuals with mTBI also underwent a diffusion-weighted imaging scan and were randomly assigned to complete either 6 weeks of daily morning BLT (N = 14) or amber light therapy (ALT; N = 14). Advanced spectral dynamic causal modeling (sDCM) and diffusion MRI connectometry were used to estimate EC patterns and structural connectivity strength within the DMN, respectively.

Results: The sDCM analysis showed dominant connectivity pattern following mTBI (pre-treatment) within the hemisphere contralateral to the one observed for HCs. BLT, but not ALT, resulted in improved directional information flow (ie, EC) from the left lateral parietal cortex (LLPC) to MPFC within the DMN. The improvement in EC from LLPC to MPFC was accompanied by stronger structural connectivity between the 2 areas. For the BLT group, the observed improvements in function and structure were correlated (at a trend level) with changes in self-reported happiness.

Conclusions: The current preliminary findings provide empirical evidence that morning short-wavelength light therapy could be used as a novel alternative rehabilitation technique for mTBI.

Trial registry: The research protocols were registered in the ClinicalTrials.gov database (CT Identifiers NCT01747811 and NCT01721356).

Keywords: Diffusion tensor imaging; effective brain connectivity; light therapy; mood; resting-state fMRI.

Conflict of interest statement

Declaration of conflicting interests:The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

© The Author(s) 2021.

Figures

Figure 1.
Figure 1.
EC for HCs and individuals with mTBI. Here we showed the subject average EC strength (in Hz) of all the connections within the DMN for HCs (A) and post mTBI (B). Positive and negative values here represent the exhibitory and inhibitory connections respectively. In Figure 1C, we showed the comparisons of EC strengths between HCs and post mTBI. The positive values here represent the connections that are stronger in HCs than post mTBI, whereas the negative values here represent the connections that are weaker in HCs than post mTBI. Connections exceeding the Pp of 95% are indicated by “*” in Figure 1(A to C), and are shown in Figure 1D (HCs), 1E (mTBI), and 1F (HCs > mTBI).
Figure 2.
Figure 2.
Comparisons of EC for APost versus APre, BPost versus BPre, and HCs versus APost and BPost: Here we showed the comparisons of EC strengths between APost and APre (A), BPost and BPre (B), HCs and APost (C), and HCs and BPost (D). The positive values (A and B) represent the connections that are stronger in APost and BPost than APre and BPre respectively, whereas the negative values here represent the connections that are weaker in APost and BPost than APre and BPre respectively. Similarly, the positive values for Figure 2C and D represent the connections that are stronger in HCs than APost and BPost respectively, whereas the negative values here represent the connections that are weaker in HCs than APost and BPost respectively. Connections exceeding the Pp of 95% are indicated by “*” (A–D) and are shown in Figures 2E (APost > APre), F (BPost > BPre), G (HCs > APost), and H (HCs > BPost).
Figure 3.
Figure 3.
White matter tractography for ALT and BLT groups. Here we showed subject averaged maps of structural connectivity (in terms of QA) between LLPC and MPFC (A: ALT Group and B: BLT Group).
Figure 4.
Figure 4.
Comparisons of FA, QA, and levels of happiness (HAP). We found that there was no significant difference in FA for tracts connecting LLPC and MPFC for either ALT group (APre vs APost) (paired t-test, P = .760) (A) or BLT group (BPre vs BPost) (paired t-test, P = .662) (B). Also, there was no significant difference in QA for tracts connecting LLPC and MPFC for ALT group (APre vs APost) (paired t-test, P = .468) (C), but there was a clear trend of greater QA for BPost compared to BPre (paired t-test, P = .057) (D). Lastly, we found non-significant reduction in levels of happiness for individuals who used amber-light therapy compared to their pre-treatment condition (paired t-test, P = .170) (E). However, levels of happiness sustained for individuals who used blue-light therapy compared to their pre-treatment condition (paired t-test: P = .924) (F). Error bars here represent “standard error of the mean.”
Figure 5.
Figure 5.
Associations between residualized changes (pre- to post-treatment) in happiness (Res HAP) versus residualized changes (pre-to post-treatment) in EC (Res EC), FA (Res FA), and QA (Res QA). We did not find significant association between residualized changes in happiness scores (Res HAP) and residualized changes in EC (Res EC) from LLPC to MPFC for ALT group (A), but there was a clear tend showing a positive association between Res HAP and Res EC from LLPC to MPFC for BLT group (B). There was no significant association between Res HAP and Res FA for tracts connecting LLPC and MPFC for ALT group (C), but there was significant positive association between Res HAP and Res FA for tracts connecting LLPC and MPFC for BLT group (D). Lastly, there was no significant association between Res HAP and Res QA for tracts connecting LLPC and MPFC for ALT group (E), but there was a clear trend showing a positive association between Res HAP and Res QA for tracts connecting LLPC and MPFC for BLT group (F).
Figure 6.
Figure 6.
Associations between residualized changes (post- to pre-treatment) in EC (Res EC) versus residualized changes (post- to pre-treatment) in FA (Res FA) and QA (Res QA). Neither of the groups ALT (A and B) or BLT (C and D) showed significant association between Res EC from LLPC to MPFC and Res FA (A, C) or Res QA (B, D) for tracts connecting LLPC and MPFC. Overall sample also did not show significant association between Res EC from LLPC to MPFC and either Res FA (E) or Res QA (F) for tracts connecting LLPC and MPFC.

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