Potential for the development of light therapies in mild traumatic brain injury

Raikes, Adam C.; Killgore, William D.S.

doi:10.2217/cnc-2018-0006

Cited by 10 publications

(7 citation statements)

References 198 publications

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“…More recent work has identified a role for light in improving depression, with animal models pointing to mechanisms related to direct neuronal projections from non-vision-forming pathways to limbic regions of the brain [ 30 , 31 , 68 , 69 ]. Few studies have found morning bight light therapy effects on sleep directly, although this has not been studied to the extent of the circadian and mood fields [ 32 , 70 ]. Some possibilities include light may have direct effects on brain regions involved in sleep (e.g., direct inhibition of the ventrolateral preoptic area), or maintenance of alertness, through the same melanopsin-dependent, non-image forming pathways as circadian rhythms and mood [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

et al. 2022

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Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.

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Section: Discussionmentioning

confidence: 99%

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

et al. 2022

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“…Consequently, precisely timed BLT has been proposed as one possible, safe, and non-pharmacological way of improving sleep and post-concussive symptoms among individuals with a TBI. 18 , 21 Prior work has shown that BLT appears to be effective at improving mood and reducing fatigue and daytime sleepiness, 18 , 22 and at changing white-matter compactness within specific areas. 23 Our recent work suggests that morning BLT may also have wide ranging effects including altered circadian timing of sleep, as well as changes in thalamic volume, functional connectivity, and white matter structural connectivity, which are in turn, correlated with improvements in cognitive abilities among those with mTBI.…”

Section: Introductionmentioning

confidence: 99%

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

Bajaj

Raikes

Razi

et al. 2021

J Cent Nerv Syst Dis

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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).

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“…Circadian rhythm is regulated primarily in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and can affect sleep, wakefulness, and all physiologic functions that vary across the day, including melatonin secretion [ 45 ]. TBI-induced circadian disruption may be caused by many brain functions, e.g., circadian hormone regulation and neurotransmitter functions [ 46 ]. Neuroinflammation due to brain injury may also initiate a prolonged immune response that changes the expression of clock genes in the SCN and circadian function [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and acceptability of blue-wavelength light therapy for post-TBI behavioral symptoms: A systematic review and meta-analysis of randomized controlled trials

et al. 2022

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Objective Behavioral symptoms are common after traumatic brain injury (TBI), but their treatments remain unsatisfactory. This systematic review and meta-analysis compared the efficacy and acceptability between blue-wavelength light therapy (BWLT) and long-wavelength/no light therapy (LW/NLT) for post-TBI sleepiness, sleep disturbance, depressive symptoms, and fatigue. Methods This study included randomized controlled trials comparing the effects of BWLT and LW/NLT on post-TBI sleepiness, sleep disturbance, depression, or fatigue. We searched Pubmed, Embase, CINAHL, and Cochrane Central Register of Controlled of Trials on April 13, 2022. The revised tool for assessing the risk of bias in randomized trials was applied. We performed a frequentist pairwise meta-analysis using a random-effects model. Results Of 233 retrieved records, six trials (N = 278) were included in this meta-analysis. TBIs ranged from mild to severe, and the interventions were administered for a median of 35 days. Most trials delivered light therapy via lightboxes. Three trials had a high risk of bias. BWLT was significantly superior to LW/NLT in reducing sleep disturbance (5 trials; SMD = -0.63; 95% CI = -1.21 to -0.05; p = 0.03; I2 = 61%) and depressive symptoms (4 trials; SMD = -1.00; 95% CI = -1.62 to -0.38; p < 0.01; I2 = 56%). There were trends that BWLT was superior to LW/NLT in reducing sleepiness (6 trials; SMD = -0.92; 95% CI = -1.84 to 0.00; p = 0.05; I2 = 88%) and fatigue (4 trials; SMD = -1.44; 95% CI = -2.95 to 0.08; p = 0.06; I2 = 91%). All-cause dropout rates were not significantly different between groups. Conclusion Limited and heterogenous evidence suggests that short-term BWLT is well accepted, has a large treatment effect on post-TBI depressive symptoms, and may have a moderate treatment effect on post-TBI sleep disturbance.

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Potential for the development of light therapies in mild traumatic brain injury

Cited by 10 publications

References 198 publications

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial

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

Efficacy and acceptability of blue-wavelength light therapy for post-TBI behavioral symptoms: A systematic review and meta-analysis of randomized controlled trials

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