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

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).

Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial.

BACKGROUND: Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine. MATERIAL AND METHODS: We recruited (29 total) patients, of whom seven had episodic migraine and 22 had chronic migraine. We used a one-way cross-over design consisting of exposure for 1-2 hours daily to white light emitting diodes for 10 weeks, followed by a 2-week washout period followed by exposure for 1-2 hours daily to green light emitting diodes for 10 weeks. Patients were allowed to continue current therapies and to initiate new treatments as directed by their physicians. Outcomes consisted of patient-reported surveys. The primary outcome measure was the number of headache days per month. Secondary outcome measures included patient-reported changes in the intensity and frequency of the headaches over a two-week period and other quality of life measures including ability to fall and stay asleep, and ability to perform work. Changes in pain medications were obtained to assess potential reduction. RESULTS: When seven episodic migraine and 22 chronic migraine patients were analyzed as separate cohorts, white light emitting diodes produced no significant change in headache days in either episodic migraine or chronic migraine patients. Combining data from the episodic migraine and chronic migraine groups showed that white light emitting diodes produced a small, but statistically significant reduction in headache days from (days ± SEM) 18.2 ± 1.8 to 16.5 ± 2.01 days. Green light emitting diodes resulted in a significant decrease in headache days from 7.9 ± 1.6 to 2.4 ± 1.1 and from 22.3 ± 1.2 to 9.4 ± 1.6 in episodic migraine and chronic migraine patients, respectively. While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes. Conclusions regarding pain medications reduction with green light emitting diode exposure were not possible. No side effects of light therapy were reported. None of the patients in the study reported initiation of new therapies. DISCUSSION: Green light emitting diodes significantly reduced the number of headache days in people with episodic migraine or chronic migraine. Additionally, green light emitting diodes significantly improved multiple secondary outcome measures including quality of life and intensity and duration of the headache attacks. As no adverse events were reported, green light emitting diodes may provide a treatment option for those patients who prefer non-pharmacological therapies or may be considered in complementing other treatment strategies. Limitations of this study are the small number of patients evaluated. The positive data obtained support implementation of larger clinical trials to determine possible effects of green light emitting diode therapy.This study is registered with clinicaltrials.gov under NCT03677206.

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

Light affects almost all aspects of human physiological functioning, including circadian rhythms, sleep-wake regulation, alertness, cognition and mood. We review the existing relevant literature on the effects of various wavelengths of light on these major domains, particularly as they pertain to recovery from mild traumatic brain injuries. Evidence suggests that light, particularly in the blue wavelengths, has powerful alerting, cognitive and circadian phase shifting properties that could be useful for treatment. Other wavelengths, such as red and green may also have important effects that, if targeted appropriately, might also be useful for facilitating recovery. Despite the known effects of light, more research is needed. We recommend a personalized medicine approach to the use of light therapy as an adjunctive treatment for patients recovering from mild traumatic brain injury.

Chronic sleep restriction affects the association between implicit bias and explicit social decision making.

OBJECTIVES: Previous work suggests that sleep restriction (SR) reduces cognitive control and may increase negative implicit biases. Here we investigated whether SR might influence decision making on a social-evaluative task where individuals had to make judgments of threat based on facial photographs. Furthermore, we investigated the effect of changes in negative implicit biases as a result of sleep restriction on this decision-making task. DESIGN: Fourteen healthy adults underwent two 3-week counterbalanced in-laboratory stays (chronic SR and control sleep [CS] conditions). Participants completed the Arab Muslim Names implicit association test (a measure of implicit bias/attitudes toward Arab Muslims) and the Karolinska Airport Task (a measure of explicit decision making). The Karolinska Airport Task requires participants to judge the potential dangerousness of individuals based on facial photographs. RESULTS: After SR, participants were more likely to deem individuals with less positive and more negative facial features as dangerous than after CS. In addition, after SR, those participants showing higher negative implicit bias toward Arab Muslims tended to consider as more dangerous individuals with more quintessentially untrustworthy facial features (r = 0.76, P = .007), whereas this relationship was nonsignificant after CS (r = 0.33, P = .28). CONCLUSIONS: These findings show not only that SR may increase implicit biases against a particular minority group but that SR also modifies how individuals make explicit decisions about another's trustworthiness based on facial features. These findings may have important implications for many occupations where workers who are routinely restricted of sleep are also responsible for making judgments about other people's trustworthiness (eg, police, security, military personnel).

Brain white matter integrity and association with age at onset in pediatric obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and debilitating neuropsychiatric illness thought to involve abnormal connectivity of widespread brain networks, including frontal-striatal-thalamic circuits. At least half of OCD cases arise in childhood and their underlying neuropathology may differ at least in part from that of adult-onset OCD. Yet, only a few studies have examined brain white matter (WM) integrity in childhood-onset OCD using diffusion tensor imaging (DTI), and none have examined potential associations with age at onset. RESULTS: In this study, 17 youth with OCD and 19 healthy control subjects, ages 10 to 19 years, underwent DTI on a 3T Siemens scanner. DSM-IV diagnoses were established with standardized interviews, and OCD symptom severity was evaluated using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Voxel-wise analyses were conducted on data processed with tract-based spatial statistics (TBSS) to derive measures of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). OCD patients had significantly lower FA in seven WM clusters, with over 80% of significant voxels in bilateral frontal cortex and corpus callosum (CC). There were no regions of significantly higher FA in patients compared with controls. Patients also had significantly higher RD in right frontal cortex and right body of the CC. Earlier age at onset of OCD correlated significantly with lower FA in the right thalamus and with higher RD in the right CC. FA and RD were not significantly associated with symptom severity. CONCLUSIONS: These findings point to compromised WM integrity and reduced myelination in some brain regions of children with OCD, particularly the CC and fiber tracts that connect the frontal lobes to widespread cortical and subcortical targets. They also suggest that age at onset may be a moderator of some of the WM changes in pediatric OCD.