Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration.

Astrocytes provide key neuronal support, and their phenotypic transformation is implicated in neurodegenerative diseases. Metabolically, astrocytes possess low mitochondrial oxidative phosphorylation (OxPhos) activity, but its pathophysiological role in neurodegeneration remains unclear. Here, we show that the brain critically depends on astrocytic OxPhos to degrade fatty acids (FAs) and maintain lipid homeostasis. Aberrant astrocytic OxPhos induces lipid droplet (LD) accumulation followed by neurodegeneration that recapitulates key features of Alzheimer's disease (AD), including synaptic loss, neuroinflammation, demyelination and cognitive impairment. Mechanistically, when FA load overwhelms astrocytic OxPhos capacity, elevated acetyl-CoA levels induce astrocyte reactivity by enhancing STAT3 acetylation and activation. Intercellularly, lipid-laden reactive astrocytes stimulate neuronal FA oxidation and oxidative stress, activate microglia through IL-3 signalling, and inhibit the biosynthesis of FAs and phospholipids required for myelin replenishment. Along with LD accumulation and impaired FA degradation manifested in an AD mouse model, we reveal a lipid-centric, AD-resembling mechanism by which astrocytic mitochondrial dysfunction progressively induces neuroinflammation and neurodegeneration.

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.

Context: Repetitive sub-concussive head impacts (RSHIs) are common in American football and result in changes to the microstructural integrity of white matter. Both docosahexaenoic acid (DHA) and eicosapentaoic acid (EPA) supplementation exerted neuroprotective effects against RSHIs in animal models and in a prior study in football players supplemented with DHA alone. Objective: Here, we present exploratory neuroimaging outcomes from a randomized controlled trial of DHA + EPA supplementation in American football players. We hypothesized that supplementation would result in less white matter integrity loss on diffusion weighted imaging over the season. Design setting participants: We conducted a double-blind placebo-controlled trial in 38 American football players between June 2019 and January 2020. Intervention: Participants were randomized to the treatment (2.442 g/day DHA and 1.020 g/day EPA) or placebo group for five times-per-week supplementation for 7 months. Of these, 27 participants were included in the neuroimaging data analysis (n = 16 placebo; n = 11 DHA + EPA). Exploratory outcome measures: Changes in white matter integrity were quantified using both voxelwise diffusion kurtosis scalars and deterministic tractography at baseline and end of season. Additional neuroimaging outcomes included changes in regional gray matter volume as well as intra-regional, edge-wise, and network level functional connectivity. Serum neurofilament light (NfL) provided a peripheral biomarker of axonal damage. Results: No voxel-wise between-group differences were identified on diffusion tensor metrics. Deterministic tractography using quantitative anisotropy (QA) revealed increased structural connectivity in ascending corticostriatal fibers and decreased connectivity in long association and commissural fibers in the DHA+EPA group compared to the placebo group. Serum NfL increases were correlated with increased mean (ρ = 0.47), axial (ρ = 0.44), and radial (ρ = 0.51) diffusivity and decreased QA (ρ = -0.52) in the corpus callosum and bilateral corona radiata irrespective of treatment group. DHA + EPA supplementation did preserve default mode/frontoparietal control network connectivity (g = 0.96, p = 0.024). Conclusions: These exploratory findings did not provide strong evidence that DHA + EPA prevented or protected against axonal damage as quantified via neuroimaging. Neuroprotective effects on functional connectivity were observed despite white matter damage. Further studies with larger samples are needed to fully establish the relationship between omega-3 supplementation, RSHIs, and neuroimaging biomarkers. Trial registration: ClinicalTrials.gov-NCT04796207.

Contributions of sex and genotype to exploratory behavior differences in an aged humanized APOE mouse model of late-onset Alzheimer's disease.

Age, genetics, and chromosomal sex have been identified as critical risk factors for late-onset Alzheimer's disease (LOAD). The predominant genetic risk factor for LOAD is the apolipoprotein E ε4 allele (APOE4), and the prevalence of LOAD is higher in females. However, the translational validity of APOE4 mouse models for AD-related cognitive impairment remains to be fully determined. The present study investigated the role of both sex and genotype on learning and memory in aged, humanized APOE knock-in mice. Aged (23.27 mo ± 1.21 mo; 39 male/37 female) APOE3/3, APOE3/4, and APOE4/4 mice performed a novel object recognition (NOR) assay. Task-related metrics were analyzed using two-way sex by genotype ANOVAs. Sex differences were more prominent relative to APOE genotype. Prior to NOR, female mice exhibited thigmotaxic center zone avoidance during the open field task relative to males, regardless of genotype. Within object familiarization and NOR tasks, females had greater object interaction and locomotion. Interestingly, only APOE4/4 females on average recognized the novel object. These results suggest that APOE4, although strongly related to LOAD pathogenesis, does not drive cognitive decline in the absence of other risk factors even in very aged mice. Chromosomal sex is a key driver of behavioral phenotypes and thus is a critical variable for translatability of interventions designed to preserve learning and memory in animal models of LOAD. Last, there was a very high degree of variability in behavioral performance across APOE genotypes. A cluster analysis of the behavioral data revealed a low-activity and a high-activity cluster. APOE4 carriers were overrepresented in the low-activity cluster, while male:female distributions did not differ. Collectively, the behavioral data indicate that chromosomal sex has the greatest impact on behavioral phenotype, and APOE4 carrier status may confer greater risk for cognitive decline in some animals.

Effects of Fish Oil on Biomarkers of Axonal Injury and Inflammation in American Football Players: A Placebo-Controlled Randomized Controlled Trial.

There are limited studies on neuroprotection from repeated subconcussive head impacts (RSHI) following docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) supplementation in contact sports athletes. We performed a randomized, placebo-controlled, double-blinded, parallel-group design trial to determine the impact of 26 weeks of DHA+EPA supplementation (n = 12) vs. placebo (high-oleic safflower oil) (n = 17) on serum concentrations of neurofilament light (NfL), a biomarker of axonal injury, and inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a)) in National Collegiate Athletic Association Division I American football athletes. DHA+EPA supplementation increased (p < 0.01) plasma DHA and EPA concentrations throughout the treatment period. NfL concentrations increased from baseline to week 26 in both groups (treatment (<0.001); placebo (p < 0.05)), with starting players (vs. non-starters) showing significant higher circulating concentrations at week 26 (p < 0.01). Fish oil (DHA+EPA) supplementation did not mitigate the adverse effects of RSHI, as measured by NfL levels; however, participants with the highest plasma DHA+EPA concentrations tended to have lower NfL levels. DHA+EPA supplementation had no effects on inflammatory cytokine levels at any of the timepoints tested. These findings emphasize the need for effective strategies to protect American football participants from the effects of RSHI.

Exploratory imaging outcomes of a phase 1b/2a clinical trial of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: Structural effects and functional connectivity outcomes.

Introduction: Allopregnanolone (ALLO), an endogenous neurosteroid, promoted neurogenesis and oligogenesis and restored cognitive function in animal models of Alzheimer's disease (AD). Based on these discovery research findings, we conducted a randomized-controlled phase 1b/2a multiple ascending dose trial of ALLO in persons with early AD (NCT02221622) to assess safety, tolerability, and pharmacokinetics. Exploratory imaging outcomes to determine whether ALLO impacted hippocampal structure, white matter integrity, and functional connectivity are reported. Methods: Twenty-four individuals participated in the trial (n = 6 placebo; n = 18 ALLO) and underwent brain magnetic resonance imaging (MRI) before and after 12 weeks of treatment. Hippocampal atrophy rate was determined from volumetric MRI, computed as rate of change, and qualitatively assessed between ALLO and placebo sex, apolipoprotein E (APOE) ε4 allele, and ALLO dose subgroups. White matter microstructural integrity was compared between placebo and ALLO using fractional and quantitative anisotropy (QA). Changes in local, inter-regional, and network-level functional connectivity were also compared between groups using resting-state functional MRI. Results: Rate of decline in hippocampal volume was slowed, and in some cases reversed, in the ALLO group compared to placebo. Gain of hippocampal volume was evident in APOE ε4 carriers (range: 0.6% to 7.8% increased hippocampal volume). Multiple measures of white matter integrity indicated evidence of preserved or improved integrity. ALLO significantly increased fractional anisotropy (FA) in 690 of 690 and QA in 1416 of 1888 fiber tracts, located primarily in the corpus callosum, bilateral thalamic radiations, and bilateral corticospinal tracts. Consistent with structural changes, ALLO strengthened local, inter-regional, and network level functional connectivity in AD-vulnerable regions, including the precuneus and posterior cingulate, and network connections between the default mode network and limbic system. Discussion: Indicators of regeneration from previous preclinical studies and these exploratory MRI-based outcomes from this phase 1b/2a clinical cohort support advancement to a phase 2 proof-of-concept efficacy clinical trial of ALLO as a regenerative therapeutic for mild AD (REGEN-BRAIN study; NCT04838301).

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).

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

Blue wavelength light has been used successfully as a treatment method for certain mood disorders, but, the underlying mechanisms behind the mood enhancing effects of light remain poorly understood. We investigated the effects of a single dose of 30 min of blue wavelength light (n = 17) vs. amber wavelength light (n = 12) exposure in a sample of healthy adults on subsequent resting-state functional and directed connectivity, and associations with changes in state affect. Individuals who received blue vs. amber wavelength light showed greater positive connectivity between the right amygdala and a region within the left dorsolateral prefrontal cortex (DLPFC). In addition, using granger causality, the findings showed that individuals who received blue wavelength light displayed greater bidirectional information flow between these two regions relative to amber light. Furthermore, the strength of amygdala-DLPFC functional connectivity was associated with greater decreases in negative mood for the blue, but not the amber light condition. Blue light exposure may positively influence mood by modulating greater information flow between the amygdala and the DLPFC, which may result in greater engagement of cognitive control strategies that are needed to perceive and regulate arousal and mood.

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

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.

Blue light exposure enhances neural efficiency of the task positive network during a cognitive interference task.

Exposure to light, particularly blue-wavelength light, has been shown to acutely increase brain activation, alertness, and some elementary aspects of cognitive performance such as working memory and emotional anticipation. Whether blue light exposure can have effects on brain activation and performance during more complex cognitive control tasks up to 30 min after light cessation is unknown. In a sample of 32 healthy adults, we examined the effects of a 30 min exposure to either blue (n = 16) or amber control (n = 16) light on subsequent brain activation and performance during the Multi-Source Interference Task (MSIT) measured a half-hour after light exposure. Performance on the MSIT did not differ between the blue and amber conditions. However, brain activation within the task positive network (TPN) to the interference condition was significantly lower in the blue relative to the amber condition, while no group differences were observed for suppression of the default mode network (DMN). These findings suggest that, compared to control, a single exposure to blue light was associated with enhanced neural efficiency, as demonstrated by reduced TPN activation to achieve the same level of performance. Blue light may be an effective method for optimizing neurocognitive performance under some conditions.

Daily Morning Blue Light Therapy Improves Daytime Sleepiness, Sleep Quality, and Quality of Life Following a Mild Traumatic Brain Injury.

OBJECTIVE: Identify the treatment effects of 6 weeks of daily 30-minute sessions of morning blue light therapy compared with placebo amber light therapy in the treatment of sleep disruption following mild traumatic brain injury. DESIGN: Placebo-controlled randomized trial. PARTICIPANTS: Adults aged 18 to 45 years with a mild traumatic brain injury within the past 18 months (n = 35). MAIN OUTCOME MEASURES: Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory II, Rivermead Post-concussion Symptom Questionnaire, Functional Outcomes of Sleep Questionnaire, and actigraphy-derived sleep measures. RESULTS: Following treatment, moderate to large improvements were observed with individuals in the blue light therapy group reporting lower Epworth Sleepiness Scale (Hedges' g = 0.882), Beck Depression Inventory II (g = 0.684), Rivermead Post-concussion Symptom Questionnaire chronic (g = 0.611), and somatic (g = 0.597) symptoms, and experiencing lower normalized wake after sleep onset (g = 0.667) than those in the amber light therapy group. In addition, individuals in the blue light therapy group experienced greater total sleep time (g = 0.529) and reported improved Functional Outcomes of Sleep Questionnaire scores (g = 0.929) than those in the amber light therapy group. CONCLUSION: Daytime sleepiness, fatigue, and sleep disruption are common following a mild traumatic brain injury. These findings further substantiate blue light therapy as a promising nonpharmacological approach to improve these sleep-related complaints with the added benefit of improved postconcussion symptoms and depression severity.

Gender differences in nonlinear motor performance following concussion.

PURPOSE: To quantify differences in nonlinear aspects of performance on a seated visual-motor tracking task between clinically asymptomatic males and females with and without a self-reported mild traumatic brain injury history. METHODS: Seventy-three individuals with a self-reported concussion history (age: 21.40 ± 2.25 years, mean ± SD) and 75 without completed the visual-motor tracking task (age: 21.50 ± 2.00 years). Participants pressed an index finger against a force sensor, tracing a line across a computer screen (visual-motor tracking). The produced signal's root-mean-square error (RMSE), sample entropy (SampEn, a measure of regularity), and average power (AvP) between 0 and 12 Hz were calculated. RESULTS: Males with a history of 0 or 1 concussion had greater RMSE (worse performance) than females with 0 (p < 0.0001) and 1 concussion (p = 0.052). Additionally, females with 2+ concussions exhibited lower SampEn than females with no history (p = 0.001) or a history of 1 concussion (p = 0.026). Finally, females with 2+ concussions had lower 8-12 Hz AvP than males with 2+ concussions (p = 0.031). Few differences were observed in the male participants. CONCLUSION: Females with a self-reported history of multiple concussions exhibited lower SampEn in the visual-motor tracking-task force output structure as compared to those with no reported history of concussion and their male counterparts. Lower SampEn and lower power between 8 and 12 Hz indicated persistent impairment in visual processing and feed-forward or predictive motor control systems.

The Role of Prefrontal Cortical Surface Area and Volume in Preclinical Suicidal Ideation in a Non-Clinical Sample.

Suicidal ideation (SUI) can occur in the absence of concomitant psychiatric diagnoses, and even normal levels can be problematic among individuals experiencing excess stress or lack of social support. The objective of this study was to investigate the neuroanatomical basis of SUI in non-clinical human populations who are within the normal limits of SUI, after accounting for elevated stress and perceived lack of social support. Neuroanatomical data were collected from 55 healthy individuals (mean age 30.9 ± 8.1 years, 27 females) whose depression severity levels were below the Diagnostic and Statistical Manual of Mental Disorders criteria. Measures of SUI, aggression, stress, non-support, and treatment rejection were collected from the treatment-consideration scales (TCS) of the Personality Assessment Inventory (PAI). Correlations between standardized SUI scores and three brain morphometry measures, including vertex wise cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV), were estimated for each participant, controlling for age, sex, intracranial volume, and the remaining TCS measures. We observed a significant negative association between scores on SUI and both CSA and CV (cluster-forming threshold of p < 0.005, clusterwise threshold of p < 0.05, FDR corrected for multiple comparisons) within the left rostral middle frontal gyrus. Our findings suggest that greater CSA and CV within the dorsolateral prefrontal cortex are associated with reduced SUI in a non-clinical population with mild levels of stress and perceived lack of social support. Because the dorsolateral prefrontal cortex has been broadly linked to cognitive reappraisal, self-critical thoughts, and emotional regulation, greater CSA and CV within these regions may lead to better mental health by protecting healthy individuals from engaging in SUI during periods of stress and perceived insufficient social support. As our data consisted of only healthy individuals with non-clinical levels of SUI, further investigation will be necessary to explore the neural basis of SUI in populations who may be at greater risk of future suicidal behavior.

Ability-Based Emotional Intelligence Is Associated With Greater Cardiac Vagal Control and Reactivity.

Several distinct models of emotional intelligence (EI) have been developed over the past two decades. The ability model conceptualizes EI as a narrow set of interconnected, objectively measured, cognitive-emotional abilities, including the ability to perceive, manage, facilitate, and understand the emotions of the self and others. By contrast, trait or mixed models focus on subjective ratings of emotional/social competencies. Theoretically, EI is associated with neurobiological processes involved in emotional regulation and reactivity. The neurovisceral integration (NVI) model proposes a positive relationship between cardiac vagal control (CVC) and cognitive-emotional abilities similar to those encompassed by EI. The current study examined the association between CVC and EI. Because ability EI is directly tied to actual performance on emotional tasks, we hypothesized that individuals with higher ability-based EI scores would show greater levels of CVC at rest, and in response to a stressful task. Because mixed-models of EI are not linked directly to observable emotional behavior, we predicted no association with CVC. Consistent with expectations, individuals with higher levels of ability EI, but not mixed EI, had higher levels of CVC. We also found that individuals with greater levels of CVC who demonstrated reactivity to a stress induction had significantly higher EI compared to individuals that did not respond to the stress induction. Our findings support the theoretically expected overlap between constructs within the NVI model and ability EI model, however, the observed effect size was small, and the associations between EI and CVC should not be taken to indicate a causal connection. Results suggest that variance in the ability to understand emotional processes in oneself and to reason about one's visceral experience may facilitate better CVC. Future work manipulating either CVC or EI may prove informative in teasing apart the causal role driving their observed relationship.

Insomnia and daytime sleepiness: risk factors for sports-related concussion.

OBJECTIVE/BACKGROUND: Poor quality and inadequate sleep are associated with impaired cognitive, motor, and behavioral components of sport performance and increased injury risk. While prior work identifies sports-related concussions as predisposing factors for poor sleep, the role of sleep as a sports-related concussion risk factor is unknown. The purpose of this study was to quantify the effect of poor sleep quality and insomnia symptoms on future sports-related concussion risk. PATIENTS/METHODS: In this study, 190 NCAA Division-1 athletes completed a survey battery, including the Insomnia Severity Index (ISI) and National Health and Nutrition Examination Survey (NHANES) Sleep module. Univariate risk ratios for future sports-related concussions were computed with ISI and NHANES sleepiness scores as independent predictors. An additional multiple logistic regression model including sport, sports-related concussion history, and significant univariate predictors jointly assessed the odds of sustaining a concussion. RESULTS: Clinically moderate-to-severe insomnia severity (RR = 3.13, 95% CI: 1.320-7.424, p = 0.015) and excessive daytime sleepiness two or more times per month (RR = 2.856, 95% CI: 0.681-11.977, p = 0.037) increased concussion risk. These variables remained significant and comparable in magnitude in a multivariate model adjusted for sport participation. CONCLUSION: Insomnia and daytime sleepiness are independently associated with increased sports-related concussion risk. More completely identifying bidirectional relationships between concussions and sleep requires further research. Clinicians and athletes should be cognizant of this relationship and take proactive measures - including assessing and treating sleep-disordered breathing, limiting insomnia risk factors, improving sleep hygiene, and developing daytime sleepiness management strategies - to reduce sports-related concussion risk and support overall athletic performance.

Evidence of actigraphic and subjective sleep disruption following mild traumatic brain injury.

OBJECTIVE/BACKGROUND: Mild traumatic brain injuries (mTBI) are frequently associated with long-term, self-reported sleep disruption. Objective corroboration of these self-reports is sparse and limited by small sample sizes. The purpose of this study was to report on actigraphically-measured sleep outcomes in individuals with and without a history of recent mTBI in two U.S. cities (Boston, MA and Tucson, AZ). PATIENTS/METHODS: Fifty-eight individuals with a recent (within 18 months) mTBI and 35 individuals with no prior mTBI history were recruited for one of four studies across two sites. Participants completed a minimum of one week of actigraphy. Additionally, mTBI participants self-reported daytime sleepiness, sleep disruption, and functional sleep-related outcomes. RESULTS: In Boston, mTBI participants obtained less average sleep with shorter sleep onset latencies (SOL) than healthy individuals. In Tucson, mTBI participants had greater SOL and less night-to-night SOL variability compared to healthy individuals. Across mTBI participants, SOL was shorter and night-to-night SOL variability was greater in Boston than Tucson. Sleep efficiency (SE) variability was greater in Tucson than Boston across both groups. Only SOL variability was significantly associated with daytime sleepiness (r = 0.274) in the mTBI group after controlling for location. CONCLUSION: Sleep quality, SOL and SE variability, are likely affected by mTBIs. Between-group differences in each site existed but went in opposite directions. These findings suggest the possibility of multiple, rather than a singular, profiles of sleep disruption following mTBI. Precision medicine models are warranted to determine whether multiple sleep disruption profiles do indeed exist following mTBI and the predisposing conditions that contribute to an individual's experience of sleep disruption.

Water Immersion Affects Episodic Memory and Postural Control in Healthy Older Adults.

BACKGROUND AND PURPOSE: Previous research has reported that younger adults make fewer cognitive errors on an auditory vigilance task while in chest-deep water compared with on land. The purpose of this study was to extend this previous work to include older adults and to examine the effect of environment (water vs land) on linear and nonlinear measures of postural control under single- and dual-task conditions. METHODS: Twenty-one older adult participants (age = 71.6 ± 8.34 years) performed a cognitive (auditory vigilance) and motor (standing balance) task separately and simultaneously on land and in chest-deep water. Listening errors (n = count) from the auditory vigilance test and sample entropy (SampEn), center of pressure area, and velocity for the balance test served as dependent measures. Environment (land vs water) and task (single vs dual) comparisons were made with a Wilcoxon matched-pair test. RESULTS: Listening errors were 111% greater during land than during water environments (single-task = 4.0 ± 3.5 vs 1.9 ± 1.7; P = .03). Conversely, SampEn values were 100% greater during water than during land environments (single-task = 0.04 ± 0.01 vs 0.02 ± 0.01; P < .001). Center of pressure area and velocity followed a similar trend to SampEn with respect to environment differences, and none of the measures were different between single- and dual-task conditions (P > .05). CONCLUSIONS: The findings of this study expand current support for the potential use of partial aquatic immersion as a viable method for challenging both cognitive and motor abilities in older adults.

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.

Resting-state functional connectivity as a biomarker of aggression in mild traumatic brain injury.

Mild traumatic brain injury (mTBI) can alter the structure of the brain and result in a range of symptoms, including elevated aggression. Neurological damage associated with mTBI is traditionally viewed as transient, yet a growing number of studies suggest long-lasting psychological and neurological changes following mTBI. However, research examining the neural basis of emotion processing in the chronic stage of mTBI recovery remains sparse. In the current study, we utilized resting state functional MRI to explore the association between default mode network connectivity and aggression in 17 healthy controls and 17 adults at least 6 months post-mTBI. The association between within-network connectivity and aggression was examined using general linear models, controlling for the effects of depression. Increased connectivity between the right hippocampus and midcingulate cortex was associated with elevated aggression in adults with mTBI, but not in healthy controls. The results provide evidence for a link between intrinsic functional network disruptions and the manifestation of postconcussive symptoms within chronic stages of recovery following mTBI. These findings expand upon the current research, providing evidence for the use of resting state functional connectivity as a potential biomarker of postconcussive aggression in chronic mTBI.

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).