Biobehavioral mechanisms underlying testosterone and mood relationships in peripubertal female adolescents.

The pubertal transition is characterized by pronounced sex hormone fluctuation, refinement of affective neural circuitry, and an increased risk of depression in female adolescents. Sex hormones, including testosterone, exert modulatory effects on frontal-limbic brain networks and are associated with emotion dysregulation and depressive symptoms. Weekly changes in hormones predict affective symptoms in peripubertal female adolescents, particularly in the context of stress; however, the biobehavioral mechanisms underlying hormone change and mood relationships during the pubertal transition have yet to be determined and was the objective of the present study. Forty-three peripubertal female adolescents (ages 11-14) collected 8-weekly salivary hormone (estrone, testosterone) samples and mood assessments to evaluate hormone-mood relationships, followed by a biobehavioral testing session with psychosocial stress and EEG. Within-person correlations between weekly hormone changes and corresponding mood were performed to determine individual differences in mood sensitivity to weekly hormone change. Increased frontal theta activity indexing emotion reactivity, reduced cortisol reactivity, and reduced vagal efficiency predicted the strength of the relationship between testosterone and mood. Further, testosterone-sensitivity strength was associated with the enhancement of negative affect following stress testing. Results identify divergent frontal theta and stress responses as potential biobehavioral mechanisms underlying mood sensitivity to peripubertal testosterone fluctuation.

Musculoskeletal Injury History Is Associated With Lower Physical and Mental Health in a Historical Cohort of Former National Football League Players.

CONTEXT: Little research has examined health-related quality of life in former National Football League (NFL) players. OBJECTIVE: Examine the association of musculoskeletal injury history and current self-reported physical and mental health in former NFL players. SETTING: Cross-sectional questionnaire. PATIENTS OR OTHER PARTICIPANTS: Historical cohort of 2,103 former NFL players that played at least one season between 1940 and 2001. INTERVENTION: Players were grouped by self-reported professional career musculoskeletal injury history and whether injuries affected current health: (1) no musculoskeletal injury history; (2) musculoskeletal injury history, currently affected by injuries; and (3) musculoskeletal injury history, not currently affected by injuries. MAIN OUTCOME MEASURE: The Short Form 36 Measurement Model for Functional Assessment of Health and Well-Being (SF-36) yielded physical and mental health composite scores (PCS and MCS, respectively); higher scores indicated better health. Multivariable linear regression computed mean differences (MD) among injury groups. Covariates included demographics, playing history characteristics, surgical intervention for musculoskeletal injuries, and whether injury resulted in premature end to career. MD with 95% CI excluding 0.00 were deemed significant. RESULTS: Overall, 90.3% reported at least one musculoskeletal injury during their professional football careers, of which 74.8% reported being affected by their injuries at time of survey completion. Adjusting for covariates, mean PCS in the "injury and affected" group was lower than the "no injury" (MD = -3.2; 95% CI: -4.8, -1.7) and "injury and not affected" groups (MD = -4.3; 95% CI: -5.4, -3.3); mean MCS did not differ. CONCLUSION: Many players reported musculoskeletal injuries, highlighting the need for developing and evaluating injury management interventions.

Objective Smartwatch Indices of Affective Switching: A Pilot Study in Premenstrual Dysphoric Disorder.

Wearable devices offer a unique opportunity to provide real-time monitoring of affective switching (the mood transition into and out of dysregulated affective state), a critical window to detect and prevent depression and suicide. To model affective switching, we studied premenstrual dysphoric disorder (PMDD): a depressive disorder with a regularly occurring monthly trigger. Results supported feasibility of smartwatch monitoring protocol and preliminary evidence that objective physiological and behavioral metrics were associated with affective state.

Expanding capabilities to evaluate readiness for return to duty after mTBI: The CAMP study protocol.

Physical Therapists affiliated with Intrepid Spirit Centers evaluate and treat Active Duty Service Members (ADSM) who have duty-limiting post-concussion symptoms to improve the ability to perform challenging tasks associated with military service. The Complex Assessment of Military Performance (CAMP) is a test battery that more closely approximates the occupational demands of ADSM without specific adherence to a particular branch of service or military occupational specialty. Subtasks were developed with military collaborators to include high level skills that all service members must be able to perform such as reacting quickly, maintaining visual stability while moving and changing positions, and scanning for, noting, and/or remembering operationally relevant information under conditions of physical exertion. OBJECTIVE: The purpose of this observational longitudinal study is to: 1- establish typical performance parameters for ADSM on the CAMP test battery 2- determine the element of the CAMP battery that demonstrate the greatest differences from standard performance and serve as predictors for successful return to duty and 3- develop clinician-facing feedback algorithms and displays and 4-develop materials for clinical dissemination. This ongoing multi-site study is currently funded through the CDMRP and has been approved by the Naval Medical Center Portsmouth IRB. METHODS: ADSM undergoing post-concussion rehabilitation at the Intrepid Spirit Centers will be tested within one week of their initial Physical Therapy evaluation and after completing Physical Therapy. Control participants will include males, females, and ADSM from the Special Operations community. Participants will complete an intake form that includes questions about demographics, military service, deployment and concussion history, and profile and duty status. Other measures include those that explore concussion symptoms, sleep quality, post-traumatic stress, and perceptions of resilience. The CAMP includes three separate 10-15 minute tasks. Movement is recorded by wearable inertial sensors and heart rate variability is recorded with a POLAR10 monitor. The "Run-Roll" task requires rapid position changes, combat rolls and quick running forwards and backwards while carrying a simulated weapon. Visual stability before and after the task is also performed. The "Dual-Task Agility" task includes rapid running with and without a weighted vest and a working memory task. The "Patrol Exertion" task requires repeated stepping onto an exercise step while watching a virtual patrol video. Additional tasks include monitoring direction of travel, observing for signs of enemy presence, and reacting to multiple auditory signals embedded in the video. DISCUSSION: Measures that evaluate relevant skills are vital to support safe return to duty for ADSM who may be exposed to imminent danger as part of training or mission demands. The CAMP is designed to be an ecologically valid and clinically feasible assessment that may be more sensitive to capturing subtle impairments that impact duty performance as test skills are integrated into dual and multi-tasks that reflect occupational demands. Assessment results may serve as a more robust indicator of readiness for full return to duty after concussion.

The Portable Warrior Test of Tactical Agility: A Novel Functional Assessment That Discriminates Service Members Diagnosed With Concussion From Controls.

INTRODUCTION: Return-to-duty (RTD) readiness assessment for service members (SM) following concussion requires complex clinical considerations. The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a functional assessment which improves on previous laboratory-based RTD assessments. METHODS: Sixty-four SM diagnosed with concussion and 60 healthy control (HC) SM participated in this study. Group differences were analyzed to validate the POWAR-TOTAL. The High-level Mobility Assessment Test (HiMAT) was used to examine concurrent construct validity. An exploratory logistic regression analysis examined predictive validity. RESULTS: The groups were demographically well-matched except for educational level. POWAR-TOTAL measures were statistically significantly different between the groups with moderate to large effect sizes. Concussed participants were less likely to be able to complete all trials of the POWAR-TOTAL. Motor scores correlated highly with HiMAT scores. POWAR-TOTAL motor task performance and membership in the control group was significantly associated with self-reported physical readiness to deploy. CONCLUSION: The POWAR-TOTAL is a clinically feasible, military relevant assessment that is sensitive to differences between concussed and HC SM. This analysis supports the discriminant and construct validity of the POWAR-TOTAL, and may be useful for medical providers evaluating RTD readiness for SM who have sustained a concussion.

Efficacy of Virtual Care for Depressive Disorders: Systematic Review and Meta-analysis.

BACKGROUND: The COVID-19 pandemic has created an epidemic of distress-related mental disorders such as depression, while simultaneously necessitating a shift to virtual domains of mental health care; yet, the evidence to support the use of virtual interventions is unclear. OBJECTIVE: The purpose of this study was to evaluate the efficacy of virtual interventions for depressive disorders by addressing three key questions: (1) Does virtual intervention provide better outcomes than no treatment or other control conditions (ie, waitlist, treatment as usual [TAU], or attention control)? (2) Does in-person intervention provide better outcomes than virtual intervention? (3) Does one type of virtual intervention provide better outcomes than another? METHODS: We searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021. We included randomized controlled trials of adults with depressive disorders that tested a virtual intervention and used a validated depression measure. Primary outcomes were defined as remission (ie, no longer meeting the clinical cutoff for depression), response (ie, a clinically significant reduction in depressive symptoms), and depression severity at posttreatment. Two researchers independently selected studies and extracted data using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias was evaluated based on Agency for Healthcare and Research Quality guidelines. We calculated odds ratios (ORs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes. RESULTS: We identified 3797 references, 24 of which were eligible. Compared with waitlist, virtual intervention had higher odds of remission (OR 10.30, 95% CI 5.70-18.60; N=619 patients) and lower posttreatment symptom severity (SMD 0.81, 95% CI 0.52-1.10; N=1071). Compared with TAU and virtual attention control conditions, virtual intervention had higher odds of remission (OR 2.27, 95% CI 1.10-3.35; N=512) and lower posttreatment symptom severity (SMD 0.25, 95% CI 0.09-0.42; N=573). In-person intervention outcomes were not significantly different from virtual intervention outcomes (eg, remission OR 0.84, CI 0.51-1.37; N=789). No eligible studies directly compared one active virtual intervention to another. CONCLUSIONS: Virtual interventions were efficacious compared with control conditions, including waitlist control, TAU, and attention control. Although the number of studies was relatively small, the strength of evidence was moderate that in-person interventions did not yield significantly better outcomes than virtual interventions for depressive disorders.

Estrogenic signaling and sociosexual behavior in wild sex-changing bluehead wrasses, Thalassoma bifasciatum.

Estrogenic signaling is an important focus in studies of gonadal and brain sexual differentiation in fishes and vertebrates generally. This study examined variation in estrogenic signaling (1) across three sexual phenotypes (female, female-mimic initial phase [IP] male, and terminal phase [TP] male), (2) during socially-controlled female-to-male sex change, and (3) during tidally-driven spawning cycles in the protogynous bluehead wrasse (Thalassoma bifasciatum). We analyzed relative abundances of messenger RNAs (mRNAs) for the brain form of aromatase (cyp19a1b) and the three nuclear estrogen receptors (ER) (ERα, ERßa, and ERßb) by qPCR. Consistent with previous reports, forebrain/midbrain cyp19a1b was highest in females, significantly lower in TP males, and lowest in IP males. By contrast, ERα and ERßb mRNA abundances were highest in TP males and increased during sex change. ERßa mRNA did not vary significantly. Across the tidally-driven spawning cycle, cyp19a1b abundances were higher in females than TP males. Interestingly, cyp19a1b levels were higher in TP males close (~1 h) to the daily spawning period when sexual and aggressive behaviors rise than males far from spawning (~10-12 h). Together with earlier findings, our results suggest alterations in neural estrogen signaling are key regulators of socially-controlled sex change and sexual phenotype differences. Additionally, these patterns suggest TP male-typical sociosexual behaviors may depend on intermediate rather than low estrogenic signaling. We discuss these results and the possibility that an inverted-U shaped relationship between neural estrogen and male-typical behaviors is more common than presently appreciated.

A pilot study on exertional tasks with physiological measures designed for the assessment of military concussion.

BACKGROUND: Guidelines for clinicians treating military concussion recommend exertional testing before return-to-duty, yet there is currently no standardized task or inclusion of an objective physiological measure like heart rate variability (HRV). METHODOLOGY & RESULTS: We pilot-tested two clinically feasible exertional tasks that include HRV measures and examined reliability of a commercially available heart rate monitor. Testing healthy participants confirmed that the 6-min step test and 2-min pushup test evoked the targeted physiological response, and the Polar H10 was reliable to the gold-standard electrocardiogram. CONCLUSION: Both tasks are brief assessments that can be implemented into primary care setting including the Polar H10 as an affordable way to access HRV. Additional research utilizing these tasks to evaluate concussion recovery can validate standardized exertional tasks for clinical use.

Identifying and Engaging Neuronal Oscillations by Transcranial Alternating Current Stimulation in Patients With Chronic Low Back Pain: A Randomized, Crossover, Double-Blind, Sham-Controlled Pilot Study.

Chronic pain is associated with maladaptive reorganization of the central nervous system. Recent studies have suggested that disorganization of large-scale electrical brain activity patterns, such as neuronal network oscillations in the thalamocortical system, plays a key role in the pathophysiology of chronic pain. Yet, little is known about whether and how such network pathologies can be targeted with noninvasive brain stimulation as a nonpharmacological treatment option. We hypothesized that alpha oscillations, a prominent thalamocortical activity pattern in the human brain, are impaired in chronic pain and can be modulated with transcranial alternating current stimulation (tACS). We performed a randomized, crossover, double-blind, sham-controlled study in patients with chronic low back pain (CLBP) to investigate how alpha oscillations relate to pain symptoms for target identification and whether tACS can engage this target and thereby induce pain relief. We used high-density electroencephalography to measure alpha oscillations and found that the oscillation strength in the somatosensory region at baseline before stimulation was negatively correlated with pain symptoms. Stimulation with alpha-tACS compared to sham (placebo) stimulation significantly enhanced alpha oscillations in the somatosensory region. The stimulation-induced increase of alpha oscillations in the somatosensory region was correlated with pain relief. Given these findings of successful target identification and engagement, we propose that modulating alpha oscillations with tACS may represent a target-specific, nonpharmacological treatment approach for CLBP. This trial has been registered in ClinicalTrials.gov (NCT03243084). PERSPECTIVE: This study suggests that a rational design of transcranial alternating current stimulation, which is target identification, engagement, and validation, could be a nonpharmacological treatment approach for patients with CLBP.

Targeting the Autonomic Nervous System Balance in Patients with Chronic Low Back Pain Using Transcranial Alternating Current Stimulation: A Randomized, Crossover, Double-Blind, Placebo-Controlled Pilot Study.

BACKGROUND: Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients. OBJECTIVE: To evaluate if non-invasive brain stimulation modulates the ANS, we analyzed HRV metrics collected in a previously published study of transcranial alternating current stimulation (tACS) for the modulation of CLBP through enhancing alpha oscillations. We hypothesized that tACS would increase RSA. METHODS: A randomized, crossover, double-blind, sham-controlled pilot study was conducted to investigate the effects of 10Hz-tACS on metrics of ANS balance calculated from electrocardiogram (ECG). ECG data were collected for 2 mins before and after 40 mins of 10Hz-tACS or sham stimulation. RESULTS: There were no significant changes in RSA or other frequency-domain HRV components from 10Hz-tACS. However, exploratory time-domain HRV analyses revealed a significant increase in the standard deviation of normal intervals between R-peaks (SDNN), a measure of ANS balance, for 10Hz-tACS relative to sham. CONCLUSION: Although tACS did not significantly increase RSA, we found in an exploratory analysis that tACS modulated an integrated HRV measure of both ANS branches. These findings support the further study of how the ANS and alpha oscillations interact and are modulated by tACS. CLINICALTRIALSGOV: Transcranial Alternating Current Stimulation in Back Pain - Pilot Study, NCT03243084.

Clinical Utility and Analysis of the Run-Roll-Aim Task: Informing Return-to-Duty Readiness Decisions in Active-Duty Service Members.

INTRODUCTION: The Assessment of Military Multitasking Performance (AMMP1) consists of six dual-task and multitask military-relevant performance-based assessments which were developed to provide assistance in making return-to-duty decisions after concussion or mild traumatic brain injury (mTBI.) The Run-Roll-Aim (RRA) task, one component of the AMMP, was developed to target vulnerabilities following mTBI including attention, visual function, dynamic stability, rapid transition, and vestibular function. One aim of this study was to assess the known-group and construct validity of the RRA, and additionally to further explore reliability limitations reported previously. MATERIALS AND METHODS: A cross-sectional study consisting of 84 Active Duty service members in two groups (healthy control - HC and individuals experiencing persistent mTBI symptoms) completed neurocognitive tests and the RRA. The RRA task requires a high level of mobility and resembles military training activities in a maneuver that includes combat rolls, fast transitions, obstacle avoidance, and visual search. Observational and inertial sensor data were compared between groups and performance across four trial times was compared within groups. Correlations between RRA results and neurocognitive test scores were analyzed. RESULTS: Simple observational measures (time, errors) did not differ between groups. Spectral power analysis of the inertial sensor data showed significant differences in motor performance between groups. Within group one-way ANOVAs showed that in HC trial 1, time was significantly different than trials 2,3 and 4 (F(3,47) = 4.60, p < 0.01, Tukey HSD p < 0.05) while the mTBI group showed no significant difference in time between trials. During testing individuals with mTBI were less likely to complete the multiple test trials or required additional rest between trials than HCs (χ2 = 10.78, p < 0.01). Small but significant correlations were seen with two neurocognitive tests of attention and RRA performance time. CONCLUSION: While observational scores were not sensitive to group differences, inertial sensor data showed motor performance on the forward run, combat roll, and backward run differed significantly between groups. The RRA task appeared challenging and provoked symptoms in the mTBI group, causing 8 of 33 mTBI participants to stop the task or require additional rest between trials while none of the HC participants had to stop. Individuals with mTBI demonstrated slower learning of the complex motor sequence compared to HCs who had significant improvement after one trial of RRA. Complex novel training maneuvers like RRA may aid clinicians in informing return to duty decisions.