Episodic memory assessment: effects of sex and age on performance and response time during a continuous recognition task.

Introduction: Continuous recognition tasks (CRTs) assess episodic memory (EM), the central functional disturbance in Alzheimer's disease and several related disorders. The online MemTrax computerized CRT provides a platform for screening and assessment that is engaging and can be repeated frequently. MemTrax presents complex visual stimuli, which require complex involvement of the lateral and medial temporal lobes and can be completed in less than 2 min. Results include number of correct recognitions (HITs), recognition failures (MISSes = 1-HITs), correct rejections (CRs), false alarms (FAs = 1-CRs), total correct (TC = HITs + CRs), and response times (RTs) for each HIT and FA. Prior analyses of MemTrax CRT data show no effects of sex but an effect of age on performance. The number of HITs corresponds to faster RT-HITs more closely than TC, and CRs do not relate to RT-HITs. RT-HITs show a typical skewed distribution, and cumulative RT-HITs fit a negative survival curve (RevEx). Thus, this study aimed to define precisely the effects of sex and age on HITS, CRs, RT-HITs, and the dynamics of RTs in an engaged population. Methods: MemTrax CRT online data on 18,255 individuals was analyzed for sex, age, and distributions of HITs, CRs, MISSes, FAs, TC, and relationships to both RT-HITs and RT-FAs. Results: HITs corresponded more closely to RT-HITs than did TC because CRs did not relate to RT-HITs. RT-FAs had a broader distribution than RT-HITs and were faster than RT-HITs in about half of the sample, slower in the other half. Performance metrics for men and women were the same. HITs declined with age as RT-HITs increased. CRs also decreased with age and RT-FAs increased, but with no correlation. The group over aged 50 years had RT-HITs distributions slower than under 50 years. For both age ranges, the RevEx model explained more than 99% of the variance in RT-HITs. Discussion: The dichotomy of HITs and CRs suggests opposing cognitive strategies: (1) less certainty about recognitions, in association with slower RT-HITs and lower HIT percentages suggests recognition difficulty, leading to more MISSes, and (2) decreased CRs (more FAs) but faster RTs to HITs and FAs, suggesting overly quick decisions leading to errors. MemTrax CRT performance provides an indication of EM (HITs and RT-HITs may relate to function of the temporal lobe), executive function (FAs may relate to function of the frontal lobe), processing speed (RTs), cognitive ability, and age-related changes. This CRT provides potential clinical screening utility for early Alzheimer's disease and other conditions affecting EM, other cognitive functions, and more accurate impairment assessment to track changes over time.

Teleyoga for Patients With Alzheimer's Disease and Chronic Musculoskeletal Pain and Their Caregivers: A Feasibility Study.

Background: Chronic musculoskeletal pain is common in patients with Alzheimer's disease (AD), and there is growing awareness that chronic pain has an impact on the progression of dementia. Yoga has shown promise in treating chronic pain. However, attending in-person yoga can be difficult for AD patients. Objective: To assess the feasibility, acceptability and preliminary efficacy of an online yoga (teleyoga) protocol suitable for AD patients with chronic pain, and their caregivers. Methods: Patients with comorbid mild AD and chronic musculoskeletal pain (n = 15, 57-95 y/o; 73% Female) and their caregivers (n = 15, 50-75 y/o; 67% Female) received 12-week of teleyoga individually (n = 5 dyads) or in groups (n = 10 dyads). Study measures included standard feasibility metrics, and secondary outcomes included the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory-II (BDI-II), and cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Caregivers also completed measures of caregiver burden, and quality of life (Short Form Health Survey-36, SF-36). Results: Feasibility measures showed adequate treatment adherence (85.1% in patients and 86.3% in caregivers), acceptability (mean acceptability rating = 3.0 for patients and 3.3 for caregivers, indicating positive approval), recruitment rate (n = 16 dyads within 1-year), retention rate (87%), missing data rate (.03%), and fidelity of treatment delivery (87%). Preliminary efficacy findings in the AD group showed significant reductions in pain severity (BPI-SF mean Δ = -.93, P = .045) and depression (BDI-II; mean Δ = -9.85, P = .005). %). Preliminary efficacy findings in the caregiver group showed significant reductions in depression (BDI-II mean Δ = -6.88, P = .036) and fatigue (SF-36 mean Δ = 9.81, P = .021). Conclusion: Results show that teleyoga is a feasible treatment for patients with comorbid mild AD and chronic musculoskeletal pain. Results also provide preliminary evidence of health benefits of teleyoga for both AD patients and their caregivers.

Emotion regulation and heart rate variability may identify the optimal posttraumatic stress disorder treatment: analyses from a randomized controlled trial.

Introduction: High variability in response and retention rates for posttraumatic stress disorder (PTSD) treatment highlights the need to identify "personalized" or "precision" medicine factors that can inform optimal intervention selection before an individual commences treatment. In secondary analyses from a non-inferiority randomized controlled trial, behavioral and physiological emotion regulation were examined as non-specific predictors (that identify which individuals are more likely to respond to treatment, regardless of treatment type) and treatment moderators (that identify which treatment works best for whom) of PTSD outcome. Methods: There were 85 US Veterans with clinically significant PTSD symptoms randomized to 6 weeks of either cognitive processing therapy (CPT; n = 44) or a breathing-based yoga practice (Sudarshan kriya yoga; SKY; n = 41). Baseline self-reported emotion regulation (Difficulties in Emotion Regulation Scale) and heart rate variability (HRV) were assessed prior to treatment, and self-reported PTSD symptoms were assessed at baseline, end-of-treatment, 1-month follow-up, and 1-year follow-up. Results: Greater baseline deficit in self-reported emotional awareness (similar to alexithymia) predicted better overall PTSD improvement in both the short- and long-term, following either CPT or SKY. High self-reported levels of emotional response non-acceptance were associated with better PTSD treatment response with CPT than with SKY. However, all significant HRV indices were stronger moderators than all self-reported emotion regulation scales, both in the short- and long-term. Veterans with lower baseline HRV had better PTSD treatment response with SKY, whereas Veterans with higher or average-to-high baseline HRV had better PTSD treatment response with CPT. Conclusions: To our knowledge, this is the first study to examine both self-reported emotion regulation and HRV, within the same study, as both non-specific predictors and moderators of PTSD treatment outcome. Veterans with poorer autonomic regulation prior to treatment had better PTSD outcome with a yoga-based intervention, whereas those with better autonomic regulation did better with a trauma-focused psychological therapy. Findings show potential for the use of HRV in clinical practice to personalize PTSD treatment. Clinical trial registration: ClinicalTrials.gov identifier, NCT02366403.

'She thought the same way I that I thought:' a qualitative study of patient-provider concordance among Gulf War Veterans with Gulf War Illness.

Objective: Medically unexplained symptoms (MUS), such as chronic fatigue syndrome, irritable bowel syndrome, and Gulf War Illness (GWI), are difficult to treat. Concordance-shared understanding between patient and provider about illness causes, course, and treatment-is an essential component of high-quality care for people with MUS. This qualitative paper focuses on the experiences of United States military Veterans living with GWI who have endured unique healthcare challenges. Methods & Measures: Qualitative interviews were conducted with 31 Veterans with GWI to explore factors that contribute to and detract from concordance with their Veteran Affairs (VA) healthcare providers. In addition to being seen by VA primary care, over half of participants also sought care at a War Related Illness and Injury Study Center, which specializes in post-deployment health. Deductive and inductive codes were used to organize the data, and themes were identified through iterative review of coded data. Results: Major themes associated with patient-provider concordance included validation of illness experiences, perceived provider expertise in GWI/MUS, and trust in providers. Invalidation, low provider expertise, and distrust detracted from concordance. Conclusion: These findings suggest providers can foster concordance with MUS patients by legitimizing patients' experiences, communicating knowledge about MUS, and establishing trust.

Yoga is effective for treating chronic pain in veterans with Gulf War Illness at long-term follow-up.

BACKGROUND: Clinical Practice Guidelines for Gulf War Illness (GWI) recommend integrative health approaches such as yoga for relief from symptoms, yet little is known about the long-term efficacy of yoga in reducing symptoms of GWI. Here, we evaluated the long-term efficacy of yoga and cognitive-behavioral therapy (CBT) chronic pain treatment in a randomized controlled trial (RCT) of 75 Veterans (57 men, 42-71 ± 7.1 years of age) with Gulf War Illness (GWI). METHODS: Participants received either 10 weeks of yoga or 10 weeks of CBT for chronic pain. The primary outcome measures were pain severity, and pain interference (Brief Pain Inventory-Short Form). The secondary outcome measures were fatigue, as indicated by a measure of functional exercise capacity (6-Minute Walk Test), depression, autonomic symptom severity, and quality of life. Piecewise linear mixed models were used to examine study hypotheses. RESULTS: Compared to the CBT group, yoga was associated with greater reductions in pain severity during the 6-month follow-up period (group × time interaction: b = 0.036, se = 0.014, p = .011). Although we did not find between-group differences in the other primary or secondary outcome measures during follow-up (p's > 0.05), exploratory analyses revealed within-group improvements in pain interference, total pain (an experimental outcome variable which combines pain severity and interference), and fatigue in the yoga group (p's < 0.05) but not in the CBT group. CONCLUSIONS: This is the first study to report long-term follow-up results of yoga as a treatment for GWI. Our results suggest that yoga may offer long-term efficacy in reducing pain, which is a core symptom of GWI. TRIAL REGISTRATION: Secondary analyses of ClinicalTrials.gov NCT02378025.

The role of the brainstem in sleep disturbances and chronic pain of Gulf War and Iraq/Afghanistan veterans.

Introduction: Gulf War Illness is a type of chronic multisymptom illness, that affects about 30% of veterans deployed to the 1990-91 Persian Gulf War. Veterans deployed to Iraq/Afghanistan after 2000 are reported to have a similar prevalence of chronic multisymptom illness. More than 30 years after the Persian Gulf War, Gulf War Illness still has an unexplained symptom complex, unknown etiology and lacks definitive diagnostic criteria and effective treatments. Our recent studies have found that substantially smaller brainstem volumes and lower fiber integrity are associated with increased sleep difficulty and pain intensity in 1990-91 Persian Gulf War veterans. This study was conducted to investigate whether veterans deployed to Iraq/Afghanistan present similar brainstem damage, and whether such brainstem structural differences are associated with major symptoms as in Gulf War Illness. Methods: Here, we used structural magnetic resonance imaging and diffusion tensor imaging to measure the volumes of subcortices, brainstem subregions and white matter integrity of brainstem fiber tracts in 188 veterans including 98 Persian Gulf War veterans and 90 Iraq/Afghanistan veterans. Results: We found that compared to healthy controls, veterans of both campaigns presented with substantially smaller volumes in brainstem subregions, accompanied by greater periaqueductal gray matter volumes. We also found that all veterans had reduced integrity in the brainstem-spinal cord tracts and the brainstem-subcortical tracts. In veterans deployed during the 1990-91 Persian Gulf War, we found that brainstem structural deficits significantly correlated with increased sleep difficulties and pain intensities, but in veterans deployed to Iraq/Afghanistan, no such effect was observed. Discussion: These structural differences in the brainstem neurons and tracts may reflect autonomic dysregulation corresponding to the symptom constellation, which is characteristic of Gulf War Illness. Understanding these neuroimaging and neuropathological relationships in Gulf War and Iraq/Afghanistan veterans may improve clinical management and treatment strategies for modern war related chronic multisymptom illness.

Correctness and response time distributions in the MemTrax continuous recognition task: Analysis of strategies and a reverse-exponential model.

A critical issue in addressing medical conditions is measurement. Memory measurement is difficult, especially episodic memory, which is disrupted by many conditions. On-line computer testing can precisely measure and assess several memory functions. This study analyzed memory performances from a large group of anonymous, on-line participants using a continuous recognition task (CRT) implemented at https://memtrax.com. These analyses estimated ranges of acceptable performance and average response time (RT). For 344,165 presumed unique individuals completing the CRT a total of 602,272 times, data were stored on a server, including each correct response (HIT), Correct Rejection, and RT to the thousandth of a second. Responses were analyzed, distributions and relationships of these parameters were ascertained, and mean RTs were determined for each participant across the population. From 322,996 valid first tests, analysis of correctness showed that 63% of these tests achieved at least 45 correct (90%), 92% scored at or above 40 correct (80%), and 3% scored 35 correct (70%) or less. The distribution of RTs was skewed with 1% faster than 0.62 s, a median at 0.890 s, and 1% slower than 1.57 s. The RT distribution was best explained by a novel model, the reverse-exponential (RevEx) function. Increased RT speed was most closely associated with increased HIT accuracy. The MemTrax on-line memory test readily provides valid and reliable metrics for assessing individual episodic memory function that could have practical clinical utility for precise assessment of memory dysfunction in many conditions, including improvement or deterioration over time.

Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans.

OBJECTIVE: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. SETTING: Outpatient Veterans Affairs healthcare centre. PARTICIPANTS: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. INTERVENTIONS: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. MEASURES: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). RESULTS: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, -5.6, d=0.41, n=41: CPT, -6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95% CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95% CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95% CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). CONCLUSIONS: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD. TRIAL REGISTRATION NUMBER: NCT02366403.

Valued living among veterans in breath-based meditation treatment or cognitive processing therapy for posttraumatic stress disorder: Exploratory outcome of a randomized controlled trial.

Background: Valued living is the extent to which an individual's behavior is consistent with what they believe is important or good. It is unknown whether many complementary and integrative treatments and psychotherapies for posttraumatic stress disorder enhance valued living, and for whom. Objectives: Measure within- and between-group changes in valued living in Veterans who completed cognitive processing therapy (CPT) and sudarshan kriya yoga (SKY) for posttraumatic stress disorder (PTSD); evaluate moderators of improvement. Methods: Participants with clinically significant symptoms of PTSD were assigned to CPT, a first line, evidence-based psychotherapy for PTSD or SKY, an emerging breath-based meditation with strong preliminary empirical support in a parallel-groups randomized controlled trial at a single Veterans Affairs healthcare center. The Valuing Questionnaire subscales for progress in valued living (VQ-P) and obstruction in valued living (VQ-O) were exploratory outcome measures. Assessors were blind to treatment assignment. Results: 59 participants completed treatment (29 CPT, 30 SKY). Participants in the CPT group improved from baseline to end of treatment in both VQ-Progress (d=0.55, p=0.02) and VQ-Obstruction (d=-0.51, p=0.03), while the SKY group did not improve on either subscale (d=0.08, p=0.69; d=0.00, p=1.00). However, differences between treatments were not statistically significant (p=0.16, 0.11, respectively). Participants reporting less valued living and more depression symptoms at baseline reported greater improvements in valued living following treatment. Conclusion: CPT may have a positive effect on valued living. Individuals lower in valued living and with more depression may derive relatively more benefit.

Now is the Time to Improve Cognitive Screening and Assessment for Clinical and Research Advancement.

Wang et al. analyze Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment accuracy as screening tests for detecting dementia associated with Alzheimer's disease (AD). Such tests are at the center of controversy regarding recognition and treatment of AD. The continued widespread use of tools such as MMSE (1975) underscores the failure of advancing cognitive screening and assessment, which has hampered the development and evaluation of AD treatments. It is time to employ readily available, efficient computerized measures for population/mass screening, clinical assessment of dementia progression, and accurate determination of approaches for prevention and treatment of AD and related conditions.

Emotion dysregulation and heart rate variability improve in US veterans undergoing treatment for posttraumatic stress disorder: Secondary exploratory analyses from a randomised controlled trial.

BACKGROUND: Emotion regulation (ER) is a key process underlying posttraumatic stress disorder (PTSD), yet, little is known about how ER changes with PTSD treatment. Understanding these effects may shed light on treatment processes. METHODS: We recently completed a non-inferiority design randomised controlled trial demonstrating that a breathing-based yoga practice (Sudarshan kriya yoga; SKY) was not clinically inferior to cognitive processing therapy (CPT) across symptoms of PTSD, depression, or negative affect. Here, in secondary exploratory analyses (intent-to-treat N = 85; per protocol N = 59), we examined whether self-reported ER (Difficulties in Emotion Regulation Scale; DERS) and physiological ER (heart rate variability; HRV) improved with treatment for clinically significant PTSD symptoms among US Veterans. RESULTS: DERS-Total and all six subscales improved with small-to-moderate effect sizes (d = .24-.66) following CPT or SKY, with no differences between treatment groups. Following SKY (but not CPT), HR max-min (average difference between maximum and minimum beats per minute), LF/HF (low-to-high frequency) ratio, and normalised HF-HRV (high frequency power) improved (moved towards a healthier profile; d = .42-.55). CONCLUSIONS: To our knowledge, this is the first study to demonstrate that a breathing-based yoga (SKY) improved both voluntary/intentional and automatic/physiological ER. In contrast, trauma-focused therapy (CPT) only reliably improved self-reported ER. Findings have implications for PTSD treatment and interventions for emotional disorders more broadly. TRIAL REGISTRATION: Secondary analyses of ClinicalTrials.gov NCT02366403 .

Posttraumatic Stress Disorder Does Not Compromise Behavioral Pain Treatment: Secondary Analysis of a Randomized Clinical Trial Among Veterans.

BACKGROUND: Individuals with posttraumatic stress disorder (PTSD) and chronic pain evince different presentations, coping strategies, and treatment utilization patterns than individuals with chronic pain alone. Theorists have suggested that comorbid PTSD may complicate chronic pain treatment, and that integrated pain and PTSD treatment may be preferable to pain treatment alone. OBJECTIVE: Assess whether comorbid PTSD moderates Veterans' response to yoga and/or cognitive behavioral therapy (CBT) for pain. METHODS: Veterans with Gulf War illness (n = 75) were assessed using the Brief Pain Inventory at baseline and posttreatment as part of a randomized clinical trial. PTSD status was abstracted from participants' medical records. RESULTS: PTSD+ participants (n = 41) reported more pain at baseline than PTSD- participants (n = 34; d = .66, p < .01). PTSD+ participants experienced more improvement in pain from baseline to posttreatment than PTSD- participants by a small to moderate, marginally statistically significant amount (d = .39, p = .07). The relationship between PTSD and treatment outcome was not moderated by treatment type (yoga vs CBT; p = .99). Observation of treatment responses across PTSD status (+ vs -) and treatment (yoga vs CBT) revealed that PTSD+ participants responded well to yoga. CONCLUSION: PTSD is not associated with reduced effectiveness of behavioral chronic pain treatment among Veterans with Gulf War illness. Therefore behavioral pain treatment should be made readily available to Veterans with pain and PTSD. Yoga deserves further consideration as a treatment for pain among individuals with PTSD.

Rapid neural reorganization during retrieval practice predicts subsequent long-term retention and false memory.

Active retrieval can alter the strength and content of a memory, yielding either enhanced or distorted subsequent recall. However, how consolidation influences these retrieval-induced seemingly contradictory outcomes remains unknown. Here we show that rapid neural reorganization over an eight-run retrieval practice predicted subsequent recall. Retrieval practice boosted memory retention following a 24-hour (long-term) but not 30-minute delay, and increased false memory at both delays. Long-term retention gains were predicted by multi-voxel representation distinctiveness in the posterior parietal cortex (PPC) that increased progressively over retrieval practice. False memory was predicted by unstable representation distinctiveness in the medial temporal lobe (MTL). Retrieval practice enhanced the efficiency of memory-related brain networks, through building up PPC and MTL connections with the ventrolateral and dorsolateral prefrontal cortex that predicted long-term retention gains and false memory, respectively. Our findings indicate that retrieval-induced rapid neural reorganization together with consecutive consolidation fosters long-term retention and false memories via distinct pathways.

Self-Reported Autonomic Dysregulation in Gulf War Illness.

INTRODUCTION: Autonomic nervous system dysregulation is commonly observed in Gulf War illness (GWI). Using a new sample, we sought to replicate and extend findings from a previous study that found autonomic symptoms predicted physical functioning in Veterans with GWI. MATERIALS AND METHODS: A linear regression model was used to predict physical functioning (36-item Short Form Health Survey (SF-36); n = 73, 75% male). First, we examined the predictive value of independent variables individually in the model including: the 31-item Composite Autonomic Symptom Score (COMPASS-31) total score, body mass index (BMI), mental health burden (i.e., post-traumatic stress disorder [PTSD] and/or depression), and COMPASS-31 subscales: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor. Next, we estimated linear regression models containing the three variables (autonomic symptoms, BMI, and mental health burden) identified as predictors of physical functioning from the prior study. RESULTS: These linear regression models significantly predicted physical functioning and accounted for 15% of the variance with COMPASS-31, 36.6% of variance with COMPASS-31 and BMI, and 38.2% of variance with COMPASS-31, BMI, and mental health burden. Then, forward step-wise linear regressions were applied to explore new models including COMPASS-31 subscales. Two new models accounted for more of the variance in physical functioning: 39.3% with added gastrointestinal symptoms (ß = -2.206, P = .001) and 43.4% of variance with both gastrointestinal (ß = -1.592, P = .008) and secretomotor subscales (ß = -1.533, P = .049). Unlike the previous study we intended to replicate, mental health burden was not a significant predictor in any of our models. CONCLUSIONS: Treatments that address autonomic dysregulation should be prioritized for research and clinical recommendations for Veterans with GWI who experience chronic pain.

Brainstem damage is associated with poorer sleep quality and increased pain in gulf war illness veterans.

AIMS: Gulf War Illness (GWI) is manifested as multiple chronic symptoms, including chronic pain, chronic fatigue, sleep problems, neuropsychiatric disorders, respiratory, gastrointestinal, and skin problems. No single target tissue or unifying pathogenic process has been identified that accounts for this variety of symptoms. The brainstem has been suspected to contribute to this multiple symptomatology. The aim of this study was to assess the role of the brainstem in chronic sleep problems and pain in GWI veterans. MATERIALS AND METHODS: We enrolled 90 veterans (Age = 50 ± 5, 87% Male) who were deployed to the 1990-91 Gulf War and presented with GWI symptoms. Sleep quality was evaluated using the global Pittsburgh Sleep Quality Index. Pain intensities were obtained with the Brief Pain Inventory sum score. Volumes in cortical, subcortical, brainstem, and brainstem subregions and diffusion tensor metrics in 10 bilateral brainstem tracts were tested for correlations with symptom measures. KEY FINDINGS: Poorer sleep quality was significantly correlated with atrophy of the whole brainstem and brainstem subregions (including midbrain, pons, medulla). Poorer sleep quality also significantly correlated with lower fractional anisotropy in the nigrostriatal tract, medial forebrain tract, and the dorsal longitudinal fasciculus. There was a significant correlation between increased pain intensity and decreased fractional anisotropy in the dorsal longitudinal fasciculus. These correlations were not altered after controlling for age, sex, total intracranial volumes, or additional factors, e.g., depression and neurological conditions. SIGNIFICANCE: These findings suggest that the brainstem plays an important role in the aberrant neuromodulation of sleep and pain symptoms in GWI.

Heart rate and heart rate variability as outcomes and longitudinal moderators of treatment for pain across follow-up in Veterans with Gulf War illness.

AIMS: Accumulating evidence suggests Gulf War illness (GWI) is characterised by autonomic nervous system dysfunction (higher heart rate [HR], lower heart rate variability [HRV]). Yoga - an ancient mind-body practice combining mindfulness, breathwork, and physical postures - is proposed to improve autonomic dysfunction yet this remains untested in GWI. We aimed to determine (i) whether HR and HRV improve among Veterans with GWI receiving either yoga or cognitive behavioural therapy (CBT) for pain; and (ii) whether baseline autonomic functioning predicts treatment-related pain outcomes across follow-up. MAIN METHODS: We present secondary analyses of 24-hour ambulatory cardiac data (mean HR, square root of the mean squared differences between successive R-R intervals [RMSSD], high frequency power [HF-HFV], and low-to-high frequency ratio [LF/HF] extracted from a 5-min window during the first hour of sleep) from our randomised controlled trial of yoga versus CBT for pain among Veterans with GWI (ClinicalTrials.govNCT02378025; N = 75). KEY FINDINGS: Veterans who received CBT tended towards higher mean HR at end-of-treatment. Better autonomic function (lower mean HR, higher RMSSD/HF-HRV) at baseline predicted greater reductions in pain across follow-up, regardless of treatment group. Better baseline autonomic function (mid-range-to-high RMSSD/HF-HRV) also predicted greater pain reductions with yoga, while worse baseline autonomic function (higher mean HR, lower RMSSD/HF-HRV) predicted greater pain reductions with CBT. SIGNIFICANCE: To our knowledge, this is the first study to suggest that among Veterans with GWI, HR may increase with CBT yet remain stable with yoga. Furthermore, HR and HRV moderated pain outcome across follow-up for yoga and CBT.

Clinical yoga program utilization in a large health care system.

The U.S. Department of Veterans Affairs (VA) offers yoga for multiple conditions. Little information is available regarding how frequently yoga is utilized, by whom, or for which medical conditions. Here we describe referral patterns and patient adoption rates in a clinical yoga program, including telehealth yoga, at VA Palo Alto Health Care System (VAPAHCS). Referral and demographic data were extracted from the electronic medical records of 953 veterans (692 male, 261 female) referred to the outpatient clinical yoga program between 2010 and 2016. Attendance data were extracted from the same time plus 1 year. Referee demographics were compared to the overall VAPAHCS population. Twenty-two of the 187 referring providers accounted for half (50.4%) of referrals, predominantly from primary care and mental health clinics. Compared to the overall VAPAHCS patient population, referees were similar age and more likely to be female. Attendance was associated with age (older veterans were more likely to attend) but not gender. Those referred for mental health reasons were more likely to attend yoga compared to those referred for physical symptoms or for wellness (e.g., strength, health, mindfulness). Telehealth yoga follow through was lower but attendance rate similar to in-person yoga. These data provide an overview of referral and uptake in a large VA setting. Overall, referral was performed by a few providers in mental health and primary care clinics. The typical demographic of attendee was a White male from the Vietnam War era, reflective of the VA population. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Yoga is effective in treating symptoms of Gulf War illness: A randomized clinical trial.

Many Veterans of the 1990-1991 Gulf War report symptoms of Gulf War Illness, a condition involving numerous chronic symptoms including pain, fatigue, and mood/cognition symptoms. Little is known about this condition's etiology and treatment. This study reports outcomes from a randomized controlled single-blind trial comparing yoga to cognitive behavioral therapy for chronic pain and other symptoms of Gulf War Illness. Participants were Veterans with symptoms of GWI: chronic pain, fatigue and cognition-mood symptoms. Seventy-five Veterans were randomized to treatment via selection of envelopes from a bag (39 yoga, 36 cognitive behavioral therapy), which consisted of ten weekly group sessions. The primary outcomes of pain severity and interference (Brief Pain Inventory- Short Form) improved in the yoga condition (Cohen's d = .35, p = 0.002 and d = 0.69, p < 0.001, respectively) but not in the CBT condition (d = 0.10, p = 0.59 and d = 0.25 p = 0.23). However, the differences between groups were not statistically significant (d = 0.25, p = 0.25; d = 0.43, p = 0.076), though the difference in an a-priori-defined experimental outcome variable which combines these two variables into a total pain variable (d = 0.47, p = 0.047) was significant. Fatigue, as indicated by a measure of functional exercise capacity (6-min walk test) was reduced significantly more in the yoga group than in the CBT group (between-group d = .27, p = 0.044). Other secondary outcomes of depression, wellbeing, and self-reported autonomic nervous system symptoms did not differ between groups. No adverse events due to treatment were reported. Yoga may be an effective treatment for core Gulf War Illness symptoms of pain and fatigue, making it one of few treatments with empirical support for GWI. Results support further evaluation of yoga for treating veterans with Gulf War Illness. CLINICAL TRIAL REGISTRY: clinicaltrials.gov Registration Number NCT02378025.

Brain and Physiological Markers of Autonomic Function Are Associated With Treatment-Related Improvements in Self-Reported Autonomic Dysfunction in Veterans With Gulf War Illness: An Exploratory Pilot Study.

BACKGROUND: Gulf War Illness (GWI) is a poorly understood condition characterized by a constellation of mood, cognitive, and physical symptoms. A growing body of evidence demonstrates autonomic nervous system (ANS) dysfunction. Few published treatment studies exist for GWI. METHOD: We recently completed a randomized controlled trial comparing a 10-week group yoga intervention to 10-week group cognitive behavioral therapy (CBT) for veterans with GWI. Here, we present exploratory data on ANS biomarkers of treatment response from a small pilot exploratory neurophysiological add-on study (n = 13) within that larger study. RESULTS: Findings suggest that veterans with GWI receiving either yoga or CBT for pain improved following treatment and that changes in biological ANS-especially for the yoga group-moved in the direction of healthy profiles: lower heart rate, higher square root of the mean squared differences between successive R-R intervals (RMSSD), greater parasympathetic activation/dominance (increased high-frequency heart rate variability [HF-HRV], decreased low-frequency/high-frequency [LF/HF] ratio), reduced right amygdala volume, and stronger amygdala-default mode/amygdala-salience network connectivity, both immediately posttreatment and at 6-month follow-up. Biological mechanisms of CBT appeared to underlie improvements in more psychologically loaded symptoms such as self-reported fatigue and energy. Higher tonic arousal and/or more sympathetic dominance (higher skin conductance, lower RMSSD, lower HF-HRV, higher LF/HF ratio) pretreatment predicted greater treatment-related improvements in self-reported ANS for both the yoga and CBT group. CONCLUSION: These exploratory pilot data provide preliminary support for the suggestion that treatment (yoga, CBT) is associated with improvements in both biological and self-reported ANS dysfunctions in GWI. The major limitation for these findings is the small sample size. Larger and more controlled studies are needed to replicate these findings and directly compare biomarkers of yoga versus CBT.

Brainstem atrophy in Gulf War Illness.

BACKGROUND: Gulf War Illness (GWI) is a condition that affects about 30 % of veterans who served in the 1990-91 Persian Gulf War. Given its broad symptomatic manifestation, including chronic pain, fatigue, neurological, gastrointestinal, respiratory, and skin problems, it is of interest to examine whether GWI is associated with changes in the brain. Existing neuroimaging studies, however, have been limited by small sample sizes, inconsistent GWI diagnosis criteria, and potential comorbidity confounds. OBJECTIVES: Using a large cohort of US veterans with GWI, we assessed regional brain volumes for their associations with GWI, and quantified the relationships between any regional volumetric changes and GWI symptoms. METHODS: Structural magnetic resonance imaging (MRI) scans from 111 veterans with GWI (Age = 49 ±â€¯6, 88 % Male) and 59 healthy controls (age = 51 ±â€¯9, 78 % male) were collected at the California War Related Illness and Injury Study Center (WRIISC-CA) and from a multicenter study of the Parkinson's Progression Marker Initiative (PPMI), respectively. Individual MRI volumes were segmented and parcellated using FreeSurfer. Regional volumes of 19 subcortical, 68 cortical, and 3 brainstem structures were evaluated in the GWI cohort relative to healthy controls. The relationships between regional volumes and GWI symptoms were also assessed. RESULTS: We found significant subcortical atrophy, but no cortical differences, in the GWI group relative to controls, with the largest effect detected in the brainstem, followed by the ventral diencephalon and the thalamus. In a subsample of 58 veterans with GWI who completed the Chronic Fatigue Scale (CFS) inventory of Centers for Disease Control and Prevention (CDC), smaller brainstem volumes were significantly correlated with increased severities of fatigue and depressive symptoms. CONCLUSION: The findings suggest that brainstem volume may be selectively affected by GWI, and that the resulting atrophy could in turn mediate or moderate GWI-related symptoms such as fatigue and depression. Consequently, the brain stem should be carefully considered in future research focusing on GWI pathology.