Erratum to "Branching out: Feasibility of examining the effects of greenspace on mental health after traumatic brain injury" [Dialogues in Health, Volume 2, 2023, 100129].

[This corrects the article DOI: 10.1016/j.dialog.2023.100129.].

Longitudinal associations of time-varying homeboundness and life satisfaction after traumatic brain injury.

PURPOSE/OBJECTIVE: To examine the association of changes in homebound status (i.e., never/rarely leaving the home) with life satisfaction in the first 10 years after traumatic brain injury (TBI). RESEARCH METHOD/DESIGN: We analyzed data from 2,294 individuals with moderate-to-severe TBI from the TBI Model Systems National Database using a longitudinal multilevel model with time-varying predictors to account for within-person changes over time as well as between-person differences. We measured homebound status (defined as leaving the home ≤ 2 days/week) and life satisfaction (defined as the total score on the Satisfaction With Life Scale) at 1, 2, 5, and 10 years post-TBI. We adjusted the models for demographic and injury-related covariates and used inverse probability weighting to account for selection bias. RESULTS: Forty-five (2%) individuals were homebound at all follow-up visits, 523 (22.8%) were homebound at least one follow-up visit, and 1,726 (75.2%) were never homebound. Individuals with TBI who were consistently homebound had > 1 SD lower life satisfaction compared to those who were never homebound, ß = -8.07, 95% confidence interval (CI) = [-9.39, -6.76], p < .001. Individuals who became homebound experienced a significant, but modest, decline in life satisfaction (ß = -2.13, 95% CI = [-2.66, -1.61], p < .001). CONCLUSIONS/IMPLICATIONS: Our results indicate that being homebound and becoming homebound are associated with decreased life satisfaction. Homeboundness is a potentially modifiable target to improve life satisfaction, and elucidation of contributing factors to homebound status will help develop interventions to ameliorate post-TBI homeboundness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Treatment with brain specific estrogen prodrug ameliorates cognitive effects of surgical menopause in mice.

Menopause is an endocrine shift leading to increased vulnerability for cognitive impairment and dementia risk factors, in part due to loss of neuroprotective circulating estrogens. Systemic replacement of estrogen post-menopause has limitations, including risk for estrogen-sensitive cancers. A promising therapeutic approach therefore might be to deliver estrogen only to the brain. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in ovariectomized mice (a surgical menopause model). We treated mice with the prodrug 10ß,17ß-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17ß-estradiol only in the brain. Young and middle-aged C57BL/6 J mice received ovariectomy and subcutaneous implant containing vehicle or DHED and underwent cognitive testing to assess memory after 1-3.5 months of treatment. Low and medium doses of DHED did not alter metabolic status in middle-aged mice. In both age groups, DHED treatment improved spatial memory in ovariectomized mice. Additional testing in middle-aged mice showed that DHED treatment improved working and recognition memory in ovariectomized mice. These results lay the foundation for future studies determining if this intervention is as efficacious in models of dementia with comorbid risk factors.

Predictors of Multidimensional Profiles of Participation After Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury. DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury). MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control). RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and Functional Independence Measure Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity. CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.

Insights into optimizing phantom pain management: A human-centered approach to end-user perspectives.

BACKGROUND: This report explores and summarizes perspectives from end users on unmet needs in achieving optimal and effective phantom pain management through a human-centered design approach. OBJECTIVE: To examine current strategies, pharmacological, nonpharmacological, surgical procedures, virtual reality, and mirror therapy, and the evidence supporting them, in the management of phantom limb pain. DESIGN: This study reviewed and analyzed transcripts acquired in nonresearch contexts from the Veterans Affairs Translational Education and Mentoring Center's commercialization training program and from a Veteran Engagement Panel. Key themes were extracted using quasi-qualitative analysis of one-on-one interviews. RESULTS: Clinicians and patients report that early patient intervention and education will yield improved management of phantom limb pain, which aligns with the growing recognition of the impact of patient-centered care on overall treatment outcomes. Mirror therapy is viewed as an effective and low-risk therapy, though compliance and buy-in may be barriers to clinical practice. Patient engagement can contribute to better treatment adherence and outcomes. CONCLUSION: The study highlights implementation barriers, importance of end-user input, and the role of the Veteran Engagement Panel in providing feedback to pain researchers. The findings help explain unaddressed challenges and areas requiring further research to direct phantom pain management.

Associations of Nightmares and Sleep Disturbance With Neurobehavioral Symptoms Postconcussion.

OBJECTIVE: This study investigates the association of nightmares beyond general sleep disturbance on neurobehavioral symptoms in adults with mild traumatic brain injury (mTBI). DESIGN: Secondary analysis of a concussion cohort study. PARTICIPANTS: One hundred and eleven adults older than 20 years with mTBI were recruited from a specialized concussion treatment center. MAIN MEASURES: Behavioral Assessment Screening Tool, Pittsburgh Sleep Quality Index, and self-report of nightmare frequency in the past 2 weeks. RESULTS: Among adults with mTBI, nightmares accounted for the greatest amount of variability in negative affect (ß = .362, P < .001), anxiety (ß = .332, P < .001), and impulsivity (ß = .270, P < .001) after adjusting for age and sex. Overall sleep disturbance had the strongest association with depression (ß = .493, P < .001), fatigue (ß = .449, P < .001), self-reported executive dysfunction (ß = .376, P < .001), and overall burden from concussive symptoms (ß = .477, P < .001). CONCLUSIONS: Nightmares and sleep disturbance are differentially associated with variance in neurobehavioral symptoms. Nightmares were independently associated with neurobehavioral symptoms representing an excess of normal functioning (eg, anxiety, impulsivity), while general sleep disturbance was associated with neurobehavioral symptoms representing functioning below normal levels (eg, depression, fatigue, self-reported executive dysfunction). Clinical and research implications are discussed.

10-year variability in high and low life satisfaction trajectories post-traumatic brain injury: a TBI model systems study.

PURPOSE: To determine how life satisfaction changes across the first 10 years following traumatic brain injury (TBI). METHODS: Participants included 1,941 individuals from the TBI Model Systems database with life satisfaction data at 1-, 5-, and 10-years post-TBI. Based on Satisfaction With Life Scale scores, individuals were characterized as having one of the five 10-year life satisfaction trajectories: 'Stable High,' 'Stable Low,' 'Increased to High,' 'Decreased to Low,' and 'Unstable.' These were analyzed for group differences in demographics and psychosocial and functional outcomes. RESULTS: Sixty percent participants had 'Stable High' or 'Increasing to High' trajectories. Approximately 25% had "Stable Low' or 'Decreasing to Low' trajectories, and approximately 15% had unstable trajectories. Higher life satisfaction trajectories were associated with the best psychosocial and functional outcomes whereas lower trajectories were associated with the worst psychosocial and functional outcomes. Trajectories were indistinguishable based on demographics. CONCLUSION: Life satisfaction over the first 10 years following TBI is dynamic, with most individuals reporting high life satisfaction by 10 years post-TBI. Examination of psychosocial and functional factors related to life satisfaction trajectories may inform community-based intervention recommendations, resources, and supports to maximize long-term satisfaction with life.

Neurobehavioral Symptom Profiles for the Behavioral Assessment Screening Tool in Chronic Traumatic Brain Injury.

OBJECTIVE: To identify neurobehavioral symptom profiles among persons with chronic traumatic brain injury (TBI) using the Behavioral Assessment Screening Tool (BAST) and to consider participant characteristics that differ between profile groups. SETTING: Community. PARTICIPANTS: Participants (n = 615) were English-speaking adults (≥18) and had a self-reported history of at least one TBI of any severity. DESIGN: Secondary analysis of cross-sectional data. MAIN MEASURES: The BAST measures neurobehavioral symptoms in the domains of Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, and Substance Misuse. RESULTS: Using latent profile analysis (LPA), we identified 3 different neurobehavioral profiles. Overall symptom frequency and differences in the pattern of symptom frequency across domains differentiated the profile groups. Average domain scores differed significantly across the profiles (P < .001) for all domains except Fatigue (P = .076). Those in profile 3 (High-Risk group) reported the most frequent symptoms across all domains (similar Negative Affect frequency as profile 1). Substance Misuse was especially high in this group. Compared to profile 2 (High Negative Affect group), participants in profile 1 (Moderate-Risk group) endorsed significantly more frequent (and more variable) symptoms across all BAST domains, particularly Impulsivity and Substance Misuse. Participants in profile 2 endorsed the least frequent symptoms across all domains. Demographic comparison showed that groups differed based on gender, age, and injury severity (mild vs moderate-severe), with profile 3 composed of the most men and the most persons in early adulthood, and profile 2 composed of the most women and those with mild TBI. CONCLUSIONS: We differentiated 3 neurobehavioral symptom profiles among persons with chronic TBI and determined differences in sociodemographic factors between the groups. Future research should focus on validating these profiles in another sample of individuals with chronic TBI. Characterizing persons according to multidimensional symptom profiles could allow for more tailored approaches to predict and prevent long-term negative outcomes.

Imbalance in Glucose Metabolism Regulates the Transition of Microglia from Homeostasis to Disease-Associated Microglia Stage 1.

Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose dyshomeostasis inhibits DAM1 activation and PKM2 plays a role. As in tumors, PKM2 was aberrantly elevated in both male and female human AD brains, but unlike in tumors, it is expressed as active tetramers, as well as among TREM2+ microglia surrounding plaques in 5XFAD male and female mice. snRNAseq analyses of microglia without Pkm2 in 5XFAD mice revealed significant increases in DAM1 markers in a distinct metabolic cluster, which is enriched in genes for glucose metabolism, DAM1, and AD risk. 5XFAD mice incidentally exhibited a significant reduction in amyloid pathology without microglial Pkm2 Surprisingly, microglia in 5XFAD without Pkm2 exhibited increases in glycolysis and spare respiratory capacity, which correlated with restoration of mitochondrial cristae alterations. In addition, in situ spatial metabolomics of plaque-bearing microglia revealed an increase in respiratory activity. These results together suggest that it is not only glycolytic but also respiratory inputs that are critical to the development of DAM signatures in 5XFAD mice.

Association Between Participation and Satisfaction With Life Over Time in Older Adults With Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVE: To examine the association between participation and satisfaction with life at 1, 2, 5, and 10 years after traumatic brain injury (TBI) in older adults. SETTING: Community. PARTICIPANTS: Participants ( N = 2362) who sustained complicated mild to severe TBI, requiring inpatient rehabilitation, at age 60 years or older and had follow-up data on participation and satisfaction with life for at least 1 follow-up time point across 1, 2, 5, and 10 years. Age at each time period was categorized as 60 to 64 years, 65 to 75 years, and 75 years or older. DESIGN: Secondary data analysis of a large multicenter database. MAIN MEASURES: Three domains (Productivity, Social Relations, Out and About) of the Participation Assessment With Recombined Tools-Objective (PART-O); Satisfaction With Life Scale (SWLS). RESULTS: SWLS increased over the 10 years after TBI and was significantly associated with greater frequency of participation across all domains. There was a significant interaction between age and PART-O Social Relations such that there was a weaker relationship between Social Relations and SWLS in the oldest group (75 years or older). There was no interaction between Productivity or Out and About and age, but greater participation in both of these domains was associated with greater life satisfaction across age groups. CONCLUSIONS: These findings indicate that greater participation is associated with increased satisfaction with life in older adults, across all participation domains over the first 10 years postinjury, suggesting that rehabilitation should target improving participation even in older adults. The decreased association of social relations with satisfaction with life in the oldest age group suggests that frequency of social relations may not be as important for life satisfaction in the oldest adults, but quality may still be important.

Community-based exercise program, self-reported health-related symptoms, and quality of life in persons with traumatic brain injury 45 + years old.

BACKGROUND: Individuals with moderate to severe traumatic brain injury (msTBI) have reported a lack of motivation, lack of time, and fatigue as perceived barriers to exercise. OBJECTIVE: To evaluate the effects of an exercise program on self-reported health-related symptoms and quality of life in persons 45-years and older with msTBI. METHODS: Post-hoc analysis of a prospective community-based 12-week exercise program of 20 adults, age 45-80 years, with msTBI. Ten were in aerobic exercise training (AET) program and 10 in a stretching and toning (SAT) program. The AET group was instructed to exercise based on their estimated maximal heart rate (HR) for 150 minutes weekly. The SAT group was to stretch for the same target time without significantly increasing HR or level of exertion. Outcome measures were Traumatic Brain Injury Quality of Life (TBI-QOL) for global, cognitive, emotional, and social health, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. RESULTS: AET was associated with improved self-reported cognitive health and sleep compared to SAT. Moderate to large, positive effect sizes were also observed in the AET group in the QOL categories of global, emotional, and social health, and depressive symptoms. CONCLUSIONS: This study offers preliminary evidence that AET may improve health-related QOL, especially for cognition and sleep, in middle-aged and older adults with msTBI.

Ten years later: An update on the status of collections of endemic Gulf of Mexico fishes put at risk by the 2010 Oil Spill.

The 2010 Gulf of Mexico Deepwater Horizon was the largest oil spill in human history that occurred during a 12-week period in a region less than 100 km from the coast of Louisiana; however, after more than a decade of post-spill research, few definitives can be said to be known about the long-term impacts on the development and distribution of fishes in and around the region of the disaster. Here, we examine endemic Gulf of Mexico fish species that may have been most impacted by noting their past distributions in the region of the spill and examining data of known collecting events and observations over the last twenty years (ten years prior to the spill, ten years post-spill). Five years post-spill, it was reported that 48 of the Gulf's endemic fish species had not been collected and, with expanded methods, we now report that 29 (of the 78 endemic species) have not been reported in collections since 2010 (five of these are only known from observations post-spill). Although the good news that some previously 'missing' species have been found may be cause to celebrate, the lack of information for many species remains a cause for concern given focused sampling efforts post-spill.

Treatment approaches and costs associated with diabetes clinical metrics as measured by Healthcare Effectiveness Data and Information Set (HEDIS).

BACKGROUND: The clinical outcomes of diabetes can be influenced by primary care providers' (PCP) treatment approaches. This study explores the association between PCP approaches to management and performance measured by established diabetes metrics and related costs. METHODS: In phase one, Electronic Medical Records were used to extract diabetes related metrics using Healthcare Effectiveness Data and Information Set (HEDIS), for patients with diabetes who had office visits to 44 PCP practices from April 2019 to March 2020. Using those metrics and scoring system, PCP practices were ranked and then categorized into high- and low-performing groups (top and bottom 25%, n = 11 each), with a total of 19,059 clinic visits by patients with a diagnosis of diabetes. Then extensive analysis was performed to evaluate a correlation between treatment approaches and diabetes outcomes across the top and bottom performing practices. In phase 2, patients with diabetes who were attributed to the aforementioned PCP practices were identified in a local health plan claims data base (a total of 3,221 patients), and the allowed amounts from their claims were used to evaluate differences in total and diabetes-related healthcare costs by providers' performance. RESULTS: Comparing 10,834 visits in high-performing practices to 8,235 visits in low-performing practices, referrals to certified diabetes care and education specialists and provider-to-provider electronic consults (e-consults) were higher in high-performing practices (Z = 6.06, p < .0001), while traditional referrals were higher in low-performing practices (Z = -6.94, p < .0001). The patient-to-provider ratio was higher in the low-performing group (M = 235.23) than in the high-performing group (M = 153.26) (Z = -2.82, p = .0048). Claims data analysis included 1,825 and 1,396 patients from high- and low-performing providers, respectively. The patient-to-provider ratio was again higher in the low-performing group (p = .009, V = 0.62). Patients receiving care from lower-performing practices were more likely to have had a diabetes-related hospital observation (5.7% vs. 3.9%, p = .02; V = 0.04) and higher diabetes-related care costs (p = .002; d = - 0.07); these differences by performance status persisted when controlling for differences in patient and physician characteristics. Patients seeing low-performing providers had higher Charlson Comorbidity Index scores (Mdn = 3) than those seeing high-performing providers (Mdn = 2). CONCLUSIONS: Referrals to the CDCES and e-Consult were associated with better measured diabetes outcomes, as were certain aspects of cost and types of hospital utilization. Higher patients to providers ratio and patients with more comorbidities were observed in low performing group.

Characterization of telerehabilitation visits and patient satisfaction in outpatient physical medicine and rehabilitation clinics from March 2020 to November 2021.

OBJECTIVE: To explore the usability of and satisfaction with telerehabilitation services provided to rehabilitation patients with various diagnoses at two large urban medical facilities during the Covid-19 pandemic. DESIGN: This was a usability study and all patients that received telerehabilitation services from March 2020 to November 2021 were included. Of the 4,070 surveys sent via mail or email links to RedCap, 405 were completed (10% Response Rate). Participants completed demographic surveys, surveys on the telerehabilitation visit characteristics, telerehabilitation usability, and overall satisfaction with the visit. RESULTS: Patients were mostly women (64.4%), White, non-hispanic (74.3%) and English speaking (99%). Most patients were seen via telerehabilitation due to Covid-19 restrictions (37.1%). Patients were generally satisfied with their telerehabilitation visit (3.64 out of 4). Additionally, patients generally found telerehab to be useful (6.4 out of 7), easy to use (6.3 out of 7), effective (6.2 out of 7), satisfactory (6.3 out of 7) and comparable to in-person visits (6.5 out of 7). CONCLUSION: Patients generally reported feeling satisfied and comfortable with telerehabilitation visits, and felt they were comparable to in-person visits. Future research should examine the impact of socioeconomic factors on telerehabilitation use, with a focus on education level and non-English speakers.

Characterizing Health Literacy and Its Correlates Among Individuals With Traumatic Brain Injury (TBI): A TBI Model Systems Study.

OBJECTIVE: To characterize health literacy among individuals with traumatic brain injury (TBI) at least a year postinjury and to explore its relationship to sociodemographic variables, injury severity, and cognition. SETTING: Community following discharge from inpatient rehabilitation. PARTICIPANTS: In total, 205 individuals with complicated mild to severe TBI who completed follow-up as part of a national longitudinal study of TBI and completed a web-based health literacy measure. DESIGN: Multicenter, cross-sectional, observational study. MAIN MEASURES: Health Literacy Assessment Using Talking Touchscreen Technology. RESULTS: Thirty-one percent of the sample demonstrated marginal/inadequate health literacy; 69% demonstrated adequate health literacy. A higher proportion of non-Hispanic White adults had adequate health literacy than non-Hispanic Black and Hispanic adults. Individuals with greater than a high school education were more likely to have adequate health literacy than those with a high school education or less. Better executive functioning performance was related to adequate health literacy. Better episodic memory performance was related to adequate health literacy, but only for those with complicated mild to moderate injury. CONCLUSIONS: A substantial proportion of individuals with TBI have marginal/inadequate health literacy, which may impact their understanding, appreciation, and use of health-related information and recommendations. While low health literacy may be preexisting, directly related to TBI, or a combination of both, it should be screened and considered by professionals when communicating with persons with TBI. Healthcare providers should tailor their communication approaches and presentation of health information, particularly for those with low health literacy.

Thiamine administration in septic shock: a post hoc analysis of two randomized trials.

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.

Convergent, discriminant, and known groups validity of the Behavioral Assessment Screening Tool (BAST) in chronic traumatic brain injury.

The Behavioral Assessment Screening Tool (BAST) measures self-reported neurobehavioral symptoms commonly experienced by adults with traumatic brain injury (TBI). To assess the convergent, discriminant, and known-groups validity of the BAST among community-dwelling adults with chronic traumatic brain injury (TBI), we conducted correlation analyses and tests of group differences with previously validated symptom measures in two samples (n = 111, n = 134). Measures used for comparison were: Patient Health Questionnaire (depression), Generalized Anxiety Disorder-7 (anxiety), Positive and Negative Affect Schedule, Frontal Systems Behavior Scale (Executive Dysfunction, Apathy, Disinhibition), Modified Fatigue Impact Scale, PROMIS Fatigue, Aggression Questionnaire (anger, hostility, physical and verbal aggression), and Alcohol Use Disorders Test (alcohol misuse). BAST subscales had stronger correlations with measures of similar (|r|=.602-.828, p < .001) and related (|r|>.30, p < .001) constructs and weaker correlations (|r|<.300) with measures of dissimilar/unrelated constructs, supporting hypotheses of convergent and discriminant validity, respectively. Statistically significant group differences (p's < .001) in BAST subscales were found, with large effect sizes (Cohen's d = 1.2-1.9), for known-groups with moderate-severe depression, moderate-severe anxiety, clinically significant fatigue, problematic disinhibited and frontal-executive behaviors, and alcohol use. Conclusions: Results support the convergent and discriminant validity of the BAST subscales. The BAST was specifically developed as a self-reported measure for remote symptom reporting, supporting its incorporation into mobile health platforms to improve chronic symptom monitoring in community-dwelling adults with TBI. With further validation research, the BAST could be used for early identification of persons with TBI who could benefit from intervention.

Voltage-gated potassium channels control extended access cocaine seeking: a role for nucleus accumbens astrocytes.

Dopaminergic signaling in the nucleus accumbens shell (NAc) regulates neuronal activity relevant to reward-related learning, including cocaine-associated behaviors. Although astrocytes respond to dopamine and cocaine with structural changes, the impact of dopamine and cocaine on astrocyte functional plasticity has not been widely studied. Specifically, behavioral implications of voltage-gated channel activity in the canonically non-excitable astrocytes are not known. We characterized potassium channel function in NAc astrocytes following exposure to exogenous dopamine or cocaine self-administration training under short (2 h/day) and extended (6 h/day) access schedules. Electrophysiological, Ca2+ imaging, mRNA, and mass spectrometry tools were used for molecular characterization. Behavioral effects were examined after NAc-targeted microinjections of channel antagonists and astroglial toxins. Exogenous dopamine increased activity of currents mediated by voltage-gated (Kv7) channels in NAc astrocytes. This was associated with a ~5-fold increase in expression of Kcnq2 transcript level in homogenized NAc micropunches. Matrix-assisted laser desorption/ionization mass spectrometry revealed increased NAc dopamine levels in extended access, relative to short access, rats. Kv7 inhibition selectively increased frequency and amplitude of astrocyte intracellular Ca2+ transients in NAc of extended access rats. Inhibition of Kv7 channels in the NAc attenuated cocaine-seeking in extended access rats only, an effect that was occluded by microinjection of the astrocyte metabolic poison, fluorocitrate. These results suggest that voltage-gated K+ channel signaling in NAc astrocytes is behaviorally relevant, support Kv7-mediated regulation of astrocyte Ca2+ signals, and propose novel mechanisms of neuroglial interactions relevant to drug use.

Emotional, Behavioral, and Cognitive Symptom Associations With Community Participation in Chronic Traumatic Brain Injury.

OBJECTIVES: To determine the association between self-reported emotional and cognitive symptoms and participation outcomes in chronic traumatic brain injury (TBI) and to explore the relative contribution of self-reported versus performance-based cognition to participation outcomes. SETTING: Community. PARTICIPANTS: Community-dwelling adults ( n = 135) with a lifetime history of mild to severe TBI. DESIGN: Secondary analysis of a cross-sectional study on neurobehavioral symptoms in chronic TBI. MAIN MEASURES: Behavioral Assessment Screening Tool (BAST) (Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, Substance Abuse subscales) measured self-reported neurobehavioral symptoms; Participation Assessment with Recombined Tools (Productivity, Social Relations, and Out and About) measured self-reported participation outcomes; and Brief Test of Adult Cognition by Telephone (BTACT) measured performance-based cognition (Episodic Memory and Executive Function summary scores) in a subsample ( n = 40). RESULTS: The BAST Executive Dysfunction was significantly associated with less frequent participation and had the strongest effect on participation in all participation domains. No other BAST subscales were associated with participation, after adjusting for all subscale scores and age, with the exception of BAST Impulsivity, which was associated with more frequent Social Relationships. Exploratory analysis in the sample including the BTACT revealed that, after accounting for subjective Executive Dysfunction using the BAST, performance-based Executive Function was associated with Productivity and Working Memory was associated with Social Relations, but neither was associated with being Out and About; the BAST Executive Dysfunction remained significant in all models even after including BTACT scores. CONCLUSIONS: Self-reported Executive Dysfunction contributed to participation outcomes after mild to severe TBI in community-dwelling adults, whereas self-reported emotional and fatigue symptoms did not. Performance-based cognition measures may capture different variability in participation after injury.

The Relationship of Health Literacy to Health Outcomes Among Individuals With Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the associations between health literacy and health outcomes among individuals with traumatic brain injury (TBI) at least a year post-injury. SETTING: Community following discharge from inpatient rehabilitation. PARTICIPANTS: A total of 205 individuals with complicated mild to severe TBI who completed a TBI Model Systems National Database follow-up interview and a web-based health literacy measure. DESIGN: A multicenter, cross-sectional, observational study. MAIN MEASURES: The Health Literacy Assessment Using Talking Touchscreen Technology (Health LiTT), number of comorbid conditions (Medical and Mental Health Comorbidities Interview [MMHCI]), perceived physical and mental health (PROMIS Global Physical and Mental Health subscales), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7). RESULTS: After controlling for sociodemographic, injury, cognition, and time post-injury, adequate health literacy was associated with higher odds of greater perceived physical health compared with participants with marginal/inadequate health literacy (odds ratio = 4.10; CI = 1.52-11.70]. Participants with inadequate/marginal health literacy had 3.50 times greater odds of depression (PHQ-9 ≥ 10) compared with those with adequate health literacy. Participants 45 years and older reported a greater number of MMHCI physical health conditions, but fewer MMHCI mental health conditions and GAD-7 anxiety symptoms compared with those who were younger. Non-Hispanic White participants and those with mild/moderate TBI were more likely to report a greater number of MMHCI mental health conditions compared with non-Hispanic Black participants or those with severe TBI. Greater time post-injury was associated with greater number of chronic physical and mental health conditions, and less odds of good-to-excellent perceived global mental health. CONCLUSIONS: Inadequate health literacy is associated with worse perceived physical health and greater depressive symptoms among adults with TBI. Greater efforts are needed to explore the mechanisms by which health literacy influences chronic disease management and mental health after TBI to improve postinjury health status and outcomes, particularly among those with limited health literacy skills.