Brain Sciences

Background: Neuroanatomy poses a significant challenge for Psychology students due to its spatial and conceptual complexity. Educational approaches that enhance the relevance and visualization of neuroanatomical content may improve students learning experiences. This study implemented a tractography-based activity focused on the virtual dissection of the arcuate fasciculus, a major white matter pathway, in undergraduate Psychology students and examined the relationships between perceived learning and students perceptions of utility, difficulty and handling, and organizational aspects of the activity. Methods: First-year undergraduate Psychology students participated in a two-session tractography-based activity combining instruction on white matter anatomy and diffusion tractography with a hands-on virtual dissection of the arcuate fasciculus using research-grade software routinely employed in neuroscience research. Following the activity, students completed an anonymous questionnaire assessing perceived learning, utility, difficulty and handling, and organizational aspects of the activity. Pearson correlations, multiple regression analyses, and relative importance analyses were performed. Results: Sixty-eight students completed the questionnaire. Students reported generally positive perceptions of the activity across the evaluated dimensions, with perceived learning receiving the highest mean score (M = 3.44, SD = .85). Perceived utility showed the strongest association with perceived learning (r = .64, p < .001). The regression model explained 41% of the variance in perceived learning (R2 = .41, adjusted R2 = .38, p < .001). Perceived utility was the only significant predictor in the model ({beta} = .59, p = .001), accounting for 67.9% of the explained variance. Conclusions: The findings support the feasibility of integrating authentic neuroimaging tools into undergraduate neuroanatomy teaching. Students who perceived the activity as more useful also reported higher perceived learning outcomes, with perceived utility emerging as the strongest predictor of perceived learning. In contrast, perceived difficulty and handling, and organizational aspects did not make significant independent contributions. These results suggest that students perceptions of educational relevance may play an important role in technology-enhanced STEM learning experiences.

Musical aesthetic experience can reveal students' cognitive, aesthetic, and emotional responses to music. However, how professional vocal training alters brain functions in female college students with varying levels of musicianship to promote these is unknown. Here we applied fMRI, psychological measures and Goldsmiths musical sophistication index (Gold-MSI) assessments to study 27 non-music major female college students consisting of instrument group (normal pitch accuracy with instrumental training), general group (normal pitch accuracy without instrumental training) and poor-pitch group (poor pitch accuracy and without instrumental training). After 1 year of one-on-one instructional practice, we found that professional vocal training enhanced information processing related to musical cognition and pleasure during musical aesthetic experiences across all three groups, involving improvements in motor control of vocalization, auditory feedback processing, musical memory and attention together with musical pleasure. Specifically, instrument group showed activation of reward circuits, general group exhibited activation of laryngeal motor control circuits, and poor-pitch group displayed activation of sensory/sensorimotor/motor control circuits. Both pre- and post-training, the instrument group exhibited higher connectivity than the other two groups in the left amygdala-dorsal anterior cingulate cortex (dACC) and the right posterior superior temporal gyrus (pSTG)-left insula pathway. After professional vocal training, the general group showed higher connectivity in the left amygdala-dACC, whereas the poor-pitch group demonstrated increased connectivity in the right pSTG-left insula and dACC-nucleus accumbens pathways. Surprisingly, professional vocal training activated the bed nucleus of the stria terminalis (BNST), a subcortical emotion center, and connectivity with the medial prefrontal cortex associated with musical information processing. Thus, vocal training can significantly improve musical cognition and aesthetic pleasure, and facilitates neural modulation in the brain's emotional centers.

Purpose Older adults with HIV are at risk of psychiatric disorders and poor sleep quality, but evidence from sub-Saharan Africa is limited, particularly regarding sustained viral suppression. This study examined the prevalence of psychiatric disorders and poor sleep quality symptoms and their association with sustained viral suppression among older adults with HIV in Nigeria. Methods: A retrospective cohort study was conducted among older adults receiving care at a tertiary HIV clinic in Ibadan, Nigeria. Viral load data from 2019-2023 were abstracted from medical records to determine sustained viral load suppression, while psychiatric morbidity and sleep quality were assessed cross-sectionally in 2023. Psychiatric assessments included major depressive disorder, anxiety disorder, bipolar disorder and mania. Mixed-effects logistic regression assessed changes in viral suppression over time and associations with psychiatric morbidity and sleep quality. Results: Among 400 participants, 63.5% were female and mean age was 58.2 years (S.D 6.5). A total of 25.8% had major depressive disorder, 17.5% had anxiety disorder, 29.3% had poor sleep quality, 3.3%, bipolar disorder, and 1.0% mania. Viral suppression improved significantly over the retrospective period. Sustained viral suppression was significantly associated with higher odds of good sleep quality (OR = 1.69, 95% CI: 1.07 to 2.66, p = 0.025), but not psychiatric morbidity. Conclusion: Psychiatric disorders and poor sleep quality are common among older adults with HIV in Nigeria. Sustained viral suppression was associated with better sleep quality but not psychiatric morbidity highlighting the importance of integrating mental health and sleep assessment into comprehensive HIV care for older adults.

Background. Alcohol use impacts sleep; however, sleep is also impacted by other 24-hour movement behaviors, including sedentary behavior (SB) and physical activity (PA). This study used compositional data analysis (CoDA) to simultaneously account for SB and PA and investigate within- and between-person associations between sleep and alcohol use behaviors. Methods. Participants were 21-44-year-old overweight/obese adults. Across 21 days, participants wore an activPAL monitor to assess sleep, PA, and SB hours, and completed morning surveys of past day alcohol use to assess drinks/day. CoDA identified the daily proportions of time spent in sleep, PA, and SB. Multilevel models investigated within- and between-person associations between sleep, demographic factors, and alcohol use. Differences in sleep, SB, and PA across drinking versus non-drinking days were investigated with individual MANOVAs for each participant. Results. Participants (N=91, Mage=30.7{+/-}6.5, 57% female, 75% White) reported drinking on 23% (n=437) of days, consumed 1 drink/day, and averaged 8.5{+/-}2.3 sleep hours, 7.4{+/-}2.8 SB hours, and 8.0{+/-}2.7 PA hours per day. Multilevel models indicated that participants slept 16.6 fewer minutes on drinking days (p=.046) each additional drink corresponded with 4.4 fewer minutes of sleep (p=.04). There was large between-person variability in time use allocations across drinking versus non-drinking days. For many the change was non-significant; however, three participants spent significantly less time sleeping on drinking days (1.16-4.74 fewer hours of sleep) and one participant spent significantly (2.62) more hours sleeping on drinking versus non-drinking days. Conclusions. Drinking days and greater alcohol consumption were associated with fewer minutes of sleep within-people; however, shifts towards PA and SB were inconsistent. Investigating contextual factors, such as the physical/social context of alcohol use, the time-of-day drinking occurs, the type of alcohol consumed, or the type of PA a person engages in could provide deeper insight into the conditions under which alcohol use detrimentally impacts sleep.

Background: Force production reflects neuromuscular capacity, central regulation, and sensory feedback, making performance-based testing vulnerable when disease-related limitations could be interpreted as reduced effort. Repeated handgrip strength (HGS) testing may quantify neuromuscular fatigability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but interpretation of within-subject variability as an effort-validity marker remains controversial. We tested whether the coefficient of variation (CV) distinguishes ME/CFS-related impairment from deliberate submaximal performance and compared it with the sum of residuals (SR), a trajectory-aware metric. Methods: We analyzed three cohorts using the same repeated-HGS protocol: two 10-trial sessions separated by one hour. We included 211 ME/CFS participants and 170 controls, including 28 instructed to perform at 50% perceived maximum force. CV and SR were determined as HGS variability measures and compared by probability-density overlap and receiver operating characteristic analyses. The primary comparison was ME/CFS versus deliberately submaximal controls. Results: CV distributions showed substantial overlap between groups. SR improved group-level separation, increasing non-overlapping fractions from 0.217 to 0.326 in the Jaekel cohort and from 0.180 to 0.361 in the MIRACLE cohort. In ROC analyses, SR consistently yielded higher discrimination than CV across cohorts, sessions, and sex strata. A commonly used 15% CV cutoff classified 42-48% of ME/CFS participants as submaximal, while correctly identifying only 57-64% of deliberately submaximal controls. Conclusions: CV may conflate ME/CFS-related fatigability with irregular force modulation and should not be used as stand-alone evidence of submaximal effort. Trajectory-aware SR partly reduced this bias and indicated that ME/CFS-related force impairment is distinguishable from deliberate submaximal force production at the group level. However, neither metric should be used alone to diagnose ME/CFS or evaluate sincerity of effort.

Chemotherapy is a common treatment for women with ovarian cancer, and many women treated with chemotherapy experience cognitive dysfunction. However, few studies have investigated the mechanisms of chemotherapy-related cognitive impairment in women with ovarian cancer. The goal of this study was to assess the relationships among neurovascular coupling, iron levels and cognitive functions in women with ovarian cancer after first-line chemotherapy. Simultaneous fNIRS and EEG data were collected in women diagnosed with advanced stage ovarian cancer at baseline (N = 13) and after 3-9 rounds of chemotherapy (N = 8). The attentional network task (ANT) was administered for neurocognitive evaluation. Blood iron levels were measured using standard clinical assays. In parallel, similar concurrent fNIRS-EEG data were acquired in a group of 10 healthy participants in a test-retest design. Cognitive performance declined, as indicated by decreases in ANT sub scores after chemotherapy. Blood iron biomarkers indexing oxygen transport also declined and were related to decreases in the ANT sub scores. Both fNIRS and EEG data responses were shown to have excellent reliability in the healthy subjects, while cancer patients showed significant decreases in oxygenated hemoglobin response in fNIRS, despite no changes in EEG responses after chemotherapy. A significant dose relationship was also found in the changes of fNIRS responses. Our data indicate that chemotherapy produced cognitive deficits and decreases in the oxygenated hemoglobin response and that these may be related to reduced oxygen transport capacity. Results also suggest the utility of using fNIRS-EEG to monitor the progression of cognitive impairment and characterize those mechanisms.

Background: Stroke survivors frequently experience post-stroke depression (PSD) and post-stroke anxiety (PSA), which may be underexamined by clinicians if patient mood status between discharge and follow-up is unknown. Digital monitoring may enable early identification of mood disturbances. Ecological momentary assessments (EMA) have been tested to capture mood fluctuations in patients regular environments, but no standardized procedure for monitoring PSA or PSD has been developed. Objective: Determine the feasibility and validity of EMA for evaluating subacute PSA and PSD in non-severe stroke patients. Methods: Patients with non-severe stroke discharged home responded to daily smartphone EMA questions concerning mood and activity for twelve weeks until follow-up. Questions based on symptoms of anxiety and depression were used to derive EMA Anx and EMA Dep indices, computed over five 15-day intervals. Convergent validity was assessed using follow-up Generalized Anxiety Disorder-7 (GAD-7) and Centre for Epidemiological Studies-Depression (CES-D) scores. Logistic regression models predicted PSA and PSD status at follow-up, with baseline models comprising stroke severity, age, sex, and mood status, to which EMA Anx or Dep were added. Results: Data from 118 patients were analyzed. EMA adherence was moderate, with 89 patients (75.4%) responding on 75 or more days. Correlations between EMA Anx and GAD-7 and between EMA Dep and CES-D generally strengthened at later intervals, with the average mood index generally showing the strongest associations. Adding EMA data from the third time interval (31-45 days) significantly improved model fit beyond the baseline models (Anxiety: {chi}-square = 7.08, p = 0.008, {delta}R-square = 0.060; Depression: {chi}-square = 28.0, p < 0.001, {delta}R-square = 0.256). Discussion: EMA is feasible in mild-to-moderate stroke patients and may facilitate early identification of post-stroke mood disturbances. Further analyses in more diverse populations are required to validate these findings.

Purpose: Electrical stimulation of the occipital cortex evokes visual percepts known as phosphenes. To date, most human studies have examined phosphenes elicited by large surface or depth electrodes. These differ considerably from the small penetrating intracortical microelectrodes capable of stimulating highly localized cortical populations that are the basis of current next-generation devices. Here, we provide a detailed characterization of phosphenes evoked by such intracortical microelectrodes. Methods: As part of the CORTIVIS clinical trial, a Utah Electrode Array with 100 penetrating electrodes was implanted in the early visual cortex of four blind volunteers. Participants completed drawing and description tasks in response to single-electrode stimulation. Two participants also performed forced-choice tasks to determine whether phosphenes elicited by different electrodes could be reliably discriminated. Results: Single-electrode stimulation reliably evoked phosphenes in all participants. Most percepts appeared in the contralateral visual field, although two participants reported near-midline ipsilateral percepts. Phosphenes ranged from simple dots to elongated, textured, circular, or otherwise idiosyncratic forms. One participant reported distinguishable phosphene colors, which depended on electrode and amplitude structure and varied across sessions. The two participants tested on forced-choice discrimination could successfully identify electrode-specific phosphenes across multiple sessions. Conclusions: Intracortical microstimulation of the human visual cortex produces phosphenes with diverse, electrode-specific appearances that are recognizable across repeated trials. These findings indicate that penetrating microelectrodes often evoke more structured percepts than simple points or blobs, providing foundational evidence that electrode-specific encoding strategies will be necessary in future visual prosthetic devices.

Cross-sectional studies suggest associations between physical exercise and white matter in older adults, but evidence from randomized controlled trials is scarce. Neurite orientation dispersion and density imaging indices are biophysically informed metrics of white matter microstructure. Here, we tested whether a remotely delivered, 8-week multicomponent physical exercise intervention impacts neurite density (NDI) and orientation dispersion (ODI) across major white matter tracts in older adults. This secondary analysis of a randomized controlled trial included participants with available diffusion MRI data (n = 66; age: 66.4 {+/-} 3.6 y; 43 females). Participants were randomized to a multicomponent exercise (PAG, n = 34) or an active control (CON, n = 32) intervention. Intervention effects on NDI/ODI were tested using linear mixed-effects and Bayesian multilevel models adjusted for age and sex. A significant Timepoint x Group interaction was observed for NDI (p = 0.003) but not for ODI (p = 0.785), further confirmed in Bayesian analyses for 22 white matter tracts, indicating a greater increase in NDI in the PAG. The standardized composite VO2max score increased from pre- to post-intervention within the PAG, although the Timepoint x Group interaction was not significant (p = 0.079). Across all participants, pre-to-post changes in mean NDI were positively correlated with changes in VO2max, but this association did not differ between groups. Our results indicate that white matter microstructure remains responsive to short-term, multicomponent physical exercise in older adults.

Objective: Published P300-speller fusion schemes fix prior trust regardless of trial reliability; we tested whether a reliability estimate improves on it. Methods: We reanalyzed 3,373 archived P300-speller selections from 47 people with ALS (BigP3BCI). A fair, matched-search-space comparison, tuning both a fixed weight and an adaptive policy out-of-fold, was evaluated across 22 evaluable language-model priors up to 46.7B parameters. Two representative priors, GPT-2 and a classical 5-gram, additionally received detailed naive and mechanistic analyses. Results: No prior's 95% CI favored adaptive fusion under the fair comparison, despite unexploited oracle headroom at every scale. Under GPT-2, the naive comparison was significantly worse for adaptive fusion; both anchors converged to a degenerate or near-degenerate fair-comparison solution. For the representative anchors, three further controllers failed to convert that headroom into benefit; the fixed-fused posterior's output probability outperformed the best controller for flagging errors (2.8- to 3.8-fold enrichment). Conclusion: A tuned fixed weight is a difficult-to-beat default across the tested scale range; reliability estimation gave no deployable adaptive advantage. Significance: Adaptive weighting should be validated against a fairly tuned baseline across model families and scales; in this dataset, the fused output's confidence identified high-risk selections better than the tested purpose-built ranker.

Purpose: There is a long-standing perception that individuals who stutter are less intelligent, with the disfluencies unique to stuttered speech often assumed to be the overt reflection of lower intelligence, despite no supporting evidence. The purpose of the present study was to explore the validity of this assumption by examining the cognitive abilities of adults who stutter compared to the general population using the NIH Toolbox (C) Cognition Battery (NIHTB-CB). Method: Sixty-three adults who stutter completed the NIHTB-CB, which includes seven standardized measures assessing crystallized cognition (Picture Vocabulary, Oral Reading) and fluid cognition (List Sorting Memory Test, Pattern Comparison Processing Speed Test, Flanker Inhibitory Control Test, Dimensional Change Card Sort Test, Picture Sequence Memory Test). The NIHTB-CB generates t-scores adjusted for demographic variables based on a large sample of neurotypical adults. Results: Composite scores of overall cognition for adults who stutter were not statistically equivalent, rather, their scores were higher than the general population. Higher scores were driven by crystallized cognition, with significantly higher scores on Oral Reading subscale. Conclusions: Present findings demonstrate that adults who stutter possess cognitive skills that are comparable to or potentially higher, than the general population. These results challenge the misconception that stuttering reflects diminished intelligence and offer evidence to mitigate stereotype threat.

Background: Virtual and Augmented Reality (VR/AR) are increasingly used in medicine and may offer novel interventions for Functional Neurological Disorder (FND) by targeting mechanisms of impaired motor control. However, evidence for the effect of different modalities on movement in FND is limited. Moreover, it is hypothesized that visual feedback of one s affected arm could reinforce FND symptoms through maladaptive self-monitoring. The present study aims to compare motor performance under visual feedback of a virtual avatar versus the real arm. Methods: Fifteen FND patients and eighteen healthy controls completed a dual motor reaching task (touching a virtual fruit such as orange or apple appearing in front of them) with a virtual headset across three modalities: Augmented Reality (AR), where participants saw their real arm; Virtual Reality (VR), with a virtual arm; and Virtual Reality Improved (VRI), with artificially enhanced straightness and larger collision zone with the target. Their movement speed, straightness and number of velocity peaks were calculated for each fruit catch. Additionally, the number of collisions between the eyes and the body was calculated with eye tracking technology. Results: FND participants were slower and produced less smooth movements in AR compared to VR (b = 1.09, z = 8.83, P < .001) and VRI (b = 0.85, z = 6.91, P < .001), while the opposite effect was found in healthy controls. Eye tracking showed that FND patients looked more at their affected hand than unaffected hand (b = -1.46, SE = 0.34, z = -4.23, p < .001; OR = 0.23). Conclusions: Virtual feedback of their limbs avatar appears to support better motor performance, while visual feedback of their real limb appears to exacerbate motor impairments in FND patients, likely reinforcing maladaptive self-monitoring. These findings highlight the therapeutic potential of VR interventions and provide the basis for future studies examining longer protocols, clinical outcome and potential implementation in standard motor rehabilitation.

Transcranial magnetic stimulation (TMS) is widely used in both clinical and research settings to study and treat neurological and neuropsychiatric disorders, yet its underlying neural mechanisms remain unclear; particularly how stimulation influences both local and distant regional activity in relation to behavior. In this study, we combined single-pulse TMS with concurrent whole-head functional near-infrared spectroscopy (fNIRS) to examine hemodynamic and behavioral responses during a working memory task, with a focus on behavioral variability. Single TMS pulses were delivered to the left dorsolateral prefrontal cortex (DLPFC) while healthy participants rested; additionally, single pulses were delivered online to the left DLPFC while participants performed the working memory task. Across all participants, we observed a reliable load-dependent increase in hemodynamic activity associated with task. However, behavioral responses to TMS varied during the task. When participants were stratified into subgroups based on performance, a distinct topographic pattern emerged. During the task, TMS systematically modulated hemodynamic responses in regions including DLPFC, superior medial gyrus, precuneus, and parietal lobule, which are areas belonging to the default mode network. Moreover, the hemodynamic response during the single pulse alone sessions without any task was also found to be associated with the behavioral responses in a coherent pattern involving DLPFC, precuneus and parietal lobules. These findings suggest that variable behavioral outcomes during online TMS task are linked to distinct hemodynamic responses in a topographic pattern of local and distant regional areas.

Impulsivity is associated with various maladaptive behaviors, although its specific role in criminology has remained largely unexplored. We investigated impulsivity in theft recidivists (TR) with and without a diagnosis of kleptomania (KA) compared to control (CT) subjects with no criminal record in this study. Impulsivity was measured using a 5-trial adjusting delay discounting task, and prefrontal cortical (PFC) hemodynamics were assessed using functional near-infrared spectroscopy. Self-report questionnaires were also administered to further evaluate the relationships between impulsivity, negative affect, and reward and punishment sensitivity. TR demonstrated significantly higher impulsivity than CT, along with altered dorsomedial PFC hemodynamic responses. In addition, negative affect was significantly higher in the TR than in the CT participants. Path analysis revealed that the moderation of negative affect on reward, but not punishment, sensitivity, mediated impulsivity in TR. Notably, heightened impulsivity was observed across the TR participants regardless of KA diagnosis, whereas severe depression specifically distinguished KA from TR without it. These findings suggest that while trait impulsivity associated with PFC alterations may be a universal feature of TR, recurrent theft may be a heterogeneous condition, with specific affective dysregulations contributing differently to TR. SIGNIFICANCE STATEMENTRecurrent thefts, such as shoplifting, are a devastating social problem, posing massive financial losses. Nonetheless, surprisingly nothing is known about the neurobehavioral mechanisms that drive people stealing. In fact, kleptomania is a psychiatric disorder that had been identified over 200 years ago, yet exceptionally few studies have investigated this psychiatric condition, and its mechanism remains essentially unknown to date. This study demonstrates that impulsivity is elevated among incarcerated individuals with recurrent thefts with and without a diagnosis of kleptomania, which is associated with the activity of the left dorsomedial prefrontal cortex. Conversely, heightened depression among negative affect is a unique characteristic to kleptomania, providing evidence of heterogeneity among theft recidivists.

BackgroundSelf-compassion has shown to be an effective emotion regulation strategy, but its neural mechanisms remain understudied in adolescents with depression who suffer from social exclusion. This study employed event-related potentials to investigate the psychophysiological mechanisms underlying impaired self-compassion in adolescents with depression during social exclusion. MethodsThirty-seven adolescents with major depressive disorder (age = 16.46 {+/-} 2.02) and thirty-two demographically matched healthy controls (age = 16.54 {+/-} 2.29) completed a social exclusion scenario imagination task. This task presented participants with social exclusion scenarios, asking them to imagine themselves as the excluded individual and subsequently rate their negative emotions. The regulation session required participants to use self-compassionate statements to regulate their emotional responses while imagining and rate how much self-compassion they have engaged in; the non-regulation required them not to use those statements and rate their negative emotions immediately following imagination. EEG signals were recorded during the task, and the late positive potential (LPP) was analyzed to examine the neural responses associated with self-compassion regulation following social exclusion. ResultsCompared with the non-regulation condition, both groups showed less negative emotion during the self-compassion regulation condition. Adolescents with depression exhibited significantly lower self-compassion ratings than healthy controls, and showed a significantly smaller decrease in negative emotions. Higher self-compassion ratings were correlated with greater emotion regulation effect, particularly in adolescents with depression. Furthermore, LPP amplitudes were significantly higher in adolescents with depression than in healthy controls during both regulation and non-regulation conditions. ConclusionsAdolescents with depression were characterized by impairment in using self-compassion to downregulate negative emotions when confronted with social exclusion. LPP amplitudes were consistently elevated in adolescents with depression, underscoring their potential as a critical focus for psychophysiologically-informed therapies.

Background: Alcohol and cannabinoids are frequently used during pregnancy, however their combined effects on offspring outcomes are currently under-investigated. In this study, co-exposure was compared to single-drug and drug-free exposures for influences on adult alcohol-seeking and cannabinoid system proteomics. Methods: Pregnant C57BL/6J mice received ethanol vapor (ALC), CP-55,940 (0.75 mg/kg; CB), both (ALC+CB), or neither on gestational days 12-15. Beginning on Postnatal Day 200, male and female offspring underwent home-cage ethanol drinking (N=108) and operant self-administration, progressive-ratio, extinction, and reinstatement testing (N=96). CNR1 and CNRIP1 protein abundance was quantified in the medial prefrontal cortex (mPFC) and dorsomedial striatum (N=57) and compared to within-subject drinking behaviors. Results: Prenatal CB exposure increased cumulative home-cage ethanol intake, primarily in males. At 40% ethanol under progressive-ratio schedules, ALC+CB males consumed more than all other male groups, whereas all exposed female groups consumed more than controls. ALC+CB males also showed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males. ALC+CB increased mPFC CNR1 in males relative to all other groups, whereas CB and ALC+CB reduced mPFC CNR1 in females. Higher mPFC CNR1 was associated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement exclusively in males. Conclusions: Prenatal co-exposure produced a persistent male phenotype of enhanced ethanol seeking that was distinct from either exposure alone and accompanied by elevated mPFC CNR1. This behavioral and molecular convergence justifies future investigations manipulating corticostriatal cannabinoid signaling to attenuate exposure-induced ethanol consumption in late adulthood.

Background: Depression symptoms following traumatic brain injury (TBI) are common and strongly associated with adverse overall outcomes in military service members, veterans, and civilians. Cognitive behavioral therapy for depression (CBT-D) is considered a first-line treatment for depression symptoms in many contexts. However, costs associated with CBT-D can be substantial, and there are insufficient numbers of providers trained to perform CBT-D. In contradistinction, digital therapeutic interventions such as smartphone apps have virtually unlimited availability and low per-patient costs. However, evidence for efficacy of digital interventions providing CBT-D in the context of TBI is limited. The aims of this study were to design, develop, and test a novel smartphone app to provide CBT-D intended for military service members with depression symptoms and history of mild TBI. Results: We designed a novel smartphone app featuring digital avatar coaches to provide CBT-D intended for military service members with depression symptoms and history of mild TBI. Key features and goals of the 12 weekly CBT lessons included stigma minimization, personal engagement, and 1-2 hours per week of personal challenge homework assignments. We performed a randomized controlled trial initially involving military service members and veterans. Inclusion criteria were later relaxed to allow for civilian participation due to practical constraints . The control group received an app providing educational lessons about concussions and depression which did not include the therapeutic components of CBT. There was no difference between the groups randomized to CBT-D (n=19) vs. educational app control (n=23) in self-reported depression symptoms. Nevertheless, there was a statistically significant benefit of the CBT-D intervention in self-reported insomnia severity at the 16-week follow-up (four weeks post intervention) assessment (Cohens D=0.45, p=0.0064). There were also statistically significant positive correlations (r= 0.46 to 0.76, p=0.046 to 0.001) between changes over time in depression symptoms and changes over time in both insomnia and PTSD symptoms in the CBT-D group. There were no such correlations in the control group. Participants reported higher therapeutic alliance (p=0.0001) and overall mobile application user rating (p=0.036) for the CBT-D app than for the control education app. More favorable therapeutic alliance and mobile application user ratings correlated significantly with greater improvements in depression symptoms in the CBT-D group (r=0.53 to 0.66, p=0.02 to 0.002). However, dropout was substantial (40/59 in the CBT-D group and 31/54 in the control group) and results may not be fully representative of the population at risk. Conclusions: There remains a major unmet need for widely available, low-cost, effective interventions for depression symptoms in the context of mild TBI. The challenges of designing and rigorously assessing the effects such interventions remain formidable. However, the lessons learned from this study and indications of benefit in a highly relevant secondary outcome measure (insomnia) suggest that remote app-based interventions remain therapeutically viable. Trial Registration: clinicaltrials.gov NCT05147506, submitted 20 July 2021, posted 7 December 2021.

Introduction: Functional hemispheric disconnection (hemispherotomy) is an established surgical treatment for drug-resistant epilepsy. We aimed to describe visual function, including refractive errors, amblyopia, visual field defects, and oculomotor abnormalities, in a French cohort of patients who underwent hemispherotomy. Methods: We retrospectively reviewed the ophthalmological records of all patients who underwent hemispherotomy at the Hopital Fondation Adolphe de Rothschild between November 1987 and September 2024. Results: Among the 368 patients who underwent hemispherotomy, 122 had a comprehensive ophthalmological assessment. Refractive errors were identified in 78 patients (66.7%). Amblyopia was diagnosed in 27 of the 89 patients in whom it could be assessed (30.3%). Of the 38 patients with reliable visual field testing, 37 (97.4%) had a homonymous hemianopia contralateral to the operated hemisphere. Oculomotor abnormalities were observed in 83 patients (68.0%), while 52 (42.6%) exhibited an abnormal head posture, suggesting compensatory mechanisms for visual field loss. Conclusions: Ophthalmological abnormalities are highly prevalent following hemispherotomy. Systematic ophthalmological screening and appropriate management of treatable conditions, particularly refractive errors and amblyopia, appear warranted in this population. Patients also seem to develop compensatory oculomotor strategies and abnormal head postures in response to contralateral homonymous hemianopia.

Introduction: HIV and childhood maltreatment (CM) are both chronic stressors that disproportionately affect women, with each contributing to accelerated biological aging. Whether biological aging markers are convergent and associate with HIV and CM is unclear. Methods: We studied 238 women (122 with HIV), characterised for CM severity, and assessed biological aging using absolute telomere length (aTL), mitochondrial DNA copy number (mtDNAcn), magnetic resonance imaging-based brain-predicted age difference (MRI-BPAD), and DNA methylation age (DNAmAge) clocks. CM was measured with the Childhood Trauma Questionnaire-Short Form total score. We examined intercorrelations among biological aging markers to assess convergence and conducted linear regression models to test moderation by HIV status and CM severity. Results: PWH had shorter aTL, lower MRI-BPAD, and higher Horvath age acceleration (HorvathAA), HannumAA, PhenoAA, and extrinsic epigenetic age acceleration (EEAA). CM had limited associations with biological aging markers. Absolute TL correlated weakly with mtDNAcn (p = 0.36), PhenoAA (p = -0.18), and EEAA (p = -0.18), while MRI-BPAD correlated weakly with PhenoAA (r = 0.20). DNAmAge clocks were moderately to strongly intercorrelated (r = 0.35 - 0.93). No robust two- or three-way moderation effects were observed after false discovery rate correction. Conclusion: Our findings support a multidimensional pattern of biological aging, with substantial convergence among epigenetic aging measures but limited relationships across different markers, largely independent of HIV status and CM severity. Longitudinal approaches are needed to clarify how distinct biological aging markers relate to one another and to health outcomes over time in vulnerable populations.

Objectives Household energy poverty has been associated with deleterious health outcomes, including poor sleep outcomes. However, no study has examined this relationship among people living with HIV (PLHIV) and the possible moderating effect of physical activity. Therefore, this study investigated the relationship between household energy poverty and sleep disorders and assessed whether various levels of physical activity (vigorous, moderate, and minimal) would moderate this relationship among PLHIV in Kenya. Methods Data for this study were drawn from the Resource Insecurity and Well-being Study on PLHIV in Kenya (N = 1,132), which included information on Insomnia, household energy poverty, a measure of physical activity levels, and demographic measures. Following univariate and bivariate analysis, we conducted multivariate linear regressions followed by interaction models with each level of physical activity. Results Of the 1132 participants, 74.2% had energy poverty scores above the mean (18.15), and 36.6% reported Insomnia scores of 7.03 and above. In the multivariate model, household energy poverty was associated with greater insomnia scores ({beta} = 0.10, 95% CI: 0.07, 0.12). Vigorous, moderate, and minimal physical activity were disparately associated with lower insomnia scores. Interactions between household energy poverty and physical activity were not statistically significant, although the model suggested a buffering effect. Conclusion Household energy poverty increases Insomnia, and engaging in any level of physical activity reduces Insomnia among PLHIV. Physical activity has the potential to buffer the effects of energy poverty on Insomnia. These findings suggest that public health interventions should address both structural and lifestyle factors to improve sleep outcomes in vulnerable populations.