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Brain and Behavior

Wiley

Preprints posted in the last 30 days, ranked by how well they match Brain and Behavior's content profile, based on 37 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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Regional distribution of white matter hyperintensity burden in coronary artery disease and links with coronary revascularization procedure

Potvin-Jutras, Z.; Tremblay, S. A.; Rezaei, A.; Sanami, S.; Sabra, D.; Intzandt, B.; Wright, L.; Gagnon, C.; Mainville-Berthiaume, A.; Parent, O.; Dadar, M.; Iglesies-Grau, J.; Steele, C. J.; Gayda, M.; Nigam, A.; Bherer, L.; Gauthier, C. J.

2026-05-15 neuroscience 10.64898/2026.05.12.724587 medRxiv
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IntroductionCoronary artery disease (CAD) increases the risk of cerebrovascular events, yet early brain injury in this population remains poorly characterized. White matter hyperintensities (WMHs), a biomarker of cerebrovascular lesions, are prevalent in CAD and are linked to risk of stroke. Beyond total burden, spatial distribution of WMHs carries pathological significance and is critical for understanding CAD-related injury. While clinical outcomes including coronary revascularization procedure and myocardial infarction influence CAD prognosis, their impact on WMH burden remains unclear. MethodsThis study investigated regional WMH burden in CAD and its relationship with clinical characteristics. 82 adults over 50 years participated, including 44 individuals with CAD and 38 controls. WMHs were segmented from fluid attenuated inversion recovery and T1-weighted MRI and categorized as total, periventricular, deep, and superficial regions. History of myocardial infarction and coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI)), was obtained from medical files. ResultsIndividuals with CAD exhibited higher total, periventricular, and deep WMH volumes than controls. Participants who underwent CABG had higher superficial WMH volumes than those with PCI, suggesting greater disease severity influences WMH burden. ConclusionCAD is characterized by a distinct pattern of cerebrovascular vulnerability, with revascularization procedures influencing WMH burden

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Higher PVS volume in adults born very preterm

Huerter, N. M.; Schmenger, V. S.; Barda, T.; Thalhammer, M.; Schmitz-Koep, B. M.; Menegaux, A.; Daamen, M.; Priller, J.; Decker, A.; Deike, K.; Zimmer, C.; Bartmann, P.; Wolke, D.; Zott, B.; Sorg, C.; Hedderich, D. M.

2026-05-25 radiology and imaging 10.64898/2026.05.23.26353943 medRxiv
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Abstract: BACKGROUND: Perivascular spaces (PVS), visible on brain MRI, contribute to the brain clearance system and are associated with age and neurodegenerative disorders. While lower volumes of PVS in the forebrains white matter and basal ganglia have been also demonstrated in preterm-born neonates, the long-term trajectory of PVS after premature birth remains unclear. This study tests for altered PVS volumes in very preterm/very low birthweight-born (VP/VLBW) adults compared to full-term controls and explores potential associations with cognitive performance. METHODS: PVS were assessed on T2-weighted MRI from 97 VP/VLBW and 89 full-term (FT) subjects at 26 years from the prospective, population-based Bavarian Longitudinal Study. PVS volume and count was based on automated nnU-Net-based segmentation. Regional PVS volumes were normalized by corresponding regional parenchyma volumes. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale. MANCOVA was used for PVS group comparisons, Spearman rank correlations for testing PVS relationships with birth variables and cognitive scores. RESULTS: VP/VLBW-born adults showed significantly higher normalized PVS volumes in bilateral basal ganglia (p < 0.001, partial eta-squared = 0.096) and insula-related white matter (p = 0.001, partial eta-squared = 0.057). In the basal ganglia, higher PVS volumes were negatively correlated with gestational age (rho = -0.223, p = 0.030) and positively correlated with the Intensity of Neonatal Treatment Index (rho = 0.222, p = 0.030) in the VP/VLBW group. PVS volume was not associated with IQ scores. CONCLUSION: We demonstrate region-specific alterations of perivascular spaces in VP/VLBW-born adults. Data suggest that prematurity has lasting impact on the PVS.

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Multivariate Machine Learning Analysis of M-ECG-derived Heart Rate Variability in TBI Veterans, With and Without Comorbid PTSD

Izadysadr, A.; Bagherzadeh, H. S.; Rowland, J.; Martindale, S. L.; Stapleton-Kotloski, J. R.; Godwin, D.

2026-06-08 psychiatry and clinical psychology 10.64898/2026.06.05.26354915 medRxiv
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Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) frequently co-occur in Veterans, producing overlapping symptoms and shared autonomic dysregulation. Heart rate variability (HRV) offers a noninvasive measure of autonomic function. Univariate HRV analyses often fail to capture complex, multivariate patterns associated with comorbidity. This study applied machine learning to HRV features extracted from MEG-derived electrocardiogram (M-ECG) signals to differentiate Veterans with TBI alone (TBI-alone; n = 42) from those with comorbid PTSD (TBI+PTSD; n = 40). Time-domain, frequency-domain, geometric, and nonlinear HRV metrics were analyzed using nested cross-validated Random Forest and XGBoost classifiers, with Boruta-based feature selection and SHapley Additive exPlanations for model interpretability. Both classifiers achieved above-chance discrimination (Random Forest AUC = 0.663; XGBoost AUC = 0.635). Multivariate models identified distributed autonomic signatures in TBI+PTSD, including altered sympathovagal balance, increased low-frequency proportion, and greater heart rate complexity. In contrast, univariate HRV differences were subtle and did not survive correction for multiple comparisons. These findings demonstrate how using multivariate machine learning HRV analysis could help with detecting comorbidity-specific autonomic patterns, suggesting that HRV-derived signatures may serve as exploratory biomarkers for risk assessment and targeted interventions in Veterans with TBI and PTSD.

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Investigating the Usability, Feasibility, and Effect of a Virtual Reality Cognitive Training System on Brain Cancer Patients with Mild Cognitive Impairment: A Quasi-Experimental (Single-Arm) Pilot Study

Faiola, A.; Villano, J. L.; Soroya, S. H.

2026-05-19 neurology 10.64898/2026.05.18.26353031 medRxiv
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(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

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Microscopic fractional anisotropy MRI differences in genetic frontotemporal dementia

So, I.; Rios-Carrillo, R.; Coleman, K. K. L.; Finger, E. C.; Baron, C. A.

2026-05-26 neurology 10.64898/2026.05.25.26354046 medRxiv
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ABSTRACT INTRODUCTION: Microscopic fractional anisotropy ({micro}FA), an emerging diffusion MRI metric, may be more sensitive than conventional metrics to gray matter microstructural changes in neurodegeneration. This pilot study compared {micro}FA, mean diffusivity (MD), and volume between genetic frontotemporal dementia (FTD) variant carriers and non-carriers in the insula, frontal pole, and medial orbitofrontal cortex (mOFC). METHODS: Carriers and familial non-carriers of FTD variants in C9orf72, GRN, or MAPT were scanned between October 2024-December 2025. Non-parametric aligned rank transform ANCOVAs were computed to analyze between-group differences in {micro}FA, MD, and volume while controlling for age. RESULTS: Carriers (n=12) exhibited lower insula {micro}FA than non-carriers (n=8): F(1,19)=5.89, 95% CI [-10.7,-0.75], p=0.027, 2p=0.26. No group-differences were observed in other metrics, including MD and volume. DISCUSSION: Reduced {micro}FA in the insula, a region vulnerable to early atrophy in FTD, may be more sensitive to early microstructural changes in genetic FTD than traditional diffusivity measures.

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Effectiveness of RMSSD-Based Adaptive Music Therapy (Skitii) in Reducing Treatment-Related Anxiety in Head and Neck Cancer Patients: Protocol for a Randomized Controlled Trial

Adhikari, P.; M, D.; Subramanium, V.; Krishna, T.; B, A.; Jain, C. B.

2026-05-15 oncology 10.64898/2026.05.13.26353099 medRxiv
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Background: Head and neck cancer (HNC) patients experience clinically significant anxiety and depression in 65-85% of cases during active treatment. Current supportive care lacks personalized, real-time non-pharmacological interventions. Skitii is a novel HRV-adaptive music therapy system that uses continuous RMSSD (root mean square of successive differences) monitoring via a Polar H10 chest sensor to select music in real-time, targeting parasympathetic recovery (RMSSD >=30ms). Methods: This is a prospective, open-label, randomized controlled trial (1:1 allocation) at Yenepoya Medical College Hospital, Mangalore, India. Adults aged 18-75 years with confirmed head and neck cancer (any subsite, Stage I-IV) undergoing radiotherapy and/or chemotherapy with baseline distress (HADS >=8 or NCCN Distress Thermometer >=4) will be enrolled. Participants are randomized to Skitii adaptive music therapy (20-minute sessions, 3 times daily, 3 weeks) or static music therapy control. Skitii uses a two-phase algorithm: Phase 1 (0-2.5 minutes) uses heart rate as a stress proxy for immediate music selection; Phase 2 (2.5-20 minutes) uses RMSSD to adapt music every 2.5 minutes when physiological state changes by >=20%. Primary endpoints are HADS-Anxiety score and resting RMSSD at Week 3. Sample size is 70 (35 per arm), powered at 80% to detect a 2.5-point HADS difference (SD=3.8, alpha=0.05, 15% dropout). Analysis is ANCOVA, intent-to-treat. Discussion: This is the first randomized controlled trial evaluating RMSSD-based adaptive music therapy in cancer patients. The active control design isolates the effect of the adaptive algorithm from music exposure alone. If positive, results will support a scalable, cost-effective supportive care intervention with objective physiological monitoring, and provide the clinical evidence base for CDSCO Class B medical device approval for Skitii in India, with future CE Mark and FDA applications planned. Trial Registration: Clinical Trials Registry - India CTRI CTRI/2025/11/116732

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The emotional impact of gambling-related advertising: an experimental functional Near-Infrared Spectroscopy study protocol

Daniel, L.-I.; Ros-Leon, A.; Molina-Rodriguez, S.; Pellicer-Porcar, O.; Cabrera-Perona, V.; Ibanez-Ballesteros, J.

2026-05-27 addiction medicine 10.64898/2026.05.20.26353682 medRxiv
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The proliferation of gambling advertising has intensified concerns regarding its influence on vulnerable populations, yet the neural mechanisms underlying cue-reactivity to these stimuli remain underexplored in ecologically valid settings. This study protocol proposes a novel methodological framework to investigate prefrontal cortical responses to gambling advertisements in individuals with varying degrees of gambling experience. Materials and methods: This cross-sectional study will recruit 44 participants, divided into a clinical group (individuals with high-frequency gambling or gambling disorder) and a matched control group. Neural activity will be recorded using fNIRS while participants view gambling-related, neutral, violent, and sexual stimuli. Secondary measures include validated scales for gambling severity (SOGS), impulsivity, sensation seeking, and alexithymia. Data analysis will primarily utilize inter-subject correlation (ISC) to quantify neural synchronization and multiband frequency decomposition to capture dynamic affective processing. Advanced preprocessing, including short-channel regression, will be applied to ensure signal robustness. Discussion: By combining portable neuroimaging with a data-driven ISC approach, this study aims to identify objective neural markers of gambling vulnerability. The findings will provide novel insights into the idiosyncratic processing of commercial stimuli, potentially informing public health policies and the development of more effective evidence-based regulations for gambling marketing.

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Trajectories of posttraumatic stress and obsessive-compulsive symptoms over twelve months following Hurricane Helene

Pinciotti, C. M. M.; Pushkarskaya, H.; Williams, I.; Olfson, E.; Adams, T. G.

2026-05-21 psychiatry and clinical psychology 10.64898/2026.05.18.26353502 medRxiv
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Separate research has evaluated trajectories of posttraumatic stress symptoms (PTSS) and obsessive-compulsive symptoms (OCS), but no study has evaluated OCS trajectories following trauma exposure nor combined PTSS/OCS trajectories. The present study evaluated combined PTSS/OCS trajectories among 585 survivors of Hurricane Helene, spanning three waves of data collection over 12 months. A 3-class solution was supported, including resilient (i.e., consistently low PTSS and OCS), chronic (i.e., elevated PTSS and OCS with gradual reduction over time), and moderate-yet-diverging (i.e., moderate elevations in PTSS and OCS with gradually declining PTSS and persistent and increasing OCS over time) classes. This study shows both overlap and differentiation in symptom trajectories from earlier research, with the moderate-yet-diverging trajectory suggesting unique OCS pathways distinct from PTSS.

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A CT-Based Study to Evaluate the Correlation Between Age-Related Cerebral Atrophy and Presenting Neurological Symptoms in Adult Patients: A Retrospective Cross-Sectional Analysis from Gujranwala, Pakistan

Noreen, S.; Tahir, M.; Habib, H.; Akram, H.; Talha, M.

2026-05-25 radiology and imaging 10.64898/2026.05.23.26353940 medRxiv
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Age related cerebral atrophy is one of the most prevalent radiological findings in ageing populations, yet its clinical significance particularly its correlation with specific neurological presenting symptoms remains insufficiently characterised in South Asian contexts. This retrospective cross sectional study was conducted at THQ Hospital Wazirabad and Chattha Hospital, Gujranwala, Pakistan over a six month period, enrolling 66 adult patients ([&ge;]40 years) who underwent non contrast computed tomography (CT) of the brain. CT scans were evaluated for Evans index, ventricular enlargement (graded 1 to 3), cerebral atrophy severity (graded 1 to 3), early ischaemic changes, and the hyperdense vessel sign. Presenting neurological symptoms headache, seizures, slurred speech, ataxia, and numbness were extracted from medical records and correlated with imaging findings using chi square tests, Spearmans rank correlation, and binary logistic regression in SPSS v31.0. The mean patient age was 52.1 to 14.3 years (range 35 83) with a male predominance (72.7%). Moderate to severe atrophy was present in 50.0% of patients. Seizures (74.2%), slurred speech (63.6%), and ataxia (62.1%) were the most prevalent symptoms. Significant positive correlations were found between atrophy grade and age (r = 0.72, p < 0.001), slurred speech (r = 0.48, p < 0.001), ataxia (r = 0.44, p < 0.001), and numbness (r = 0.39, p = 0.001). Headache showed no significant correlation with atrophy severity (p = 0.42). Logistic regression revealed that each one grade increase in atrophy severity raised the odds of motor/speech symptoms by 2.8 fold (95% CI: 1.6 to 4.9, p <0.001), independent of age. These findings support the integration of standardised CT based atrophy reporting into routine radiology practice for older adults, especially in resource limited settings where MRI is not readily accessible.

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Therapeutic Alliance and Treatment Outcomes Among Patients with Depression in Benue State

Onah, C.; Ogwuche, C. H.; Otumala, B. O.

2026-05-22 psychiatry and clinical psychology 10.64898/2026.05.19.26353601 medRxiv
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Depression remains a major public health concern globally, particularly in low resource settings where access to quality mental health care is limited and treatment outcomes are often suboptimal. In this context, the quality of the clinician patient relationship has been increasingly recognised as a critical determinant of therapeutic success. This study examined the influence of clinician patient therapeutic alliance and relational factors on treatment outcomes among patients with depression in Benue State, Nigeria. A crosssectional correlational design was adopted, involving patients diagnosed with depression and receiving care in selected health facilities. Data were analysed using Structural Equation Modelling to test hypothesised relationships among therapeutic alliance, relational factors, and treatment outcomes. The measurement model demonstrated strong psychometric properties, with all factor loadings exceeding 0.60, composite reliability above 0.90, and adequate convergent and discriminant validity. Results revealed that therapeutic alliance significantly predicted treatment outcomes, while relational factors also had a significant positive effect. Therapeutic alliance further significantly predicted relational factors. The model explained 61 percent of the variance in treatment outcomes. Mediation analysis indicated that relational factors partially mediated the relationship between therapeutic alliance and treatment outcomes, accounting for 29 percent of the total effect. The study concludes that therapeutic alliance, strengthened through trust, empathy, and collaboration, plays a central role in improving depression outcomes. Strengthening relational competencies in clinical practice is therefore essential for enhancing mental health care delivery in Nigeria.

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Fast-Imagery Reversal Script for Trauma-release (FIRST): proof of concept in two populations with employment-related PTSD

Sturt, J. A.; Grealish, A.; Tzouvara, V.; Rogers, R. E.; de Rijk, L.; Armour, C.; Cameron, D.; Croak, B.; Cui, M.; Fiorentino, F.; Harris, R.; Heralall, E.; Idowu, O.; Kreft, J.; Murray, A.; Pile, V.; Rowland, E.; Shepherd, J.; Spikol, E.; Stevelink, S.; Strang, H.; Winter, H.; Wright-Hughes, A.; Greenberg, N.

2026-05-13 psychiatry and clinical psychology 10.64898/2026.05.11.26352892 medRxiv
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Structured AbstractO_ST_ABSBackgroundC_ST_ABSPost-Traumatic Stress Disorder (PTSD) is a mental health condition affecting people who experience traumatic events. Trauma-exposed occupational groups report higher rates of PTSD than the general population. Current treatments, and access, often take months and may cause distress when people are required to talk about the trauma. ObjectiveTo determine the proof of concept of FIRST, a brief, non-trauma focussed therapy, in two separate populations with employment-associated PTSD. MethodTwo independent, single-arm, experimental therapy pilot trials were conducted. Trial one recruited 20 military veterans who received FIRST therapy via trained third-sector therapists. Trial two recruited 16 health and social care workers with FIRST therapy delivered by healthcare provider therapists. All participants were adults with PTSD (confirmed via CAPS-5 in trial one, and symptom score of [&ge;]33 on the PCL5 in trial two). Primary outcomes were recruitment feasibility, retention, data quality and reduction in PTSD symptoms. Secondary outcomes were anxiety and depression symptoms, daily life functioning and perceived health status. Veterans were followed up at 12 weeks post-enrolment and healthcare workers at 8 weeks. ResultsThe veteran trial progression criteria to main trial were met. Seventy-nine people screened eligible, 43 attended a CAPS-5 assessment; 20 had confirmed PTSD and were enrolled. Seventeen completed therapy and 12-week outcome measures. Mean PCL-5 scores decreased from 48.7 (SD = 13.02, n=20) at baseline to 23.5 (SD = 15.30, n=17) at 12-weeks. The healthcare worker trial obtained informed consent from 16 participants, 10 commenced therapy and were included in analysis with eight completing therapy. Mean PCL-5 scores decreased from 42.60 (12.23, (n=10) at baseline to 22.00 (19.92, n=8) at 8-weeks. ConclusionsProof of concept of FIRST was established. PTSD symptom reductions exceeded the PCL-5 minimal clinically important difference. Undertaking a fully powered randomised controlled trial of FIRST therapy is feasible within both healthcare and third sectors. HighlightsO_LIPost-traumatic stress disorder (PTSD) is more common in military veterans and health workers than the general population C_LIO_LITherapy can be challenging to commence and complete when it requires a focus on the trauma incident C_LIO_LIFIRST offers a promising, brief, non-trauma focused therapy for the treatment of PTSD C_LI

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Psychosocial outcomes of a multidomain lifestyle and empowerment program for mild cognitive impairment

Vickers, K. L.; De Wit, L.; Goldstein, F. C.; Thelin, J.; Giannotto, E. L.; Saurman, J. L.; Levey, A. I.; Rodriguez, A. D.

2026-05-26 psychiatry and clinical psychology 10.64898/2026.05.21.26353503 medRxiv
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Background: Individuals with mild cognitive impairment (MCI) experience cognitive and functional declines that can negatively impact mood and reduce feelings of self-efficacy. These changes can also lead to elevated distress in care partners (CPs). Therefore, interventions that address quality of life and psychosocial factors in people with MCI and their CPs are needed. Objective: The present study evaluated the impact of a multidomain lifestyle program, the Cognitive Empowerment Program (CEP), on changes in psychosocial functioning, particularly empowerment, in people with MCI and their CPs. Methods: Participants were 94 people with MCI (Mean= 75.1 years old, 45.7% female, 81.9% white) and their CPs (Mean= 69.1 years old, 71.3% female, 87.3% white) that completed the 12-month CEP program comprised of physical, cognitive, and psychosocial interventions. Questionnaires were administered pre- and post-program to assess empowerment, self-efficacy, meaning and purpose, depression, and stress in participants with MCI alongside empowerment, depression, stress, and caregiving burden in CPs. Results: After completing the CEP program, participants with MCI endorsed higher empowerment and self-efficacy as well as fewer symptoms of depression and perceived stress. CPs endorsed feeling more empowered despite elevated caregiver burden. Conclusions: These results suggest multidomain lifestyle programs can positively impact wellbeing in MCI. Future research should focus on refining delivery models, exploring integration with pharmacological treatments, prioritizing inclusion of diverse populations, and measuring long-term outcomes to strengthen the reach and impact of programs like CEP.

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Personality factors and childhood adversity in psychiatric patients with and without recent suicide attempts: a cross-sectional study

Colic, L.; Musslick, J.; Zerekidze, A.; Bahlmann, L.; Buske, B.; Walter, M.; Jollant, F.; Wagner, G.

2026-05-26 psychiatry and clinical psychology 10.64898/2026.05.25.26354029 medRxiv
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Background: Childhood adversity (CA) is recognized as a distal risk-factor for suicide attempts (SA) in individuals with psychiatric disorders. However, not all individuals with experiences of CA will engage in SA. Contributing to this relationship may be proximal factors such as impulsivity, inward anger and self-aggression. However, these factors are often conceptually blended and measured in different samples. We sought to clarify association among CA and personality factors in persons with SA. Methods: Participants from two studies comprised individuals with a diagnosed psychiatric disorder and history of SA (n= 139) and individuals with depressive disorder (clinical controls, CC; n= 24). We investigated self-reported levels of CA, impulsivity, inward anger, and self-aggression between the SA and CC (pcorr< .012). We tested the relationship among the factors using regression (pcorr<.017) and mediation model (indirect effects, p<.05) within the SA group. Sensitivity models were run controlling for age, gender, symptom severity, trait anger, and externally oriented aggression. Results: SA group had higher impulsivity (pcorr=.067) in a model controlled for age and gender. Other factors did not differ among groups. Within the SA group the analyses revealed positive association among CA and personality factors (pcorr<.06) in basic and model with age and gender, however the association was not specific for internally (self) oriented factors (coefficient comparison, p<.07). Parallel mediation model indicated that CA had indirect effect on self-aggression through impulsivity (p=.001) and to a lesser extent through inward anger (p=.066). Generally, models controlling for cognitive depression symptoms showed less prominent effects (pcorr>.1). Limitations: The study was cross-sectional and did not include behavioral tasks (state) measures of proximal factors. Conclusions: CA and personality factors showed similar severity levels among the SA and CC groups suggesting they may relate to broader psychopathologies, rather than specifically to SA. The association of CA with anger and aggression was unspecific to internally oriented factors indicating the need for more precise measuring instruments developed specifically for individuals with SA. Overall, the study highlights personality factors as being associated with risk in broader vulnerable populations.

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White matter markers of chronic pain and trauma in UK Biobank

Lim, T. E.; Gustin, S. M.; Quide, Y.

2026-05-22 psychiatry and clinical psychology 10.64898/2026.05.19.26353622 medRxiv
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Background. Lifetime exposure to trauma is associated with chronic pain. Separate studies of chronic pain and trauma report overlapping alterations in white matter microstructure, yet their distinct and cumulative effects remain unclear. Methods. White matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) from the UK Biobank (N = 21,995) were analysed using linear mixed-effects models. First, group effects (chronic pain versus control) on white matter integrity within this cohort were established. To investigate distinct and cumulative impacts of trauma exposure at different developmental stages, main and interactive effects of group and trauma severity on FA and MD were examined in separate groups exposed to childhood maltreatment only, adulthood trauma only, and both. Sex-stratified analyses were conducted. Results. Chronic pain was associated with widespread alterations and was spatially refined to brainstem tracts and cingulum when accounting for maltreatment/trauma severity. Accounting for chronic pain, cumulative trauma severity was associated with alterations in brainstem, frontal and parietal tracts, whereas adulthood trauma showed comparable but attenuated patterns. Childhood maltreatment severity was associated with localised FA and MD reductions in brainstem tracts, sagittal stratum and superior longitudinal fasciculus. These effects were more pronounced in females than males. A chronic pain-by-maltreatment/trauma severity interaction was observed for FA in the superior cerebellar peduncle in females exposed to childhood maltreatment only. Conclusions. Distinct and interactive effects of chronic pain and maltreatment/trauma severity on white matter microstructure were evident. The findings suggest that trauma-informed care should be tailored by timing of exposure and sex in this population.

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Caregiving Demands and Depression Symptoms among Caregivers of Individuals with Down Syndrome during the COVID-19 Pandemic

Nguyen, J.; Wall, C.; Jo, E.; Allen, L. K.; Wheeler, N.; Baumer, N.; D'Aguilar, A.; York, T. P.; Capone, G.; Jackson-Cook, C.; Amstadter, A. B.; Brown, R. C.

2026-05-22 psychiatry and clinical psychology 10.64898/2026.05.20.26353699 medRxiv
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Background: This study examined the association between caregiving demands and depression symptoms among caregivers of individuals with Down syndrome during the COVID-19 pandemic. Method: We conducted an online survey of 200 caregivers of children and adults with Down syndrome, including demographic data, the Patient Health Questionnaire-8 (PHQ-8), and questions about lack of childcare and taking over instruction during the pandemic. A multiple linear regression analysis identified predictors of caregiver depression symptoms. Results: Household income (B = -3.45, p < .001) and having to take over instruction (B = 2.24, p < .001) were significant predictors of PHQ-8 scores. Child age, caregiver gender, difficulty paying for health insurance, and lack of childcare were not significant predictors. Conclusions: Lower income and instructional caregiving demands were associated with higher depression symptoms among caregivers of individuals with Down syndrome, suggesting potential targets for policy and intervention during future public health emergencies.

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Anterior middle cingulate cortex gamma-aminobutyric acid level is elevated in children with both familial and prenatal alcohol exposure-associated attention deficit hyperactivity disorder

Alger, J. R.; Gupta, I.; Farkouh, L.; Korthas, J.; Shah, A.; Silverberg, A.; Salamon, N.; Schneider, B. N.; Joshi, S. H.; O'Connor, M. J.; O'Neill, J.

2026-05-26 psychiatry and clinical psychology 10.64898/2026.05.25.26354065 medRxiv
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Background: Prior neuroimaging suggests brain differences between children with attention deficit hyperactivity disorder due to prenatal alcohol exposure (ADHD+PAE) and non-exposed children with ADHD due to other, e.g., familial, causes (ADHD-PAE). There has been interest in regional brain levels of ;gamma-aminobutyric acid (GABA) and glutamate (Glu) measured in vivo with magnetic resonance spectroscopy (MRS) as possible indicators of local inhibitory, respectively, excitatory activity in ADHD. For the first time, we report here a comparison of GABA and Glu in ADHD+PAE vs. ADHD-PAE. Methods: At 3 T, we used J-difference-edited single-voxel MRS to assay GABA and Glu in 28 children with ADHD+PAE, 20 with ADHD-PAE, and 28 typically developing (TD) controls, all aged 8-14 years. MRS was sampled from midline anterior middle cingulate cortex (aMCC), the cognitive cingulate considered functionally relevant to ADHD. Spectra were fit with custom software, including a unique technique for isolating the GABA signal from the confounding macromolecular baseline (MMBL). Results: aMCC GABA was higher in ADHD+PAE and ADHD-PAE than in TD. GABA increased with age in TD, but not in ADHD+PAE or ADHD-PAE. Similar effects were observed for the ratios GABA/Glu and GABA/Glx. For GABA+MMBL (GABA+) these effects were not seen, rather GABA+ and MMBL increased with age for the ADHD+PAE group only. No significant effects were found for Glu or Glx. Conclusions: GABA in the aMCC does not distinguish the two etiologies of ADHD, rather elevated GABA that follows an abnormal developmental appears to be common to both. High GABA may reflect increased inhibition of the aMCC impairing its cognitive functions. GABA+ results in ADHD may not tract reliably with underlying GABA values. Negative results for Glu and Glx should be reexamined at shorter echo-times.

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Cortical activity during narrative discourse production in individuals with post-stroke aphasia and controls measured via functional near-infrared spectroscopy

Braun, E. J.; Carpenter, E. A.; Gao, Y.; Yucel, M. A.; Boas, D. A.; Kiran, S.

2026-06-10 rehabilitation medicine and physical therapy 10.64898/2026.06.05.26354921 medRxiv
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Introduction: Aphasia is an acquired language disorder with a significant negative functional impact. Much of the research on aphasia has focused on word-level language comprehension and production. Further evaluation of discourse-level tasks, both at behavioral and neural levels, will allow for an ecologically valid understanding of the functional implications of language impairment in this population. Method: This study evaluated bilateral frontal, temporal, and parietal cortical activity during computer-based narrative production in 14 young neurotypical individuals, 17 individuals with post-stroke aphasia, and 15 age-matched neurotypical participants using functional near-infrared spectroscopy (fNIRS). Oxygenated hemoglobin (HbO) was measured during narrative production following short video clips and compared to HbO during counting aloud. In addition, behavioral measures quantifying in-task performance were correlated with averaged HbO values. Results: Young neurotypical individuals showed greater cortical activity in bilateral language regions for narrative production compared to counting aloud. In contrast, people with aphasia showed positive condition-related effects in the right frontal ROI and the age-matched group showed positive condition-related effects in the left frontal and right precentral ROIs. Each group showed different patterns in relationships between cortical activity and discourse performance measures. Conclusion: Overall, young participants showing more consistent condition-related effects for narrative discourse production than individuals with aphasia and age-matched controls. This study shows the potential for fNIRS to evaluate cortical activity for ecologically valid language tasks in individuals with post-stroke aphasia.

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Phase of transcranial alternating current stimulation modulates working memory processing speed

Dimmendaal, J.; Wang, X.; Dijkslag, B. J.; Huizinga, L. E.; Maalderink, S.; Priest, M.; van Dam, F. J. E.; Span, M. M.; Wischnewski, M.

2026-05-29 neuroscience 10.64898/2026.05.26.727793 medRxiv
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BackgroundTheta-frequency transcranial alternating current stimulation (tACS) over prefrontal cortex has been proposed to modulate working memory (WM), yet behavioral effects are often inconsistent. One potential source of variability is the tACS phase during stimulus presentation. ObjectiveWe tested whether behavioral performance during WM depends on the phase of prefrontal theta-tACS. MethodsTwenty participants completed two sessions of prefrontal 4 Hz tACS in a within-subject design, receiving active and sham stimulation in separate sessions. Participants performed a visuospatial change detection task (CDT) and a verbal N-back task. Stimulation effects on overall accuracy and reaction time were analyzed. Subsequently, phase-specific analyses related stimulation phase at task-relevant stimulus presentation to behavioral performance using circular regression models. Preferred phases across participants were tested using Rayleigh tests. ResultsNo significant overall effects of active compared with sham tACS on accuracy or reaction time were observed in either task. However, phase-specific analyses revealed stronger phase-dependent modulation of reaction time during active tACS compared with sham. In the CDT, this effect was present across difficulty levels, whereas in the N-back task it was observed only in the 3-back condition. No reliable phase-dependent effects were observed for accuracy. Preferred phases varied across participants and did not cluster around a common phase. ConclusionsPrefrontal theta-tACS can modulate WM performance in a phase-dependent manner even in the absence of average behavioral effects. The observation of phase-dependent reaction-time modulation across visuospatial and verbal WM tasks suggests that stimulation phase may be a relevant source of variability across cognitive domains.

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Development, Validation, and Implementation of a Stress Management Intervention for Rescue Workers in Rawalpindi: A protocol for a mixed-method study

Yasir, I.; Ahmad, I.; Bhatti, U. F.; Khan, S. A.; Malik, A.

2026-05-12 public and global health 10.64898/2026.05.09.26352786 medRxiv
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IntroductionOccupational stress among rescue workers is a major global public health concern. Rescue workers, including paramedics, firefighters, and disaster response teams, are consistently exposed to traumatic events, long working hours, physical hazards, and emotionally charged situations. These chronic stressors make them one of the most vulnerable groups to psychological distress, burnout, anxiety, depression, and post-traumatic stress disorders. In the local context of Pakistan, workplace mental health remains a neglected area. Despite stress and burnout being widely reported in these sectors, limited evidence-based interventions are available. Therefore, the study aims to develop and evaluate a locally tailored intervention to improve the mental health and psychosocial well-being of rescue workers. ObjectivesO_LITo develop a culturally appropriate stress management intervention to promote mental health for rescue workers in Rawalpindi. C_LIO_LITo validate the content and structure of stress management intervention for rescue workers C_LIO_LITo evaluate the effectiveness of stress management intervention for rescue workers in Rawalpindi C_LI MethodThe ethical approval of the study has already been obtained from the ethical review board of Health Services Academy (00013/HSA/PhD-2022) and Rescue 1122 District Headquarters, Rawalpindi. Data will be collected after obtaining informed written consent from relevant stakeholders. Data collection will start from April 2026 and will be completed in six months. Data compilation and results are expected by December 2026. Data collection will involve a scoping review to explore stress determinants and intervention components, and then a qualitative phase in which data will be collected through focus group discussions from potential Stakeholders (rescue workers, mental health experts, and program managers) to identify and validate stress determinants. Triangulation of data will be done to integrate qualitative findings with findings from the review. In the second phase, validation will be done by intervention development experts. The third phase aims to evaluate the effectiveness of the developed intervention using a quasi-experimental pre-post design. A total of 154 participants evaluated with the Perceived Stress Scale Score will be employed through a stratified sampling technique. The primary outcome is defined as remission from stress at 3 months, measured with the PSS. DiscussionIt is anticipated that the study will result in the development of a culturally appropriate and evidence-based stress management intervention for rescue workers, thus contributing to sustainable improvement in rescuers mental health and job performance.

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Exploring the Relationship Between Apathy, Dopaminergic Signal, and Head Injury in Neurodevelopmental Disorders

Malik, R.; Al-Saoud, S. A. A.; Rogers, K.; Duerden, E. G.

2026-05-18 pediatrics 10.64898/2026.05.14.26353215 medRxiv
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Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.