Brain and Behavior

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

Prehabilitation (PRH) is a preoperative process aimed at optimizing patients functional capacity to improve surgical outcomes and overall well-being. While its physical and cognitive benefits are increasingly documented, its emotional impact, particularly in neuro-oncology patients, remains less explored. This study assessed the psychological effects of a PRH program on 29 brain tumor patients. The primary outcome, emotional well-being, was measured using quality of life and emotional distress metrices. Secondary outcomes included perceived stress levels and control attitudes. Additionally, qualitative data from structured interviews provided further insights into the psychological effects of the intervention. The results indicated significant improvements in quality of life and reductions in emotional distress, particularly among women. While perceived stress levels remained stable, control attitudes showed an increase. Qualitative analysis further highlighted the positive changes in the control sense and identified additional factors, such as the importance of social support sources during the PRH process. Overall, these findings suggest that PRH interventions play a significant role in enhancing emotional well-being among neuro-oncological patients in the preoperative phase. These results underscore the importance of implementing comprehensive and personalized PRH approaches to optimize clinical status both before and after surgery, thereby promoting sustained psychological benefits in this population. This study is based on data collected at Institut Guttmann in Barcelona in the context of the Prehabilita project (ClinicalTrials.gov identifier: NCT05844605; registration date: 06/05/2023).

Background and Objectives: Normal appearing white matter (NAWM) may already harbor subtle microstructural alterations not yet visible on conventional MRI. Quantitative Multi-Parametric Mapping (qMPM) such as Magnetization Transfer saturation (MTsat), longitudinal relaxation rate (R1), and Proton Density (PD) offer new possibilities for analyzing NAWM which are sensitive to demyelination, axonal loss, and edema. We aimed to characterize these alterations within white matter hyperintensities (WMH) and the perilesional NAWM (pNAWM), to gain insights into the underlying process of lesion progression. We also investigated their association with cerebrovascular risk factors (CVRF) and long-term cognitive performance. Methods: This investigation included the cerebral MRI data of 245 participants from the prospective Berlin Longterm Observation of Vascular Events (BeLOVE) study. Furthermore, 121 participants cognitive performance was evaluated at baseline and longitudinally at 2 years follow-up using Montreal Cognitive Assessment (MoCA). Regions of interest (ROIs) of WMH, pNAWM at 1, 2, 3 mm were assessed in comparison to the mirrored contralesional white matter (cWM). Linear mixed effects models were employed to demonstrate the pairwise comparisons between each region using estimated marginal means and the association of MPM metrics with CVRFs. Linear regression was used to assess the association with cognitive performance. Results: In 245 participants, (mean age 62 years, SD: 12 years; 29.8% females), MPM metrics demonstrated a clear spatial gradient of microstructural injury. MTsat and R1 values were lower in WMH compared to cWM (lower case Greek beta = -0.48 (-0.52 - -0.44) and lower case Greek beta = -0.07 (-0.08 - -0.06), p<0.001, respectively) and showed gradual recovery with increasing distance indicating a microstructural gradient in pNAWM. Conversely, PD values were higher in WMH and decreased peripherally (lower case Greek beta = 2.32 (2.05 - 2.61, p<0.001). No substantial associations were found between MPM parameters and CVRFs in our cohort. At baseline and 2-year follow-up, cognitive performance was associated with higher pNAWM R1 values, whereas MTsat were only moderately associated. Discussion: Quantitative MPM reliably detects microstructural alterations not only within WMH, but also in pNAWM, confirming the high sensitivity of qMPM to subtle tissue pathology and support its utility as a promising biomarker for longitudinal studies and monitoring therapeutic effects.

Stroke is the third leading cause of death and disability combined worldwide and often results in hemiparesis. Functional magnetic resonance imaging (fMRI) is a non-invasive technique used to investigate changes in brain activations during tasks aimed at restoring the lost motor function. Participants with chronic stroke and residual hemiparesis in the upper extremity were recruited for a clinical intervention that included neurofeedback training and fMRI sessions with motor-execution and motor-imagery tasks. The present study provides a baseline characterization of brain activations prior to neurofeedback training. Since lesion site and volume varied across participants, two fMRI preprocessing pipelines were applied. The first one was used for twelve participants with lesions restricted to a single hemisphere and for one participant with small secondary lesions in the contralesional hemisphere, whereas the second one was used for two participants with large bilateral lesions. These were followed by quality control measures and statistical analysis. First-level (i.e., single-participant) analysis returned the strongest and most extensive activation across participants during motor-execution tasks, with clusters identified in the ipsilesional parietal lobe, bilateral occipital lobes, and cerebellum after Family-Wise Error correction. Second-level (i.e., group-level) analysis involving participants who underwent the first fMRI preprocessing pipeline revealed a significant cluster in the cerebellum after False Discovery Rate correction. These results are consistent with previous studies involving participants with chronic stroke performing motor-tasks. Cerebellar recruitment observed consistently across participants could reflect compensatory mechanisms supporting motor control after stroke.

Introduction: Glioblastoma multiforme (GBM) remains the most lethal primary brain tumor with median survival of 14-15 months. Current prognostic markers inadequately stratify patient outcomes. PINK1 (PTEN-induced putative kinase 1), a mitochondrial kinase regulating mitophagy and cellular stress responses, has emerged as a promising prognostic candidate. Our preliminary analysis of 20 GBM cases demonstrated significant PINK1 expression with correlation to aggressive phenotypes (Turizo Smith et al., 2025). This multicenter study aims to prospectively validate PINK1 as a prognostic biomarker for survival and functional outcomes in a Latin American cohort. Methods and analysis: PINK1-GBM Colombia is a multicenter, observational cohort study across four tertiary hospitals in Bogota, Colombia (Hospital de Kennedy, Hospital El Tunal, Hospital Santa Clara and Hospital Universitario de la Samaritana). We will enroll at least 26-50 adults (18+ years) with newly diagnosed IDH-wild type GBM undergoing surgical resection. PINK1 expression will be quantified by immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue using standardized protocols. Primary outcomes: overall survival (OS) and progression-free survival (PFS). Secondary outcomes: functional status trajectories (KPS/ECOG). Follow-up extends 24 months with clinical, imaging (RANO 2.0), and telephone assessments. Survival analyses will employ Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models adjusted for established prognostic factors. Ethics and dissemination: Approved by Universidad Nacional de Colombia Ethics Committee (Acta 001, February 5, 2026; Ref: 2.FM.1.002-CE-002-26), Subred Sur Occidente (P-AP-19-2025, July 11, 2025), and Subred Centro Oriente (CEI 067/2025, October 24, 2025). Conducted per Declaration of Helsinki and Colombian Resolution 8430/1993. Results will be disseminated via peer-reviewed publication, international conferences, and thesis submission.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

An inflammatory subtype of major depressive disorder (MDD) is associated with treatment resistance pointing to an unmet need for adjunctive treatments. To evaluate treatment-related changes in brain inflammation, diffusion basis spectrum imaging (DBSI) is a promising non-radiation-based technique for longitudinal designs which has been verified with histopathology. However, its use as an endpoint in clinical trials is dependent on its individual-level reliability to robustly track changes. Here, we evaluated two DBSI runs acquired in 94 participants (including 43 participants with MDD) on the same day about 1.5 h apart to assess short-term test-retest reliability. Fiber fraction (reflecting axonal/dendrite density) and hindered fraction (reflecting edema) showed moderate to high test-retest reliability in both gray and white matter regions, whereas restricted fraction (reflecting cellularity) showed lower values in gray and white matter. Group-level reliability was similar in participants with MDD, except for lower reliability of hindered fraction in gray matter. Re-identification rates of individual brain maps were higher using voxel-level white matter signatures compared to gray matter regions of interest (ROIs) (p<.001). Crucially, participants with MDD showed reduced fiber fraction (tmax=4.68, k=38) and elevated hindered fraction (tmax=4.74, k=32) in the cingulate bundle, consistent with increased white matter inflammation, while gray matter ROI-based classification failed to identify cases. We conclude that DBSI is a promising technique to track inflammatory signatures in MDD, particularly in white matter tracts. Since several frontal and subcortical gray matter ROIs showed insufficient reliability, their assessment would require multiple DBSI runs to provide robust estimates.

BACKGROUNDMild traumatic brain injury (mTBI) is a signature injury in civilian and military populations that remains invisible to detection by conventional radiological methods. Diffusion MRI has been identified as a potential clinical tool for revealing subtle microstructural alterations associated with mTBI. OBJECTIVEThis study evaluates whether a comprehensive and powerful diffusion MRI (dMRI) technique called mean apparent propagator (MAP) MRI can detect sequelae of mTBI. METHODSWe analyzed data from 417 participants of the GE/NFL prospective mTBI study which included 143 matched controls (mean age, 21.9 {+/-} 8.3 years; 76 women) and 274 patients with acute mTBI and GCS [&ge;]13 (mean age, 21.9 {+/-} 8.5 years; 131 women). All participants underwent MRI exams at up to four visits including structural high-resolution T1W, T2W, FLAIR-T2W, and dMRI, in addition to clinical assessments of post-concussive physical symptoms (RPQ-3), psychosocial functioning and lifestyle symptoms (RPQ-13), and postural stability (BESS). The dMRI data for each subject were co-registered across all visits and analyzed using the MAP-MRI framework to measure and map the distribution of net microscopic displacements of diffusing water molecules in tissue and ultimately compute the microstructural MAP-MRI tissue parameters including propagator anisotropy (PA), Non-Gaussianity (NG), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP). We quantified voxel-wise and region-of-interest (ROI)-based changes in these parameters across all four visits. RESULTSMAP-MRI parameter values were within the expected ranges and showed relatively little variation across visits. We found no significant differences in the longitudinal trajectories of these parameters between mTBI patients and controls. At acute post-injury timepoints, RPQ-3 and RPQ-13 scores were increased in mTBI patients relative to controls, while BESS scores were not significantly different between groups. Analysis of dMRI metrics and clinical mTBI markers showed significant correspondence between MAP-MRI metrics in cortical gray matter, caudate and pallidum and BESS scores. CONCLUSIONWe developed and tested a state-of-the-art quantitative image processing pipeline for sensitive analysis and detection of subtle tissue changes in longitudinal clinical diffusion MRI data. The absence of a significant statistical difference between populations in the dMRI parameters in this study suggests that the mTBI corresponded to acute post-injury clinical symptoms but that the injury was not severe enough to cause detectable microstructural damage/alterations, and that increased diffusion sensitization combined with improved analysis techniques may be needed. CLINICAL IMPACTThese findings suggest that acute mTBI (GCS[&ge;]13) may not be detectable with diffusion MRI. TRIAL REGISTRATIONClinicalTrials.gov NCT02556177

ObjectiveNicotinic acetylcholinergic receptors (nAChRs), comprising of and {beta} subunits are present in the brain and whole body. The less abundant 2-subunit is a fast-acting receptor subtype and plays an important role in cognition and learning. To understand cellular functional consequences, this study evaluated glucose metabolism using [18F]FDG PET/CT in 2 knockout (2KO) and 2 hypersensitive (2HS) mice. MethodsControl (CN; 4M, 4F), 2 knockout (2KO; 4M, 4F) and 2 hypersensitive (2HS; 4M,4F), 12-16 month old mice were used. Mice were fasted and injected with [18F]FDG (3-5 MBq) while awake. After 40 minutes they underwent whole body PET/CT. On a separate day, nicotine challenge [18F]FDG studies were done. Reconstructed images were analyzed to obtain standard uptake values (SUV) of [18F]FDG in brain and interscapular brown adipose tissue (IBAT). Statistical analysis was performed. ResultsThe 2HS male mice exhibited the largest brain increase in [18F]FDG compared to 2KO male mice. The rank order of brain [18F]FDG uptake in the 3 groups: 2HS[male]> CN[male]> 2KO[male]> CN[female]= 2KO[female][&ge;] 2HS[female]. Nicotine treatment reduced brain [18F]FDG uptake in all mice. Females had lower [18F]FDG uptake compared to males and were less sensitive to 2 nAChR. In the case of IBAT, 2KO mice had significantly higher baseline [18F]FDG uptake compared to the other two groups: 2KO[male]> 2KO[female]> 2HS[female]> 2HS[male]> CN[female]> CN[male]. Nicotine decreased IBAT in 2KO mice rather than increase as observed in CN and 2HS mice. Conclusions2 nAChRs plays a significant role in brain activation as exhibited by the increase in [18F]FDG in 2HS mice. In the absence of regulatory control by the 2 nAChR, the 2KO mice IBAT exhibited higher [18F]FDG IBAT compared to controls and 2HS mice. Female mice were less affected by nicotine compared to the male mice. Overall, 2 nAChRs played a significant role in glucose metabolism in the brain and IBAT.

Wellbeing is commonly defined as the combination of feeling good and functioning well and typically conceptualized as two related but distinct components. Hedonic wellbeing emphasizes pleasure, happiness, and life satisfaction, while eudaimonic wellbeing focuses on meaning, personal growth, flourishing, and the realization of ones potential. The Mental Health Continuum-Short Form was developed as a comprehensive measure of wellbeing and includes three subscales assessing emotional, social, and psychological wellbeing. Although the Mental Health Continuum total score is often interpreted as an indicator of overall wellbeing, the underlying genetic structure of its three subscales and its genetic overlap with other commonly used wellbeing measures remains unclear. Using data from 5,212 individuals from the Netherlands Twin Register (72% female, mean age 36.4), we fitted multivariate twin models to examine the genetic architecture of the Mental Health Continuum and its associations with other wellbeing measures (quality of life, life satisfaction, subjective happiness, and flourishing). Results indicate that, at the genetic level, the Mental Health Continuum is best explained by its three distinct subscales rather than by a latent factor. When considering the Mental Health Continuum together with the other wellbeing measures, we found moderate to high genetic correlations (r = 0.52 - 0.83), indicating substantial overlap in the genetics underlying the wellbeing constructs. However, we did not find evidence for a single common genetic factor underlying all constructs. These findings highlight the multidimensional structure of wellbeing, but the moderate to high genetic correlations across measures suggest that it is important to align the level of measurement (phenotypic vs genetic) with the research question.

Stressors are commonly used in rats to induce models of anxiety or depression. The effectiveness of these stressors is often evaluated using specific behavioural tests. In a previous meta-analysis of chronic variable stress (CVS) procedures, we predicted that longer and more intensive stress procedures would result in larger effect sizes in behavioural tests. However, we found that the duration or intensity of CVS procedures did not correlate strongly with the magnitude of the effect sizes reported in behaviouraltests. In that study, we were concerned that the large and unexplained diversity in CVS procedure design, both in terms of duration and the types of stressors used, made it challenging to detect the factors that were influencing effect size. In an effort to address this, we explore here the use of a much simpler stress procedure - chronic restraint stress (CRS) - to study the relationship between the duration of CRS procedures and the effect sizes obtained in subsequent behavioural tests. We searched PubMed for articles using CRS procedures with rats, systematically documented the total duration of restraint, and carried out a meta-analysis of the effect sizes obtained in four behavioural tests: the forced swim test (FST), the sucrose preference test (SPT), the elevated plus maze (EPM) and the open field test (OFT). We found that chronic restraint stress increased immobility in the FST, decreased sucrose preference in the SPT, decreased time spent in the open arms of the EPM but had no effect on time spent in the centre of the OFT. However, the effect sizes in all behavioural tests, except the SPT, were not moderated by the duration of the CRS procedure, indicating that longer CRS procedures are associated with larger effect sizes in the SPT but not in the FST or EPM.

Background: Substance use disorders (SUDs), including alcohol and drug dependence, and smoking, pose a public health threat with their high prevalence and comorbidity with other diseases, and contribution to mortality. SUDs are highly correlated, and their genetic background is shared to some degree. Objectives: We aimed to investigate the genetic associations of previously reported loci for a wide range of SUDs in an unstudied Ukrainian population. Methods: We collected data from 595 individuals (339 women, 253 men), including 321 participants from two rehab centres. Based on clinical review and questionnaire data we defined drug dependence, alcohol dependence, alcohol abuse, binge drinking, smoking, opiate, amphetamine, cannabis, and hallucinogen use, along with several intermediary alcohol use and smoking variables considering the amount of use and the level of dependence. We genotyped COMT-rs4680, ADH1B-ADH1C-rs1789891, and HTR2A-rs6313, and applied logistic and ordered logistic regression assuming an additive inheritance model, controlling for the recruitment group, other substance uses, age, and sex, in the association analyses. Results: We replicate (P<0.05) the associations at COMT-rs4680 with smoking status (OR[95% CI]=1.56[1.01-2.41], P=0.047) and heaviness (1.37[1.04-1.80], P=0.026), and at ADH1B-ADH1C-rs1789891 and HTR2A-rs6313 with alcohol dependence (1.69[1.03-2.76], P=0.038 and 0.66[0.47-0.92, P=0.016], respectively). Furthermore, we provide evidence for an association at HTR2A-rs6313 with hallucinogen use (0.58[0.35-0.98], P=0.040). Conclusion: In this study on multiple SUDs we shed light on the genetic background of SUDs in Ukrainians and provide further evidence that variation at COMT is mainly associated with smoking, at ADH1B-ADH1C with alcohol-related variables, whereas HTR2A is a more general SUD-associated locus.

Purpose: This study aimed to examine the effects of formative and summative assessments on college students tennis performance and basic psychological needs. Methods: A total of 128 undergraduate students (64 males, 64 females; Mage = 19.22, SD = 0.91) participated in this study. Participants were cluster-randomized to either a formative assessment group (n = 64) or a summative assessment group (n = 64). The formative assessment intervention involved setting personalized learning goals and success criteria, administering periodic tests, and providing process-oriented and individualized feedback. The summative assessment intervention involved setting uniform goals for all students, offering instructor feedback only on common problems, and requiring students to practice independently after class without personalized guidance. Both interventions were implemented over 10 weeks, with one 90-minute session each week. Tennis skills and basic psychological needs (i.e., autonomy, competence, and relatedness) were assessed before and after the intervention. Tennis skills were reassessed 1 week after the intervention. Two-way mixed-effects analysis of variance (ANOVA) was used to examine the impact of group, time, and their interaction on tennis skills and basic psychological needs. Results: The results showed that the interaction between group and time was significant for all of the outcome variables. Simple effects analyses indicated that, at pre-test, the two groups did not differ significantly in tennis performance or in satisfaction of autonomy, competence, and relatedness (p > 0.05). At post-intervention, the formative assessment group demonstrated significantly better performance than the summative assessment group in tennis skills (MD = 3.50, 95% CI = [1.303, 5.697], p = 0.002), autonomy (MD = 2.44, 95% CI = [1.816, 3.059], p < 0.001), relatedness (MD = 1.33, 95% CI = [0.679, 1.977], p < 0.001), and competence (MD = 1.75, 95% CI = [1.046, 2.454], p < 0.001). At the 1-week follow-up session, the formative assessment group also showed significantly better tennis performance than the summative assessment group (MD = 6.81, 95% CI = [4.667, 8.958], p < 0.001). Conclusion: Formative assessment was more effective than summative assessment in improving college students tennis performance and satisfying their basic psychological needs. These findings suggest that incorporating personalized goals, process-oriented evaluation, and individualized feedback into tennis instruction could promote both skill development and psychological outcomes in college physical education.

Exercise is a positive health behaviour associated with improved mood. However, the mechanisms underlying the benefits of exercise on affective health are unclear, particularly with respect to type of exercise and sex. Chronic exercise decreases neuroinflammation, which is linked to improvements in mood and anxiety. However, exercise is also a physiological stressor that can transiently upregulate systemic inflammation, and its effects on neuroinflammation are not well understood. This study examined how acute and chronic exercise affect circulating and brain cytokine levels and anxiety-related behaviour in young healthy male and female mice. In Experiment 1, mice were placed on a treadmill for a two-hour bout of moderate exercise. Two hours after exercise, animals were either tested in the open field or euthanized for measurement of cytokines (IL-1{beta}, TNF, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-{gamma}, KC/GRO). In Experiment 2, mice underwent an 8-week moderate treadmill exercise paradigm followed by open field testing and tissue collection. Acute exercise decreased time spent in the centre of the open field in males only, suggesting increased anxiety-like behaviour in males. Acute exercise increased IL-6 and decreased TNF in serum, and increased amygdala principal component 1 (loading IL-12p70, IL-10, IFN-{gamma}, and TNF) in both sexes. Chronic exercise increased open field centre entries, increased IL-6 in the prefrontal cortex, decreased TNF in the dorsal hippocampus, and had minimal effects on circulating cytokines in both sexes. These results demonstrate that the effects of exercise on anxiety-related behaviour and cytokine levels depend on recurrence, tissue, and brain region. New & NoteworthyOur work highlights the contrast between anxiogenic and anxiolytic effects of acute versus chronic exercise, respectively, in healthy mice. Acute and chronic exercise differentially affected circulating and brain cytokines, providing insight into physiological adaptations to exercise. Both sexes demonstrated similar cytokine responses to exercise. These similarities are novel with respect to exercise research and noteworthy given sex differences in anxiety with respect to acute exercise.

Background: The etiology and nosological status of seasonal affective disorder (SAD) as a specifier of depressive episodes versus a transdiagnostic disorder are the subject of debate. In this study, we investigated the underlying etiology of SAD and dimensional seasonality by examining their association with latitude and genetic risk for a range of traits, and investigated gene-environment interactions. Methods: This study included 12,460 adults aged 18-90 with a history of depression from the Australian Genetics of Depression Study. Regression models included predictors for latitude (distance from equator) and polygenic scores for eight traits; major depressive disorder, bipolar disorder, anxiety disorders, chronotype, sleep duration, body mass index, vitamin D levels, and educational attainment. Outcomes were SAD status and general seasonality score. Results: SAD was positively associated with latitude (OR[95%CI] = 1.05[1.03-1.06], padjusted<0.001), and there was nominal evidence of additive and multiplicative interactions between chronotype genetic risk and latitude (OR = 0.99[0.99-0.99], padjusted=0.381; OR=0.98[0.97-0.99], padjusted=0.489). General seasonality score was associated with latitude (IRR=1.01[1.01-1.01], padjusted 0.001) and genetic risk for major depressive disorder (IRR =1.02[1.01-1.03], padjusted<0.001), bipolar disorder (IRR=1.02[1.01-1.03], padjusted=0.001), anxiety disorders (IRR=1.03[1.01-1.04], padjusted<0.001), vitamin D levels (OR=0.89[0.80-0.95], padjusted=0.048), and educational attainment (IRR=0.97[0.96-0.99], padjusted<0.001). Conclusions: These findings enhance understanding of SAD etiology, highlighting contributions of psychiatric genetic risk and geographic measures on seasonal behavior, and support examining seasonality as a continuous dimension.

Background. Brain development is altered in neonates with congenital heart disease (CHD). However, development in the perioperative period remains incompletely understood. Purpose. This study used Structural Covariance Component (SCC) analysis to identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and healthy controls, as well as pre-to postoperative changes and effects of perioperative risk factors. Study type. Prospective. Population. The cohort included 41 neonates with CHD who underwent cardiac surgery or catheterization and 359 healthy neonates. Field strength and sequence. 3 Tesla T2-weighted turbo-spin-echo sequence. Assessment: Brain MRI were motion-corrected and reconstructed using an established neonatal algorithm. Jacobian determinants calculated from non-linear registration of MRI to a neonatal template were input into an Independent Component Analysis to identify SCCs (N=40). SCC weightings were extracted, reflecting the degree to which the pattern of covariance is expressed in each neonate. Statistical tests. Postoperative SCC weightings were compared to healthy neonates using a general linear model or robust regression. Pre- and postoperative SCC weightings were compared using a linear mixed effect model. Pre- to postoperative differences were calculated and associations with age at surgery, cardiopulmonary bypass duration, and postoperative paediatric intensive care unit stay were assessed using partial spearman's rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate. Results. 16/40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep grey matter, brainstem, and CSF regions, with seven also showing significant perioperative change. A further nine SCCs only showed significant perioperative change. Perioperative risk factors were not associated with perioperative change. Data conclusion. This data-driven approach highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. Evidence level. 1. Technical Efficacy. Stage 3.

BackgroundDepression is a mood disorder frequently associated with episodic memory impairment. However, it remains unclear whether functional brain activity differs between depressed and non-depressed individuals during encoding or retrieval of autobiographical or non-autobiographical memories. Clarifying these differences is important for refining theoretical models of memory impairment in depression and, potentially, for developing targeted interventions. MethodsWe conducted three coordinate-based meta-analyses examining encoding and retrieval of autobiographical and non-autobiographical memory in control participants and individuals with current, remitted, or subthreshold depression, or those at risk for depression. Studies were identified via database searches and analysed using Seed-based d Mapping. ResultsWe included coordinates from 21 fMRI studies. During encoding, depression was associated with reduced activity in the thalamus, the caudate, the salience network, the frontoparietal executive control network, and motor-related areas (ten studies, N = 506). During non-autobiographical retrieval, depression was associated with higher activity in the right inferior frontal gyrus (six studies, N = 332). During autobiographical retrieval, depression was associated with reduced activity in the right insula and fusiform gyrus, alongside increased activity in the left anterior cingulate cortex and the left middle frontal gyrus (ten studies, N = 423). Between-study heterogeneity was low and no evidence for publication bias was found. DiscussionOur results indicate that depression may be associated with impaired salience integration during encoding and autobiographical retrieval. In contrast, during non-autobiographical retrieval, increased frontal activity suggests a more vigilant or self-monitoring retrieval mode. Functional brain activity changes in depression therefore appear stage- and content-specific.

Background: Neurite orientation dispersion and density imaging (NODDI) shows promise in providing specific insights into the neurite morphology underlying white matter (WM) damage in neurodegenerative diseases. This study aimed to advance the currently limited knowledge by characterizing NODDI-derived microstructural WM alterations in Wilson disease (WD) and examining their relationships with clinical symptoms. Methods: 30 WD patients, including 19 with predominant neurological involvement (neuro-WD) and 11 with hepatic manifestation (hep-WD), and 30 matched healthy controls underwent multi-shell diffusion-weighted magnetic resonance imaging. NODDI metrics, including neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF), and diffusion tensor imaging-based fractional anisotropy (FA) were estimated. Group differences in diffusion parameters across the WM skeleton were determined using tract-based spatial statistics. Additionally, voxel-wise correlations with neurological and cognitive scores were investigated. Results: We observed widespread NDI and ODI reductions in neuro-WD patients and ISOVF increases in hep-WD patients compared with healthy controls, particularly involving the corpus callosum, corona radiata, superior longitudinal fasciculus, external and internal capsule, and superior fronto-occipital fasciculus. A comparable yet more subtle pattern was found when comparing phenotypes. Distinct NDI and ODI constellations were identified as the microstructural determinants of FA alterations. Decreased NDI in the aforementioned fibers were correlated with neurological impairment, processing speed, and visual attention. Conclusions: Phenotype-specific microstructural WM alterations were identified, characterized by globally reduced axonal density and fiber organization in neuro-WD and excess free water in hep-WD. NODDI could be useful as an imaging biomarker for forecasting conversion to neurological WD manifestations and monitoring of disease progression.

BACKGROUND: Prostate cancer (PrCa) is the most commonly diagnosed cancer in men in many countries and is the most heritable of the common cancers. Precision medicine approaches to disease management are not routinely available to most men, yet we know that germline genetic testing can help identify those at high-risk of developing advanced or lethal disease and can influence selection of therapeutics. An integral part of healthcare delivery design is the inclusion of patients/consumers in the development of frameworks for managing health interventions that are tailored to meet their needs. METHODS: In Phase I, we undertook focus group discussions with men previously diagnosed with PrCa (n=20), to determine their opinions, perceptions and expectations of germline genetic testing for PrCa. Focus groups were tape-recorded, transcribed verbatim, coded and then thematically analysed using NVivo. In Phase II, themes were then used to design and development a Precision Medicine in Prostate Cancer Information Toolkit, which was reviewed by patients (n=14), their carers/family members (n=4) and healthcare providers (n=14). RESULTS: In Phase I, knowledge about precision medicine and genetic testing was generally low. The strongest motivation for undertaking testing was to identify family members' risk levels (n=7), and the biggest concern pertained to insurance discrimination (n=5). Phase II data revealed that generally healthcare providers (n=8) found the purpose of the toolkit to be clearer than patients (n=5). Though, patients found the task of imagining the usefulness of the toolkit at the time of diagnosis or beforehand when assessing genetic risk, quite difficult. Participants highlighted that information regarding life insurance, implications for their family and costs associated with testing were of concern. CONCLUSIONS: This study has revealed critical knowledge gaps, preferred communication/support needs, and concerns/risks associated with germline genetic testing in PrCa. Concerns pertaining to family members and insurance discrimination are obvious topics that need to be addressed. Our toolkit may be helpful in addressing knowledge gaps, but further testing is needed to ensure its accessibility across literary and cultural contexts.

Introduction The aim of this study was to determine the annual age- and sex-specific prevalence of gender-affirming hormone and puberty blocker use among young people with a gender incongruence (GI) diagnosis in Norway. Methods We integrated data from multiple Norwegian national registers to perform a nationwide register-based study of individuals with known sex assigned at birth who were born in the period 1975-2017 and resident in Norway for all or part of the period 2008-2022. We first calculated the annual age- and sex-specific incidence of GI diagnoses in the population. Then, we calculated the annual age- and sex-specific prevalence of androgen, estrogen, and puberty blocker use among individuals with a GI diagnosis who were under age 25 (for androgens and estrogens) or 18 (for puberty blockers) in the year that they collected the prescription. Results The incidence of GI diagnoses has increased among youth in Norway, most notably since 2015 and with the largest increase among teens assigned female at birth. The prevalence of feminizing and masculinizing hormone therapy has increased in this period as well, but mainly among the oldest teens and young adults. The prevalence of puberty suppression is mostly low but has also increased since 2015, especially in recent years among teens assigned male at birth. Conclusion The prevalence of gender-affirming hormone and puberty blocker use has increased among transgender youth in Norway, concurrently with an increase in the incidence of GI diagnoses.