Neuroimage: Reports

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.

Background and Objectives In ADHD, a heterogeneous neurodevelopmental condition, behavioral and motor manifestations may reflect multiple inefficient or perturbed inhibitory systems. To evaluate Transcranial Magnetic Stimulation (TMS) evoked cortical silent period (CSP) duration, an indicator of GABA(B) receptor-mediated inhibition in motor cortex, as a potential biomarker of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. Method We retrospectively analyzed TMS data, obtained using both round and figure-of-8 coils, from three cross-sectional studies conducted in 8- to 12-year-old children with ADHD (n=79; 10.7 +/- 1.5 years old) and age-and-sex-matched typically developing controls (n=96; 10.5 +/- 1.4 years old). Results Median CSP was 32% shorter in ADHD (p=0.02). Regression analysis demonstrated a relationship between shorter CSP and both lower active motor thresholds (p < 0.0001) and more severe hyperactivity symptom rating (p = 0.026). Test-retest CSP measures in 83 children showed moderate reliability (intraclass correlation 0.77 [ADHD], 0.75 [controls]). Conclusion TMS-evoked CSP may be a useful biomarker in future investigations of ADHD subtypes, domains of impaired function, or treatment outcomes.

Background: Adverse childhood experiences (ACEs) are traumatic or adverse events in early life that can have lasting effects on behavioral, emotional, and psychological functioning. Prior research suggests ACEs relate to later psychiatric outcomes through threshold, cumulative, and individual-specific risk patterns. Few studies, however, have operationalized all three models to test ACE-specific associations with diagnosed psychiatric disorders in individuals who are adopted or with foster care histories. Methods: We conducted a cross-sectional retrospective study using electronic health record data from foster care and adopted patients aged 0-21 years old seen at the University of Minnesota Adoption Medicine Clinic (UMN-AMC) between 2014-2024. Extracted measures included ACE history, demographics, and psychiatric diagnoses. We used latent class analysis and logistic regression to identify clusters of adversity and estimate associations with psychiatric diagnosis domains, adjusting for Sex and Age at Initial Visit. Results: ACEs showed a threshold pattern across psychiatric domains, with higher ACE counts associated with greater odds of psychiatric diagnoses. Individual risk modeling indicated that exposure to abuse or violence was associated with higher odds of psychiatric diagnoses. Across cumulative and individual risk approaches, Anxiety Disorders, Mood Disorders, and Behavioral or Emotional Disorders showed the greatest sensitivity to adversity. Conclusion: Current ACE models may not fully capture neurodevelopmental impacts reflected in diagnosed psychiatric disorders among adolescents, particularly in high-risk groups such as foster and adopted individuals. In a large clinic sample our findings support a nuanced association between ACEs and later psychiatric diagnoses and highlight the need for ACE-focused assessment, prevention, and treatment strategies tailored to foster care and adopted populations.

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.

In a single-blind randomized controlled trial, we investigated the effectiveness of real-time fMRI neurofeedback delivered in 7 runs over three sessions across two weeks in N = 65 patients with alcohol use disorder. The intervention targeted modulation of ventral striatal cue reactivity to alcohol-related cues as well as enhancement of prefrontal control mechanisms in the right inferior frontal gyrus. The study design incorporate three experimental groups that either were instructed to downregulate a ventral striatum signal, upregulate the right inferior frontal gyrus, or upregulate negative functional connectivity between these two structures. In two active control groups participants were instructed to either up- or downregulate the primary auditory cortex. We did not find an effect of ventral striatal downregulation or negative connectivity feedback, and a reduced striatal activation in the right inferior frontal gyrus upregulation group was accompanied by concurrent lower activation in the target structure, suggesting that our intended modulation approaches were not effective. Identified problems that might have contributed to this unexpected outcome might have been the use of continuous feedback presentation that potentially confuses regulation target and reward processing in the ventral striatum, counterintuitive regulation directions, a lack of explicit strategy guidance and transparency about the targeted process, and generally the difficulty to recruit a sufficient number of eligible voluntary participants for a well-powered study with a complex design. These insights emphasize the complex challenges of real-time fMRI neurofeedback interventions for the treatment of substance use disorders and could provide guidance for the development of more effective future approaches.

Background: Prenatal substance exposure (PSE) occurs when an individual is exposed to substances in utero. PSEs may have lasting effects on mental health. We tested whether PSEs show threshold, cumulative, or individual substance associations with childhood psychiatric diagnoses. Methods: Clinical variables (demographics, ICD-9/10 diagnoses, PSE history) were extracted from electronic health records from the University of Minnesota Adoption Medicine Clinic. PSEs were identified from caregiver and child-protective-services narratives and/or toxicology (cord tissue/blood, meconium). For each ICD-9/10 diagnostic category, we fit logistic regression models comparing (1) exposure thresholds (0, 1, 2, 3, 4+ exposures), (2) a cumulative exposure count, and (3) individual substances to estimate marginal odds ratios (ORs) with 95% Confidence Intervals (CIs). Results: Psychiatric diagnoses increased with the number of PSEs. Relative to no exposure, odds of an Anxiety Disorder rose from OR 1.47 (95% CI 1.16-1.87) with one exposure to OR 2.03 (1.64-2.52) with >=4 exposures. Higher cumulative exposure scores were associated with Anxiety Disorders (OR 1.28, 1.18-1.38), Behavioral and Emotional Disorders (OR 1.42, 1.31-1.54), Substance Use Disorders (OR 1.52, 1.29-1.79), and Mood Disorders (OR 1.16, 1.04-1.30). Alcohol, tobacco, and marijuana exposures were associated with increased odds of at least one psychiatric diagnosis, and each substance showed at least one significant diagnostic cluster when modeled independently. Conclusion: Increasing numbers of PSEs were associated with higher odds of psychiatric diagnoses, with patterns varying by substance and outcome. These findings motivate research on exposure timing and combinations to support earlier identification and intervention for at-risk children.

Background: Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Methods: Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG {delta}/{beta} ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. Results: The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p<0.001, d=1.913), as did the global EEG {delta}/{beta} ratio (N=14; W=17, p=0.025, r=0.68), with the degree of frontal slowing positively predicting behavioral gains ({tau}b=0.51, p=0.016). Glucose metabolism decreased bilaterally in thalamus and frontal, temporal, and parietal cortices at both post-tFUS timepoints compared to baseline. Finally, N2 sleep increased by 33% following tFUS (N=11; t(10)=2.386, p=0.038, d=0.72), though this did not survive correction. No severe adverse events were observed. Conclusion: Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.

Although the associations between cerebrovascular dysfunctions and Alzheimer's disease are increasingly appreciated, the relationship of cerebral blood flow and white matter hyperintensities with tau and amyloid-{beta} pathology remains unclear, particularly in the longitudinal context. This study investigated cross-sectional and longitudinal associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-{beta} pathology using multimodal imaging and blood biomarkers in 179 participants from the ADNI3 cohort. Participants underwent structural (T1-weighted, T2-weighted FLAIR) and arterial spin labelling perfusion MRI, tau and amyloid-{beta} PET, and plasma assay tests for amyloid-{beta} 42, amyloid-{beta} 40, and phosphorylated tau-217. Tau from PET was negatively associated with cerebral blood flow both cross-sectionally and longitudinally in the posterior brain, independent of amyloid-{beta} quantified from PET. Higher white matter hyperintensities volumes were associated with higher levels of tau and amyloid-{beta} at baseline, but the associations were significantly attenuated after further adjusting for amyloid-{beta} and tau, respectively. Plasma amyloid-{beta} 42/40 ratio was negatively associated with white matter hyperintensity volumes both cross-sectionally and longitudinally. In conclusion, tau pathology showed spatially specific associations with cerebral hypoperfusion, independent of amyloid-{beta}, particularly in posterior regions. The attenuation of associations of white matter hyperintensities with amyloid-{beta} and tau after adjustment may reflect shared disease-related variance rather than distinct independent effects. Keywords: Alzheimer's disease, Cerebral blood flow, White matter hyperintensities, Tau pathology, Amyloid-{beta}.

INTRODUCTION: MethylCog is a 29-CpG blood DNA methylation (DNAm) proxy for general cognitive ability (g). Its incremental association with blood biomarkers of Alzheimer's disease and related dementias (ADRD) and prospective cognitive ability remains unclear. METHODS: In the held-out test set from the original MethylCog study, we tested whether MethylCog explained baseline g beyond four ADRD blood biomarkers, and whether it predicted six-year follow-up g beyond baseline g and biomarkers. RESULTS: MethylCog showed a stronger age-adjusted association with baseline g than individual biomarkers (r=.368 vs absolute r=.083-.162). MethylCog added 10.0% variance beyond all four biomarkers cross-sectionally (p<.001) and predicted six-year follow-up g in the biomarker-adjusted model (beta=.108, p=.002). No individual ADRD biomarker independently predicted follow-up g. DISCUSSION: MethylCog may provide cognition-related DNAm information complementary to blood-based ADRD biomarkers.

Objective: Cognitive impairment is common among older adults with epilepsy, although efficient screening tools suitable for routine use are lacking. Here we examine, for the first time, the utility of the Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) as a screening tool to identify cognitive impairment in older adults with epilepsy. Methods: Participants included 83 adults (ages over 55) with epilepsy from the Brain, Aging, and Cognition in Epilepsy (BrACE) study and 83 age-, sex-, and education-matched cognitively healthy controls from the Alzheimers Disease Neuroimaging Initiative (ADNI-3). All completed the ADAS-Cog and a comprehensive neuropsychological battery to identify cognitive phenotypes (intact vs impaired). Performance on individual ADAS-Cog items and the total score was assessed, and diagnostic efficiency statistics were determined. Results: Epilepsy participants (mean age=66.4 years) performed significantly worse across the ADAS-Cog total score and 8 of the 13 individual test items compared to controls. The largest effect sizes were observed on verbal learning and memory tasks, particularly word recall (d=0.87) and delayed word recall (d=1.06). An ADAS-Cog total score of at or exceeding 15 yielded optimal diagnostic efficiency (67.5% accuracy, 68.8% sensitivity, 66.7% specificity) for identifying cognitive impairment. Significance: The ADAS-Cog is sensitive to detecting cognitive impairment in older adults with epilepsy and may represent a scalable screening option in this population. Additional comparative studies in older epilepsy populations are needed to determine the sensitivity of this measure to longitudinal change, cross-cultural applicability, and availability across languages. Plain language summary: Cognitive decline is common among older adults with epilepsy, although sufficient evidence supporting the use of screening tools to identify cognitive impairment in this population is lacking. The ADAS-Cog may be a useful screening option in epilepsy research and clinical care, although additional studies are needed to compare it with other cognitive screening tests and to confirm its applicability for clinical care and across cultures and healthcare settings.

Abstract Background Prediction of long-term neurodevelopmental outcomes remains challenging after perinatal asphyxia. Here, we studied whether computational metrics of brain function derived from neonatal EEG are associated with long-term neurodevelopment in infants with perinatal asphyxia. Methods Total of 36 term-born infants with perinatal asphyxia with or without hypoxic-ischemic encephalopathy were studied with neonatal multichannel electroencephalography (EEG). We computed local EEG amplitudes and phase-amplitude coupling (PAC), as well as large-scale functional cortical networks estimated using amplitude-amplitude correlations (AAC) and phase-phase correlations (PPC). These EEG-derived markers were tested for associations with neurodevelopmental outcomes at two years, assessed using the Griffiths Scales of Child Development, 3rd edition (GMDS-III). Results EEG amplitudes showed positive associations with GMDS-III Foundations of Learning and General Development scores across most electrodes during quiet sleep, with the strongest effects observed at frontal and central regions (r = 0.44-0.66). PAC showed negative associations with the same scores mainly over parietal and temporal regions (r = -0.45 to -0.55). Cortical AAC networks demonstrated the most robust and widespread negative associations in all frequency bands during quiet sleep (r = -0.47 to -0.54), with 70-72% of connections significant in high delta frequency. In turn, PPC networks showed frequency-selective and more spatially constrained negative associations during quiet sleep (r = -0.48 to -0.53), involving 5-12% of the network. Conclusions Both local and network-based metrics in the newborn brain show significant association with neurodevelopmental outcome at 2 years after perinatal asphyxia.

Importance: Little is known about the impact of returning Alzheimer disease (AD) biomarkers to cognitively unimpaired (CU) research participants. Objective: Does return of research results (RoRR) negatively impact longitudinal symptoms of depression and cognition. Design: Randomized, noninferiority, delayed-start clinical trial, 2021-2025 Setting: AD biomarker research results offered to CU participants in a longitudinal study of aging Participants: CU participants age 65+ were offered research AD biomarker results (APOE genotype and either plasma AB42/40 or amyloid PET and MRI hippocampal volume) with an estimated 5-year risk of symptomatic AD. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): 147 participants were randomized to receive results either soon after consent (RoRR arm, N=73) or one year later (delayed-start arm, N=74). Main Outcome(s) and Measure(s): Longitudinal change in Geriatric Depression Scale (GDS), Clinical Dementia Rating sum of boxes (CDR-SB), and global cognitive composite. Outcomes were measured at annual assessments for a longitudinal study of aging. Results: 187 participants received results: 70 in RoRR arm (average age 75, 60% female), 66 in delayed-start arm (average age 73, 53% female). The observed changes in annual measures did not differ between arms in both those with elevated amyloid (AB+) and in those without elevated amyloid (AB-) for GDS (AB+ difference 0.7, 95% CI 0.0-1.3; AB- difference -0.1, 95% CI -0.7-0.5; clinically significant decline >4.0), CDR-SB (AB+ difference 0.0, 95% CI -0.1-0.1; AB difference 0.0, 95% CI 0.0-0.1; clinically significant decline >0.5), and cognitive composite (AB+ difference -0.10, 95% CI -0.25-0.06; AB- difference -0.05, 95% CI -0.17-0.07; clinically significant decline < -0.26). Secondary analyses found no evidence of association between RoRR and proximity to follow-up testing. Conclusions and Relevance: In the first randomized, delayed-start clinical trial of returning AD research results to CU older-adult participants, no effect was seen on longitudinal changes in symptoms of depression or cognition. This supports evidence that there are no harms to returning AD research results, although the results may not apply to more diverse populations not included in this study. Trial Registration: NCT04699786

Generalizable neuroimaging biomarkers that detect cerebral cortical changes after traumatic brain injury (TBI) and predict patient outcomes are needed to improve care and to develop targeted therapies. We used morphometric inverse divergence (MIND) analysis of structural MRI to investigate cortical gray matter morphological networks cross-sectionally and longitudinally after TBI and correlate these with symptoms, disability and cognition six months after injury. Our findings support the Triple Network Model from functional MRI of post-traumatic alterations in the relationship between task-positive, default mode and salience networks. However, the strongest associations between early cortical similarity metrics and long-term patient outcomes involved the dorsal attention network and the limbic network as well as similarity metrics across Mesulam's hierarchy of laminar differentiation. Since MIND mapping of cortical gray matter networks only requires data that is a routine part of standard clinical MRI protocols and does not need image harmonization across different scanners, this work reports a promising new tool that is immediately available for advancing research and clinical care in TBI.

Objective: Cross-sectional studies indicate associations between self-reported social media use and adolescent wellbeing outcomes. We aimed to evaluate longitudinal associations of objectively measured smartphone and social media use with psychosocial wellbeing. Design: Observational study with one year of follow-up Setting: High schools in Finland from 2022 to 2023 Population: 259 adolescent girls (mean age 16.3 years at baseline) Main outcome measures: screenshots depicting smartphone and social media use, Bergen Social Media Addiction Scale (BSMAS), Generalized Anxiety Disorder-7 questionnaire, Body Appreciation Scale 2 (BAS-2) and visual analogue scales (VAS) of mood, tiredness, and loneliness Results: Across one year of follow-up, anxiety, body appreciation, and mood improved, but possible social media addiction increased from 15% to 17%. Social media addiction at baseline was associated with increased anxiety (r=0.29, p<0.001), lower body appreciation (r=-0.15, p=0.022), and more loneliness (r=0.20, p=0.001) at follow-up. Anxiety at baseline was associated with social media addiction at follow-up (r=0.19, p=0.005). The highest quartile of TikTok users reported more social media addiction (BSMAS 19 [IQR 16-21] vs. 17 [IQR 14-20]; p=0.009) and lower body appreciation (BAS-2 32 [IQR 28-38] vs. 35 [IQR 29-40]; p=0.003) than did others. The highest quartile of Snapchat users reported more social media addiction (BSMAS 19 [IQR 15-21] vs. 17 [IQR 14-20]; p=0.007) and tiredness (VAS 21 [IQR 13-32] vs. 26 [IQR 15-35]; p=0.049) than did others. Conclusions: Consistent with cross-sectional studies, social media addiction was associated with poorer psychosocial outcomes across follow-up. Policies to protect adolescents from social media addiction are urgently needed.

Background: Cannabis use is highly prevalent among emerging adults (18-25 years), a developmental period marked by ongoing neurodevelopment and heightened risk for cannabis use disorder (CUD). Structural alterations in the orbitofrontal cortex (OFC) and medial prefrontal/anterior cingulate cortex (mPFC/ACC) have been linked to cannabis use, though findings remain inconsistent in directionality. To address this, we examined cortical thickness and surface area of the OFC and mPFC/ACC subregions using the high-resolution Glasser atlas, allowing for more granular characterization of associations with CUD severity. Method: One hundred eleven emerging adults (41% male, aged=20.6{+/-}1.1 years) reporting significant alcohol and/or cannabis use completed clinical assessments and structural MRI. The OFC and mPFC/ACC were segmented into seven and six subregions per hemisphere, respectively. Multiple linear regressions tested associations between cortical thickness or surface area and DSM-5 CUD symptom count, controlling for alcohol use and intracranial volume. Subregions surviving false discovery rate correction were examined in relation to depression, trauma-related symptoms, impulsivity, and cannabis use motives. Results: Greater CUD severity was associated with lower cortical surface area and greater cortical thickness in OFC and mPFC/ACC subregions. Lower OFC surface area was correlated with coping- and enhancement-related cannabis use motives. Lower mPFC/ACC surface area and greater thickness were associated with more severe depression, trauma-related symptoms, and impulsivity. Conclusion: In high-risk emerging adults, greater CUD symptom burden is associated with lower surface area and greater thickness in OFC and mPFC/ACC subregions. Using the high-resolution Glasser atlas, these findings provide a more precise characterization of structural correlates of CUD and highlight potential neurobiological markers linked to affective and motivational processes underlying cannabis use.

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.

Blood biomarker models are increasingly used in Alzheimer's disease and related dementia translational research, but predictive performance can be inflated when the same dataset is used for both model development and evaluation. We assess the effect of data double dipping using simulations and NULISA proteomic data from the MYHAT-NI community-based cohort to predict brain amyloid-beta neuroimaging status. In both settings, training AUC increased as more biomarkers were added, while testing AUC peaked earlier and then declined. These findings show that data double dipping can inflate model performance and highlight the need for external validation or internal validation with data partitioning.

Background: Individuals with body dysmorphic disorder misperceive defects of their physical appearance. Current evidence suggests that visual processing abnormalities may underlie this core symptom. Separate pre-clinical studies testing perceptual and attentional interventions and non-invasive neuromodulation suggest that these visual processing abnormalities may be modifiable, but their combined effects on neural connectivity and perceptual processing remain unclear. Methods: Thirty-nine unmedicated men and women with body dysmorphic disorder or subclinical body dysmorphic disorder received intermittent theta burst stimulation and continuous theta burst stimulation targeting the lateral parietal cortex combined with a visual attention modification paradigm during functional magnetic resonance imaging, in a crossover design. Dynamic effective connectivity within dorsal and ventral visual stream pathways was calculated, and global visual processing biases were assessed using the face inversion effect before and after stimulation plus attention modification. Results: Intermittent theta burst stimulation resulted in increased connectivity in higher-level dorsal visual stream pathways during naturalistic viewing following attention modification, whereas continuous theta burst stimulation was associated with reduced connectivity in lower-level dorsal pathways and increased connectivity in ventral stream pathways. These changes were accompanied by differential effects on global visual processing, with stimulation type modulating the magnitude of the face inversion effect. Conclusions: Combined neuromodulation and visual attention modification modulate visual system connectivity and perceptual processing in individuals with body dysmorphic disorder symptoms. These findings support a mechanistic link between dorsal-ventral stream dynamics and perceptual biases. Integrating neuromodulation with perceptual retraining may represent a viable approach for targeting core symptoms of distorted appearance perception.

The impact of social parameters on brain health among people with traumatic brain injury (TBI) has been extensively documented. However, translation of this evidence into policy and clinical practice remains limited. This may reflect a lack of coordinated and equity-driven approaches to brain health that integrate diverse stakeholder perspectives, limiting progress toward equity-oriented research and service delivery models. We conducted a convergent parallel mixed-methods study guided by the REporting guideline for PRIority SEtting of health research (REPRISE). We utilized the PROGRESS-Plus framework (Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and context-specific parameters) to ensure systematic consideration of social parameters in the study. For Objective 1, we synthesized existing evidence on social parameters and brain health outcomes. For Objective 2, we surveyed people with lived experience of TBI, family members/friends, clinicians, researchers, and community leaders across the globe to assess their prioritization of social parameters relevant to brain health. For Objective 3, we integrated evidence synthesis and stakeholder input through a structured Round Robin consensus activity to prioritize actionable areas for feasibility and impact. The activity culminated in the development of a knowledge mobilization agenda designed to inform equity-centred policy, research, and clinical practice. In Objective 1, we identified 59 publications with evidence on the effect of PROGRESS-Plus parameters on brain health outcomes following TBI. Meta-research highlighted that education, age, and country-level indicators are prognostic for brain health after TBI. In Objective 2, the highest-ranked priorities of 113 stakeholders across four continents (North America, Europe, Africa, and Oceania) were education, access to benefits, and income. These priorities were at the centre of discussion in Objective 3, which comprised idea sharing, refinement and thematic clustering, and a final prioritization poll. The resulting final 15 priorities were organized into two tracks: Track A, actions feasible in the short term, and Track B, longer-term implementation priorities. Building on this priority-setting process, co-created with stakeholders around the globe, the findings provide a roadmap for integration of social parameters in TBI research, knowledge exchange, policy, and practice.

Background Treatment guidelines for borderline personality disorder (BPD) recommend assessment, diagnosis, and psychoeducation. We report on the feasibility and safety of a randomized controlled trial protocol of online psychoeducation, assessment, and personalized feedback as an immediate first step of care for BPD. Methods Newly diagnosed participants were randomized to receive 10 videos about BPD or general mental health for two weeks. Half the participants receiving BPD videos were randomized to receive personalized feedback on changes in symptom ratings and cognitive performance. Ecological momentary assessment (EMA) evaluated interpersonal interactions, emotions, and behaviors for 30 days. BPD symptoms, depression, and personality functioning were assessed at baseline, after videos, after feedback, and one month later. Results Eighty-two participants were randomized into three conditions that did not differ significantly in terms of demographics or baseline variables. Dropout occurred for 32.9% of the sample. No differences in rate of emergency room visits, hospitalizations, or other escalations in level of care were reported among groups. Satisfaction was higher for those receiving psychoeducational videos about BPD. Improvement in BPD knowledge in the psychoeducation conditions was significantly greater than the control condition. No statistically significant differences were found regarding reduction of BPD symptoms. The psychoeducation with feedback arm showed significantly greater improvements in self-impairment compared to controls with medium effect size at the final timepoint. Modeling of the relationship between time spent alone and BPD symptoms showed a positive correlation in the control condition, but in the group receiving both psychoeducation about BPD and feedback, this relationship was negative. Conclusion Online psychoeducational videos and assessment were safe, feasible, and acceptable to participants with newly diagnosed BPD. Psychoeducation with personalized feedback appears to be more effective than either BPD or general psychoeducation alone in improving deficits in self-functioning, which may relate to an increased capacity to be alone with fewer symptoms. The protocol was registered with ClinicalTrials.gov (NCT05358925, https://clinicaltrials.gov/study/NCT05358925) on April 28th, 2022.