Brain Imaging and Behavior

Low statistical power remains a persistent concern in functional magnetic resonance imaging (fMRI) research, largely due to small sample sizes. Although prior work has documented gradual increases in sample size over time, it remains unclear whether structural factors in the publication process are associated with study design characteristics such as sample size. This review addresses this gap by analyzing a large sample of fMRI studies to assess how institutional prestige, journal impact factor, and journal review practices are associated with sample size. We analyzed articles published in 2021-2024 reporting new fMRI data collection in adult humans and including a measure of memory. We found studies with specialized populations, such as patient populations, had smaller sample sizes, as did studies with task-based designs compared to resting-state designs. We also found larger sample sizes were associated with journals with a double-blind review process. Institutional prestige was positively associated with sample size such that more highly ranked institutions tended to have larger samples, but there was no interaction between review type (single-vs. double-blind) and prestige, indicating this difference is not likely due to reviewer bias. Journal impact factor was not associated with sample size, however institutional prestige score predicted journal impact factor. These results suggest structural factors at the institutional level likely have a stronger influence on published study sample size than reviewer practices or biases.

BackgroundTo understand the neurobiology underlying psychopathology, we need valid measurements of brain function. Group atlases for brain functional connectivity (FC) allow for efficient comparisons, but they fail to account for inter-individual variability in network topography, a problem that personalized methods address. We assess the validity and predictive utility of group and personalized approaches of quantifying FC by 1) comparing effect sizes of associations with clinical metrics; and 2) accounting for spatial features of brain networks when examining the association between FC and clinical metrics. Methods324 teens ages 13-16 participated. Personalized networks were estimated using a hierarchical Bayesian model. Effect size comparisons were done by comparing the correlations between FC and clinical metrics (depression, ruminative coping style, and sensitivity to punishment/reward) with Steiglers Z-test. We also conducted regressions, with clinical metrics as the dependent variables. Those models included FC and spatial features, together and alone. ResultsThe effect size comparisons did not survive FDR correction. However, exploratory permutation tests show that 1) the magnitude of the correlations with depression are larger on average for the intersection estimates of FC than the group estimates; and 2) the magnitude of the correlations with a ruminative coping style are larger on average for the intersection estimates of FC than the personalized estimate. The other comparisons conducted using permutation tests are not significant. Multiple regression analyses demonstrated that only spatial features of networks, not FC, are associated with sensitivity to reward. DiscussionThese results imply that the intersection estimates are more valid than the group estimates, and that the intersection estimates have greater predictive utility than personalized estimates. Further, spatial features of functions networks may be useful in and of themselves in certain contexts. Therefore, researchers in psychiatry should take into consideration functional network topography in order to gain a better understanding of the neurobiology underlying psychopathology.

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.

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

Self-referential processing is a fundamental cognitive function, and abnormalities in its neural implementation have been reported across a range of psychiatric disorders, leading to the proposal that such alterations may constitute a transdiagnostic neurobiological feature. Yet claiming transdiagnostic requires rigorous evidence. Here, we examined the evidence for such a hypothesis by conducting a systematic review and coordinate-based meta-analysis of psychiatric neuroimaging studies that employed self-referential tasks. The systematic review identified 36 neuroimaging studies across 9 broad categories of psychiatric disorders, suggesting that the neural aberrancy of self-referential processing is indeed of great interest across different diagnosis. Of these, 27 studies were eligible for the ALE meta-analysis. The ALE results revealed hypoactivation of the right precuneus in psychiatric groups relative to health controls, alongside hyperactivation of the right triangular part of the inferior frontal gyrus (IFGtri) during self-referential processing in psychiatric groups. Notably the precuneus and IFGtri are core nodes of the default mode network and the frontal-parietal control network, respectively, suggesting that aberrant self-referential processing across psychiatric disorders may be characterized by disrupted default mode network engagement accompanied by compensatory or maladaptive recruitment of control-related frontal regions. Together, our findings revealed a strong research interest in neural aberrancy of self-referential processing as a transdiagnostic feature. However, available evidence only provided preliminary evidence for such statement. To move forward, the field needs coordinated efforts to systematically accumulate data and collecting new datasets.

IntroductionThe thalamic nuclei play a crucial role in regulating information flow to the cortex and supports diverse cognitive functions. Although previous studies have linked thalamic structural and functional characteristics to cognition, these measures do not fully capture the thalamuss role in dynamic control, which is essential for complex cognitive processes. Moreover, it remains unclear how these different metrics relate to each other in the way they account for cognition. MethodsT1-weighted MRI, diffusion MRI, resting-state fMRI, and neuropsychological data were obtained from 419 unrelated participants in the Human Connectome Project. We measured grey matter volume, white matter integrity, and functional controllability of each thalamic nucleus to examine their associations with cognitive performance across domains identified through clustering analysis of the neuropsychological data. We also assessed the relationships among these structural and functional metrics and evaluated their individual and combined contributions in capturing covariance with performance in various cognitive domains. ResultsSignificant correlations were observed between thalamic grey matter volume and white matter integrity; however, thalamic functional controllability showed no significant association with either structural metric. White matter integrity demonstrated the strongest association with sequence working memory and language processing. In contrast, thalamic controllability metrics accounted more for performance in executive function, reasoning and encoding, visuospatial processing, and impulse control, outperforming the combination of grey and white matter structural metrics. ConclusionThis study highlights the critical role of the thalamus from a dynamic control perspective, demonstrating that thalamic structural and functional metrics provide complementary rather than redundant information related to cognitive performance. These findings underscore a promising new direction for understanding the complex and dynamic contributions of the thalamus to human cognition.

BackgroundSchizophrenia is marked by impairments in emotional processing and social cognition, yet traditional neuroimaging paradigms often lack the ecological validity to capture these deficits in real-world contexts. MethodsIn this study, we used intersubject correlation (ISC) analysis of functional MRI data to examine shared neural representations of naturalistic visual narratives in individuals with schizophrenia and healthy controls. Participants viewed short films designed to evoke happy, sad, and emotionally neutral responses, allowing us to compare how synchronized brain activity varied with emotional content across and within groups. ResultsHealthy controls showed greater ISC in regions associated with affective salience, emotion recognition, and social understanding, including the amygdala, insula, and temporal cortices. In contrast, participants with schizophrenia displayed higher synchrony in visual, subcortical, and frontal areas, suggesting a reliance on perceptual and executive systems. To isolate the effects of emotion from general visual processing, we compared ISC during emotional clips relative to neutral videos. This revealed significantly reduced synchrony in the bilateral amygdala in patients, highlighting a core dysfunction in affective engagement. Interestingly, neutral stimuli elicited unexpectedly strong synchronization in frontal and limbic regions in the schizophrenia group, possibly reflecting altered salience attribution to ambiguous or emotionally ambiguous content. ConclusionsThese results point to a functional reorganization of affective processing in schizophrenia, where impaired limbic recruitment is accompanied by compensatory engagement of perceptual and cognitive control networks. ISC during naturalistic stimulation emerges as a powerful tool for capturing subtle disruptions in shared emotional experience in psychiatric populations.

Prior studies in bilinguals have reported relationships between brain structure and the dimensions of (i) language proficiency or (ii) language balance (the discrepancy between a bilinguals two proficiencies), but rarely both, even though they are highly related. These studies were often conducted in late bilinguals and the analyses limited to regions of interest. Here, we tested for relationships between brain structure and these two dimensions in 46 early cultural Spanish-English bilinguals (mean age = 16.7 years) at the level of the whole brain for gray matter volume (GMV) and cortical thickness (CT). Results revealed a positive association between GMV and proficiency in the weaker language in the right angular gyrus (AG; BA 39) extending into the superior temporal gyrus (BA 22). More balanced bilingualism was also associated with more GMV in the AG (BA 39), in addition to less GMV in left postcentral gyrus (BA 1), right cerebellum lobule IX and right superior occipital gyrus (BA 18). However, these relationships between GMV and balance disappeared after controlling for language proficiency. No significant associations were observed for CT and these two dimensions of language. Our findings suggest that relationships between GMV and balance are driven by language proficiency, and that the relationship between GMV and language proficiency likely does not involve language-specific mechanisms, given the location of the association is in the right inferior parietal cortex. Together, this study separates the neuroanatomical bases of these two language dimensions and places them in brain regions outside those usually targeted in prior studies. HighlightsO_LINeuroanatomy was correlated with proficiencies in early Spanish-English bilinguals C_LIO_LIRight angular gyrus gray matter volume (GMV) was positively related to proficiency C_LIO_LIGMV was positively related to balance, but not after controlling for proficiency C_LIO_LIRelations with these language dimensions are located outside of language cortex C_LIO_LINo significant associations were observed for cortical thickness C_LI

BackgroundThe developmental timing of trauma exposure may critically shape neurobiological outcomes, yet distinctions between childhood-onset trauma (CT) and adulthood-onset trauma (AT) remain poorly understood. AimThis study explores whether trauma onset timing is associated with distinct resting-state functional connectivity (rsFC) pattern using data-driven approach. MethodsSeventy-seven trauma-exposed individuals (Mage=36.74 years) with post-traumatic stress disorder (PTSD), PTSD with major depressive disorder (MDD), and trauma-exposed healthy controls (TEHC) underwent resting-state fMRI. Of these participants, 15 with CT only, 17 with both CT and AT, and 47 with AT only. RsFC was calculated across the amygdala, hippocampus, nucleus accumbens (NAcc), the salience (SN), default mode (DMN), and frontoparietal networks (FPN). K-means clustering identified subgroups based on rsFC, with robustness assessed via bootstrapping, cross-validation, and replication using Gaussian Mixture Modeling. The identified clusters were compared on trauma timing, type, cumulative exposure, and clinical measures. ResultsA two-cluster solution provided the most stable fit. The two generated clusters were significantly different in CT-only prevalence (p < 0.05; Cramers V = 0.26, 95% CI). The CT cluster was marked by hyperconnectivity between amygdala-FPN, DMN-SN, NAcc-SN, and hippocampus-FPN relative to the AT cluster. Individuals with both CT and AT were evenly distributed across clusters. Clusters did not differ in PTSD or comorbid diagnoses, trauma type, or cumulative exposure. ConclusionData-driven clustering revealed distinct neurobiological profiles differentiating CT and AT. CT was associated with hyperconnectivity across salience, reward, and regulatory circuits, supporting developmental timing as a determinant of brain network organization in trauma-exposed populations.

BackgroundLarge-scale T1-weighted MRI studies have established grey-matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white-matter pathways, yet prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretic metrics. MethodsCross-sectional structural and diffusion MRI scans from 449 individuals with BD (35.7{+/-}12.6 years) and 510 controls (33.3{+/-}12.6 years), aged 18-65, were analyzed across 16 ENIGMA-BD sites. Standardized segmentation/parcellation and constrained spherical deconvolution tractography generated individual structural connectivity matrices. Graph-theoretic metrics of global and subnetwork organization were related to symptom severity and medications. ResultsBD showed widespread network alterations (lower density and efficiency, longer path length, and higher betweenness centrality), altered microstructural organization in a limbic-basal ganglia circuit, and abnormal streamline counts in a default-mode/salience/fronto-limbic-basal ganglia network. Longer illness duration, later onset, and psychosis history were associated with greater abnormalities in network architecture, whereas more manic episodes were associated with greater fronto-limbic connectivity. Antidepressant (particularly SSRI), anticonvulsant, and antipsychotic use related to poorer global and fronto-limbic connectivity; no clear lithium effects emerged. ConclusionsAs the largest structural connectivity study in BD, we reveal widespread disruption in reward and emotion-regulation networks influenced by illness severity and medication use. Results show that multisite harmonization is feasible and highlight ENIGMA-BD as a scalable framework for identifying reproducible neurobiological markers.

BackgroundSchizophrenia is a severe neuropsychiatric disorder. Efforts to describe the underlying biology and establish diagnostic markers through non-invasive neuroimaging methods are ongoing, resulting in a range of theoretical brain-based frameworks. Prominent frameworks for aberrant schizophrenia-associated functional connectivity in resting-state functional magnetic resonance imaging (rsfMRI) include the dysconnectivity hypothesis, theory of cognitive dysmetria, and triple network theory. Although informative, prior work can be improved by increasing sample size, avoiding confirmation bias, and accounting for individual variability and the effects of medication and chronicity. MethodsWith these recommendations in mind, we employed a data-driven, whole-brain approach using a large multi-site rsfMRI dataset (N = 2,656; schizophrenia = 1,248). We used reference-guided independent component analysis (ICA) to generate subject-specific whole-brain functional network connectivity (FNC) and extract imaging markers of similarity to schizophrenia patterns. We modeled the relationship between medication dosage, age of onset, chronicity, symptom severity, and cognitive performance and FNC. ResultsOur analysis identified a reliable schizophrenia-FNC signature characterized by aberrantly stronger negative cerebellothalamic and positive thalamocortical connectivity, implicating sensory, motor, and associative cortical circuits. While medication and chronicity were significantly associated with these signatures, the core cerebellothalamic disruptions remained a robust marker of schizophrenia. ConclusionsThis work represents the largest schizophrenia-specific rsfMRI study to date, refines existing theoretical frameworks with a more nuanced map of how clinical variables interact with brain connectivity, and provides a high-fidelity template of schizophrenia-related connectivity. We have released this template as an open-source resource to facilitate reproducibility and accelerate the development of reliable rsfMRI-based schizophrenia biomarkers.

ObjectiveFinding indicators of early response to antidepressant treatment in EEG signals recorded from patients suffering from major depressive disorder. MethodsFunctional brain connectivity networks based on weighted imaginary coherence and weighted imaginary mean phase coherence were computed for 176 patients for 6 different EEG frequency bands. Cross-hemispheric connectivity (CH) and lateral asymmetry (LA) were estimated from these networks based on EEG signals recorded before the beginning of treatment (V is1) and one week after the start of the treatment (V is2). Repeated measures ANOVA was used to check for statistically significant changes in connectivity based on these measures at V is2 w.r.t. V is1. Post-hoc analysis was performed with multiple pairwise comparison tests to determine which group means were significantly different. ResultsIt was found that CHV is2 was significantly reduced w.r.t. CHV is1 in the {beta}1 [12.5 - 17.5 Hz] frequency band for the responders to treatment. Also, LAV is2 was significantly increased w.r.t. LAV is1 in the {beta}1 frequency band for the responders. No such significant changes were observed for the non-responders. Brain networks constructed using both weighted imaginary coherence and weighted imaginary mean phase coherence were found to exhibit these results. For the CH connectivity changes, binarized networks and for the LA connectivity changes, weighted networks were found to be more reliable. ConclusionsResponders were found to show a reduction in cross-hemispheric connectivity and an increase in lateral asymmetry, both in the {beta}1 band while no such change was observed for the non-responders. SignificanceDecrease in cross-hemispheric connectivity and increase in lateral asymmetry in the {beta}1 band may represent candidate neurophysiological indicators of early treatment response, but they require independent replication before any clinical application can be considered.

Background: Persistent neurological and cognitive symptoms following SARS-CoV-2 infection point to long-term alterations in brain structure and function. The thalamus, orbitofrontal cortex, and limbic networks are particularly susceptible to inflammatory and neurovascular stressors. However, the relationship between cortical, white-matter, and thalamocortical alterations in post-COVID syndrome remains unclear. Methods: 76 COVID-19 recovered participants (CRPs) and 51 healthy controls (HCs) underwent multimodal MRI comprising T1-weighted structural, diffusion, and resting-state functional acquisitions. Grey-matter morphology was assessed using voxel-based morphometry (VBM), white-matter microstructure using tract-based spatial statistics (TBSS), and thalamocortical functional connectivity (TC-FC) using seed-based analyses from major thalamic nuclei. Results were evaluated both across the groups (HC vs. CRP) and after stratifying CRPs by hospitalisation status (HC vs. Non-hospitalized patients (NHPs) vs. Hospitalized patients (HPs)). Results: No group-level grey-matter differences were observed between HCs and CRPs; however, HPs showed localized volume loss in the orbitofrontal and frontal-pole cortices (pFWE < 0.05). TBSS revealed widespread microstructural abnormalities, including reduced fractional anisotropy and mean diffusivity across association and commissural tracts (pcorr < 0.05), with regional increases in mode of anisotropy indicating selective loss of crossing fibres (pcorr < 0.05). Resting-state analyses revealed increased TC-FC from the mediodorsal thalamic nucleus to anterior cingulate, parietal, and occipital cortices (pcorr < 0.05), while differences in pulvinar and ventrolateral nuclei were not significant (pcorr > 0.05). Conclusions: Our findings indicate that COVID-19 recovery is associated with enduring alterations in fronto-limbic and thalamo-cortical circuits, most prominently in individuals with severe infection. Convergent structural and functional changes involving the orbitofrontal cortex and mediodorsal thalamus suggest network-specific reorganisation that may underpin persistent cognitive and affective symptoms of post-COVID syndrome.

It has been proposed that bilinguals have better executive function (EF) arising from the constant selection of one language while inhibiting the other, and gray matter has been found to differ in bilinguals in regions linked to EF (frontal-parietal and subcortical structures). Attention Deficit Hyperactivity Disorder (ADHD) is associated with poorer EF and neuroanatomical differences underlying EF. Given the EF advantage in bilinguals, we investigated whether a bilingual experience affects EF performance and brain structure differentially in those with ADHD. Using the Adolescent Brain and Cognitive Development Study, we compared early Spanish-English bilinguals and English-speaking monolinguals with and without ADHD. ANOVAs for the Flanker, Working Memory, and Card Sort Tasks revealed no main effects of Language Experience (Bilingual versus Monolingual), a main effect of Diagnostic Group for Card Sort (ADHD worse than Controls), and no interaction effects on performance for any task. ANOVAs for gray matter volume (GMV) revealed a main effect of Language Experience in many regions, a main effect of Diagnostic Group in some regions, but no interactions. GMV in left thalamus was affected by both ADHD and bilingualism, but the effect of ADHD was not significantly diminished or enhanced by the dual-language experience. For cortical thickness, there was a main effect of Language Experience in several regions, no main effect of Diagnostic Group, and no interactions. Taken together, bilingualism has some impact on EF performance, a strong impact on neuroanatomy, but there was no disproportionate impact by bilingualism on the differences caused by ADHD for any measure. Research HighlightsExecutive function and brain structure differ in ADHD and in bilinguals, prompting the need to investigate interactive effects. Bilingualism did not disproportionately affect performance differences in ADHD for executive function, nor for gray matter volume or for cortical thickness differences in ADHD. Gray matter volume was less in ADHD than non-ADHD, as well as greater in bilinguals than monolinguals in the left thalamus, but without interaction effect. These independent effects indicate that the brain basis of ADHD is not impacted by a dual-language experience.

BackgroundThe relationship between neighborhood-level socioeconomic disadvantage and brain health is an emerging area of research with critical implications for public health and clinical practice, yet its influence on brain structure remains unclear. PurposeTo investigate the epidemiological association between neighborhood-level socioeconomic disadvantage [Area Deprivation Index (ADI)] and morphometric neuroimaging variables in a consecutive, non-disease enriched patient population. Materials and MethodsThis study, conducted at an academic medical center and associated community partners, used consecutive cross-sectional MRI neuroimaging data from 2,826 inpatient and outpatient individuals without radiological evidence of disease from January 2024 to June 2024. ADI, a geospatially determined index of neighborhood-level disadvantage, was calculated for each individual. Linear regressions tested the relationship between ADI and multiple morphometric variables: brain age gap (BAG; estimated - chronological BA), total brain tissue volume (TBV; total gray + white matter), five subcortical region volumes (hippocampus, thalamus, caudate, putamen, and nucleus accumbens) and four cortical region volumes [anterior cingulate cortex, posterior cingulate cortex, medial prefrontal cortex (MPFC), lateral PFC (LPFC)]. Volumetric measures were normalized to intracranial volume. Models controlled for age, sex, and total white matter hyperintensity volume (WMHV). Results2,826 individuals (mean age, 52.7 {+/-} 18.8 [standard deviation]; 1732 women) were evaluated. Residence in the 20% most disadvantaged neighborhoods was associated with a higher BAG ({beta}s > 2.12, Ps < .01) and decreased TBV ({beta}s < -5.12, Ps < .05). Additionally, increased WMHV was higher among those in the most disadvantaged neighborhoods (ts < - 2.50, Ps < .05) and associated with lower volume in most regions. Interaction models showed increased negative associations between WMHV and volumes of the caudate, nucleus accumbens, and lateral prefrontal cortex among those in the most disadvantaged neighborhoods. ConclusionsNeighborhood disadvantage is associated with adverse brain morphometry, including higher BAG, lower TBV, and amplified vascular-related regional volume loss. Key ResultsO_LIIn 2,826 adults (mean age, 53 years {+/-} 19; 1,732 women), residence in the most disadvantaged neighborhoods (national: 116/2,826, 4%; state: 129/2826, 5%) was associated with higher brain age gap at the national ({beta} = 2.12, 95% CI = 0.81 to 3.43, P = .001) and state levels ({beta} = 2.36; 95% CI = 1.10 to 3.61, P < .001). C_LIO_LITotal brain tissue volume was lower at the national ({beta} = -5.12, 95% CI = -10.13 to -0.11, P = .045) and state levels ({beta} = -6.13, 95% CI = -10.90 to -1.37, P = .011). C_LIO_LIWhite matter hyperintensity volume was higher in the most disadvantaged group (national: P = .013; state: P = .003) and demonstrated amplified associations with caudate, nucleus accumbens, and lateral prefrontal cortex volumes in the most disadvantaged group at the national and/or state levels (Ps < .05). C_LI

BackgroundNon-suicidal self-injury (NSSI) represents a growing public health concern, particularly in adolescents. Emotion dysregulation is central to prevailing NSSI models, yet it remains unclear whether acceptance-based emotion regulation (ER) and its underlying neural processes are disrupted in naturalistic, dynamic contexts. MethodsPre-registered neuroimaging trial in recently diagnosed and treatment-naive adolescents with NSSI (n=25) and healthy controls (n=25) using an ER paradigm with dynamic video clips and concomitant functional magnetic resonance imaging. Behavioral, neural activity, and connectivity indices during emotion reactivity and acceptance-based regulation were compared between groups. ResultsAdolescents with NSSI experienced elevated negative feelings during neutral clips, reflecting heightened baseline negativity. In comparison to controls, they displayed reduced temporal and ventrolateral prefrontal engagement during emotional reactivity, but increased engagement of regions implicated in both emotion reactivity (right amygdala, insula) and ER (right dlPFC, dmPFC, vlPFC) when utilizing acceptance. Higher activation in the right dlPFC was positively associated with difficulties in accessing ER strategies in everyday life. Adolescents with NSSI showed reduced functional connectivity between the right amygdala and left dlPFC. ConclusionsAdolescents with NSSI exhibited a baseline negativity bias and altered neural engagement during both negative emotional reactivity and acceptance-based regulation, characterized by increased activation and reduced amygdala-dlPFC connectivity. These findings highlight atypical emotion processing in real-life contexts in individuals with NSSI. Targeting acceptance-based regulation and prefrontal-limbic circuitry may represent a promising intervention approach for adolescents with NSSI.

IntroductionThe anterior limb of the internal capsule (ALIC) is a major white matter highway connecting prefrontal cortical (PFC) regions to the thalamus, brainstem, and subthalamic nucleus. Structural and functional abnormalities within the ALIC circuit have been associated with many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and depression, and deep brain stimulation (DBS) may provide effective treatment to some of these patients. However, it remains unclear whether the well-characterized topographic organization of the ALIC observed in healthy individuals and preclinical models is preserved in treatment-resistant psychiatric populations. MethodsWe first used diffusion tractography to evaluate the topography of PFC and subcortical fibers through the ALIC in patients with treatment-resistant OCD (n=18) and depression (n=5). In depression patients, we also evaluated ALIC topography using cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse electrical stimulation (SPES) of DBS leads in the ALIC and recordings in the ventral PFC (vPFC). ResultsThe topographic organization of PFC and subcortical projections is preserved in the ALIC among treatment-resistant psychiatric patients, consistent with patterns observed in healthy individuals and preclinical models. CCEP recordings in the ventral PFC showed a ventral ALIC to medial vPFC/dorsal ALIC to lateral vPFC response pattern in the left hemisphere, but not in the right. ConclusionOur findings confirm that topographic patterns within the ALIC previously identified using preclinical models and healthy controls are preserved in treatment-resistant psychiatric patients. Furthermore, by linking white matter topography to stimulation effects, this work supports more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.

BackgroundDepression is associated with social dysfunction, but the mechanisms linking affective symptoms to disrupted close relationships remain poorly understood. One possibility is that depression alters how people experience rewards shared with close others and how they interpret partners actions. It remains unclear whether neural sensitivity to shared reward predicts social valuation during more complex interactions such as reciprocated trust. MethodsIn this preregistered fMRI study, participants completed a reward-sharing task and a Trust Game with a close friend, a stranger, and a computer. We measured striatal shared reward sensitivity (SRS; friend > computer) and tested whether it related to subsequent investment behavior and brain responses to trust reciprocation. Depressive symptoms and perceived closeness were assessed via self-report. ResultsIn a final sample of n = 123, participants reporting more depressive symptoms invested more in their friend than in the computer. Striatal SRS predicted temporoparietal junction responses to reciprocated trust, but this association depended jointly on social closeness and depression -- with depression reversing the expected pattern among individuals reporting closer relationships. Striatal SRS was also inversely associated with connectivity between the default mode network and cerebellum during reciprocity. ConclusionsThese findings suggest that closeness calibrates the striatal SRS link to regional activity and network-level responses during social exchange, while depression alters how striatal SRS relates to regional activity, potentially disrupting how individuals interpret and respond to close others.

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.

ObjectivesNeuropsychiatric symptoms (NPS) are prevalent in individuals of cognitive impairement (CI). However, the similarities and disparatenesses in whole-brain dynamics between individuals of CI and NPS are controversy. Electroencephalography (EEG) microstates reflect the whole-brain dynamics. This study aimed to investigate the differential EEG microstates parameters between CI and NPS and to construct related diagnostic model. Methods/designThis study was a cross-sectional study. Clinical and EEG data were collected, and an EEG microstate analysis were performed. The Least absolute shrinkage and selection operation (LASSO) regression model was used to identify significant differential EEG microstates parameters between CI and NPS and to construct a diagnostic model. The model performance was tested by the receiver operating characteristic curve (ROC). ResultsThis study enrolled 78 participants. A total of 36 EEG microstates parameters were identified and included in the differential analysis. In the LASSO regression model, 4 significant differential EEG microstates parameters were selected, including the duration of class C, TPAB, TPBA, and TPDC. The ROC results showed that the diagnostic model for distinguishing NPS patients from CI patients achieved an area under the curve (AUC) of 0.905(95% CI: 0.784-1.000), with a sensitivity of 100.0% and a specificity of 76.9%. ConclusionsThe diagnostic model based on EEG microstate parameters showed a good performance for differentiating NPS patients from CI patients.