Brain Imaging and Behavior

A single injection of a subanesthetic dose of ketamine, an NMDA receptor antagonist, induces schizophrenia-like behavior in mice. Previous studies investigated the effect of single injection of ketamine on behavior and c-Fos expression in mice dose-dependently. However, there has not been functional magnetic resonance imaging (fMRI) study to investigate the effect of ketamine in mice. Here, we used awake fMRI and investigated the dose-dependent effect of single injection of ketamine in awaked mice. The lower-dose (5 mg/kg) ketamine increased functional connectivity (FC) with the thalamus and the hypothalamic nuclei. Higher-dose (50 mg/kg) ketamine increased widespread FC with cerebral cortex as well as hippocampus and thalamic nuclei. Graph theory analysis reveals that several regions of hypothalamus and cerebral cortex are essential for the network change by ketamine injection. These results indicate that sub-anesthetic ketamine dose-dependently alters the brain and indues the abnormal behavior in mice.

Background and Hypothesis Negative symptoms in schizophrenia spectrum disorder (SSD) are associated with poor functional outcomes and reduced quality of life; however, effective treatments remain limited. A better understanding of the underlying brain mechanisms is needed to develop better treatments. Neuroimaging studies implicate multiple brain networks in negative symptoms, though findings remain heterogeneous, potentially reflecting the multidimensionality of both symptoms and brain networks. Larger, more systematic dissections are required to identify the key hub(s) underlying negative symptoms. Study Design Structural MRI data from 394 participants (210 SSD, 184 healthy controls [HC]) were analyzed to identify cortical thickness and subcortical volume demonstrating both SSD-HC differences and associations with negative symptoms measured by the Brief Negative Symptom Scale (BNSS). Regions meeting both criteria were selected as seeds for resting-state functional connectivity analyses in 143 SSD patients to examine association with negative symptoms and their subdomains. Study Results The thalamus was the only region demonstrating significant structural abnormalities both in SSD and an association with BNSS total score (p-FDR<0.05). Functional-network-defined thalamic subregions were subsequently examined. Several thalamic hypoconnectivities were significantly corresponded with negative symptoms, involving thalamic subregions associated with the cortical default mode, somatosensory, medial temporal, and dorsal attention networks (p=0.001, corrected<0.05). Blunted affect showed the most extensive thalamic connectivity alterations, involving the striatum, cerebellum, and temporoparietal junction/superior temporal sulcus (TPJ-STS). Thalamic hypoconnectivity with TPJ-STS was also associated with overall negative symptoms and anhedonia. Conclusions This study identifies the thalamus as a central hub of negative symptom-related dysfunction in SSD and highlights specific thalamic subnetworks as potential targets for circuit-based interventions.

Background: Schizophrenia has been conceptualised as a disorder of brain disconnectivity, with white matter abnormalities contributing to altered neural communication. However, fibre-specific white matter alterations in early illness and their potential sex-related differences remain insufficiently characterised. We applied fixel-based analysis to investigate sex-stratified white matter microstructural alterations in first-episode schizophrenia (FES). Methods: Diffusion MRI data from individuals with FES and healthy controls were stratified by biological sex. The male cohort included 79 patients and 29 controls, and the female cohort included 48 patients and 46 controls. Fixel-based analysis was performed separately in males and females to assess fibre density, fibre-bundle cross-section, and their combined measure. Head motion was included as a covariate in the fixel-based analyses. A descriptive follow-up voxel-scale analysis extracted mean fibre density from a binary mask derived from significant male fixels and applied the same region to the female cohort. Results: Males with first-episode schizophrenia showed significantly reduced fibre density compared with male controls, primarily in bilateral frontal white matter and a thin segment of the anterior corpus callosum. The voxel-scale follow-up confirmed lower mean fibre density in males within the significant fixel-derived mask. In contrast, females showed no significant group differences in any fixel-based metric or within the male-derived region. Conclusions: Early white matter microstructural alterations were detected in males with FES but not in females. These findings highlight a differential pattern emerging from sex-stratified analyses and support further investigation of sex-related differences in white matter alterations during the early stages of schizophrenia.

BackgroundLong COVID is characterized by persistent symptoms following SARS-CoV-2 infection, including cognitive deficits among its most disabling manifestations. However, their neurobiological basis is poorly understood. Previous neuroimaging studies reported structural brain alterations, but few have integrated cognitive assessment, network-based analyses, and longitudinal imaging to identify neurobiological subtypes. MethodsWe studied 42 individuals with persistent post-COVID cognitive symptoms and 14 matched healthy controls using cognitive assessment and structural MRI. Multilayer brain networks were constructed from regional morphometric measures, and hierarchical clustering identified patient subgroups. Cross-sectional and longitudinal comparisons of brain structure, cognition, and function were performed, with exploratory brain-behavior correlations over six months. ResultsClustering identified two subgroups with distinct structural patterns. Compared with controls, one subgroup showed reduced gray matter density in cerebellar lobules VIIIa/VIIIb and the putamen (p < 0.05, TFCE-corrected), whereas the other showed no significant alterations. Cognitive differences between clusters did not survive multiple-comparison correction; however, several measures showed medium-to-large effect sizes (d = 0.70-1.01), suggesting meaningful cognitive differences requiring confirmation in larger cohorts. Longitudinal analyses revealed increased medial frontal gray matter density (p < 0.05) associated with visuospatial/executive performance. ConclusionsThese exploratory findings suggest that post-COVID cognitive symptoms are associated with heterogeneous neurobiological profiles rather than a uniform pattern of impairment. Structural alterations involving cerebellar, striatal, and frontal regions may reflect distinct neuroanatomical phenotypes. Longitudinal findings suggest medial frontal structural reorganization with functional relevance. These findings support data-driven stratification for characterizing neurobiological heterogeneity in Long COVID and provide a foundation for future hypothesis-driven studies.

Abstract Background The neuropsychiatric sequelae (cognitive deficits, anxiety and depression) post-COVID-19 exist as part of the spectrum of the multisystemic long COVID. People with these symptoms have been shown to have worse functional outcomes. Hence, this significantly impacts the economy, primarily due to productivity losses. Yet, the precise underlying pathogenesis remains unknown, as do any diagnostic or prognostic biomarkers. Aim This study aims to identify functionally impacted brain regions in those with post-COVID-19 neurological sequelae and to evaluate how alterations in brain function relate to acute serum inflammatory mediators and brain injury biomarkers. Methods The study will utilise data from the COVID-19 Clinical Neuroscience Study (CNS), a large UK multicentre study conducted during the pandemic. This sub-study will be a secondary analysis of the COVID-19 CNS, a prospective observational study that compared COVID-19-positive participants with negative controls. Participants had an MRI, blood tested for acute serum inflammatory mediators and brain injury biomarkers, and neuropsychiatric assessment (cognitron test, PHQ-9 and GAD-7) post-acutely and at follow-up. The DPABI (Data Processing & Analysis for Brain Imaging) toolbox will be used for pre-processing and analysis of the neuroimaging data (resting state functional MRI) to obtain regional homogeneity (ReHo). The association between ReHO and neuropsychiatric symptoms, acute inflammatory mediators and brain injury biomarkers will be explored. Regression models would be used to determine the risk and protective factors for developing these symptoms. Conclusion It is anticipated that the study will provide new insights into the functional basis of post-acute COVID-19 neuropsychiatric manifestations and identify new diagnostic biomarkers. Key words: Regional Homogeneity, COVID-19, functional MRI, neuropsychiatry, biomarkers

Background: Large language models have been proposed to improve patient comprehension of radiology reports. However, whether they improve objective understanding remains unproven. Purpose: To evaluate the effect of appending an LLM-generated lay summary to brain MRI reports on objective and subjective patient comprehension in a randomized controlled trial. Materials and Methods: In this randomized controlled trial, 2,727 adult participants from the ComPaRe e-cohort were randomly assigned to interpret six standardized brain MRI reports for headache, presented either in their native format (control; n = 1,401) or appended with a lay summary generated by an open-weights LLM (Mistral Small 3.2) (intervention; n = 1,326). The primary outcome was objective comprehension, defined as the rate of correct classification of whether the report provided a probable explanation for the headache, with ground truth established by four-radiologist consensus. Secondary outcomes included satisfaction, subjective comprehension, anxiety, and willingness to contact a healthcare professional. Generalized estimating equations accounted for repeated within-participant observations. Results: A total of 2,727 participants (mean age, 52 years +/- 15; 75.2% women) were evaluated. Objective comprehension did not differ between arms (58.3% vs 59.4%; odds ratio (OR) 0.97; 95% CI: 0.90-1.06; P = .54). The intervention significantly improved overall satisfaction (64.9% vs 36.7%; OR 3.26; 95% CI: 2.93-3.64; P < .001) and subjective comprehension (50.3% vs 24.0%; OR 3.17; 95% CI: 2.82-3.56; P < .001). High anxiety was modestly reduced (25.1% vs 26.6%; OR 0.92; P = .037). The effect on objective comprehension varied by report type (P for interaction < .001): summaries improved comprehension of symptom-explaining reports (42.4% vs 37.4%; P < .001) but reduced it for normal reports (72.5% vs 76.6%; P = .001). Conclusion: LLM-generated lay summaries appended to brain MRI reports improved patient satisfaction and subjective comprehension but did not improve objective comprehension, indicating a gap between perceived and actual understanding that should be addressed before clinical integration.

Background: Neuroimaging studies implicate network alterations in functional motor disorder (FND-motor), yet white matter remains poorly characterized. Objectives: To characterize white matter microstructure in FND-motor relative to healthy (HCs) and psychiatric (PCs) controls and examine symptom associations. Methods: Fifty individuals with FND-motor, 50 age- and sex-matched HCs, and 50 PCs matched on age, sex, depression, anxiety, and post-traumatic stress disorder severity underwent multi-shell diffusion MRI. Voxel-based analyses examined whole-brain white matter using diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity [MD]) and neurite orientation dispersion and density imaging (NODDI) (neurite density index [NDI], orientation dispersion index, and free water fraction [FWF]) metrics. Cross-metric convergence was characterized using atlas-based tract overlap analyses and probabilistic tractography. Associations with FND symptoms and transdiagnostic physical symptoms were also evaluated. Results: Compared with HCs, FND-motor showed higher FA/NDI and lower MD/FWF, predominantly in the middle cerebellar peduncle. Compared with PCs, differences were limited to lower MD/FWF, involving the corpus callosum, middle cerebellar peduncle, and left inferior longitudinal fasciculus. Greater FND symptom severity was associated with a lower FA/NDI and higher MD/FWF in the corpus callosum and right-lateralized association and projection pathways, whereas greater transdiagnostic physical symptom burden across FND-motor and PCs was associated with higher FA and lower MD/FWF in the middle cerebellar peduncle. Conclusions: This study provides a comprehensive multi-metric diffusion-weighted characterization of white matter microstructure in FND-motor relative to both HCs and PCs - highlighting cortico-cerebellar connections via the middle cerebellar peduncle as distinct in FND-motor and associated transdiagnostically with physical symptom burden.

Dysfunctions in reward circuits, including projections from the orbitofrontal cortex (OFC) to the nucleus accumbens (NAcc), have been implicated in psychopathology. The OFC is functionally divided into the medial OFC (mOFC), which processes rewards, and the lateral OFC (lOFC), which responds to non-reward or punishment stimuli. We investigated the structural connectivity of the lOFC-NAcc and mOFC-NAcc pathways and their associations with psychopathological traits using tractography-defined ROI analysis. Diffusion-weighted imaging data from 165 participants (aged 22 - 35, 53% male) in the Human Connectome Project (HCP) were analysed using spherical deconvolution tractography. MegaTrack, a novel tool, enabled tract segmentation via a single manual dissection mapped back to native space. Virtual dissection identified four bilateral pathways connecting the lOFC and mOFC to the NAcc, from which fractional anisotropy (FA) was extracted, and an lOFC/mOFC ratio was computed. Psychopathological traits were measured using HCP Achenbach Adult Self-Report scores. The lOFC-NAcc pathway showed positive associations with psychopathology and the mOFC-NAcc pathway negative associations. The lOFC/mOFC ratio emerged as a stronger predictor than individual pathways, with significant associations for depression, somatic problems, anti-social personality traits, and inattention. Effects were lateralized to the left hemisphere. These findings show that the lOFC-NAcc and mOFC-NAcc pathways can be structurally separated with tractography and display opposing correlations with psychopathological traits in a healthy population. Their ratio may index reward-processing dysfunction, and future research should test whether it is sensitive to dysfunction in clinical populations.

Background: Childhood trauma is a well-established risk factor for adverse mental health outcomes, yet large-scale cross-national evidence from the Arab region remains limited. This study examined the prevalence of childhood trauma and its associations with multiple transdiagnostic outcomes across 17 Arab countries. Methods: A cross-sectional online survey was conducted between September and October 2025 among 6,181 adults from 17 Arab countries. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Transdiagnostic mental health outcomes included depression, anxiety, posttraumatic stress symptoms (PTSS), maladaptive behavior, and social/functional impairment. Descriptive statistics, Pearson correlations, and multiple linear regression analyses were performed via IBM SPSS Statistics. Confirmatory factor analysis and structural equation modeling were conducted via R (Lavaan) to evaluate a second-order latent construct representing global childhood trauma. Results: Childhood trauma was widely reported across the sample, with physical neglect and emotional neglect emerging as the most frequently endorsed domains. All trauma domains were significantly associated with poorer mental health outcomes (p < .001). In regression analyses adjusted for demographic factors, emotional abuse emerged as the strongest predictor of depression ({beta} = .472, p < .001) and PTSS ({beta} =.439, p < .001). Structural equation modeling supported a second-order global trauma construct, which showed strong associations with depression ({beta} = .70), anxiety ({beta} = .64), PTSS ({beta} = .68), maladaptive behavior ({beta} = .68), and social impairment ({beta} = .67). This latent factor showed strong associations with all mental health outcomes, explaining substantial variance in depression (R2 = .52), anxiety (R2 = .43), and PTSS (R2 = .48). The structural model demonstrated borderline-to-acceptable fit (CFI = .899, TLI = .890, RMSEA = .058, SRMR = .085), supporting the hypothesized latent structure while indicating scope for further model refinement. Conclusions: Childhood trauma is highly prevalent across the Arab region and is strongly associated with multiple dimensions of psychological distress, highlighting the urgent need for trauma-informed prevention, screening, and early intervention programs in the Arab region.

BackgroundSocial dysfunction is a major source of disability in schizophrenia, yet the neural mechanisms that contribute to impaired social understanding remain poorly understood. Converging evidence points to the role of the default mode network (DMN) in integrating social information over time to construct interpretations of social behaviors. Here, we tested the hypothesis that individuals with schizophrenia show reduced stimulus-driven coordination between brain regions within the DMN during free viewing of naturalistic social stimuli. MethodsA sample of 124 adults (schizophrenia: n=63; healthy controls: n=61) viewed naturalistic video clips during fMRI. Inter-subject functional connectivity (ISFC) was computed within the two groups. Group differences were identified via permutation testing. We also explored group differences in other brain networks to examine whether effects were specific to the DMN. ResultsIndividuals with schizophrenia showed weaker stimulus-driven coupling within the DMN compared to healthy controls, specifically between areas such as the parahippocampal gyrus, precuneus, and medial prefrontal cortex. Group differences in ISFC were specific to the DMN. Furthermore, no between-group differences emerged for within-participant functional connectivity in the DMN, suggesting that the observed effects reflect reduced stimulus-driven coordination among DMN regions when processing social stimuli rather than a more general decline in DMN connectivity. ConclusionsSchizophrenia is characterized by impaired coordination within the DMN as it dynamically integrates social information over time, which could contribute to difficulties in constructing coherent interpretations of real-world social situations. These findings suggest that disrupted stimulus-driven network coordination might underlie social cognitive impairments in schizophrenia, highlighting the value of naturalistic paradigms for revealing network-level dysfunction under conditions that closely approximate real-world experience.

Treatment resistance in obsessive-compulsive disorder (OCD) is common, with 40-60% of patients failing to respond to pharmacotherapy. Identifying functional differences between responders and non-responders may guide alternative treatment strategies. We investigated resting-state brain differences between selective serotonin reuptake inhibitor (SSRI) responders and non-responders and compared them with healthy controls (HC). 3T MRI scans were acquired from 80 participants with OCD and 50 HCs. Structural and 5-minute resting-state data were processed using the CONN toolbox. Regions showing group differences in amplitude of low-frequency fluctuation (ALFF) were identified for seed-based connectivity analysis. ANCOVA revealed significant ALFF differences among groups in the anterior middle temporal gyrus (R-aMTG) and temporal pole (R-TP). SSRI responders showed reductions in seed-to-voxel connectivity than non-responders between these regions and the left superior and inferior occipital cortices, left superior parietal lobule, and left temporo-occipital middle temporal gyrus. Responders also showed reductions in connectivity with the left superior parietal lobule compared with HCs. Across the OCD group, Y-BOCS scores positively correlated with ALFF in the R-aMTG (p=0.008) and R-TP (p=0.044). Altered temporal cortical activity and connectivity with posterior regions were associated with SSRI treatment response, supporting a role for temporal-posterior cortical networks in OCD treatment response.

Post-traumatic stress disorder (PTSD) has been associated with impairments in cognitive function, including working memory, and may involve altered glutamatergic regulation in the prefrontal cortex. In this study, we used 7T functional magnetic resonance spectroscopy (fMRS) to examine dorsolateral prefrontal cortex (DLPFC) glutamate during working memory in individuals with PTSD, trauma exposure without PTSD (TE), and no trauma exposure (NT). Eighty participants (27 PTSD, 27 TE, 26 NT) underwent baseline MRS followed by fMRS during a letter n-back task. A linear mixed-effects model was used to evaluate glutamate concentrations across baseline, 0-back, 1-back, 2-back, and post-task fixation conditions. Behavioral performance was assessed using repeated-measures ANOVA for percentage correct, reaction time, and the discrimination index (d) across the 0-back, 1-back, and 2-back conditions. Glutamate differed significantly by group, condition, and the group x condition interaction. Individuals with PTSD exhibited lower glutamate than NT at baseline and during the 0-back, 1-back, and 2-back conditions. TE participants also showed lower glutamate than NT during the 1-back and 2-back conditions. Within-group analyses showed higher glutamate during the 0-back, 1-back, and 2-back conditions than at baseline in the NT group, whereas these baseline-to-task differences were limited in the PTSD and TE groups. Accuracy decreased and reaction time increased with increasing working memory load, and discrimination (d) was lower in PTSD than NT. These findings demonstrate altered DLPFC glutamate dynamics during working memory in PTSD and trauma-exposed individuals. Functional MRS provides complementary information beyond resting-state MRS by characterizing glutamatergic responses during cognitive engagement and may improve our understanding of neurochemical alterations associated with trauma and PTSD.

Introduction: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric disorder. Human neuroimaging studies increasingly frame its neurobiological substrate in terms of alterations of large-scale brain network organization. Resting-state fMRI findings broadly align with this view, yet remaining highly heterogeneous, reflecting both clinical and analytic variability. Predominant approaches largely characterize functional organization in terms of pairwise relationships between regions, which may limit the ability to capture more global features of brain organization associated with depression and its course. Here we use novel methods from Topological Data Analysis to provide new perspectives on these brain-behavior associations Objectives: The main objective of this study was to determine whether whole-brain topological descriptors of functional connectivity capture alterations associated with MDD. In particular, we examined whether these features vary along clinically relevant dimensions of heterogeneity, focusing on illness course (single-episode vs. recurrent MDD) and current antidepressant medication status. To this end, we analyzed the area under the curve (AUC) of the zeroth and first Betti numbers (B and B), which index global network integration and higher-order cycle structure across scales, respectively. Methods: Neuroimaging (resting state fMRI) and phenotypic data were obtained from 1,490 participants (776 individuals with MDD and 714 never-depressed controls) included in the REST-meta-MDD project of the DIRECT consortium. Functional connectivity matrices were computed using Pearson correlations between regions defined by the Power-264 atlas and harmonized across sites using CovBat. Topological Data Analysis was applied to characterize whole-brain network organization across connectivity thresholds using B and B curves and their areas under the curve (AUC). B associated cycle counts and their coarse anatomical configurations were further examined. Group differences and effects of illness course and medication status were assessed using multiple linear and generalized linear regression models. Results: Compared with controls, individuals with MDD showed significantly higher B AUC, indicating altered global integration profiles across connectivity thresholds. B AUC did not differ by illness course, illness duration, or symptom severity. In contrast, B AUC showed a graded increase across illness courses, with the highest values observed in recurrent depression. This effect was driven by an increased number of one-dimensional cycles rather than greater cycle persistence. Medication status further modulated B alterations, with elevated values observed in unmedicated single-episode and medicated recurrent MDD. Anatomical decomposition revealed that higher-order alterations were primarily driven by inter-network configurations spanning multiple large-scale functional systems. Discussion:These findings indicate that MDD is associated with altered multiscale functional organization, combining less compact global integration with an increased prevalence of cross-network hole-defining cycles, with these features varying systematically with illness course and current medication, suggesting that topology-informed measures capture clinically relevant variability in brain organization in depression.

Socio-cognitive alterations are widely observed across different psychiatric conditions, yet it remains unclear whether these deficits map onto distinct diagnostic categories or represent a shared transdiagnostic phenotype, driven by dimensional psychopathological symptom severity.This study evaluates Theory of Mind (ToM) network activation during a naturalistic functional magnetic resonance imaging (fMRI) movie paradigm in 313 participants, including 91 healthy controls and 222 psychiatric inpatients across five distinct diagnostic clusters (substance use, schizophrenia spectrum, affective, anxiety, and personality disorders). Frequentist analyses revealed decreased ToM-selective activity in psychiatric patients, compared to controls across all ToM regions of interest (ROIs). No significant difference emerged between diagnostic groups, but ROI activation correlated negatively with Adult Self-Report (ASR) scales (Total Problems, Internalising, Externalising). Subsequent Bayesian analysis of covariance (ANCOVAs) consistently favoured models that excluded traditional categorical diagnoses, suggesting that dimensional measures, especially Total Problems and Internalising, provided substantially greater predictive utility for ToM-related regional brain activation. Our findings challenge traditional categorical classifications in neurobiological research as they suggest that atypical mentalising might reflect a shared transdiagnostic vulnerability.

Neuroimaging is becoming an increasingly prominent tool to understand intimate partner violence (IPV) and partner-inflicted brain injury (BI). Yet, by nature of IPV and partner-inflicted BI, those most affected may be the least likely to be eligible, participate, and produce usable data in neuroimaging studies. A critical question therefore remains of who is represented in neuroimaging research on IPV and related BI. Here, we examined representativeness at three major stages of neuroimaging sample construction using screening records from 352 women and a subsequent cohort of 207 enrolled women with lifetime exposure to physical IPV. At the eligibility stage, three in five women eligible for behavioral research were deemed ineligible for magnetic resonance imaging (MRI) at initial screening. At the participation stage, the 61 women who underwent resting-state functional MRI (fMRI) had more education, were more likely to be employed, and reported lower psychiatric and neurobehavioral symptom burden than enrolled women who did not undergo neuroimaging. Finally, at the quality-control stage following fMRI, motion-based exclusion disproportionately removed women who had sustained the most partner-inflicted BIs. Our findings empirically reveal that eligibility, participation, and quality control each bias the demographic, clinical, abuse, and BI burden represented in an fMRI sample, and therefore have key implications for generalizability. Measuring and reporting representation bias can help identify whose experiences are underrepresented in the evidence, and accordingly reduce the risk that IPV neuroimaging research understates the very harms it seeks to characterize.

Objective: Women with premenstrual syndrome (PMS) experience affective lability, irritability, depressed mood, and anxiety during the late luteal phase of the menstrual cycle. Stress reactivity may contribute to the development of these symptoms, yet neural correlates remain unexplored. We examined neural, behavioral and endocrine stress responses across menstrual cycle phases in women with and without PMS. Methods: 26 women with PMS and 24 women without PMS participated in two fMRI sessions, during the mid-follicular (days 5 to 11) and late-luteal phases (days -7 to -1). Participants completed the Montreal Imaging Stress Task (MIST). Subjective stress ratings and salivary cortisol were collected at six time points before and after stress induction. Stress-related brain activation was assessed using whole-brain and region-of-interest analyses. Results: Subjective stress ratings increased as expected from before to after the MIST, with no group or phase differences. Salivary cortisol was significantly higher during the mid-follicular phase, with no group effect or significant pre-post MIST difference. While the stress task elicited activation patterns in stress-related regions, whole-brain analysis revealed no significant effects of group (PMS vs. no PMS) or menstrual cycle phase (follicular vs. luteal) on the neural stress response. Considering premenstrual symptom severity as a predictor revealed significant group-by-symptom severity interactions in the right inferior frontal gyrus and the right superior temporal gyrus. Conclusion: Using a within-subject repeated-measures design, we found neural responses to psychosocial stress to be stable across menstrual cycle phases. Individual differences in symptom severity may nevertheless be associated with differences in stress-related brain activation.

Aims Excitatory/inhibitory imbalance - the equilibrium between glutamatergic excitation and {gamma}-Aminobutyric acid (GABA)ergic inhibition - is implicated in psychosis and may precede psychosis onset. Methods To investigate whether excitatory/inhibitory balance relates to subclinical psychotic experiences, anxiety and depression, we developed a network-level measure integrating Magnetic Resonance Spectroscopy Glutamate/GABA ratios with effective connectivity during resting-state fMRI. In 20 healthy young adults (aged between 18-32; 50% female), we first measured excitatory/inhibitory balance, operationalised as Glutamate/GABA and Glutamate+Glutamine(Glx)/GABA ratio, in the dorsal anterior cingulate cortex. Second, we applied Two-state Dynamic Causal Modelling to assess effective connectivity of the default-mode network, using these ratios as empirical priors to determine how they translate into network connectivity. Third, we ran Bayesian Model Selection at the model and family levels to identify the optimal models. Results The two-state model with Glx/GABA ratio as direct input into the posterior cingulate cortex best explained the data. This best-fitting model incorporated the neurometabolite ratio with Glutamate and GABA and used two-state connectivity. Conclusions Excitatory/inhibitory balance underlies resting-state effective connectivity, with the Glx/GABA ratio shaping connectivity networks. This pathway highlights excitatory/inhibitory balance as a predictor of two-state brain networks, potentially aiding identification of high-risk individuals and informing new interventions.

Abstract Background: Long COVID frequently includes post-exertional malaise, neuromuscular fatigue, internal vibrations, tremor-like symptoms, orthostatic intolerance, sleep disturbance, cognitive dysfunction, and autonomic instability. Neuroimaging studies in Long COVID and post-infectious ME/CFS have identified abnormalities across limbic, thalamic, mesiotemporal, brainstem, cerebellar, and white-matter systems, but no single established circuit accounts for this clinical phenotype. We examined whether abnormalities cluster at the mammillary body-fornix-superior tuberal hypothalamic interface and within connected brainstem-cerebellar pathways. Methods: Structural MRI and diffusion tensor imaging were analysed in 88 participants with clinician-diagnosed Long COVID and 34 healthy controls (total N = 122). Thirty-three patients were classified as bedridden. Volumetric and diffusion analyses focused on the mammillary bodies, superior tuberal hypothalamic region, fornix, dorsal and median raphe, midbrain reticular formation, and cerebellar peduncles. Fractional anisotropy was used as an index of white-matter microstructural organisation. Exploratory clinical associations included motor impairment, proprioceptive dysfunction, autonomic symptoms, fatigue, internal vibrations, and tremor-like symptoms. Results: Three mammillary-body volume phenotypes were identified: reduced, enlarged, and control-range. Left and right mammillary-body volumes differed across groups, with large effect estimates. Segmentation showed narrowing or loss of a visible internal passage at the superior tuberal-mammillary interface, while the fornix showed altered diffusion measures and reduced tract coherence in the hypothesised gate region. Additional findings included lower superior cerebellar peduncle volume, lower middle cerebellar peduncle fractional anisotropy, and lower dorsal raphe and midbrain reticular formation volumes in Long COVID. Conclusions: The findings support an exploratory mammillary body-fornix gate model in which a vulnerable periventricular hypothalamic-limbic interface may contribute to network dysfunction in a subgroup of patients with severe Long COVID. The data do not establish direct viral invasion, a coronavirus entry route, axonal destruction, or a single causal pathway. Prospective replication with standardised acquisition, preregistered regions of interest, correction for multiple comparisons, objective movement and autonomic measures, and longitudinal follow-up is required. Keywords: Long COVID; post-COVID condition; ME/CFS; mammillary body; fornix; hypothalamus; diffusion tensor imaging; internal vibrations; tremor-like symptoms; neuromuscular fatigue; dysautonomia; brainstem

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

Background: Cervical spinal cord (CSC) compression and myelopathy are frequent, severe complications in mucopolysaccharidosis (MPS) types I and VI. Early detection is critical to prevent irreversible neurological deficits and preserve quality of life. This prospective study aimed to identify quantitative neuroimaging biomarkers of structural CSC damage and myelopathy in MPS I and VI. Methods: Structural and diffusion magnetic resonance imaging (MRI) of the CSC was analyzed in 17 MPS I patients, 3 MPS VI patients (19{+/-}7 years), and 19 case-matched healthy controls (20{+/-}7 years). CSC macrostructure (cross-sectional area, diameters) and microstructure (fractional anisotropy [FA], radial [RD], mean, axial diffusivities) were evaluated within and beyond the maximal compression areas. Results: MPS patients demonstrated reduced CSC cross-sectional area and anterior-posterior diameter at upper cervical levels, alongside widespread microstructural alterations (lower FA, higher RD) throughout the CSC versus controls (pFDR<0.05). Restricted foramen magnum space was associated with microstructural damage at lower cervical levels without overt macrostructural compression. Morphological and microstructural metrics were sensitive to CSC compression and myelopathy severity (pFDR<0.05). Lower CSC integrity correlated with more advanced growth retardation (p<0.001). Among patients receiving hematopoietic stem cell transplantation, earlier treatment correlated with preserved upper CSC morphology (p<0.05). Distinct neuroimaging phenotypes were observed across MPS genotypes (pFDR<0.05). Conclusions: CSC MRI provides candidate neuroimaging biomarkers for early detection and characterization of myelopathy in MPS I and VI. Structural damage extends beyond primary maximal compression areas, highlighting these markers for clinical monitoring and future therapeutic trials.