Psychiatry Research: Neuroimaging

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.

Background Alcohol use disorder (AUD) is highly prevalent in schizophrenia, yet the neurobiological basis of this vulnerability remains poorly understood. Neurodevelopmental models suggest that pre-existing brain dysconnectivity may increase vulnerability to AUD. We therefore tested whether schizophrenia-like neurodevelopmental pathology alters how alcohol-related experience is incorporated into large-scale brain networks. Methods Resting-state functional connectivity was assessed in male Sprague-Dawley rats (n = 18-21/group) with neonatal ventral hippocampal lesions (NVHL), a neurodevelopmental model of schizophrenia, and sham-operated controls, with or without voluntary adolescent alcohol exposure. Functional connectivity was assessed using seed-to-voxel and seed-to-seed analyses within a cortico-striato-limbic network. We additionally examined whether individual alcohol intake during adolescence predicted adult functional connectivity according to neurodevelopmental status. Results NVHL and adolescent alcohol exposure independently produced predominantly hypoconnected cortico-striato-limbic networks. However, alcohol exposure did not exacerbate NVHL-associated dysconnectivity but instead induced a distinct network reorganization characterized by functional hyperconnectivity. Although alcohol intake was comparable between groups, dose-dependent relationships between adolescent alcohol consumption and adult functional connectivity were observed in sham animals but were absent or markedly attenuated in NVHL rats. These effects were primarily centered on prelimbic cortex connectivity with the amygdala, hippocampus, and dorsal striatum, highlighting this circuitry as a major locus of altered experience-dependent remodeling. Conclusions These findings suggest that vulnerability to AUD associated with schizophrenia-like neurodevelopment may arise less from additive network dysfunction than from an altered capacity of large-scale brain networks for experience-dependent functional remodeling. Schizophrenia-like neurodevelopmental pathology may therefore change how alcohol-related experience is translated into persistent brain network organization.

Psychosis has been linked to changes in diffusion-derived fractional anisotropy (FA) across multiple white matter tracts, yet most evidence is cross-sectional. Longitudinal findings are inconsistent, and the clinical relevance of white matter changes over time remains unclear. To address this gap, we investigated longitudinal white matter changes and their clinical correlates in early psychosis in a large, multi-centre diffusion-tensor imaging study. Across 18 sites, 407 participants (healthy controls: n = 97, 59.8% men, mean age 23.9{+/-}4.6 years; clinical high risk of psychosis: n = 158, 53.5% men, mean age 23.0{+/-}4.9 years; first-episode psychosis: n = 152, 71.1% men, mean age 25.1{+/-}5.4 years) were scanned at up to three time points over 12 months. FA was assessed in the cingulum bundle, the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and at the whole brain level. FA trajectories were analysed using linear mixed-effects models to test effects of group, social and occupational functioning, and (attenuated) psychotic symptoms, while controlling for demographic and socioeconomic covariates. No significant group differences in FA were observed, either globally or within tracts (p > .05). Longitudinal FA trajectories were not associated with changes in (attenuated) psychotic symptoms or functioning (p > .05). In contrast, higher baseline antipsychotic medication dose was significantly associated with lower FA (pcorr < .05). Overall, these findings indicate that white matter microstructure is relatively stable during the clinical-high-risk and first-episode phases of psychosis, and that it is not clearly associated with variation in symptom severity or functional outcomes over time.

Background Brain abnormalities related to childhood adversity (CA) have been reported across clinical presentations in psychotic disorder (PD) and bipolar disorder (BD). This systematic review and meta-analysis examined gray matter volume (GMV) alterations linked to CA in PD and BD. Methods A PRISMA-compliant systematic review was conducted (PROSPERO ID: CRD42022351133). The EMBASE, MEDLINE, and PsycINFO databases were searched from inception to June 2024 for studies investigating CA and structural brain imaging in PD and BD. Study quality was assessed with the Newcastle Ottawa Scale (NOS). Data were extracted and synthesized accounting for sex differences and CA subtypes with brain findings categorized by the presence and direction of associations. Meta-analyses were performed for hippocampal and amygdala volumes. Results In the systematic review (k = 29), 3,056 participants with PD and BD (mean age = 36.6; SD =16.1; 47% female), published between 2011 and 2023, were included. Study quality was fair, with high heterogeneity. Most studies reported significant negative associations between CA and GMV, especially in prefrontal regions, while findings for the hippocampus and amygdala were largely null or inconsistent. Meta-analyses of a study subset identified no significant association between CA and hemisphere-specific and combined volumes of the hippocampus (k = 5; p [&ge;] 8805; 0.66) or amygdala (k = 4; p [&ge;] 8805; 0.87). Conclusion CA was not consistently associated with hippocampal or amygdala volume alterations in PD and BD. More consistent evidence emerged for reduced GMV in prefrontal regions, suggesting that neurobiological impact of CA may be more robustly captured at the cortical level.

Background: Cognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample. Methods: Individuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction. Results: In the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor. Conclusions: DMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.

BackgroundIndividuals with early psychosis (EP) have elevated risk for suicide, the leading cause of death in the first five years following diagnosis. Non-suicidal self-injury (NSSI) significantly predicts suicidal behavior, yet studies of self-injury often exclude participants with psychosis. We investigated effective connectivity in emotion regulation and reward network regions among participants with lifetime history of NSSI or suicide attempt (SA) with and without EP. MethodsResting-state fMRI data were acquired for 23 individuals with EP and 34 non-clinical controls (NCC). We estimated effective connectivity models for regions implicated in the self-injury literature: middle cingulate cortex (MCC), posterior cingulate cortex (PCC), caudate, putamen, posterior superior temporal gyrus (STG), orbitofrontal cortex (OFC), and insula. There were 3 models characterizing different groupings: diagnosis (NCC vs. EP); NSSI (present[+], n=21 vs. absent[-], n=36); and SA (present[+], n=21 vs. absent[-], n=36). ResultsEP was associated with increased STG to PCC and insula to putamen connectivity. NSSI+ (n=7 NCC, 14 EP) had increased PCC to insula lagged connectivity and increased contemporaneous bilateral putamen activity, relative to NSSI- (n=27 NCC, 9 EP). NSSI was positively correlated with lagged insula to putamen activity (p=0.016). SA and NSSI were associated with reduced PCC to caudate connectivity. ConclusionNSSI is associated with increased connectivity within emotion regulation regions and disrupted connectivity between emotion regulation and reward networks modulated by the STG and striatum. Findings are consistent with broader self-injury literature, supporting the utility of using similar interventions from other disorders to address self-injury within EP.

Schizophrenia is characterized by persistent executive dysfunction and atypical engagement of prefrontal circuits underlying attentional control. However, the neural dynamics of executive processing during ecologically relevant tasks remain underexplored. This study examined frontal theta/beta oscillatory patterns and trial level EEG responsiveness as indices of adaptive cognitive control in schizophrenia compared to healthy controls. Thirty adults with schizophrenia (M age = 39.9, SD = 9.10 years) and a matched healthy control group (N = 30; M age = 32.25, SD = 6.50 years) underwent quantitative EEG during an eyes-open resting state and while performing two executive tasks: an augmented reality visuomotor challenge (LCAR) and a mobile guided daily routine task (B2B). Frontal theta/beta ratios (TBR) at Fz and Cz indexed attentional engagement. Trial level responsiveness was assessed via discrete Stimulus Response Events (SREs). Results: Both LCAR and B2B elicited significant TBR increases relative to eyes open rest at midline frontal sites (p < .001), reflecting elevated executive demand. Compared to healthy controls, participants with schizophrenia exhibited higher baseline TBR and reduced modulation across task segments. In contrast, controls showed stronger SRE linked variability and greater memory gains, indicating more efficient task locked cognitive adaptation. Age related effects were also observed, with participants under 40 years showing higher resting TBR at Fp1 (p =.01). Conclusion: Findings advance understanding of prefrontal theta/beta modulation as a neurophysiological marker of adaptive executive control during complex, ecologically valid tasks. By integrating real-world paradigms with trial level EEG analyses, this study contributes to models of dynamic information processing and cognitive resource allocation in schizophrenia. Keywords: schizophrenia; healthy controls; theta/beta ratio; QEEG; executive function; augmented reality; neural biomarkers

In treatment-resistant schizophrenia, clozapine treatment has been associated with longitudinal reductions in subcortical volumes, ventricular enlargement, and widespread cortical thinning. However, it is unknown how these structural changes relate to clozapines pharmacological profile and clinical efficacy. We combined five longitudinal datasets with MRI acquired before and on average 5 months after clozapine initiation in 143 individuals to quantify brain structural changes and their association with normative maps relating to neuroreceptor architecture and physiological systems, and improvement in symptom severity. Clozapine treatment was associated with grey matter volume reductions across multiple subcortical regions (including the amygdala, hippocampus, thalamus, caudate, putamen and nucleus accumbens), increases in pallidal volume, ventricular enlargement, and widespread cortical thinning. Cortical regions showing the greatest magnitude of thinning corresponded to areas with higher normative densities of serotonergic 5-HT1A, 5-HT2A and 5-HT4 receptors. Changes in subcortical volume or cortical thickness during clozapine treatment were not associated with changes in total or positive symptom severity. In addition, baseline subcortical volume, cortical thickness, or gyrification prior to starting clozapine did not predict subsequent symptom improvement. Cortical thinning may partly reflect clozapines activity at serotonergic receptors, which have been implicated in cortical network stabilisation and neuroplasticity, however structural remodelling during clozapine treatment may reflect a process independent from its clinical efficacy in improving core symptoms of psychosis.

Schizophrenia is associated with cognitive impairments, including deficits in implicit learning. Probabilistic serial reaction time tasks (SRTT) offer an objective approach to characterizing these deficits through both motor execution (ME) and motor imagery (MI), the mental simulation of movement without physical action. Whether implicit probabilistic sequence learning is impaired across both modalities in schizophrenia remains poorly understood. Thirty individuals with schizophrenia (ME: n=12; MI: n=13) and 40 healthy controls (ME: n=20; MI: n=20) completed an auditory probabilistic SRTT. Symptom severity was assessed with the PANSS and cognitive functioning with the MCCB. Healthy controls demonstrated a robust signature of implicit probabilistic sequence learning, whereas participants with schizophrenia exhibited weaker and less consistent learning signatures, particularly during motor imagery. Sensitivity to probabilistic structure differed significantly between groups during motor execution but not motor imagery. Participants with schizophrenia also showed significantly longer reaction times than controls across both modalities, consistent with generalized psychomotor slowing. Greater PANSS-General severity was associated with greater deviation from the probabilistic learning patterns observed in healthy controls during ME, whereas higher MCCB verbal learning scores were associated with greater similarity to these learning patterns during MI. These findings indicate that implicit probabilistic sequence learning is impaired in schizophrenia across both motor execution and motor imagery, and that these deficits are meaningfully associated with clinical symptom severity and cognitive functioning.

Anhedonia and motivational impairment are central features of major depressive disorder, yet the neural processes linking reward information to sustained goal-directed behaviour remain insufficiently understood. Using functional magnetic resonance imaging, we examined representations of reward levels during sustained effort expenditure (a construct in the RDoc framework) as a distinct component of reward processing in depressive patients under escitalopram treatment. Twenty-eight unmedicated patients with a current depressive episode and forty-three healthy control participants underwent fMRI scanning at two time points three weeks apart; patients started escitalopram immediately after the first measurement. Across participants, sustained effort expenditure engaged midbrain reward circuitry (ventral tegmental area, VTA), even in the absence of immediate reinforcement. A targeted analysis also revealed changes in activity of the dorsal raphe nucleus (DRN) in patients. Increases in VTA activity were associated with improvements in clinician-rated depressive symptoms, whereas self-reported anhedonia remained unchanged. By isolating neural mechanisms supporting sustained goal-directed behaviour, the study identifies novel and clinically relevant imaging phenotypes of reward processing and a potential pathway of escitalopram treatment in depression.

Exposure to adverse childhood experiences is a pervasive risk factor for psychosis, exhibiting a linear relationship across the psychosis spectrum from subclinical schizotypal traits to schizophrenia spectrum disorders. While this association is often conceptualised within the vulnerability-stress framework, the systemic mechanisms through which childhood trauma reconfigures the brain-personality interactome remain poorly understood. We examined clinical, neuropsychological, and neuroimaging data from a sample of low- and high-schizotypy individuals, and patients with a diagnosis of schizophrenia spectrum disorder (N=120). Our aim was to map how trauma reconfigures interactions between neurobiology and schizotypal phenomenology. We adopted a mixed graphical model approach to jointly estimate conditional dependencies between childhood trauma, regional brain morphometry, and schizotypal traits across the psychosis spectrum. Our results show that childhood trauma reconfigures the brain-personality network, shifting it from a state driven by cognitive processes to one anchored in emotional (limbic) reactivity. This transition is marked by the increased influence of impulsive traits and a significant strengthening of connections within the salience network. These changes converge with a reduced thickness of the frontal executive regions, the brain's control centres, identified in our models. Collectively, our results suggest a structural phenomenological decoupling, where trauma conditioned affective circuits may bypass weakened top-down regulatory controls. These findings highlight the necessity of using integrative frameworks to capture how trauma fundamentally reshapes the relationship between the brain and schizotypal personality.

Resting-state functional MRI (rs-fMRI) studies in schizophrenia commonly rely on normalization to volumetric templates and fixed atlas parcellations derived from neurotypical populations. While these approaches enable group-level comparisons, they may obscure individual variation in cortical organization and intrinsic brain dynamics. In this study, we compared four preprocessing and parcellation strategies across two independent schizophrenia cohorts (MRI site 1, n=159; MRI site 2, n=255) to evaluate how analytic choices affect static functional connectivity and dynamic quasi-periodic pattern (QPP) measures, including default mode-dorsal attention network opposition, QPP component rank, explained variance, event rate, and associations with PANSS symptom severity. Across datasets, individualized surface-based parcellation (IndiPar) consistently detected more pronounced QPP dynamics, stronger default mode / dorsal attention network opposition, and greater explained variance of QPPs relative to atlas-based pipelines. IndiPar also produced larger and more reproducible patient-control differences in functional connectivity and QPP event-rate measures, suggesting improved sensitivity through preservation of subject-specific organization. IndiPar additionally detected a significantly increased QPP event rate and more symptom associations in patients in the larger dataset. However, associations between fMRI measures and symptom severity showed limited stability across cohorts. These findings extend previous reports of altered resting-state activity in schizophrenia, and demonstrate that preprocessing and parcellation choices substantially influence both static and dynamic rs-fMRI results. Individualized surface-based parcellation appears to better preserve subject-specific variability and improves detection of intrinsic brain dynamics. At the same time, the limited cross-dataset replication of symptom associations highlights the challenges of deriving stable brain-symptom relationships from heterogeneous psychiatric cohorts.

Impulsivity is associated with various maladaptive behaviors, although its specific role in criminology has remained largely unexplored. We investigated impulsivity in theft recidivists (TR) with and without a diagnosis of kleptomania (KA) compared to control (CT) subjects with no criminal record in this study. Impulsivity was measured using a 5-trial adjusting delay discounting task, and prefrontal cortical (PFC) hemodynamics were assessed using functional near-infrared spectroscopy. Self-report questionnaires were also administered to further evaluate the relationships between impulsivity, negative affect, and reward and punishment sensitivity. TR demonstrated significantly higher impulsivity than CT, along with altered dorsomedial PFC hemodynamic responses. In addition, negative affect was significantly higher in the TR than in the CT participants. Path analysis revealed that the moderation of negative affect on reward, but not punishment, sensitivity, mediated impulsivity in TR. Notably, heightened impulsivity was observed across the TR participants regardless of KA diagnosis, whereas severe depression specifically distinguished KA from TR without it. These findings suggest that while trait impulsivity associated with PFC alterations may be a universal feature of TR, recurrent theft may be a heterogeneous condition, with specific affective dysregulations contributing differently to TR. SIGNIFICANCE STATEMENTRecurrent thefts, such as shoplifting, are a devastating social problem, posing massive financial losses. Nonetheless, surprisingly nothing is known about the neurobehavioral mechanisms that drive people stealing. In fact, kleptomania is a psychiatric disorder that had been identified over 200 years ago, yet exceptionally few studies have investigated this psychiatric condition, and its mechanism remains essentially unknown to date. This study demonstrates that impulsivity is elevated among incarcerated individuals with recurrent thefts with and without a diagnosis of kleptomania, which is associated with the activity of the left dorsomedial prefrontal cortex. Conversely, heightened depression among negative affect is a unique characteristic to kleptomania, providing evidence of heterogeneity among theft recidivists.

Cognitive flexibility is an executive function that allows individuals to adjust behaviour in response to changing environmental demands. We assessed volitional switching under uncertainty, without rule-based learning, in the Change Your Mind task. Nineteen patients with obsessive-compulsive disorder (OCD), 19 patients with attention-deficit hyperactivity disorder (ADHD) and matched control participants (20 per group) completed the task whilst undergoing a functional MRI scan. The task was a two-alternative forced choice paradigm where each stimulus was presented twice successively, with spurious feedback following the first presentation. This allowed participants the opportunity to repeat or change their response. Participants with ADHD changed their response more frequently than controls following a previously correct response, associated with reduced accuracy on the second trial. This was accompanied with smaller differences between change and repeat trials in the superior frontal gyrus, paracingulate gyrus and frontal pole compared to controls. Participants with OCD did not differ from healthy controls in their performance but exhibited greater activity on both change and repeat trials in the pre- and postcentral gyri than controls. These results point to distinct neurobehavioural differences in patients with ADHD and OCD underlying what is often termed more broadly inflexible behaviour.

Moderate-to-severe traumatic brain injury (msTBI) is recognized as a chronic and evolving neurological condition characterized by progressive structural brain changes and persistent cognitive impairment. While prior studies have demonstrated widespread atrophy following msTBI, less is known regarding the longitudinal trajectory of gray matter (GM) changes during recovery and post-rehabilitation. The current study used longitudinal voxel-based morphometry (VBM) to characterize GM volume changes over a period of 9 months, in individuals with msTBI relative to healthy controls (HC). Associations between regional GM volume and neuropsychological functioning were examined. Twenty-eight participants (14 msTBI, 14 HC) completed MRI and neuropsychological assessments across three timepoints spanning outpatient rehabilitation and follow-up. Longitudinal VBM analyses revealed significant group and time interactions within subcortical and limbic regions. Relative to HC, individuals with msTBI showed lower GM volume in these regions at baseline, with trajectories that converged toward HC values (right hippocampus) or increased relative to HC over the rehabilitation period (bilateral pulvinar), whereas the right amygdala and inferior cerebellar vermis remained persistently reduced. Significant longitudinal improvements in memory and psychomotor speed during the rehabilitation period were demonstrated in msTBI. Greater (preserved) GM volume within the right hippocampus, thalamus, and bilateral pulvinar was associated with better performance across measures of verbal memory, processing speed, executive functioning, and cognitive flexibility. These findings suggest that msTBI is associated with dynamic structural brain changes involving subcortical, limbic, and cerebellar networks, and that the rehabilitation period was accompanied by relative volumetric stabilization in these regions and by meaningful cognitive improvement.

Relatively preserved insight distinguishes individuals at risk for psychosis from those with full-blown psychosis. Metacognitive processes thought to support insight and uncertainty monitoring may therefore serve as early markers of illness progression. Yet findings have been inconsistent, perhaps partly due to reliance on explicit confidence ratings that introduce reflection and response biases. To address these limitations, we used a novel implicit confidence measure derived from post-decision gaze in a virtual-reality probabilistic learning task. Gaze-based confidence quantifies the alignment between spatial predictions and gaze direction. We assessed first-order learning and gaze-based metacognition in four groups: clinical high-risk for psychosis (CHR-P), first episode psychosis (FEP), help-seeking controls (HSC), and healthy controls (HC). We tested whether implicit metacognition differentiates psychosis risk from psychosis. Learning accuracy was reduced in both CHR-P and FEP compared to control groups. At the metacognitive level, CHR-P confidence levels were approximately commensurate with their reduced first-order performance, indicating preserved confidence calibration, along with preserved metacognitive sensitivity--the ability to distinguish correct from incorrect decisions. In contrast, FEP showed impaired confidence calibration and reduced metacognitive sensitivity. Metacognitive calibration and sensitivity distinguished CHR-P from FEP and provided predictive value in distinguishing CHR-P from FEP, whereas learning accuracy did not. These findings reveal a dissociation between first-order cognitive processes and distinct aspects of implicit metacognition, including confidence calibration and metacognitive sensitivity, across the psychosis continuum. This dissociation may refine early clinical characterization and improve identification of preserved insight-related mechanisms in psychosis risk.

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.

Background: MRI has increasingly been explored as a biomarker for detecting structural and functional brain changes. For clinical decision-making, it is crucial to validate observed changes in MRI indices at the individual level. The uncertainty in longitudinal MRI indices can be quantified using the repeatability coefficient (RC). Methods: Twenty healthy controls (10 males, 10 females) underwent two test-retest sessions of structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) on the same day, separated by a 30-minute interval. RC values and their 95% confidence intervals (CI) were estimated for subcortical volumes, cortical thickness, and within-network functional connectivity. Additionally, 33 patients with mental health disorders underwent MRI before and after 20 sessions of transcranial magnetic stimulation (TMS). Percentage changes in MRI-derived indices were assessed at the individual level, with changes exceeding the RC threshold considered indicative of true change beyond measurement uncertainty. Results: The RC showed measurement variability in subcortical volumetric in the range of 8% to 17.5% for caudate and left amygdala, respectively. For cortical thickness, the RC was measured between 3.5% and 16.5% for the left occipital pole and the left temporal pole, respectively. The RC% for fractional anisotropy (FA) measures were variable between 11.3% (the left middle cingulum) and 62.9% (the right anterior cingulum). For within-network connectivity, the RC was measured in a range of 9.7% and 29.4% for sensorimotor and visual networks, respectively. TMS-treated patients exhibited no changes beyond the RC in almost all subcortical volumes and within-network connectivity. The most frequent changes beyond the uncertainty were observed in FA measures, particularly in the posterior cingulum, where 17 out of 23 patients exhibited clinically meaningful alterations. Conclusion: Structural brain features extracted from MRI demonstrated high reliability. Among all measures, FA, reflecting white matter integrity, was most sensitive in detecting neural changes following TMS, highlighting its potential utility as a treatment-responsive biomarker.

Machine learning approaches may support individual-level classification in psychiatry, but many EEG-based schizophrenia studies have relied on small samples or conventional summary features. We evaluated whether trial-level auditory oddball event-related potential (ERP) waveforms could support schizophrenia versus healthy-control classification using deep learning. The study included 258 patients with schizophrenia and 142 healthy controls. EEG recordings from an auditory duration oddball paradigm were segmented into -100 to 500 ms epochs, and trial-level mismatch waveforms were generated by subtracting each participant's mean standard response from accepted deviant trials. Models were trained using a fixed participant-level training, validation, and test split, with demographic residualization fit only in the training set. Five deep learning architectures were trained on full residualized ERP waveforms and compared with classical machine learning models trained on 18 conventional ERP summary features. Deep learning models achieved higher test set discrimination than classical feature-based models, with AUROC values ranging from 0.797 to 0.857 versus 0.705 to 0.720. Benchmark analyses suggested that performance depended on the combination of waveform-level input and deep learning architecture. These findings support trial-level auditory oddball ERP waveforms as promising classification inputs and candidate electrophysiological biomarkers of schizophrenia-related neural information processing.

Introduction: Disturbed interpersonal attunement is a core but poorly operationalised feature of the psychopathology of schizophrenia. Language Style Matching (LSM), the largely unconscious alignment of two speakers' function words during ordinary conversation, offers an observable, dialogue-derived index of this dyadic attunement. An open question is where altered alignment mark who a patient (a stable trait of inner experience) is or how they are (a fluctuating state that shifts with symptom severity)? Objective: To characterise LSM over 12 months in early psychosis relative to controls, and to test, at both between- and within-person levels, whether alignment covaries with core psychopathological dimensions across self-referential (autobiographical) and externally directed discourse. Methods: First-episode and recent-onset patients (n = 109) and controls (n = 60) completed semi-structured interviews at baseline and 12 months. LSM was computed per context and modelled with linear mixed-effects; a Mundlak decomposition partitioned the LSM-symptom association into between- and within-person components. Results: LSM is not a fixed trait: groups were indistinguishable at baseline but diverged by 12 months (Group x Timepoint {beta}=-0.018, p = .029), and the deficit was specific to autobiographical speech. Within individuals, autobiographical alignment tightened as formal thought disorder rose above a patient's own average and as negative symptoms worsened, independent of antipsychotic dose. Conclusion: Patients aligned less than controls when speaking about themselves, yet aligned more as symptoms deteriorated, a shift from self-generated toward partner-scaffolded speech when self-organisation fails. LSM indexes disordered self-anchoring and interpersonal attunement in the negative-disorganized dimension of psychosis.