Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

ObjectiveTo delineate the phenotype of juvenile myoclonic epilepsy (JME) with a focus on obsessive-compulsive personality disorder (OCPD) using multimodal psychiatric, neuropsychological, quantitative EEG (qEEG), and structural MRI markers within a predictive-processing/free-energy framework. MethodsWe prospectively studied 65 patients with JME and 68 matched healthy controls (HC). Participants completed DSM-IV SCID I/II interviews and a neuropsychological battery assessing working memory, psyc...

In-scanner head motion is a recognized source of bias in structural magnetic resonance imaging (sMRI), yet it remains under-addressed in psychiatric neuroimaging where structural difference in patient populations are considered foundational. We examined motion-related bias in grey matter volume estimates across eight independent cohorts comprising 9,664 individuals, including 8,979 neurotypical controls (NC), 497 patients with schizophrenia (SCZ), and 188 patients with bipolar disorder (BD). Mot...

BackgroundTo clarify the working mechanisms of psychotherapy for obsessive-compulsive disorder (OCD), we studied the neural effects of two psychotherapies: cognitive behavioral therapy with exposure and response prevention (CBT-ERP) and inference-based cognitive behavioral therapy (I-CBT). MethodsFifty-five individuals with OCD completed an emotional processing task during fMRI before and after 20 weekly psychotherapy sessions, using general fear and OCD-related visual stimuli. Forty-two health...

Psychotic disorders are increasingly recognized as the extreme end of a progressive psychopathology continuum, with less advanced stages including the asymptomatic familial high-risk state (FHR), the help-seeking clinical high-risk state (CHR), and first episode psychosis (FEP). However, we lack a comprehensive study of clinical, cognitive, functional, and neuroanatomical markers across all three early stages of psychosis, limiting our understanding of how the multimodal phenotypes which define ...

Schizophrenia spectrum disorders (SSD) are characterized by altered brain structure, reflecting widespread dysconnectivity across brain-specific networks. However, the role of hierarchical organization on cortical morphometric networks in shaping clinical outcomes over the course of the disease remains unclear. Connectome-derived gradients have increasingly been used to investigate spatial transitions in brain organization. Here, we computed cortical and subcortical Morphometric INverse Divergen...

ObjectiveCognitive deficits are a leading cause of disability in schizophrenia and are linked to poor functional outcomes. There are no first line treatments for these deficits, and their neural basis is poorly understood. While schizophrenia is associated with widespread cognitive deficits, information processing speed is most profoundly impaired. Processing speed deficits have been associated with hyperconnectivity in the Default Mode Network (DMN). We therefore tested if modulating DMN connec...

Background and HypothesisAbnormal default mode network (DMN) connectivity was observed in both tobacco use and psychotic spectrum disorders, but it remains unknown how psychosis impacts the relationship between connectivity and tobacco use. Interventions targeting the left lateral parietal DMN node (LLPDMN) have modulated DMN connectivity and nicotine craving in psychosis. We aimed to investigate relationships between DMN connectivity, psychotic illness, and tobacco use. Study Design336 partici...

Deficits in inhibitory control are common across a wide range of psychiatric disorders and are closely linked to symptom severity, including emotional dysregulation, anxiety, substance misuse, and self-harm, making them an appealing target for intervention. Cognitive training offers a low-cost, scalable, and non-invasive strategy to strengthen inhibitory control; however, most existing paradigms target only a single facet of inhibition and rarely account for environmental influences, such as aff...

ObjectiveWe examined the clinical utility of resting state electroencephalography (rsEEG) by evaluating its temporal stability, discriminant validity for B-SNIP psychosis Biotypes, and suitability as a treatment target for brain stimulation. MethodsWe collected 5 minutes of eyes-open rsEEG from 1401 participants with psychosis and 750 healthy persons. A subset of participants was re-tested after 6 months and 12 months (N=109). In a pilot target engagement study (n=5) we collected rsEEG before a...

BackgroundEEG microstates provide a window into rapid, large-scale brain network dynamics. Despite showing alterations in schizophrenia, evidence in first-episode schizophrenia spectrum psychosis (FESSP) is limited. We assessed whether microstate temporal and transition features could identify a multivariate signature of FESSP, and whether these dynamics can track symptom severity. MethodsResting-state EEG was analysed in 69 participants (FESSP n=41, mean age: 22.49 years; healthy controls n=28...

INTRODUCTIONCognitive decline in Alzheimers disease (AD) may arise not only from neuronal loss but also from disrupted temporal coordination across distributed networks. Prior works in healthy individuals has shown memory-related modulation of hippocampal-cortical phase-amplitude coupling (PAC). We hypothesized alteration of resting-state hippocampo-cortical PAC in AD which relates to cognitive impairment. METHODSResting-state magnetoencephalography (MEG) data were obtained from 78 AD patients ...

Evidence-based psychotherapies are first-line treatments for psychiatric disorders, yet response rates remain suboptimal. Noninvasive brain stimulation (NIBS) may augment psychotherapy by modulating treatment-engaged circuits. We conducted a systematic review and meta-analysis of randomized controlled trials comparing active NIBS plus evidence-based psychotherapy versus sham NIBS plus psychotherapy. Following Cochrane methods, we searched six databases through February 2025, screening 1,017 reco...

Cognitive heterogeneity is a core feature of schizophrenia (SCZ). Conventional approaches examine this heterogeneity using domain-specific scores, which may not fully reflect the underlying cognitive structure. In this study, a norm-anchored cognitive structural deviation (NCSD) framework was developed to examine such heterogeneity from a structure-informed perspective. The HC-derived latent cognitive structure (N-LCS) captured performance across the assessed tasks and remained stable under exte...

Psychiatric disorders are fundamentally challenged by symptom heterogeneity, high comorbidity, and the absence of objective biomarkers, which together result in substantial variability in clinical assessment and treatment selection. Patient-generated language captures rich information about subjective experience and symptom severity, which can be systematically encoded and analyzed using computational models, making it a scalable signal for psychiatric assessment. We compare two approaches: (i) ...

BackgroundMajor depressive disorder (MDD) involves immune-metabolic dysregulation, psychosocial adversity, and multidomain cognitive disturbances, yet single cognitive indices often show small and inconsistent effects. We derived a multivariate Cambridge Neuropsychological Test Automated Battery (CANTAB)-based cognitive phenotype ("cognitype") and tested whether it adds explanatory value beyond adverse childhood experiences (ACEs) and an acute-phase protein (APP) index in acute-phase MDD. Metho...

Mild Behavioural Impairment (MBI) is defined by later-life onset of persistent behavioural changes and is recognized as a risk marker for cognitive decline and dementia. Apathy, a core MBI domain characterized by diminished interest, initiative, and emotional reactivity, can emerge before dementia and is hypothesized to be associated with structural brain changes. While previous studies have explored Alzheimer disease (AD)-related neuroanatomical substrates of apathy in the dementia clinical st...

BackgroundLipidomic alterations have been reported across schizophrenia (SCZ) and bipolar disorder (BD), but findings are heterogeneous and often overlap across diagnoses, limiting diagnostic specificity. Associations between lipid profiles and illness severity have also been inconsistent when assessed using single symptom scales, raising the possibility that unidimensional measures fail to capture biologically relevant variation. Whether plasma lipidomic alterations relate to multidimensional p...

Actigraphy is a popular behavioral sleep assessment tool in research and clinical practice. Hierarchical hand-scoring approaches remain the standard for actigraphy rest interval estimation, but can be impractical for large cohort studies and suffer from reproducibility problems. We developed a semi-automated pipeline (actiSleep) to set rest intervals consistent with best-practice hand-scoring algorithms incorporating event marker, diary, light, and activity data. To evaluate actiSleep performanc...

Understanding factors that predict the course of schizophrenia remains essential for improving long-term clinical management. Rate and severity of symptom exacerbations vary widely across individuals, and although prior studies have examined potential predictors, findings have been inconsistent and often limited by small samples, infrequent assessments, and non-standardized measures. Using data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), which include...

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. de...