Search bioRxiv⌕ Search

Biology subjects

Neria, Y.

Publications and source records attributed to Neria, Y..

5 recordsLinked to original sources

Transdiagnostic Neurobiological Biotypes of Trauma Timing: Data-driven approach of Childhood and Adulthood-Onset Trauma

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.

neuroscience↗

Volumetric Differences of Thalamic Nuclei are Associated with Post-Trauma Psychopathology

Previous investigations of whole thalamus and thalamic nuclei volumes in post-trauma psychopathology have been sparse, limited in scope, and yielded inconsistent results. To address this, volumetric estimates of whole thalamus and thalamic nuclei were obtained from structural brain MRI scans from 2,058 participants across 20 worldwide sites in the ENIGMA PTSD working group. Thalamic volumes were compared between trauma-exposed participants with posttraumatic stress disorder (PTSD) (n=238), major depressive disorder (MDD) (n=184), comorbid PTSD+MDD (n=618), and trauma-exposed control participants (n=1,018). PTSD and MDD symptom severity, PTSD symptom clusters, and childhood trauma were similarly examined for associations with thalamic volume. Participants with PTSD only compared to controls had smaller thalamic nuclei volumes in sensorimotor nuclei, including the parafascicular (Pf), ventral anterior magnocellular (VAmc), medial pulvinar (PuM), and anterior pulvinar (PuA) nuclei of the thalamus. MDD only and comorbid PTSD+MDD participants exhibited smaller mediodorsal thalamus volumes compared to controls. Overall PTSD and MDD symptom severity negatively correlated with the volume of the mediodorsal thalamus. A significant interaction between PTSD and MDD severity was found, such that MDD severity was positively associated with thalamic volume only among individuals with high PTSD severity. Avoidance and hyperarousal symptoms of PTSD were positively associated with thalamic volume, while re- experiencing and negative mood/cognition symptoms were negatively associated with thalamic volume. Childhood physical and emotional abuse were positively and negatively associated with thalamic volume, respectively. Whole thalamus volume and volumes of the sensorimotor and limbic thalamus may play an important role in the development of PTSD and MDD in the aftermath of trauma exposure. The interaction between PTSD and MDD symptoms and contrasting effects across PTSD symptom clusters and types of childhood adversity suggests multiple neurobiological mechanisms are involved in shaping thalamic volume post-trauma.

neuroscience↗

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

neuroscience↗

Explaining Deep Learning-Based Representations of Resting State Functional Connectivity Data: Focusing on Interpreting Nonlinear Patterns in Autism Spectrum Disorder

BackgroundResting state Functional Magnetic Resonance Imaging fMRI (rs-fMRI) has been used to study brain function in psychiatric disorders, yielding insight into brain organization. However, the high dimensionality of the rs-fMRI data presents challenges, and requires dimensionality reduction before applying machine learning techniques. Neural networks, specifically variational autoencoders (VAEs), have been instrumental in extracting low-dimensional latent representations of resting state functional connectivity patterns, addressing the complex nonlinear structure of rs-fMRI. However, interpreting those latent representations remains a challenge. This paper aims to address this gap by creating explainable VAE models and testing their utility using rs-fMRI data in autism spectrum disorder (ASD). MethodsOne-thousand one hundred and fifty participants (601 HC and 549 patients with ASD) were included in the analysis. We extracted functional connectivity correlation matrices from the preprocessed rs-fMRI data using Power atlas with 264 ROIs. Then VAEs were trained in an unsupervised fashion. Lastly, we introduce our latent contribution scores to explain the relationship between estimated representations and the original rs-fMRI brain measures. ResultsWe quantified the latent contribution scores for the ASD and control groups at the network level. We found that both ASD and control groups share the top network connectivity that contribute to all estimated latent components. For example, latent 0 was driven by resting state functional connectivity patterns (rsFC) within ventral attention network in both the ASD and control. However, significant differences in the latent contribution scores between the ASD and control groups were discovered within the ventral attention network in latent 0 and the sensory/somatomotor network in latent 2. ConclusionThis study introduced latent contribution scores to interpret nonlinear patterns identified by VAEs. These scores effectively capture changes in each observed rsFC features as estimated latent representation changes, enabling an explainable deep learning model to better understand the underlying neural mechanism of ASD.

neuroscience↗

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

BackgroundThe cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions. MethodsWe quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640; Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate (p-FDR < .05). ResultsPTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. ConclusionsThese findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

neuroscience↗