Subtyping psychotic disorders using a data-driven approach reveals divergent cortical and cellular signatures.

Structural brain abnormalities in psychosis are well-replicated but heterogenous posing a barrier to uncovering the pathophysiology, etiology, and treatment of psychosis. To parse neurostructural heterogeneity and assess for the presence of anatomically-derived subtypes, we applied a data-driven method, similarity network fusion (SNF), to structural neuroimaging data in a broad cohort of individuals with psychosis (schizophrenia spectrum disorders (SSD) n=280; bipolar disorder with psychotic features (BD) n=101). SNF identified two transdiagnostic subtypes in psychosis (subtype 1: n=158 SSD, n=75 BD; subtype 2: n=122 SSD, n=26 BD) that exhibited divergent patterns of abnormal cortical surface area and subcortical volumes.

Episode-specific cortical functional connectome reorganization and neurobiological correlates in bipolar disorder: a cross-sectional study.

Background: Bipolar disorder (BD) is a heterogeneous psychiatric condition characterized by distinct episodes: manic (BipM), depressive (BipD), mixed (mBD), and remission (rBD). Current evidence indicates alterations in brain functional connectivity in BD, yet a comprehensive understanding across all episodes remains incomplete.

Methods: Here, to investigate how different BD episodes alter brain functional organization, we calculated the sensory-association axis using diffusion map embedding on the functional connectome matrix and compared this axis between the four BD groups and neurotypical controls.

Network-based Molecular Constraints on Synaptic Density Alterations in Schizophrenia.

Converging neuroimaging, genetic, and post-mortem evidence show a fundamental role of synaptic deficits in schizophrenia pathogenesis. However, the underlying molecular and cellular mechanisms that drive the onset and progression of synaptic pathology remain to be established. Here, we used synaptic density positron emission tomography (PET) imaging using the [C]UCB-J radiotracer to reveal a prominent widespread pattern ( < 0.

The cell-type underpinnings of the human functional cortical connectome.

The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cerebral cortex. The cortical sheet can be broadly divided into distinct networks, which are embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here using microarray data from the Allen Human Brain Atlas and single-nucleus RNA-sequencing data from multiple cortical territories, we demonstrate that cell-type distributions are spatially coupled to the functional organization of cortex, as estimated through functional magnetic resonance imaging.

Ventral attention network connectivity is linked to cortical maturation and cognitive ability in childhood.

The human brain experiences functional changes through childhood and adolescence, shifting from an organizational framework anchored within sensorimotor and visual regions into one that is balanced through interactions with later-maturing aspects of association cortex. Here, we link this profile of functional reorganization to the development of ventral attention network connectivity across independent datasets. We demonstrate that maturational changes in cortical organization link preferentially to within-network connectivity and heightened degree centrality in the ventral attention network, whereas connectivity within network-linked vertices predicts cognitive ability.

The Cellular Underpinnings of the Human Cortical Connectome.

The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cortex. The cortical sheet can be broadly divided into distinct networks, which are further embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here, using transcriptional data from the Allen Human Brain Atlas, we demonstrate that imputed cell type distributions are spatially coupled to the functional organization of cortex, as estimated through fMRI.

Wave-like properties of functional dynamics across the cortical sheet.

The human cortex is organized in a hierarchical manner. Pines et al. show that wave-like hemodynamic activity flows along this architecture, from unimodal through association cortices, providing fertile ground for researchers seeking to map links across behavioral and cognitive states.

Brain-Based Predictions of Psychiatric Illness-Linked Behaviors Across the Sexes.

Background: Individual differences in functional brain connectivity can be used to predict both the presence of psychiatric illness and variability in associated behaviors. However, despite evidence for sex differences in functional network connectivity and in the prevalence, presentation, and trajectory of psychiatric illnesses, the extent to which disorder-relevant aspects of network connectivity are shared or unique across the sexes remains to be determined.

Methods: In this work, we used predictive modeling approaches to evaluate whether shared or unique functional connectivity correlates underlie the expression of psychiatric illness-linked behaviors in males and females in data from the Adolescent Brain Cognitive Development Study (N = 5260; 2571 females).