Biology subjects

Mulvey, A. G.

Publications and source records attributed to Mulvey, A. G..

3 recordsLinked to original sources

bioRxiv2026

Distinct associations between multimodal brain measures and psychopathology domains predict adolescent functioning

Adolescent psychopathology is partly rooted in measurable disruptions across key neural networks, yet the field still lacks an integrated, multimodal understanding of these brain-behavior links. Here, we examined how structural, microstructural, and functional measures across corticostriatal, corticolimbic, and executive control networks relate to psychopathology domains and explored how these associations predicted future psychosocial functioning. We used data from the Adolescent Brain Cognitive DevelopmentSM Study (n=5,408) and ran a regularized canonical correlation analysis to identify distinct modes of covariation between multiple brain measures and psychopathology domains when youth were 13-14 years old. The resulting canonical brain and psychopathology scores were used to predict school-related impairment one year later. First, higher diffusivity and decreased activation during a reward task across all three networks as well as lower corticostriatal surface area were related to higher broad psychopathology. Second, lower corticolimbic diffusivity, executive control volume and surface area, and cortical thickness across all three networks as well as higher corticostriatal and corticolimbic volumes were related to higher anxiety but lower externalizing. For the first mode, higher psychopathology scores predicted more school-related impairment one year later. For the second mode, higher brain and higher psychopathology scores predicted less school-related impairment one year later. Identifying how specific neural measures align with psychopathology domains, as well as how both forecast reallilworld functioning, advances the conceptualization of adolescent mental health. This approach clarifies which levels of analysis provide distinct versus shared information about youth functioning and highlights potential mechanisms that may inform future targets for change.

neuroscience↗

bioRxiv2025

Cell Density and mRNA Expression of Inhibitory Interneurons in Schizophrenia: A Meta-Analysis

Introduction GABAergic interneurons are implicated in the pathophysiology of schizophrenia, yet evidence regarding the nature of deficits across brain areas and interneuron subtypes remains conflicting. We adopted a meta-analytic, multi-level linear modeling approach to identify interneurons, cortical layers, and brain areas involved, and the implications for circuit functions in schizophrenia. Methods Following PRISMA guidelines, we conducted a systematic search and meta-analysis from inception to November 2025, for studies examining parvalbumin, somatostatin, calbindin, and calretinin interneuron density or mRNA expression in schizophrenia. We included data from 44 studies, comprising 736 individuals with schizophrenia and 814 healthy controls. Non-cell-specific, non-human, or indirect proxy studies were excluded. Linear mixed-effects models quantified deficits while accounting for cortical layer, cell-type, and brain area, providing a map of interneuron pathology. We further analyzed changes in GABAergic interneurons to determine whether deficits preferentially target cortical layers, cell-types, and brain areas more associated with top-down or bottom-up processing. Results Parvalbumin and somatostatin interneurons showed robust reductions, particularly in layers 3/4, whilst calbindin and calretinin interneurons were less affected. Deficits were widespread across cortical and subcortical regions. Contrasts revealed that schizophrenia is characterized by interneuron deficits preferentially affecting bottom-up signaling -- notably parvalbumin and somatostatin interneurons in layers 3/4, which are critical for gamma-band synchronization and feedforward sensory processing. Discussion These findings provide the most comprehensive meta-analysis on GABAergic interneurons in schizophrenia to-date, as well as a novel perspective on circuit dysfunctions, with implications for computational models. These results highlight the need for more widespread sampling across the brain using methodologies that can pinpoint deficits in molecularly more precise ways.

neuroscience↗

bioRxiv2024

The laminar organization of cell types in macaque cortex and its relationship to neuronal oscillations

The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6. Here, we investigate whether specific conserved cell types may produce the spectrolaminar motif. We collected laminar histological and electrophysiological data in 11 distinct cortical areas spanning the visual hierarchy: V1, V2, V3, V4, TEO, MT, MST, LIP, 8A/FEF, PMD, and LPFC (area 46), and anatomical data in DP and 7A. We stained representative slices for the three main inhibitory subtypes, Parvalbumin (PV), Calbindin (CB), and Calretinin (CR) positive neurons, as well as pyramidal cells marked with Neurogranin (NRGN). We found a conserved laminar structure of PV, CB, CR, and pyramidal cells. We also found a consistent relationship between the laminar distribution of inhibitory subtypes with power in the local field potential. PV interneuron density positively correlated with gamma (40-150 Hz) power. CR and CB density negatively correlated with alpha (8-12 Hz) and beta (13-30 Hz) oscillations. The conserved, layer-specific pattern of inhibition and excitation across layers is therefore likely the anatomical substrate of the spectrolaminar motif. Significance StatementNeuronal oscillations emerge as an interplay between excitatory and inhibitory neurons and underlie cognitive functions and conscious states. These oscillations have distinct expression patterns across cortical layers. Does cellular anatomy enable these oscillations to emerge in specific cortical layers? We present a comprehensive analysis of the laminar distribution of the three main inhibitory cell types in primate cortex (Parvalbumin, Calbindin, and Calretinin positive) and excitatory pyramidal cells. We found a canonical relationship between the laminar anatomy and electrophysiology in 11 distinct primate areas spanning from primary visual to prefrontal cortex. The laminar anatomy explained the expression patterns of neuronal oscillations in different frequencies. Our work provides insight into the cortex-wide cellular mechanisms that generate neuronal oscillations in primates.

neuroscience↗