bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/423574

Disruptions in White Matter Maturation and Mediation of Cognitive Development in Youth on the Psychosis Spectrum

Hegarty, C. E.·Jolles, D.·Mennigen, E.·Jalbrzikowski, M.·Bearden, C.·Karlsgodt, K. H.
View original source ↗Export metadata ↓

Abstract

BackgroundPsychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence as well. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examine whether regional white matter (WM) development is disrupted in psychosis spectrum (PS) youth whether WM maturation mediates the relationship between age and cognition in typically developing (TD) and PS youth. A third group with intermediate symptom severity (limited PS [LPS]) was included in follow-up analyses to determine whether age-related disruptions in WM scaled with symptom severity.\n\nMethodsWe examined WM microstructure, as assessed via diffusion tensor imaging, in 707 individuals (aged 10-22 years; 499 TD, 171 PS, 37 LPS) by using Tract-Based Spatial Statistics. Multiple regressions were used to evaluate age x group interactions on regional WM indices. Mediation analyses were conducted using a bootstrapping approach.\n\nResultsThere were age x group interactions on fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and retrolenticular internal capsule (RLIC). SLF FA mediated the relationship between age and Complex Cognition in TD, but not PS. Further, inclusion of LPS youth showed that the relationship between age and SLF FA decreased with increasing symptom severity\n\nConclusionsOur results show aberrant age-related changes in SLF and RLIC FA in PS youth. SLF development supports emergence of specific higher-order cognitive functions in TD youth, but not in PS. Future mechanistic explanations for these relationships could facilitate development of earlier and refined targets for therapeutic interventions.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hegarty, C. E., Jolles, D., Mennigen, E., Jalbrzikowski, M., Bearden, C., Karlsgodt, K. H.. 2018-09-21. Disruptions in White Matter Maturation and Mediation of Cognitive Development in Youth on the Psychosis Spectrum. https://doi.org/10.1101/423574

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Human iEEG recordings during audiovisual speech violations support and extend predictive routing models

Rather than constantly reconstructing the world solely through sensory input, predictive processing theories posit that the brain utilizes predictions maintained as internal representations to guide sensory processing. An emerging model, predictive routing, proposes that an interplay between neuronal gamma (40-150 Hz) and alpha-beta (10-30 Hz) rhythms implements a dynamic mechanism for predictive processing. Namely, predictions enhance alpha-beta oscillations that suppress gamma activity during the processing of predicted inputs. While this model is supported by animal studies, its validity has not been fully explored within the human brain. The present study addresses this by leveraging human intracranial EEG (iEEG) recordings across superior temporal and prefrontal/premotor areas of seven presurgical epilepsy patients during an audiovisual speech paradigm. We calculated iEEG power in the theta, alpha-beta, and high gamma bands during simple auditory deviance, multisensory integration, and a condition where an incongruent visual cue (lip movements) clashed with an auditory stimulus (a syllable), creating audiovisual incongruence that can elicit the McGurk illusion. Results revealed increased high-gamma and decreased alpha-beta power in the superior temporal cortex in response to auditory deviance and the McGurk condition, while frontal areas, despite reflecting a similar decrease in alpha-beta power, did not present this high gamma prediction error signal. Instead, the theta band revealed a strong prediction error signal in the McGurk condition, consistent with theories on the role of theta in reorganizing cortical networks. These results both support and extend existing predictive routing models for human-specific forms of predictive processing.

neuroscience↗
bioRxiv2026

A Unified World Model in Human Posterior Parietal Cortex

How does the brain understand the physical world, predict future events, and plan actions? Are these problems solved by a unified world model, as hypothesized by cognitive scientists and artificial intelligence researchers? Posterior parietal cortex has been implicated in all these functions, but whether the same neurons support each of them is unknown. We recorded from the superior parietal lobule (SPL) of two tetraplegic participants implanted with microelectrode arrays. SPL units preferentially engaged by intuitive physics, judging block-tower stability and viewing naturalistic physical events, also predicted whether moving objects would collide hundreds of milliseconds before contact, generalizing between different physical scenarios. These populations also encoded which hand action the participant intended to perform. These findings identify SPL as a substrate for physical world modeling.

neuroscience↗
bioRxiv2026

Cortical long-range dynamics track excitation-inhibition balance across cognitive states and organizational principles

A fundamental question in systems neuroscience is how the brain's excitation-inhibition (E/I) balance shapes the temporal structure of neural activity and whether we can non-invasively recover this relationship from neural scaling properties. We show that MRS-derived E/I balance is expressed in long-range temporal dynamics and constrained by cytoarchitecture. The laminar organisation of inhibitory circuits, spanning agranular to granular cortex, determines how faithfully regional dynamics reflect E/I balance. This neurochemical signature is state-dependent: its relationship with cortical dynamics reverses during task engagement, consistent with traversal of dynamical regimes around a critical point. It extends beyond fMRI to arousal-linked dynamics, indexed by pupil diameter and microsaccades, indicating a global mode of cortical state rather than a regionally isolated property. The imprint of E/I balance on long-range dynamics follows the sensory-association axis at rest, and is reconfigured during task engagement. These findings establish E/I balance as a neurochemical quantity with structured, scalable signatures across the temporal and spatial organization of the human cortex.

neuroscience↗