Mapping intrinsic neural timescale alterations in first-episode, drug-naïve adolescent-onset schizophrenia

Schizophrenia is commonly associated with impairments in higher-order cognitive functions, yet its neurobiological mechanisms remain incompletely understood. Intrinsic neural timescale (INT), a recently developed neuroimaging metric, quantifies the temporal persistence of neural signals within localized brain regions and is thought to index their capacity for information integration. Accordingly, the present study examined whether adolescent-onset schizophrenia (AOS) is characterized by disruptions in intrinsic neural dynamics, alongside alterations in gray matter volume (GMV) and their spatial associations with neurotransmitter distribution patterns.

Structural and resting-state functional magnetic resonance imaging data were acquired from 21 first-episode, drug-naïve patients with AOS and 21 demographically matched healthy controls (HC). INTs were estimated by quantifying the autocorrelation properties of spontaneous neural activity. Additionally, voxel-based morphometry was applied to calculate whole-brain GMV. Associations between altered INT and clinical measures were subsequently examined. Furthermore, the JuSpace toolbox was employed to investigate the spatial correlation between INT alterations and atlas-based neurotransmitter distributions.

Compared to HC, patients with AOS exhibited shorter intrinsic timescale in the right middle frontal gyrus. The shortened INT in the right middle frontal gyrus was negatively correlated with illness duration. Furthermore, the INT shortening pattern observed in AOS was significantly correlated with the spatial distribution of the dopaminergic (DAT) and serotonergic (SERT) systems.

This study reveals abnormalities in local neurodynamics of AOS and their associations with clinical characteristics and neurotransmitter distribution patterns. These findings provide integrated insights into the neurobiological mechanisms underlying AOS and highlight potential directions for further investigation of neurotransmitter-related mechanisms.