Abnormal cortical topographic patterns associated with auditory verbal hallucination in first-episode schizophrenia.

Convergent phenomenological and neuroimaging evidence support that the dysregulated segregation and integration between brain networks have been implicated in the neural mechanism of auditory verbal hallucination (AVH) in schizophrenia. Nevertheless, the macroscale topographical alterations of functional networks in patients with AVH remain elusive. Cortical gradient mapping provides a novel approach to characterize the distribution pattern of functional organization in a multidimensional connectivity space. Here, leveraging resting-state functional MRI data from 104 first-episode drug-naïve schizophrenia (64 with AVH, 40 without AVH) and 90 matched healthy controls (HC), we extracted intrinsic connectivity gradients and measured the range of each gradient, manifold eccentricity, global, within- and between-network dispersions in a three-dimensional gradient space to characterize the topographical structure of the brain. We then combined publicly available genetic and neurotransmitter distribution data to further unveil the potential molecular basis underlying the AVH-related topographical changes. Our analysis revealed a degradation of the principal unimodal-to-transmodal gradient in patients with AVH compared with those without AVH and HC, as well as the reduced 3D manifold dispersion, especially between high-order transmodal networks. The disrupted topographic pattern related to AVH was linked with expression maps of specific genes enriched for synaptic development and signaling and aligned with the distribution of the noradrenaline and acetylcholine systems. Our work depicts the comprehensive landscape of topographic abnormalities in AVH, underscoring the vital role of disrupted cortical hierarchy and network integration in its pathophysiology.