Multiscale Network Disruption of Auditory-Language Circuits Underlying Auditory Hallucinations in Schizophrenia
Andrew C Murphy, Antigona Martinez, Yadi Chen, Michael Avissar, Bahar Hazal Yalçınkaya, Juan Sanchez-Pena, Gaurav H Patel, Daniel C Javitt
Study at a glance
AI-extracted from the abstract| Characteristics | Observational neuroimaging study with independent replication |
|---|---|
| Sample size | 171 |
| Population | Patients with schizophrenia and healthy controls; 56 patients and 22 controls in the primary dataset, plus 93 patients in the HCP-EP replication sample |
| Measures | PANSS P3 |
| Key findings | Auditory-language connectivity disruptions were concentrated in belt cortex and ventral what-stream connections, and auditory network segregation scaled with hallucination severity. Belt cortex emerged as the primary integrative hub for auditory-to-language routing efficiency. Reduced belt cortex coupling and elevated network segregation replicated in an independent sample, leading the authors to propose belt cortex as a candidate neuromodulatory target. |
Abstract
Abstract:
Background: Auditory verbal hallucinations (AVH) are among the most disabling symptoms of schizophrenia, yet the network-level mechanisms linking auditory dysfunction to hallucination severity remain poorly characterized, limiting targeted therapeutic development.
Methods: Using resting-state fMRI and high-resolution surface-based parcellation (HCP-MMP), we examined auditory-language functional connectivity and mesoscale network organization in 56 patients with schizophrenia and 22 healthy controls (primary dataset, N=78). Pairwise auditory-language connectivity associations with hallucination severity (PANSS P3) were examined alongside auditory network community structure, assortativity, hub organization, and routing efficiency. To further characterize these parcel-level findings at the vertex level, we applied a region-growing approach to identify auditory-frontal connectivity patterns maximally associated with severity. In silico perturbation analyses tested the causal role of belt cortex connectivity. Key findings were independently replicated in 93 patients from the Human Connectome Project for Early Psychosis (HCP-EP), for a combined total of 171 participants.
Results: Auditory-language connectivity disruptions were concentrated in belt cortex and specifically implicated ventral what-stream connections, with a vertex-wise analysis converging on the same anatomy. Auditory network segregation scaled with hallucination severity, with belt cortex emerging as the primary integrative hub governing auditory-to-language routing efficiency. Perturbation analyses showed that strengthening earlier-hierarchy auditory regions reduced network segregation more than strengthening later-hierarchy regions. Reduced belt cortex coupling and elevated network segregation replicated independently in the HCP-EP sample.
Conclusions: Auditory network disorganization scales with hallucination severity and replicates across independent samples, with belt cortex as the critical locus of connectivity disruption and network integration failure, identifying it as a candidate neuromodulatory target.