Front-end and Back-end Computational Modeling of 40-Hz Auditory Steady-State Response Abnormalities in Schizophrenia

Abstract

40-Hz ASSR is reduced in schizophrenia, but it is unclear if this reflects altered auditory input or cortical E/I dynamics. We hypothesized that similar group differences could arise via distinct model mechanisms. EEG gamma% and ITPC from 21 HC and 21 SCZ constrained an auditory front-end coupled to a Wilson-Cowan E/I model. We compared front-end-restricted, back-end-restricted, and full-joint parameter searches, plus perturbation and fixed-point analyses. HC means exceeded SCZ for both metrics (not individually significant). All three models reproduced HC>SCZ but located group differences differently: front-end via input transformation, back-end via cortical dynamics, full-joint via both. The full-joint solution was most robust to perturbation. Fixed-point analysis revealed similar outputs with distinct local dynamics. All models reproduced the HC>SCZ pattern, suggesting schizophrenia pathophysiology may involve altered sensory encoding, altered cortical E/I, or both. This framework enables future patient-level mechanistic comparison and, after validation, may support individualized stratification.