Volume and Tempo: Cortical Excitability and Trial-to-Trial Consistency of Auditory Responses Distinguish Psychosis Biotypes

ERPs average neural responses to stimuli across trials. This accentuates consistent activity over time but obscures differences in response strength and phase consistency from trial to trial. The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) identified three transdiagnostic psychosis Biotypes (BT1, BT2, BT3) that differ in cortical excitability and temporal coherence of neural responses. Single-trial power (STP) and inter-trial coherence (ITC) were measured across 3–55 Hz in auditory paired-stimuli and oddball tasks using a large multi-site cohort (n = 2 373). One-way ANOVAs over a continuous time-frequency epoch with FDR and cluster correction identified group differences, resulting in 15 significant STP and ITC features. Linear discriminant analysis of these features identified the dimensions that maximally separated Biotypes. The STP differences covered the entire trial epoch, showing the strongest alterations in the beta band (18–32 Hz), graded BT2 > > BT3 > HC > > BT1. The ITC differences were seen at specific time points primarily in low-frequency bands (3–17 Hz), graded HC > BT3 > BT1 > BT2. These dimensions were orthogonal and did not mirror ERP amplitudes across Biotypes. Biotypes were better distinguished by STP and ITC (Euclidean distances 0.9–2.2) than by DSM diagnosis (0.10–0.45). DSM groups alone did not benefit from this breakdown. Cortical excitability and phase precision are unique neurophysiological targets for the etiological investigation of psychosis Biotypes, which traditional ERP averaging obscures.