Deviant sound frequency and time stimuli in auditory oddball tasks reveal persistent aberrant brain activity in patients with psychosis and symptomatic remission

The detection of rare or deviant stimuli shares common brain circuits involved in temporal processing and salience, critical for cognitive control. Disruption in these processes may contribute to the mechanisms of the disease and explain cognitive deficits observed in psychosis and related disorders. We designed a neuroimaging study, using oddball task-based functional sequences (fMRI) and diffusion tensor imaging (DTI), comparing healthy controls (HC, n = 14, 7 females) and patients with stable psychosis (PSY, n = 20, 10 females). The PSY individuals had schizophrenia or bipolar disorder diagnosis (ICD-10), meeting symptom remission criteria in the last 6 months. Two variants of the auditory oddball paradigm were employed, focusing on sound frequency (SF) and time discrimination (TD) tasks, adapted for fMRI. We used a general linear model to analyze fMRI data and a random effects model for group analysis, complemented by an exploratory statistical agnostic mapping analysis. DTI data were processed using FSL (FMRIB Software Library) and TBSS (Tract Based Spatial Statistics). Distinct activation patterns between groups were observed, with increased brain activity in PSY in TD and SF oddball tasks. In response to increased task difficulty, HC predominantly activated cerebellar regions, whereas PSY relied more on frontal regions. Reduced fractional anisotropy in PSY correlated with lower performance scores in the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB). The study underscores aberrant brain activity and white matter deficits in stable psychosis patients, highlighting distinct responses to cognitive challenges compared to HC. These findings may support the hypothesis of cognitive dysmetria as a potential underlying mechanism in psychosis and highlight future therapeutic strategies, including non-invasive brain stimulation techniques.