Altered cingulate and substantia nigra/ventral tegmental activation to novelty and emotional salience in antipsychotic naïve first episode psychosis patients

Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness. We studied 14 antipsychotic naive participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) and the cingulate gyrus for novelty, negative emotional salience and targetness; reduced striatal signalling to novelty and negative emotional salience, and reduced signalling in the right amygdala to negative emotional salience. There was reduced cerebellar activation to targetness in the patients, consistent with abnormal efference copy transmission in preparation of a motor response. Our results indicate that generalised salience processing alterations in patients with psychosis, mainly involving the dopaminergic SN/VTA, the cingulate gyrus and the striatum.