Activation of the motivation-related ventral striatum during delusional experience

Delusion is the most characteristic symptom of psychosis, occurring in almost all first-episode psychosis patients. The motivational salience hypothesis suggests delusion to originate from the experience of abnormal motivational salience. Whether the motivation-related brain circuitries are activated during the actual delusional experience remains, however, unknown. We used a forced-choice answering tree at random intervals during functional magnetic resonance imaging to capture delusional and non-delusional spontaneous experiences in patients with first-episode psychosis (n = 31) or clinical high-risk state (n = 7). The motivation-related brain regions were identified by an automated meta-analysis of 149 studies. Thirteen first-episode patients reported both delusional and non-delusional spontaneous experiences. In these patients, delusional experiences were related to stronger activation of the ventral striatum in both hemispheres. This activation overlapped with the most strongly motivation-related brain regions. These findings provide an empirical link between the actual delusional experience and the motivational salience hypothesis. Further use and development of the present methods in localizing the neurobiological basis of the most characteristic symptoms may be useful in the search for etiopathogenic pathways that result in psychotic disorders.