Abstract
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.
Highlights
Delusion is the most characteristic symptom of psychosis, occurring in about 96%1 of first-episode psychosis patients
Mapping the brain regions related to such a key symptom would be valuable for understanding the neurobiological basis of psychotic disorders
We modeled the ventral striatal regions of interest (ROI) as a sphere with an 8-mm radius, centered at the mean coordinates of the two nearby maxima that were related to abnormal functioning in patients with delusion of reference in the study of Menon and co-workers (x, y, z = −20, 13, −4; Supplementary Fig. 1)[18]
Summary
Delusion is the most characteristic symptom of psychosis, occurring in about 96%1 of first-episode psychosis patients. The brain correlates of delusion could be linked to upstream factors to elucidate etiopathogenic pathways as a target for better diagnostic and treatment methods[2]. Unraveling the neuronal origins of delusion could help to assess the more general question about how the sense of reality is constructed in the human mind and brain. Delusion is described in the DSM-5 as a fixed belief that is not amenable to change in light of conflicting evidence. Even though such a symptom is typically associated with thinking, early delusional experiences have been considered to be “something basic and primary which comes before thought”[3]. We refer to sensations and feelings with delusional contents as well as to the delusional thoughts as “delusional experience”
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