Garofalo, S.; Justicia, A.; Arrondo Ostíz, Gonzalo
; Ermakova, A. O.; Ramachandra, P.; Tudor-Sfetea, C.; Robbins, T. W.; Barker, R. A.; Fletcher, P. C.; Murray, G. K.
Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n¿=¿12), or without (n¿=¿17), a history of psychotic symptoms, along with a sample of healthy controls (n¿=¿24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p¿<¿0.05 small volume corrected). The results suggest that cortical and striatal