Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

Abstract

Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.

Neurochemistry of Visual Attention

“…DA is also an important determinant of basal ganglia (BG) function—a brain region that is known for its involvement in eye movement generation and attentional control ( Hikosaka et al, 2000 ). Striatal DA has been implicated in reward processing ( Berridge and Robinson, 1998 ; Haber, 2011 ; Deserno et al, 2016 ; Katthagen et al, 2020 ), voluntary motor behavior ( Albin et al, 1989 ; Joshua et al, 2009 ; Klaus et al, 2019 ), learning and motivation ( Berridge and Robinson, 1998 ; Waelti et al, 2001 ; Graybiel, 2008 ) as well as in the involuntary attention orienting toward reward-related cues ( Anderson et al, 2016 ). For example, Cameron et al (2018) orally administered tolcapone capsules (Catechyl-O-Methyltransferase (COMT) inhibitor) and bromocriptine capsules (D2 agonist) to human participants performing a visual attention task, that required switching between pro- and anti-saccade responses.…”

Biosensors and sensors for dopamine detection

“…A high dopamine level indicates cardiotoxicity leading to rapid heart rates, hypertension, heart failure, and drug addiction 6 . However, a low dopamine level may cause stress, Parkinson's disease, 7 schizophrenia, 8 Alzheimer's disease, 9 and depression 10 . It is obvious that dopamine measurements are required for understanding its biological functions and related biological processes and mechanisms.…”

The prediction-error hypothesis of schizophrenia: new data point to circuit-specific changes in dopamine activity

“…Studies using functional magnetic resonance imaging (fMRI) during reinforcement learning have corroborated this physiological evidence in some respects. For example, there is some evidence for hypo-frontality during learning in patients with schizophrenia [11,82,99,[109][110][111], though this does not appear to be the case for all frontal regions; while activity in some frontal regions is decreased, other show an increase in activity [112]. Further, fMRI data reveals that ventral striatal activity during reinforcement-learning tasks does not suggest an increase in dopamine function per se [82,113].…”