Dopaminergic mechanisms of reinforcement learning and working memory deficits in schizophrenia patients

• Applicant: Professor Dr. Florian Schlagenhauf, since 10/2018
• Subject Area: Biological Psychiatry
• Term: from 2012 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204208448

Dysfunction of dopaminergic neurotransmission with a hyperdopaminergic state in the basal ganglia is a corner stone in current pathophysiological theories of schizophrenia. Molecular brain imaging studies in schizophrenia patients have confirmed increased striatal dopamine synthesis capacity. Alterations in the mesolimbic dopaminergic system can alter reinforcement learning functions such as prediction error signalling. Altered prediction error signalling and value representation have been proposed to contribute to central aspects of the disorder including aberrant salience attribution as well as motivational impairments. Alterations in the mesocortical dopaminergic system have been related to cognitive deficits such as working memory impairments caused by dysfunctions in fronto-parietal networks. For the therapy of schizophrenia antipsychotic medication is of great importance. Antidopaminergic antipsychotic medication is known to reduce psychotic symptoms and acts mainly via blocking of dopamine D2 receptors. However, little is known about how antipsychotic treatment effects presynaptic dopamine synthesis capacity and how treatment changes in presynaptic dopamine synthesis relate to changes in reinforcement learning, salience attribution and working memory function in schizophrenia patients. Therefore, we will investigate unmedicated schizophrenia patients before and after antipsychotic treatment in a longitudinal, multimodal study combining functional magnetic resonance imaging (fMRI) with positron emission tomography (PET) using the radioligand [18F]fluorodopa (FDOPA) to measure dopamine synthesis capacity. Detailed computational modeling will be used to describe alterations of reinforcement learning and working memory on the behavioral and neuronal level. We will compare pre- to post-treatment measures and test associations between the (hypothetical) change in dopamine synthesis capacity and changes in salience attribution, reward-dependent learning and working memory function in schizophrenia patients. This will enhance our understanding of the mechanisms of antipsychotic treatment on the dopaminergic dysfunction and core aberrant cognitive processes in schizophrenia patients.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Ralph Buchert, Ph.D., until 9/2018