The role of dopamine in sensory inference and delusions: a systems medicine approach to psychosis

Psychotic disorders such as schizophrenia represent an important class of mental diseases because they are chronic conditions and difficult to treat . The neural mechanisms are not yet understood. In particular, we lack data that could link dysregulated processing at the level of single neurons or networks of neurons to the symptoms of psychosis on a behavioural level. In a systems medicine approach, this research collaboration will bring together medical doctors, neurophysiologists and theoreticians to investigate the neurobiological basis of the formation of delusions, the core symptom of psychosis. Delusional experiences are hypothesized to arise from dysfunction in the brain’s inferencing mechanisms, whereby new sensory events in the environment are not properly integrated with learned predictions. To investigate this hypothesis, the projects of the collaboration will combine a variety of different methods including behavioral studies, genetic analyses and neuroimaging experiments in healthy subjects and schizophrenia patients as well as electrophysiological measurements of single neurons in rodents and deep-brain stimulated neurosurgical patients. The collaboration will offer an unparalleled description of the neuronal mechanisms by which dopamine controls sensory inference and thus may govern how we perceive and interpret our environment in health and psychosis. The long-term objective of the consortium is to foster accurate diagnosis and effective therapies by means of a better understanding of the mechanisms of psychotic disorders.

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