Oxytocin’s Modulation of the Salience and Reward System in Humans (OXSARESY)

• Applicant: Dr. Katja Brodmann
• Subject Area: Human Cognitive and Systems Neuroscience ; General, Cognitive and Mathematical Psychology ; Cognitive, Systems and Behavioural Neurobiology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405877245

Oxytocin (OT) is a key player in human social cognition, and is currently investigated as a potential treatment for social deficits in psychiatric disorders. A major theory claims that OT acts by assigning salience to social stimuli, via interaction with the dopamine (DA) system – itself robustly implicated in general-purpose salience and reinforcement learning. However, neither the theory nor OT’s specificity to social contexts has ever been clearly demonstrated in humans. As such, it is urgent we shed light on the neurobiological mechanisms of OT in humans. OXSARESY aims to address three questions: 1) how selective is OT’s action to the social dimensions of salience processing and reinforcement learning? 2) How, if so, does it interact with the DA system in the healthy population? And, for further converging evidence of the latter, 3) how is such interaction modulated by genetically variations in OT and DA regulating genes? My goal is to demonstrate, for the first time, the commonly theorized OT-DA interplay in the human brain for social salience and reinforcement learning. For this, I will innovatively combine well-established approaches from different fields of neuroscience to efficiently advance our characterization of OT’s central role in human social cognition.My highly interdisciplinary approach allows for the investigation of two cognitive processes: 1) salience attribution (by a salience attribution task) and, 2) reinforcement learning (by a probabilistic reinforcement learning task), each including social and non-social dimensions to be contrasted. I will measure the behavioural and neural activity consequences of: 1) a double-blind placebo-controlled acute pharmacological cross-administration of intranasal OT and of L-Dopa, and of, 2) natural genetically variability in OT and DA receptors likely to affect drug-response. Neural activity will be measured by means of electroencephalography and functional magnetic resonance imaging, each in combination with eye-tracking and heart rate. Converging a pharmacological and a genetic stream of evidence, and based on current literature and my own previous PhD findings, I expect that OT facilitates both social salience processing and reinforcement learning, via interaction with the DA system. OXSARESY’s rich and efficient data collection and analysis is unprecedented, as most OT research has been mono-disciplinary, disregarding the influence of other neuromodulators and genetic background. Building steeply on my PhD skills and findings, it will allow me to bring back to Germany a rare and increasingly demanded interdisciplinary know-how. The results of my project will contribute highly to the current knowledge regarding neuropeptide x neurotransmitter interaction in the human brain. Moreover, OXSARESY will inform personalized pharmacogenetic OT and DA therapies and etiological and therapeutic models of psychiatric illness afflicted by social symptoms such as autism and schizophrenia.

• DFG Programme: Research Fellowships
• International Connection: Portugal, United Kingdom
• Host: Privatdozentin Dr. Diana Maria Pinto Prata