The role of orbitofrontal noradrenaline in cognitive flexibility

Our survival is dependent on the fundamental ability to flexibly adapt our behaviour according to changes in the environment. In a range of psychiatric disorders, this ability is impaired and manifests as compulsivity, which causes substantial disability, but cannot at present be adequately treated. Therefore, it is necessary to investigate the brain systems underlying compulsive behaviour to develop better treatments. The brain systems involved in compulsivity are unknown, but based on own work on rats, I suggest that it may be the result of a functional imbalance between specific prefrontal cortex areas possibly regulated by noradrenaline. To investigate if this is also the case in humans, I will bridge results from animal models (allowing for direct mechanistic interventions) and functional imaging in human subjects to determine the role of specific prefrontal cortex regions and noradrenaline in compulsive behaviour. This work will provide an important foundation for the future development of personalised therapies in patients with compulsive behaviour.

Mentors:

Basic mentor: Professor Ulrik Gether, Department of Neuroscience, University of Copenhagen

Clinical mentor: Clinical Professor Hartwig Roman Siebner, Department of Neurology, Hvidovre Hospital