Neuronal basis of impaired motivation and inhibition of actions in patients with Parkinson's disease and behavioural addictions

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Pathological gambling and hypersexuality are increasingly recognized as non-substance (behavioural) addictions. For the development of substance related addictions, there is an influential neurobiological model which postulates that abnormally increased dopaminergic reward signalling drives dysfunction of neuronal systems for appetitive motivation / salience attribution and inhibitory response control. It is unclear, whether this model may also apply to the development of behavioural addictions. Relatively rapid development of behavioural addictions is a frequent (approx. 14%) adverse effect of dopaminergic therapy in patients with Parkinson’s disease (PD). The aim of the proposed research scheme is to identify dysfunctional neuronal networks, which are associated with the development of pathological gambling or hypersexuality in PD patients. Two hypotheses will be tested. According to the first hypothesis, in PD patients with medication-induced behavioural addictions (e.g. hypersexuality), dopamine agonists lead to a hyperactive bottom-up system of appetitive motivation along with a hypoactivity of top-down systems of inhibitory control. In an fMRI experiment, the effect of dopamine agonists on brain activation due to addiction-related stimuli (e.g. images of sexual content) following an inhibitory priming (e.g. images of contagious skin diseases) or neutral priming (e.g. images of healthy skin) will be investigated. It is hypothesized, that in PD patients with medication-induced behavioural addictions, dopamine agonists are increasing activation of the reward system due to addiction-related stimuli, while additionally decreasing the inhibitory priming effect on stimulus-related activation of the reward system. Behavioural therapy of behavioural addictions is sometimes based on positive reinforcement of the omission of addictive behaviour. However, it may well be that dopamine agonists block the very neurobiological mechanism that is responsible for this important factor of behavioural adaptation. This is the second hypothesis that will be tested. In healthy individuals, activity of the reward system briefly decreases when it is anticipated that the omission of an action is rewarded. It will be experimentally tested with fMRI, if dopamine agonists counteract this brief deactivation of the reward system.Results of the proposed studies could drive innovative strategies in therapy or secondary prevention of behavioural addictions by targeting modulation of identified dysfunctional networks.