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Dopaminergic treatment may impair the ability to suppress impulsive behaviours in patients with Parkinson's disease, triggering impulse control disorders. It is unclear how dopaminergic medication affects the neural networks that contribute to withholding inappropriate actions. To address this question, we mapped task-related brain activity with whole-brain functional magnetic resonance imaging at 3 Tesla in 26 patients with Parkinson's disease. Patients performed a sequential gambling task while being ON and OFF their regular dopaminergic treatment. During a gambling round, patients repeatedly decided between the option to continue with gambling and accumulate more monetary reward under increasing risk or the option to bank the current balance and start a new round. 13 patients had an impulse control disorder (ICD + group). These patients did not differ in risk-taking attitude during sequential gambling from 13 patients without impulse control disorder (ICD - group), but they displayed differences in gambling-related activity in cortico-subcortical brain areas supporting inhibitory control. First, the ICD + group showed reduced "continue-to-gamble" activity in right inferior frontal gyrus and subthalamic nucleus. Second, the individual risk-attitude scaled positively with "continue-to-gamble" activity in right subthalamic nucleus and striatum in the ICD - group only. Third, ICD + patients differed in their functional neural responses to dopaminergic treatment from ICD - patients: dopaminergic therapy reduced functional connectivity between inferior frontal gyrus and subthalamic nucleus during "continue-to-gamble" decisions and attenuated striatal responses towards accumulating reward and risk. Together, the medication-independent (trait) and medication-related (state) differences in neural activity may set a permissive stage for the emergence of impulse control disorders during dopamine replacement therapy in Parkinson's disease.
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