Objective: To study the neural correlates of impulse control in Parkinson’s disease (PD) patients before and after the start of dopamine replacement therapy (follow up period: 3.1±1.0 yrs). We hypothesized that the pre-existing failure in response inhibition at baseline would worsen after treatment, both on the behavioral and neural level.

Background: Response inhibition is an experimental operationalization of impulse control referring to the ability to inhibit inappropriate responses. The study of response inhibition in PD opens a window onto the pathophysiology of impulse control disorders (ICD) that develop in as many as 15% of all PD patients on dopaminergic medication.

Methods: Twenty-one PD patients and 37 matched healthy controls performed a stop-signal during MRI scanning. Brain activity and behavioral performance were recorded. PD patients were medication-naïve at baseline. Fourteen PD patients and 16 healthy controls were re-assessed after 3.1±1.0 years. Patients were scanned in an optimal ON state.

Results: Results on brain activity differences at baseline have been published previously (Vriend et al. 2015). Briefly, brain activity in the left and right inferior frontal gyrus was decreased in PD patients versus healthy controls but behavioral performance was comparable. We now show that at baseline in PD (compared with controls) the right insula, another major node in the inhibition-related network, and right inferior frontal gyrus also show decreased functional coupling with other task-relevant brain areas. At follow-up, behavioral performance showed an effect of group, due to increased performance over time in healthy controls but not PD patients. Conversely, and contrary to expectations, PD patients showed normalized functional activity at follow-up in the previously hypoactivated left inferior frontal gyrus. Two PD patients had developed ICD symptoms after commencing dopamine replacement therapy. There were no between-group differences in brain activation at follow-up and no correlations with clinical measures.

Conclusions: Similar to brain activity, functional coupling is reduced in medication-naïve PD patients compared with healthy controls, suggesting a more widespread hypoactivation of the inhibition network, with preservation of behavior. Over time these functional deficits normalize, presumably due to dopaminergic medication.

Vriend et al. (2015) Neurobiol Aging 36(1): 470-5.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-deficits-during-response-inhibition-improve-after-dopaminergic-medication-for-parkinson/