Objective: Our aim was to examine the neural correlates of stimulus-response (SR) learning in patients with Parkinson’s disease (PD) on and off dopaminergic (DA) therapy using functional magnetic resonance imaging (fMRI).

Background: Dorsal striatum (DS) function is impaired whereas ventral striatum (VS) processes are relatively spared in PD. These brain regions are also differentially affected by DA medication in PD. DS function is remediated by DA therapy, whereas VS processes are impaired by DA therapy presumably due to dopamine overdose. Previously, we examined the neural correlates of SR learning in healthy individuals using fMRI and found that DS mediates response selection whereas VS mediates learning. In a separate experiment, we showed that dopaminergic therapy impaired SR learning in PD patients.

Methods: 17 PD and 15 age- and education-matched healthy controls completed an SR learning task during which they learned to associate abstract images with one of three button-press responses via feedback while brain activation was measured using fMRI. During Session 1 (i.e. learning phase), feedback was provided after each response, facilitating learning through trial and error. Participants performed Session 2 after distraction, where they provided the previously-learned button-press responses in the absence of feedback. Patients with PD completed the task twice on consecutive days, once ON and once OFF dopaminergic medication. Healthy controls also completed the task twice but did not take any dopaminergic therapy during either testing day.

Results: Data from the healthy elderly controls replicated our previous findings with healthy young controls. Preferential DS activation correlated with SR decision-making events, and VS was recruited when learning through feedback occurred. Suggesting that VS mediates learning whereas DS underlies decision processes based on previous learning. Learning slope was steeper, suggesting more efficient SR learning for PD patients off relative to on dopaminergic therapy, though greater DS activation occurred at the time of decision making for PD patients on compared to off dopaminergic therapy. VS activation, at the time of feedback, was depressed in PD patients compared to controls.

Conclusions: These results suggest that overdose of VTA-innervated brain regions, such as VS, is a mechanism for cognitive dysfunction in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-dopaminergic-therapy-on-stimulus-response-learning-and-decision-making-in-parkinsons-disease-using-fmri/