D-2-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D-2 receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded n-amphetamine (dAMPH) study. Participants completed [F-18]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BP ND ) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D-2 -like BPND in the amygdala and hippocampus (right cluster q(FDR-corr) = 0.026, left duster q(FDR-corr) = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = -48.26, p= 0.005) and hippocampus (coefficient = -104.94, p= 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected.