Accentuated Paralimbic and Reduced Mesolimbic D_2/3-Impulsivity Associations in Parkinson's Disease

Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D-2/3 autoreceptors in mesocorticolimbic circuits. While altered D-2/3 binding is noted in ICB+ PD patients, there is limited prior assessment of the trait impulsivity-D-2/3 relationship in PD, and no prior direct comparison with patterns in HCs. We examined 54 PD (36 M; 18 F) and 31 sex- and age-matched HC (21 M; 10 F) subjects using [F-18]fallypride, a high-affinity D-2/3 receptor ligand, to measure striatal and extrastriatal D-2/3 nondisplaceable binding potential (BPND). Subcortical and cortical assessment exclusively used ROI or exploratory-voxelwise methods, respectively. All completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. Subcortical ROI analyses indicated a negative relationship between trait impulsivity and D-2/3 BPND in the ventral striatum and amygdala of HCs but not in PD. By contrast, voxelwise methods demonstrated a positive trait impulsivity-D-2/3 BPND correlation in ventral frontal olfactocentric-paralimbic cortex of subjects with PD but not HCs. Subscale analysis also highlighted different aspects of impulsivity, with significant interactions between group and motor impulsivity in the ventral striatum, and attentional impulsivity in the amygdala and frontal paralimbic cortex. These results suggest that dopamine functioning in distinct regions of the mesocorticolimbic circuit influence aspects of impulsivity, with the relative importance of regional dopamine functions shifting in the neuropharmacological context of PD.