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. 2017 Nov;32(11):1574-1583.
doi: 10.1002/mds.27047. Epub 2017 Jun 19.

Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors

Daniel O Claassen  1 , Adam J Stark  1 , Charis A Spears  1 , Kalen J Petersen  1 , Nelleke C van Wouwe  1 , Robert M Kessler  2 , David H Zald  3   4 , Manus J Donahue  1   5   3
Affiliations

Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors

Daniel O Claassen et al. Mov Disord. 2017 Nov.

Abstract

Background: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation.

Objectives: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors.

Methods: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity.

Results: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions.

Conclusions: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; cerebral blood flow; dopamine; impulse control disorder; impulsive compulsive behaviors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cerebral blood flow (CBF) response to dopamine agonist (DAgonist). (A) Orthogonal representation of the 2 mm T1-weighted structural atlas, along with (B) quantitative CBF values (ml/100g/min) in the Off-DAgonist and (C) On-DAgonist states for ICB− (left) and ICB+ (right) patients. Limited CBF changes are observed in the ICB− group, yet increases in CBF in striatal (black arrow) and frontal (magenta arrow) regions are observed in the ICB+ patients.
Figure 2
Figure 2
Subcortical structural and cerebral blood flow (CBF) analysis. (A–C) Representative coronal and axial slices for a single subject show an example of the automated segmentation routine for three different structures, including (A) total gray matter, (B) caudate, and (C) ventral striatum. (D–F) Bar graphs of the mean CBF change in response to agonist in the three aforementioned regions for the ICB+ and ICB− patients, with the error bars representing the standard deviation of all subjects in each group, respectively. There was no significant difference in CBF change in (D) total gray matter or (E) caudate, but there was a significantly increased CBF change localized to the (F) ventral striatum in the ICB+ group compared to the ICB− group. In order to emphasize the specificity of significant CBF change to the ventral striatum, gray matter and caudate are displayed to illustrate the lack of response in global (gray matter) and dorsal striatal (caudate) regions.
Figure 3
Figure 3
Relationship between CBF response to agonist and QUIP-RS score on dopamine agonist (On-DAgonist) in all patients. Open circles indicate ICB− individuals, and closed circles indicate ICB+ individuals. The relationship is plotted for three structures, including (A) total gray matter, (B) caudate, and (C) ventral striatum. In a similar manner to Figure 2, gray matter and caudate were selected as representatives of global and dorsal striatal regions respectively, to better visualize specific localization of a CBF/QUIP-RS relationship to the ventral striatum. These data demonstrate that in the ventral striatum, the CBF response is highest in subjects with greater QUIP-RS scores, indicative of increased levels of impulsivity. These data are consistent with CBF changes in response to DAgonist in ventral striatum correlating with behavioral phenotype. This relationship is not evident in total gray matter or caudate, implying that it is localized to the ventral striatum and not a global or generalized striatal effect.
Figure 4
Figure 4
Results of the voxel-wise analysis of cerebral blood flow (CBF) response to dopamine agonist (DAgonist). (A) Orthogonal slices from the 2 mm T1-weighted atlas, along with regions that show positive and negative changes in CBF with DAgonist for ICB+ patients relative to the ICB− patients. Positive changes after DAgonist administration are shown by the red-yellow scale, with yellow signifying a greater z-stat, and negative changes after DAgonist are shown by the dark blue-light blue scale, with light blue signifying the greater z-stat. All gray matter regions were included in analysis, with the exception of bi-occipital lobes and cerebellum where slice coverage was incomplete in some subjects. ICB− patients exhibit limited changes in CBF in response to agonist, whereas ICB patients showed more widespread patterns of changes throughout the striatum and frontal lobe, including (A) the ventral striatum, (B) the insular cortex, (C) the midbrain, and (D) the ventromedial prefrontal cortex. Supplementary Table 1 provides the spatial coordinates of all 14 clusters meeting activation criteria.
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