Ventral striatal network connectivity reflects reward learning and behavior in patients withParkinson's disease

Abstract

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward-driven behaviors, which can result in life-altering morbidity. The mesocorticolimbic dopamine network guides reward-motivated behavior; however, its role in this treatment-related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward-learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD-fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex-matched PD patients with (n 5 19) or without (n 5 18) ICB. An incentive-based task was administered to a subset of patients (n 5 20) to quantify positively or negatively reinforced learning. Whole-brain voxelwise analyses and region-of-interest-based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P 5 0.013), orbitofrontal cortex (P 5 0.034), insula (P 5 0.044), putamen (P 5 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala-to-midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum-to-subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment-avoidance learning. These data indicate that PD-ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward-based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509-521, 2018.

Abnormalities of striatal morphology in gambling disorder and at-risk gambling

“…The striatum encodes reward through dopaminergic signaling, 8 and aberrant functional connectivity between such structures has been found in impulse control problems in Parkinson's disease, perhaps arising from prodopaminergic therapy. 16 The current data not only enhance existing neurobiological models of gambling disorder 13 but also extend beyond these models by suggesting that pallidum abnormalities, in particular, may be a vulnerability marker associated more broadly Correlation between the mean curvature (vertex value) of the right pallidum in a cluster for group difference and impulsivity on the Eysenck Impulsivity Questionnaire (EIQ). The correlation was significant with all subjects pooled and in the combined GD þ AR group (r = 0.45, P < 0.001), but not in the controls (r = 0.03, P > 0.3).…”

“…15 In functional imaging, such impulsive symptoms in Parkinson's disease were associated with heightened connectivity from the ventral striatum to the putamen and pallidum. 16 Though striatal brain regions are demonstrably involved in decision-making 8 and functional imaging data have identified altered responses to reward in such regions in gambling disorder, 13 direct quantification of structural changes in these regions in patients is lacking. One voxel-based morphology (VBM) investigation found that gambling disorder was associated with increased gray matter volumes in the ventral striatum.…”

Self‐reported rates of impulsivity in Parkinson’s Disease

“…This approach simultaneously performs regularization and variable selection, which allows for a higher prediction accuracy and specificity of interpretation. The variable with ≥ 80% chosen is deemed significant in relation to either PD/HC or ICB+/– status 50,51 . LASSO regression was performed using the glmnet package and bootstrapped in R statistical software 52…”

MRI of Motor and Nonmotor Therapy‐Induced Complications in Parkinson's Disease

“…Gambling‐related visual cues, such as scratch cards, determined increased activation in bilateral superior frontal gyrus, precuneus, right inferior parietal lobule, left ventral striatum, right mesial prefrontal cortex, and bilateral anterior cingulate cortex . The same brain structures were involved during the execution of an incentive‐based task (goal of this task was to learn how to maximize earnings by gaining rewards and avoiding losses) and during risk taking while performing the Balloon Analogue Risk Task . These data suggest a common neural pathway underlying different facets of the reward system.…”

“…The authors suggested the presence of an altered function of basal ganglia and their connections with the cortical areas involved in the limbic loop during decision‐making in PD patients . Similar findings showed the presence of striatofrontal and mesocorticolimbic disconnection involving the anterior putamen, inferior temporal and anterior cingulate cortices, and insular area, modulated by dopaminergic therapy, in PD patients with ICBs compared with those without, resulting in an imbalance between reward integration and control mechanisms . On the other hand, another task‐related fMRI study using a go–no go and delay discounting tasks showed not only decreased activation in the dorsolateral prefrontal cortex and bilateral striatum, but also diverse functional connectivity abnormalities of both caudate nuclei as decreased connectivity to the superior parietal cortex and increased connectivity to the insular area, indicating that orbitofrontostriatal and mesolimbic network changes are not the exclusive mechanisms underlying ICBs in PD .…”