A failure to communicate: Preliminary evidence for cortico‐striatal dysconnection with pathological gambling in Parkinson's disease

Pathological gambling (PG) and other impulse control disorders (ICDs), including compulsive buying, sexual behavior, and eating, occur relatively commonly in Parkinson’s disease (PD). They may lead to significant impairments in functioning, quality of life, interpersonal relationships, financial status, and physical health. ICDs in PD usually occur in the context of dopamine agonist (DA) treatment, other PD medication use (e.g., levodopa or amantadine), or even in the context of deep brain stimulation (DBS). Other possible risk factors include a personal or familial history of alcoholism or gambling, impulsive or novelty-seeking personality traits, younger age, men sex, early PD onset, being unmarried, and current cigarette smoking. The neural substrate of ICDs in PD, and its potential to inform our understanding of ‘‘behavioral addictions’’ and substance abuse disorders in the general population, is of great scientific interest, in part because of striatal dopamine depletion that occurs secondary to PD-related neurodegeneration, the use of dopamine replacement therapies as a staple of PD management, the relative sparing of the ventral versus dorsal striatum early in the course of PD, and the common occurrence of ICD-related cognitive and executive deficits in PD patients. Against this backdrop, Cilia et al. in this issue of Movement Disorders present results from a single photon emission tomography (SPECT) imaging study that examined regions and patterns of resting brain perfusion in a cohort of PD patients with PG. Although previous neuroimaging studies have suggested alterations within the reward system in PD patients with ICDs, this is the first study to specifically examine changes in a purported neural network subserving these behaviors. Thirty PD patients (15 with active PG and 15 non-PG patients matched on demographic and clinical characteristics) and 15 healthy control subjects underwent SPECT scanning with 99mTc-ethyl cysteinate dimer bicisate to measure resting regional cerebral blood flow (CBF) using Statistical Parametric Mapping (SPM5). The severity of gambling was assessed with the South Oaks Gambling Scale. First, covariance analysis was applied to identify individual brain volumes whose activity was associated with gambling severity. Second, these volumes of interest were then used as ‘‘seeds’’ to identify functionally interconnected neural interactions using voxel-wise covariance analysis. Finally, a path analysis was performed within the framework of structural equation modeling. The path analysis is a multivariate regression technique that models the covariance structure of a set of variables based on a subset of possible paths linking these variables, and in contrast to basic functional connectivity analyses allows inferences to be made regarding the direction of influence. The primary and most interesting findings of the study were: (1) Decreased prefrontal cortex, cingulate, insula, parahippocampal gyrus, and striatal resting perfusion with increasing gambling severity in PG patients. These are regions previously identified as important to reward and risk processing, error detection, learning and decision making, and impulse control, all of which are relevant to ICD expression in PD and (2) In PD patients with PG, a lack of ‘‘connectivity’’ between certain brain regions in the functional network identified, specifically a lack of correlation between activity in the anterior cingulate cortex (ACC) and the striatum. In the Discussion, the authors note that these results are consistent with previous research demonstrating an ACC-striatum disconnection in patients with impulsive behaviors and relevant learning impairments. The authors hypothesize that ACC-striatal disconnection may underlie a specific impairment in the ability to shift behaviors after negative outcomes, possibly explaining why PD patients with PG perseverate on risktaking behaviors despite self-destructive consequences. The study is well conducted and the results are intriguing, but there are several limitations worth noting to inform future research in this area. The data presented here are actually secondary analyses, the initial SPECT analyses for 11 of the 15 PG patients already having been published. In the initial manuscript, increased brain perfusion was noted in PD patients with PG in a right hemisphere network that overlaps ------------------------------------------------------------