The structural connectivity of discrete networks underlies impulsivity and gambling in Parkinson's disease

Abstract

Impulsivity in Parkinson's disease may be mediated by faulty evaluation of rewards or the failure to inhibit inappropriate choices. Despite prior work suggesting that distinct neural networks underlie these cognitive operations, there has been little study of these networks in Parkinson's disease, and their relationship to inter-individual differences in impulsivity. High-resolution diffusion MRI data were acquired from 57 individuals with Parkinson's disease (19 females, mean age 62, mean Hoehn and Yahr stage 2.6) prior to surgery for deep brain stimulation. Reward evaluation and response inhibition networks were reconstructed with seed-based probabilistic tractography. Impulsivity was evaluated using two approaches: (i) neuropsychiatric instruments were used to assess latent constructs of impulsivity, including trait impulsiveness and compulsivity, disinhibition, and also impatience; and (ii) participants gambled in an ecologically-valid virtual casino to obtain a behavioural read-out of explorative, risk-taking, impulsive behaviour. Multivariate analyses revealed that different components of impulsivity were associated with distinct variations in structural connectivity, implicating both reward evaluation and response inhibition networks. Larger bet sizes in the virtual casino were associated with greater connectivity of the reward evaluation network, particularly bilateral fibre tracts between the ventral striatum and ventromedial prefrontal cortex. In contrast, weaker connectivity of the response inhibition network was associated with increased exploration of alternative slot machines in the virtual casino, with right-hemispheric tracts between the subthalamic nucleus and the pre-supplementary motor area contributing most strongly. Further, reduced connectivity of the reward evaluation network was associated with more 'double or nothing' gambles, weighted by connections between the subthalamic nucleus and ventromedial prefrontal cortex. Notably, the variance explained by structural connectivity was higher for behavioural indices of impulsivity, derived from clinician-administered tasks and the gambling paradigm, as compared to questionnaire data. Lastly, a clinically-meaningful distinction could be made amongst participants with a history of impulse control behaviours based on the interaction of their network connectivity with medication dosage and gambling behaviour. In summary, we report structural brain-behaviour covariation in Parkinson's disease with distinct reward evaluation and response inhibition networks that underlie dissociable aspects of impulsivity (cf. choosing and stopping). More broadly, our findings demonstrate the potential of using naturalistic paradigms and neuroimaging techniques in clinical settings to assist in the identification of those susceptible to harmful behaviours.

Keywords: Parkinson’s disease; gambling; impulsivity; subthalamic nucleus; tractography.