Clinical and functional neuroimaging studies on impulse control disorders and related behaviours in Parkinson’s disease

Abstract

In this thesis, I use clinical assessments and neuroimaging modalities to investigate the pathophysiology underlying impulse control disorders (ICDs) and related addictive behaviours in Parkinson’s disease (PD).

Using PET with 11C-raclopride, I found that PD patients with a range of ICDs showed an increase in dopamine release in their ventral striatum on exposure to reward-related visual cues compared to PD controls. Further, the amount of increased dopamine release in patients with single ICD was similar to those with comorbid ICDs, suggesting the sensitisation of ventral striatum of PD ICD patients, regardless of their disease load. I also found that PD ICD patients with punding, characterised by stereotypical behaviours with similarities to obsessive compulsive disorders, had lower baseline dopamine D2 receptor binding in the dorsal, but not ventral, striatum at rest compared to controls.

In the fMRI imaging study with a block design paradigm, PD patients with compulsive sexual behaviours (CSB) showed increase in sexual desire on exposure to sexual visual cues compared to controls with a corresponding change in blood oxygen level-dependent signal in brain regions corresponding to emotional, cognitive, autonomic, visual and motivational processes. When OFF medication, CSB patients showed decreases in activation during the presentation of sexual cues relative to rest, which was not seen when ON medication. This provides evidence that passive visual cues can act as motivational cues for vulnerable individuals.

In the final data chapter, I show that the Internet use habits of PD ICD patients had greater interference (increased time spent, obsessive thoughts) with life functioning compared to PD and healthy subjects, suggesting that PD ICD patients have an increased tendency towards excessive Internet use, which may coexist as an addictive behaviour.

These studies show that PD patients on dopaminergic medication have a propensity toward impulse control disorders and related behaviours via sensitisation of the dorsal and ventral striatum. There is also an increased tendency to excessive Internet use in PD ICD subjects. These findings contribute to our understanding of the mechanisms through which a subset of PD patients choose to pursue aberrant rewarding behaviours despite negative consequences, with direct implication for clinicians managing this patient group.