A systematic, cross-sectional, and patient-informed approach to examining impulsivity and inhibitory control in Parkinson's

Abstract

Parkinson's is primarily a movement disorder but can lead to many non-motor symptoms either directly, due to the loss of dopamine cells through degeneration in the substantia nigra, or indirectly due to the medication which aims to alleviate the motor symptoms of Parkinson's. Impulse control behaviours (ICBs) can include gambling, hypersexuality, compulsive shopping, binge eating, hobbyism, and punding, and are thought to occur primarily as a result of dopamine agonist medications. However, it is unclear how impulsivity (which covers a range of tasks and processes) and inhibitory control (withholding from an action) are affected in Parkinson's without ICBs, to what extent this is affected in ICBs, and what other aspects related to Parkinson's may affect it. Firstly, I used a task of response inhibition (Stop Signal task) and response inhibition under conflict (Simon task) in a group of people with Parkinson's (PwPs) and a group of healthy controls (HCs), as the literature contained mixed results as to whether PwP showed reduced response inhibition or not. Response force placed upon the response keys was recorded as an additional sensitive measure of inhibitory cognitive control, and I found no significant group differences on either task for both traditional button-press measures and for response force. To more thoroughly explore group differences in the literature so far, I conducted a systematic review of 246 studies examining impulsivity and inhibitory control, across a broad range of measures, in PwP, PwP with additional ICBs (PwP+ICBs), and HCs. The review uncovered largely mixed results with unclear conclusions as to whether PwP showed any impairment among different measures of impulsivity compared to HCs, and additionally whether PwP+ICBs showed any impairment compared to PwP. Exceptions where a clearer picture emerged included an impairment in PwP for response conflict and decision making under ambiguous risk, and both higher trait impulsivity and reduced ability to delay gratification for PwP+ICBs compared to PwP. Next, I conducted a cross-sectional study using many of the tasks identified through the review with three groups of participants: PwP+ICBs, PwP without ICBs, and HCs. The study revealed largely null results; PwP+ICBs showed no significantly greater impulsivity than PwP on these behavioural measures, and PwP showed no greater impulsivity than HCs except on a Go/No-Go task where PwP showed significantly reduced action restraint compared to both PwP+ICBs and HCs. Taken together, the evidence from these three studies suggests that there is no clear impairment for PwP and/or PwP+ICBs in terms of reduced inhibitory control or increased impulsivity as measured with behavioural and cognitive tasks. This may be due to the heterogeneity of Parkinson's, the types of ICBs that PwP experience, and issues with methodological quality. Finally, in parallel with the preceding chapters, I developed a proof-of-concept behavioural intervention aimed at reducing the impact of ICBs in PwP. The protocol was developed with considerable input from patient and public involvement volunteers and demonstrates the importance of taking a patient-centred approach. Overall, this approach confirmed that research into ICBs and how impulsivity in general affects PwP is an important avenue for further inquiry for PwP, and better methodological rigour will greatly help to meet patient needs.

Date of Award	22 Nov 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Ellen Poliakoff (Main Supervisor), Iracema Leroi (Co Supervisor) & Jennifer Mcbride (Co Supervisor)