Rawji, Vishal; (2019) Impulsivity in Parkinson’s disease and Tourette syndrome, and human motor decision making. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Motor response inhibition pertains to the ability to inhibit motor actions. It is hypothesised that a breakdown in motor response inhibition might underlie impulsivity in Parkinson’s disease and tics in Tourette syndrome. This thesis outlines how motor response inhibition is modulated in these clinical disorders by first characterising them in healthy subjects. We use TMS to show that one set of inputs to the motor cortex are inhibited during motor preparation whilst the other inputs reflect uncertainty about potential stopping. In the next chapter, we challenged an assumption that movement preparation during proactive inhibition always preceded movement execution and found that movement preparation and execution are two independent processes. With this in mind, we investigated features of motor response inhibition and movement preparation and execution in patients with Tourette syndrome, finding that these were remarkably similar to healthy controls, suggesting that volitional features of movement and inhibition are normal in Tourette syndrome. However, we did find a specific impairment of automatic inhibition in Tourette syndrome, which correlated with motor tic severity. As dopamine agonists are implicated as triggers for impulsivity in Parkinson’s disease, we first investigated the influence of ropinirole on motor response inhibition in healthy control subjects, finding that motor response inhibition was globally impaired. This was accompanied by analyses suggesting that ropinirole impaired the ability to adjust the decision threshold when stopping might be required. However, investigation of motor inhibition in Parkinson’s disease patients on dopamine agonists showed unremarkable effects compared to patients without dopamine agonist use. Our data provide a novel insight into the basic mechanisms of voluntary movement and propose a new theory for tic generation in Tourette syndrome.

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