Mechanisms of Impulse Control: Potential Implications for Parkinson’s Disease

Abstract

Controlling inappropriate urges or impulses is essential to function in society. However impulse control is impaired in numerous psychiatric and neurological conditions. This thesis investigated the behavioural, neurophysiological and geneticmechanisms of motor impulse control utilizing a response inhibition task, and considered how these mechanisms may be influenced by dopamine dysregulation. Electromyography, transcranial magnetic stimulation (TMS), and computational modelling were used to further our understanding of how we achieve behaviourally selective cancellation of a bimanual motor act, and why the continued response is markedly delayed. Bimanualmovement components were integrated into a single response in anticipation of execution. Interestingly, both components were affected simultaneously by the requirement to cancel only one component of the response. Single-pulse TMS was used to demonstrate suppression of corticomotor excitability (CME) toward the continued component, indicative of a nonselective cancellation process. Pairedpulse TMS revealed that short-latency intracortical inhibitory circuits within the primary motor cortex were unlikely to be the neural mechanism underlying nonselective suppression of CME. A computational model was developed to explain the temporal modulation of CME in the continued component which reflected anticipation, suppression and subsequent initiation of movement. The model dictated that a secondary activation process was needed following nonselective suppression in order to complete the task goal. The second activation process can be conceptualized as selective initiation of a newly programmed unimanual response, subsequent to the cancellation of the default bimanual response. The reinitiation of muscle activity was sensitive to the strength of coupling between response components, indicating that uncoupling of components was necessary for selective initiation. The first four experiments collectively demonstrate that we achieve behaviourally selective impulse control from neurally selective reinitiation of movement, as opposed to selective inhibition. The final experiment provided the first evidence that a polygenic dopamine genetic risk score can be used to predict a person’s baseline level of performance on a response inhibition task, and the effect that dopamine agonist medication will have on their impulse control. It remains to be determined whether measures of motor impulse control have clinical utility to identify people at risk of developing impulse control disorders on dopaminergic medication.