Adam, RJ; (2014) Dopamine and oculomotor impulsivity in health and disease. Doctoral thesis , UCL (University College London).

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Abstract

The role of subcortical pathology in altered cognition is increasingly recognised. However, measurement and monitoring of impairments in motivation and behaviour due to subcortical disease is challenging. Basal ganglia – cortico-thalamo-cortical loops and the neurotransmitter, dopamine, are recognised to be important in modulating both reward learning and oculomotor performance. This thesis considers the use of novel and adapted oculomotor (saccadic) tasks as a means of interrogating these dynamic circuits as measures of rewarded decision-making under risk and time pressure. I first describe a novel rewarded oculomotor task, the Traffic Light Task, which provokes two distributions of saccades – one anticipatory, and one reactive. The balance of these distributions, the number of errors and the reward obtained are used to index oculomotor decision-making. Demonstrated effects of healthy aging include a significant reduction in anticipatory responding and consequent reduction in reward. I then compare behavioural oculomotor task responses in healthy controls with established “self-report” measures of impulsivity, finding significant correlations. Next, I consider a patient with focal lesions of the basal ganglia causing profound apathy. I demonstrate reduced oculomotor anticipatory responding and reward sensitivity. I then show the positive effects of dopaminergic medications (levodopa and ropinirole) upon his oculomotor decision-making in tandem with a clinical improvement in his motivational state. To further qualify this dopaminergic effect, I then assess the effects of two dopaminergic drugs (levodopa and methylphenidate) upon healthy volunteers. Finally, I use oculomotor tasks to compare patients with Parkinson’s Disease, with and without impulse control disorders, with both healthy volunteers and pathological gamblers without neurological disease. The results of these experiments raise questions regarding the development of models of basal ganglia – cortico-thalamo-cortical loops and how best to understand them.

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