Neural circuitry underlying anti-saccade task performance investigated with fMRI and single-neuron recordings

The anti-saccade task, in which a subject is instructed to look away from a flashed visual stimulus, requires both suppression of a reflexive response and generation of a voluntary behaviour. This task is ideally suited to study the flexible control of behaviour and has been used successfully in both humans and monkeys. Previous anti-saccade research has left a number of critical questions unanswered. The experiments described in chapters two and three investigate the cortical networks involved in the performance of the anti-saccade task utilizing fMRI in human subjects. Our results suggest the preparation of an anti-saccade activates a large frontal and parietal network, and activation of frontal cortical areas before stimulus presentation is associated with subjects' performance in the anti-saccade task. In Chapter Four we utilize fMRI in monkeys to explore the validity of the monkey as a model of human frontal lobe function. Previous human fMRI findings conflict with monkey single-neuron recordings regarding the role of the frontal eye fields (FEF) in the anti-saccades. Our results indicate monkeys show a similar pattern of fMRI activation to human subjects during performance of anti-saccades, thus validating the monkey model, and emphasizing the potential for differences between single-neuron recordings and fMRI. In Chapter Five we record from single neurons in the caudate nucleus (CN) of two monkeys while they perform pro- and anti-saccade trials. The basal ganglia (BG) play a central role in movement, and it has been demonstrated that the discharge rate of neurons in these structures are modulated by the behavioural context of a given task. This experiment investigates the role of the CN, a major input structure of the BG in flexible behaviour. We identified two populations of neurons, those that preferred contralateral saccades (CSN) and those that preferred ipsilateral saccades. CSNs increased their firing rates for pro-saccades, but not for anti-saccades, and ISNs increased their firing rates for anti-saccades, but not for pro-saccades. Together these experiments contribute novel findings to the body of knowledge describing the neural circuitry underlying anti-saccade performance, and in addition highlight the utility of using multiple techniques in such investigations.;Key words. Single-neuron electrophysiology, fMRI, event-related, oculomotor control, executive control, response inhibition, anti-saccade, saccade, neuroimaging, monkey, frontal eye field, caudate nucleus, basal ganglia.