Our behaviour is guided by the ability to predict future events. The predictive saccade paradigm has been shown to be a valuable tool that uses eye movements to measure the control of predictive behaviour. In this task, subjects follow a visual target that alternates or “steps” between two fixed locations at either predictable or unpredictable inter-stimulus time intervals (ISIs). Response times can be measured by subtracting the time of saccade initiation from the time of target appearance. When the ISI is predictable, saccadic reaction times (SRTs) become predictive (SRT <100ms) within 3-4 target steps, but when the ISI is unpredictable, the SRTs remain reactive to target appearance (SRT >100ms). The goal of our study was to investigate neural mechanisms controlling prediction by contrasting areas in the brain that were more active for predictive (PRED) versus reactive (REACT) saccades in young healthy adults using functional magnetic resonance imaging (fMRI). fMRI analysis revealed two distinct neural networks more recruited for REACT and PRED tasks. We observed greater activation for the REACT task compared to the PRED task in oculomotor network areas including the frontal, supplementary, parietal eye fields, dorsolateral prefrontal cortex, thalamus, and putamen. These structures are all involved with the control of saccades. We also observed greater activation for the PRED task compared to the REACT task in default network areas, including the medial prefrontal cortex, posterior cingulate cortex, inferior parietal lobule, and hippocampus. These structures are known to be involved with passive thinking when subjects are not focused on their external environments. We also observed greater activation for the PRED task in the cerebellum (crus I), which may serve as the internal clock that drives the regular rhythmic behaviour observed for predictive saccades. In summary, our findings suggest brain activation in the PRED task reflects automated and motor-timed responses, while that for the REACT task reflects externally-driven responses. Therefore, the predictive saccade task is an excellent tool for measuring prediction involving fast internally-guided responses. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2011-08-12 10:21:37.744

Patients with Amyotrophic lateral sclerosis (ALS) often experience cognitive impairment that accompanies degeneration of the motor system. A valuable tool for assessing cognitive control over behaviour is the antisaccade task which requires: 1) inhibition of the automatic response to look towards an eccentric visual stimulus (prosaccade) to instead 2) redirect gaze in the opposite direction of the stimulus (antisaccade). Psychometric tests were used to quantify the degree of impairment, while eye tracking, functional magnetic resonance imaging (fMRI) and structural MRI were combined to identify the neural correlates of cognitive impairment in ALS. We predict ALS patients will have executive dysfunction and grey matter loss in executive and oculomotor control areas that will affect antisaccade performance and will alter the corresponding brain activation. ALS patients and age-matched controls participated in a rapid-event-related fMRI design with interleaved pro- and antisaccade trials. Catch trials (no stimulus presented after instructional cue to prepare pro- or antisaccade) allowed us to discern the preparatory period from the execution period. ALS patients were biased towards automatic saccade responses, and had greater difficulty with antisaccades relative to controls in terms of correct and timely responses. We found that worsened antisaccade performance in ALS correlated with the degree of cognitive impairment. Generally, we found trends of increased brain activation during the preparatory period of antisaccades in ALS patients compared to controls in most oculomotor areas; meanwhile few differences were seen during execution. Structural analyses revealed ALS patients had decreased grey matter thickness in frontotemporal and oculomotor regions such as the frontal and supplementary eye fields (FEF, SEF) and the dorsolateral prefrontal cortex (DLPFC). These findings suggest that loss of structural integrity and executive dysfunction may elicit compensation mechanisms to improve functional and behavioural performance. Despite this compensation, ALS patients still performed worse on antisaccades than controls. Further investigation to expand the current data set should improve our ability to assuredly identify the neural correlates of cognitive decline in ALS, and may provide a model system to use for critical evaluation of future therapies and interventions for ALS. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2011-09-22 14:20:39.704