Functional magnetic resonance imaging of eye movements and response to pharmacological challenge in schizophrenia

Functional magnetic resonance imaging (fMRI) was used to investigate normal brain function during performance of a smooth pursuit eye movement task, altered function during the task in subjects with schizophrenia, and the effect of nicotine on brain response during the pursuit task in schizophrenia. The first study presented explores brain hemodynamic response in 15 healthy controls during performance of a simple eye movement task, in which subjects follow a small target oscillating horizontally at a constant velocity. This study identified a consistent pattern of neuronal activity, including the frontal eye fields, supplementary eye fields, parietal eye fields, primary visual cortex (V1), area MT/MST, cingulate gyrus and cerebellum. Results were from a whole-brain, random effects analysis, allowing inferences to the population.; A novel method was developed to evaluate eye movements during imaging experiments using the same gradient-echo images acquired to detect changes in brain hemodynamic response. By examining axial slices that contain the eye and optic nerve, it is possible to view and quantify eye movements during the pursuit task. This information is valuable in verifying task compliance, and in assessing the potentially negative effects of eye movements on whole-head motion correction procedures.; Altered brain function during poor performance of the pursuit task in schizophrenia was then explored by comparing activation during the task in 14 subjects with schizophrenia to 14 age-matched healthy controls. This study revealed that the hippocampus was significantly more active during the task in subjects with schizophrenia. Smaller group differences were observed in the fusiform gyrus, parietal eye fields and in frontal regions.; Finally, the model of nicotinic cholinergic dysfunction in schizophrenia was explored by pharmacologic challenge with nicotine during the smooth pursuit task in nine subjects with schizophrenia. The largest observed difference in activation was a reduction in activity of the hippocampus following nicotine administration compared to placebo. This finding is consistent with nicotinic cholinergic mediated improvement in inhibitory function of the hippocampus in schizophrenia. Differences observed in other brain regions, including the parietal eye fields, cingulate gyrus, precuneus and area MT, may result from direct nicotinic stimulation of these regions or their afferent connections.