Ocular motor performance provides a powerful behavioral means for studying what is specifically different about the functioning of schizophrenia subjects' brains, and for evaluating functional deviations that are correlated with predisposition for developing this illness. Identifying and refining schizophrenia-specific ocular motor abnormalities will serve at least two important functions. First, the ocular motor system is well understood both functionally and neuroanatomically. Dysfunction in particular parts of its neural control system result in characteristic patterns of ocular motor response. By presenting subjects with the appropriate set of tasks and monitoring their performance, hypotheses about the location of neuropathology can be tested. Ocular motor measurement, therefore, can aid the investigation of schizophrenia's neuropathology. Second, schizophrenia patients' clinically normal biological relatives seem to have the same pattern of ocular motor abnormalities as the patients themselves. These findings suggest that some aspect of ocular motor system dysfunction is assessing a component of brain functioning closely associated with a neurobiological predisposition for this illness. Further research on this phenomenon, therefore, could lead to the development of highly sensitive indicators of clinically unaffected gene carriers. A research programme appropriate for these undertakings requires collecting data on ocular motor performance across a range of tasks, a strategy we have used with considerable success. It is remarkable to think that studies of schizophrenia subjects' behavioral performance can provide consistent and theoretically meaningful neurologically localizing information. This is exactly the conclusion that could be drawn with data from some additional clarifying studies. Research conducted with this grant will allow us to (1) rule out the possibility that schizophrenia subjects have a primary dysfunction of their smooth pursuit systems, (2) provide data inconsistent with the thesis that schizophrenia subjects have dysfunction of either posterior parietal cortex ocular motor-related regions or frontal eye fields, and (3) corroborate the hypothesis that the ocular motor abnormalities observed among schizophrenia subjects are a consequence of dysfunction in dorsolateral prefrontal cortex and/or its related subcortical circuitry. These data will be critically important for the success and efficiency of future functional neuroimaging and genetic linkage studies, because research with these important, but expensive, technologies will be suboptimal if they are based on the wrong behavioral measures. In this regard, it will be especially important to refine stimulus conditions to the point where measurement error is reduced as much as is practically feasible, a goal toward which we will aspire with our proposed research.
