Understanding how the brain changes as a result of use has implications for researchers studying topics as diverse as learning a new skill, to functional recovery following traumatic brain injury. Experience with a task can lead to changes in performance and in the underlying neural circuitry. Like other motor tasks, saccadic tasks are malleable and are affected by practice. Practicing anti-saccades (glances toward the mirror image of a peripheral stimulus) results in a decrease of anti-saccade errors. In contrast, practicing pro-saccades (glances toward a peripheral stimulus) can result in an increase in the number of direction errors on the anti-saccade task (Dyckman & McDowell, 2005). These behavioral changes provide a template for determining how neural pathways supporting pro- and anti-saccade performance may be modified across time. The putative role of prefrontal cortex in mediating anti-saccade performance, as well as the documented hypofrontality and poor anti-saccade performance among schizophrenia subjects, suggests that manipulating anti-saccade performance in subjects with schizophrenia may be particularly informative. The overall aim of this research proposal is to understand practice-based neural plasticity among normal and schizophrenia subjects. Subjects in this study will take part in a two-week trial. Pro- and anti-saccade performance will be tested in the fMRI environment at 3 time points: 1) Pre-Test, 2) Mid-Test, and 3) Post- Test. Between the test sessions, subjects will visit the eye movement laboratory daily (8 time points) to practice either pro- or anti-saccade tasks. It is hypothesized that both normal and schizophrenia subjects will improve on anti-saccade performance after practicing anti-saccades. Changes in neural circuitry across time will differ between the two groups. Initially schizophrenia subjects will show decreased anti-saccade associated prefrontal cortex activity compared to normal subjects. After practice, anti-saccade improvement among the schizophrenia subjects will be accompanied by an increase in prefrontal cortex activity. Normal subjects, however, will show a practice-related decrease in prefrontal cortex activity as the anti-saccades become more automatic and less effortful to perform. The manner in which schizophrenia subjects' brains differ from normal subjects' brains in their response to practice may have important implications for understanding the durability of and mechanisms supporting functional rehabilitation within this group. ? ? ?