Neural circuitry plasticity resulting from saccadic practice in schizophrenia

描述（由申请人提供）：了解大脑如何因使用而变化，对研究人员研究从学习新技能到创伤性脑损伤后的功能恢复等各种主题具有重要意义。完成一项任务的经验会导致表现和潜在神经回路的变化。像其他运动任务一样，跳跃性任务具有可塑性，并受到练习的影响。练习反扫视（看向周围刺激的镜像）可以减少反扫视错误。相反，练习前扫视（看向周边刺激）会导致反扫视任务的方向错误数量增加（Dyckman & McDowell, 2005）。这些行为变化为确定支持前扫视和反扫视表现的神经通路如何随着时间的推移而改变提供了模板。前额叶皮层在调节抗扫视表现中的假定作用，以及在精神分裂症受试者中记录的额叶功能低下和较差的抗扫视表现，表明操纵精神分裂症受试者的抗扫视表现可能特别有用。本研究计划的总体目标是了解正常和精神分裂症受试者中基于实践的神经可塑性。本研究的受试者将参加为期两周的试验。在fMRI环境中，将在3个时间点测试亲扫视和反扫视性能：1)测试前，2)测试中，3)测试后。在测试期间，受试者将每天（8个时间点）访问眼动实验室，练习促进或反扫视任务。假设正常人和精神分裂症受试者在进行反扫视练习后，其反扫视表现均有改善。随着时间的推移，两组人的神经回路变化会有所不同。与正常受试者相比，精神分裂症受试者最初会表现出与抗扫视相关的前额皮质活动减少。练习后，精神分裂症受试者的抗扫视改善将伴随着前额叶皮层活动的增加。然而，正常受试者的前额叶皮层活动会出现练习相关的减少，因为反扫视变得更加自动化，不那么费力。精神分裂症受试者的大脑在对练习的反应上与正常受试者的大脑不同，这种方式可能对理解这一群体中支持功能康复的持久性和机制具有重要意义。

DESCRIPTION (provided by applicant): 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.