Neural circuitry plasticity resulting from saccadic practice in schizophrenia

描述(由申请人提供)：了解大脑因使用而发生的变化，对于研究从学习一项新技能到创伤性脑损伤后的功能恢复等各种主题的研究人员具有重要意义。一项任务的经验可能会导致性能和潜在神经回路的变化。像其他运动任务一样，扫视任务是可塑性的，受练习的影响。练习反眼跳(瞥一眼周围刺激的镜像)会减少反眼跳错误。相比之下，练习前眼跳(瞥一眼外围刺激)会导致反眼跳任务中方向错误的数量增加(Dyackman&McDowell，2005)。这些行为变化提供了一个模板，用于确定支持眼跳和眼跳的神经通路如何随着时间的推移而改变。前额叶皮质在调节抗眼跳表现方面的假定作用，以及有记录的精神分裂症受试者的额下性和不良的抗扫视表现，表明操纵精神分裂症受试者的抗扫视表现可能特别有用。这项研究计划的总体目标是了解正常受试者和精神分裂症受试者之间基于实践的神经可塑性。这项研究的受试者将参加为期两周的试验。支持和反眼跳性能将在功能磁共振成像环境中的3个时间点进行测试：1)前测试、2)中测试和3)后测试。在测试期间，受试者将每天(8个时间点)访问眼动实验室，练习支持或反对眼跳的任务。假设正常受试者和精神分裂症受试者在练习反眼跳后都会提高抗眼跳能力。神经回路随时间的变化在两组之间会有所不同。最初，精神分裂症受试者与正常受试者相比，将表现出与前额叶皮质相关的抗眼跳活动减少。练习后，精神分裂症受试者的抗眼跳能力改善将伴随着前额叶皮质活动的增加。然而，正常受试者会表现出与练习相关的前额叶皮质活动的减少，因为反眼跳变得更加自动，执行起来不那么费力。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大脑的不同方式，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.