Attentional Dysfunction in Fragile X Syndrome

超出空间 提供了 这个项目的目的是了解神经系统参与的注意力缺陷在脆弱的X 综合征（FXS），以便设计有效的治疗方法。注意力障碍的特点是 FXS比他们的智商更严重，我们假设三种不同的缺陷 大脑系统相互作用产生了这些极端的注意力困难。第一，执行功能受损 已被证明有助于FXS的注意力缺陷。第二，感官加工异常 信息可能会损害注意力，并导致过度唤醒，损害注意力。最后， 下丘脑-垂体-肾上腺轴的异常可能会导致觉醒和认知能力降低。 功能我们将使用新开发和验证的5臂迷宫注意力测量。的影响 本研究亦会探讨分散注意力的刺激对这项任务表现的影响。主动回避是一项任务， 发现了注意力和情绪因素的深刻影响。由于这项任务的参数可以变化， 系统地确定学习问题的性质，将此任务用于确定影响 感觉和情绪上的困难对认知能力的影响。HPA轴尚未研究， 而患有FXS的人类在应激后恢复到基础皮质酮水平的速度更慢 Eberwine和Greenough的发现预测了这一结果，FMRP 与糖皮质激素受体（GR）结合，导致海马GR水平下降25%， Fmr 1 KO小鼠我们将进行一个彻底的检查皮质酮每日节律，反应 在其他GR降低对HPA轴影响的动物模型中， 很难预测，所以脑和肾上腺表达的标记物为整个轴（GR，MR，CRF，ACTH， POMC皮质酮）将被检查，因为这些分子在大脑中的表达可能具有深远的意义。 影响认知和行为。当我们有好的措施时，所有这些目标都有助于实现最终目标。 注意力和认知能力，并知道HPA轴的异常，我们可以选择药物 可能会影响我们假设与FXS注意力缺陷有关的三个系统。个人 这些药物的md组合测试将确定这些系统中每一个的相对作用，并导致 在FXS中，这个重要问题的联合治疗。

EXCEED THE SPACE PROVIDED. The objective of this project is to understand the neural systems involved in the attention deficits in fragile X syndrome (FXS), so that effective treatments can be devised. The attention impairment characteristic of FXS are more severe than would be expected for their'I.Q, We hypothesize that defects in three different brain systems interact to produce these extreme attention difficulties. First, impairment of executive function ha been shown to contribute to attention deficits in FXS. Second, abnormal processing of sensory information likely impairs attention as well as leading to over arousal that impairs attention. Finally, abnormalities in the hypothalamic pituitary adrenal axis likely contribute to arousal and lower cognitive function. We will use the newly developed and validated 5-arm maze attention measure. Effects of distracting stimuli on performance on this task will also be explored. Active avoidance is a task on whichWe have found profound effects of attentional and emotional factors. As parameters of this task can be varied systematically to determine the nature of the learning problem, this task will be used to determine the impact of the sensory and emotional difficulties on cognitive performance. The HPA axis has not been studied in the Fmr1 KO mouse, but humans with FXS return to basal corticosterone levels more slowly after stress than do controls, a result that would be predicted by the finding from Eberwine and Greenough that FMRP binds to the glucocorticoid receptor (GR), resulting in a 25% decrease in GR levels Inthe hippocampus in the Fmr1 KO mouse. We will conduct a thorough examination of the corticosterone daily rhythm, response to and recovery from stress, In other animal models of reduced GR effects on the HPA axis have been difficult to predict, so brain and adrenal expression of markers for the entire axis (GR, MR, CRF, ACTH, POMC corticosterone) will be examined, as expression of these molecules in the brain can have profound effects upon cognition and behavior. All of these aims build to the final aim, When we have good measures of attention and cognitive performance and know the abnormalities in the HPA axis, we can select drugs likely to impact the three systems we hypothesize to be involved in the attention deficits in FXS. Individual md combination tests of these drugs will determine the relative roles of each of these systems, and lead to ¿-,-combination treatments for this Important problem In FXS.