FUNCTIONAL AND NEURONAL MECHANISM OF INTERVAL TIMING

目前的建议是一个项目的竞争延续 研究患者时间加工的功能和神经机制 帕金森病（PD）患者。以前的工作已经脱离了 存储（编码）和检索（解码）缺陷，和孤立的具体 神经基板的时间处理与明显的认知缺陷。 在正常老化中也观察到了平行效应，并且被孤立于 时间域。延续将遵循这些结果在五个不同的 方向：（1）进一步的工作与帕金森氏症患者开/关左旋多巴 药物治疗旨在阐明不同功能障碍的病因， 成分，因为这些在疾病的早期（从头）和晚期发展;（2） 慢性脑深部电刺激（DBS）将用于隔离功能障碍， 基底神经节的特殊结构，特别是丘脑底核， 核（STn）和苍白球的内部和外部。 苍白球的刺激将通过以下方式与可比性能进行对比： 治疗性苍白球切开术前后的患者;（3）部分但不是全部的 在PD中观察到的时间处理功能障碍已经在老年人中观察到。 人口也是。反馈的作用，被证明是一个重要因素， 老年人的时间学习和记忆研究的设计， 将记忆更新与策略调整分开;（4）使用 将存储过程与检索过程分开的类似程序 多巴胺（DA）拮抗剂开始具有单一时间值。这将是 扩展到两个时间值和DA激动剂;最后，（5） 该项目的理论工作正在进行中，研究一个 联结主义起搏器/蓄电池模型（Miall，1992）。这个模型允许 研究了一类非线性随机系统，在我们的研究中， DA数据。

The present proposal is a competing continuation of a project studying the functional and neural mechanisms of temporal processing in patient populations with Parkinson's Disease (PD). The previous work has dissociated storage (encoding) and retrieval (decoding) deficits, and isolated specific neural substrates of temporal processing with distinct cognitive deficits. Parallel effects have been seen with normal aging as well, and are isolated to the time domain. The continuation would follow these results in five different directions: (1) Further work with Parkinson's patients ON/OFF Levodopa medication is designed to clarify the etiology of different dysfunctional components as these develop early (de novo) and later in the disease; (2) chronic deep brain stimulation (DBS) will be used to isolate dysfunctions to particular structures in the basal ganglia, particularly the subthalamic nucleus (STn) and the internal and external portions of the globus pallidus. Stimulation of the pallidus will be contrasted with comparable performance by patients before and after therapeutic pallidotomy; (3) some but not all of the temporal processing dysfunctions observed in PD have been seen in aged populations as well. The role of feedback, shown to be an important factor in temporal learning and memory for the aged is studied with designs which separate memory updating from strategic adjustment; (4) work with rats using comparable procedures to separate storage from retrieval processes under dopamine (DA) antagonists has begun with a single time value. This will be expanded to two time values and DA agonists as well; and finally, (5) theoretical work on the project is ongoing, studying an adaptation of a connectionist pacemaker/accumulator model (Miall, 1992). This modeling permits study of a non-linear stochastic systems, which are forced by retrieval in our DA data.