FUNCTIONAL AND NEURONAL MECHANISM OF INTERVAL TIMING

本提案是一个项目的竞争性延续 研究患者时间加工的功能和神经机制 帕金森氏症(PD)患者。以前的工作已经脱离了 存储(编码)和检索(解码)缺陷，以及孤立的特定 具有明显认知缺陷的时间加工的神经基础。 在正常衰老中也可以看到类似的影响，并被隔离为 时间域。在这些结果之后，将在五个不同的 指导：(1)对帕金森氏症患者使用/停用左旋多巴的进一步研究 药物治疗的目的是阐明不同功能障碍的病因 这些成分在疾病中发展得早(从头开始)和晚些时候； 慢性脑深部刺激(DBS)将用于隔离功能障碍 基底节的特殊结构，尤其是丘脑底核 核团(STN)和苍白球的内外部分。 对苍白球的刺激将与类似的表现形成对比， 治疗性苍白球切开术前后患者；(3)部分但不是全部 帕金森病的时间加工功能障碍见于老年人 人口也是如此。反馈的作用，被证明是一个重要因素 研究老年人的时间学习和记忆的设计 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)拮抗剂从单一时间值开始。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，研究一种 连接型起搏器/蓄电池模型(Miall，1992)。此建模允许 一类非线性随机系统的检索强迫问题的研究 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.