ATTENTIONAL PROCESSING OF TEMPORAL INFORMATION

描述(由申请人提供)：基本的行为过程，如联想学习、速率计算和决策，关键依赖于对秒到分钟范围内的时间间隔的估计和再现(间隔计时)。这些过程在帕金森氏症、亨廷顿病和精神分裂症中被破坏。这个项目将通过调查事件特征对保持时间跟踪能力的影响，进一步了解这些障碍中认知过程的中断。大多数计时理论的基本假设之一是，受试者能够容易地从输入刺激中提取时间信息，并根据该线索调整他们的行为，而不考虑实际计时事件的非时间属性。相反，有证据表明，动物和人类的计时都对计时信号的性质高度敏感。这些数据支持资源分配理论，该理论认为，专用于间隔计时的注意力和记忆资源可能会被重新分配给其他认知过程，这反过来可能会阻碍计时。这项建议的主要目的是使用行为、生理和计算方法相结合的方法来研究时间信息在秒到分钟范围内的注意加工(间隔计时)。在行为上，我们将研究事件的非时间性特征对被试在一个或多个持续时间上重新分配注意和记忆资源的影响。在生理水平上，我们建议使用神经精神药理学的方法来剖析参与内部时钟和资源分配机制相互作用的神经回路，特别是通过在神经回路的关键部位局部注射特定的激动剂和拮抗剂来操纵神经回路并了解其功能。在计算上，我们建议评估两种资源重新分配模型，以解决行为和药物操纵对时间信息注意加工的影响，并得出值得进一步实验研究的预测。这些研究将有助于阐明我们注意到时间刺激时涉及的行为、神经和计算机制，并将提高我们对注意因素对需要时间信息的复杂认知过程的影响的理解，这些过程可能会在帕金森、亨廷顿和精神分裂症等疾病中中断。该项目的结果可以用来设计行为测量方法，以便对此类障碍进行早期评估，并了解当这些底物功能失调时，认知过程受到的干扰。这一信息对于在此类疾病的动物模型中评估潜在治疗策略的价值/效率至关重要。 公共卫生相关性：跟踪事件发生的时间及其持续时间，对于学习、发病率估计和决策至关重要。帕金森氏症、亨廷顿病、精神分裂症和阅读障碍患者的这些过程都受到了损害。通过研究注意因素对需要时间处理的认知机制的影响，本项目将：(A)为这些疾病的早期诊断制定易于使用的标准，(B)加强我们对这些疾病所涉及的大脑回路的了解，(C)有助于在此类疾病的动物模型中评估潜在治疗策略的价值/效率，这对开发临床治疗至关重要。

DESCRIPTION (provided by applicant): Fundamental behavioral processes such as associative learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals in the seconds-to-minutes range (interval timing). These processes are disrupted in Parkinson's disease, Huntington's disease, and Schizophrenia. This project will further our understanding of the disruptions of cognitive processes in these disorders by investigating the impact of characteristics of events on the ability to keep track of time. One of the underlying assumptions of most timing theories is that subjects are able to readily abstract from the input stimulus the temporal information, and to tune their behavior according to this cue, irrespective of non-temporal properties the real timed event. In contrast, evidence suggests that both animal and human timing is highly sensitive to properties of the timed signal. Such data support a resource allocation theory which posits that attentional and memory resources dedicated to interval timing may be re-allocated for other cognitive processes, which in turn may hinder timing. The main objective of this proposal is to study attentional processing of temporal information in the seconds-to-minutes range (interval timing) using combined behavioral, physiological, and computational approaches. Behaviorally, we will study the effects of non-temporal features of events on the re-allocation of attentional and memory resources when subjects time one or multiple durations. At the physiological level, we propose to dissect the neural circuits involved in the interaction between the internal clock and the resource allocation mechanisms using neuropsychopharmacological methods, specifically by local infusions of specific agonist and antagonists in key sites of the neural circuit in order to manipulate it and gain knowledge of its functioning. Computationally, we propose to evaluate two models of re-allocation of resources, in order to address the effect of behavioral and pharmacological manipulations on attentional processing of temporal information, and to arrive at predictions that warrant further experimental investigation. The studies will help elucidate the behavioral, neural, and computational mechanisms involved when we pay attention to timed stimuli, and will improve our understanding of the impact of attentional factors on complex cognitive processes that require temporal information, processes which may be disrupted in disorders like Parkinson, Huntington, and Schizophrenia. The results of the project can be used to devise behavioral measures for the early assessment of such disorders, and to understand the cognitive processes disrupted when these substrates are dysfunctional. This information is crucial to assessing the value/efficiency of potential treatment strategies in animal models of such disorders. PUBLIC HEALTH RELEVANCE: Keeping track of when events occur, and their duration, is fundamental for learning, rate estimation, and decision making. These processes are impaired in patients with Parkinson's disease, Huntington's disease, Schizophrenia and Dyslexia. By studying the impact of attentional factors on cognitive mechanisms that require temporal processing, the present project will (a) allow the development of easy to use criteria for early diagnose of these disorders, (b) enhance our understanding of the brain circuits involved in these disorders, (c) help the assessment of the value/efficiency of potential treatment strategies in animal models of such disorders, which is crucial for developing clinical treatments.