MODULATION OF FEAR-POTENTIATED STARTLE IN HUMANS

这项申请提出了一项为期4年的研究，以检查恐惧兴奋和 使用条件反射的健康人的恐惧抑制过程 从人体以下研究中衍生出来的程序。关于动物厌恶症的研究 条件反射强调了记忆在维持和维持记忆中的作用 将恐惧概括为理解恐惧的基础 情绪失调症的维持。 拟议研究的概念框架以动物为基础。 条件性恐惧、条件性抑制和消亡的模型。 这些模型表明，兴奋性恐惧的保留 条件反射是强健和持久的，但保留抑制性 恐惧的条件反射是脆弱的，会随着时间的推移而被打乱 以及上下文信息的变化。本提案将 评估这些发现在人类身上的概括性和局限性。 从理论上讲，将动物研究成果推广到人类身上将 认为恐惧的过度泛化是由于 强健的恐惧制约机制和弱小的恐惧相结合 抑制性过程。干扰变量的识别 通过减少恐惧的有效性，程序可能会潜在地 指导治疗干预。 我们建议进行四项研究。书房L将成立一家 基于一种动物模型的条件性抑制过程 连续的刺激演示。研究2将研究保留 跨越时间和背景的条件性恐惧和恐惧抑制。研究3 将评估在不同时间和背景下物种灭绝的保留情况。学习 4将考察背景恐惧，而不是对特定刺激的恐惧。 这项提议的一个重要方面是使用多种措施 条件反射(即电击预期措施、惊恐反射皮肤 电导和心率)，以检查联想的性质 在条件反射过程中。惊吓反射也将使 在人类和非人类身上实施非常类似的实验。 将本提案的结果与以下研究相结合 条件反射的兴奋和抑制的神经生物学 耶鲁大学目前正在进行的动物惊吓实验 可以阐明这种机制的神经生物学基础 这影响了人类恐惧的强度和维持。结果是 也将为进一步的药理学研究提供必要的基础 条件性恐惧和条件性恐惧抑制的临床研究 在人类身上。

This application proposes a 4-year study to examine fear excitation and fear inhibition processes in healthy individuals using conditioning procedures derived from infra-human studies. Research on animal aversive conditioning has emphasized the role of memory on the maintenance and generalization of fear as a basis for the understanding of the maintenance of emotional disorders. The conceptual framework of the proposed studies is based on animal models of conditioned fear, conditioned inhibition, and extinction. These models have indicated that the retention of excitatory fear conditioning is robust and long lasting, but the retention of inhibitory fear conditioning is fragile, and is disrupted by the passage of time and by changes in contextual information. The present proposal will assess the generalizability and limitations of such findings in humans. Theoretically, the extension of the animal findings to humans would suggest that the over-generalization of fear results from the combination of robust fear conditioning mechanisms and weak fear inhibitory processes. The identification of variables that interfere with the effectiveness of fear reduction procedures could potentially guide therapeutic interventions. We propose to carry out four studies. Study l will establish a conditioned inhibition procedure based on an animal model that uses a serial stimulus presentation. Study 2 will examine the retention of conditioned fear and fear inhibition across time and contexts. Study 3 will assess the retention of extinction across time and contexts. Study 4 will examine contextual fear as opposed to fear to specific stimuli. One important aspect of this proposal is the use of multiple measures of conditioning (i.e., shock expectancy measures, startle reflex skin conductance, and heart rate) to examine the nature of the associative processes during conditioning. The startle reflex will also allow the implementation of very similar experiments in humans and infra-humans. The integration of the results of the present proposal with studies of the neurobiology of the excitation and the inhibition of conditioned fear-potentiated startle in animals, currently under way at Yale University, could clarify the neurobiological bases of the mechanisms that impact the intensity and maintenance of fear in humans. The results will also provide the necessary foundation for further pharmacological and clinical studies of conditioned fear and conditioned fear inhibition in humans.