MODULATION OF FEAR-POTENTIATED STARTLE IN HUMANS

这项申请提出了一项为期4年的研究，以检查恐惧的兴奋和 恐惧抑制过程中的健康人使用条件反射 来自人类研究的程序。动物厌恶的研究 条件反射强调了记忆在维持和 恐惧的概括作为理解的基础， 情绪障碍的维持。 拟议研究的概念框架是基于动物 条件性恐惧、条件性抑制和灭绝的模型。 这些模型表明，兴奋性恐惧的保留 条件反射是强大和持久的，但抑制性的保留 恐惧条件反射是脆弱的，随着时间的推移而被破坏 以及上下文信息的变化。本提案将 评估这些发现在人类中的普遍性和局限性。 从理论上讲，将动物研究结果推广到人类， 这表明，恐惧的过度泛化是由于 强大的恐惧条件反射机制和微弱的恐惧 抑制过程。识别干扰的变量 减少恐惧程序的有效性， 指导治疗干预。 我们建议进行四项研究。研究l将建立一个 条件抑制程序的基础上的动物模型，使用 连续刺激呈现研究2将检查保留 条件性恐惧和恐惧抑制在时间和情境中的变化。研究3 将评估在不同时间和背景下对灭绝的保留。研究 4将研究背景恐惧，而不是对特定刺激的恐惧。 这项建议的一个重要方面是使用多种措施， 调节（即，电击预期测量，惊吓反射皮肤 电导和心率）来检查关联的性质。 在调节过程中。惊吓反射也会让 在人类和亚人类身上进行非常相似的实验。 将本提案的结果与下列研究结合起来， 条件反射的兴奋和抑制的神经生物学 目前正在耶鲁大学进行的一项研究， 大学，可以澄清机制的神经生物学基础， 影响人类恐惧的强度和持续性。结果 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.