Cognitive Regulation and Reversal of Fear: Physiological and Neural Mechanisms

描述（由申请人提供）：对威胁性线索的预期恐惧很容易促使防御性激活，为应对即将发生的厌恶性事件做准备。病理性焦虑，尤其是恐惧症的一个标志是对恐惧刺激的过度和持续的情绪反应。与恐惧事件的预期相关的强烈恐惧和焦虑通常会导致可能干扰日常生活的回避行为。涉及疼痛恐惧症的情况尤其如此，恐惧往往因预防性护理的延误而对健康产生负面影响。虽然在理解恐惧的获得和表达所涉及的神经回路方面已经取得了相当大的进展，但重要的翻译步骤是确定恐惧抑制和持续反应的神经基础。最近的研究使用口头指令将中性刺激与电击的可能性联系起来，发现这种简单的威胁会引发与防御激活一致的生理反应。被称为指令性恐惧，这种形式的恐惧学习的可塑性尚未被探索。拟议中的研究涉及比较大脑功能活动和心理生理反应的视觉线索，信号的可能性电击（“威胁”）或不（“安全”）。在最初的学习阶段，恐惧将通过将一组视觉线索（例如颜色）的一个属性与威胁或安全相关联的指令口头实例化。在实验过程中，第二组指令会将所指示的恐惧偶然性转移到不同的感知维度，导致一半的线索逆转其情感意义。自主神经和躯体反应性和功能性磁共振成像（fMRI）的措施将被用来评估恐惧可塑性的生理和神经指标，并衡量参与眶额皮质的信号逆转条件性恐惧。额外的假设解决是否增加牙科恐惧损害或增强恐惧反应在逆转学习。

DESCRIPTION (provided by applicant): Anticipatory fear in response to threatening cues readily prompts defensive activation in preparation for responding to an impending aversive event. A hallmark of pathological anxiety, especially fearful disorders, is excessive and persistent emotional responding in anticipation of feared stimuli. The intense fear and anxiety associated with the anticipation of a phobic event often leads to avoidance behaviors that can interfere with daily life. This is especially the case regarding phobias involving fear of pain, where fearfulness often negatively impacts health through delays in preventive care. While considerable advances have been made in understanding the neurocircuitry involved in the acquisition and expression of fear, an important translational step is in determining the neural underpinnings of fear inhibition and perseverative responding. Recent studies using verbal instructions to associate a neutral stimulus with the potential of electric shock have found that this simple threat prompts physiological reactions consistent with defensive activation. Dubbed instructed fear, the plasticity of this form of fear learning has not yet been explored. The proposed research involves comparisons of functional brain activity and psychophysiological responses to visual cues that signal the possibility of electric shock ("threat") or not ("safety"). In an initial learning phase fear will be verbally instantiated through instructions that associate one property of a set of visual cues (e.g. color) with threat or safety. Over the course of the experiment a second set of instructions will shift the instructed fear contingency to a different perceptual dimension causing half of the cues to reverse their affective meaning. Measures of autonomic and somatic reactivity and functional magnetic resonance imaging (fMRI) will be used to assess physiological and neural indicators of fear plasticity, and to gauge the involvement of orbitofrontal cortex in signaling reversals of conditioned fear. Additional hypotheses address whether increases in dental fear impair or enhance fearful responses during reversal learning.