Cognitive Regulation and Reversal of Fear: Physiological and Neural Mechanisms

描述(由申请人提供)：对威胁提示的预见性恐惧很容易促使防御性激活，为应对迫在眉睫的厌恶事件做准备。病理性焦虑的一个特征，尤其是恐惧障碍，是对恐惧刺激的过度和持续的情绪反应。与对恐惧症事件的预期相关的强烈恐惧和焦虑往往会导致可能干扰日常生活的回避行为。尤其是涉及对疼痛的恐惧的恐惧症，在这种情况下，恐惧往往通过延误预防护理而对健康产生负面影响。虽然在理解与恐惧的获得和表达有关的神经回路方面取得了相当大的进展，但一个重要的转换步骤是确定恐惧抑制和持之以恒反应的神经基础。最近使用口头指令将中性刺激与电击的可能性联系起来的研究发现，这种简单的威胁会引发与防御性激活一致的生理反应。被称为指导性恐惧，这种形式的恐惧学习的可塑性尚未被探索。这项拟议的研究涉及对大脑功能活动和对视觉提示的心理生理反应的比较，视觉提示表示可能发生电击(“威胁”)或不可能发生电击(“安全”)。在最初的学习阶段，恐惧将通过将一组视觉线索(如颜色)的一种属性与威胁或安全相关联的指令来口头实例化。在实验过程中，第二组指令会将指示的恐惧偶发转移到不同的感知维度，导致一半的线索颠倒其情感意义。自主神经和躯体反应性的测量以及功能磁共振成像(FMRI)将用于评估恐惧可塑性的生理和神经指标，并评估眼眶前额叶皮质参与信号逆转条件性恐惧的情况。其他假说解决了牙齿恐惧的增加是否会损害或增强反转学习过程中的恐惧反应。

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.