PREDICTING FEAR RESPONSES

预测恐惧反应

• 批准号: 8359919
• 负责人: WALTER R. FRONTERA
• 金额: $ 6.65万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359919
• 关键词: Amygdaloid structure; Animals; Anxiety; Anxiety Disorders; Area; Biological Process; Brain; Clinic; Clinical; Clinical Research; Cues; Emotional; Equipment; Exposure to; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; Funding; Grant; Human; Image; Learning; Measures; Modality; National Center for Research Resources; Neuropsychological Tests; Patients; Physiological; Population; Prefrontal Cortex; Principal Investigator; Psychopathology; Puerto Rico; Reaction Time; Relapse; Research; Research Infrastructure; Resources; Risk Factors; Shock; Source; Stimulus; Study Subject; Testing; Therapeutic; Time; Training; Translational Research; United States National Institutes of Health; base; conditioned fear; conditioning; cost; learning extinction; neuroimaging; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Fear is a normal human response to threatening stimuli. Anxiety disorders are present when fear is expressed in an exaggerated manner or under inappropriate circumstances. Decades of research have delineated the brain circuits involved in fear learning. Even more importantly, in recent years various studies have proposed the biological processes involved in extinction of fear. Understanding the brain mechanisms of learning not to fear (or fear extinction) has important clinical implications. Fear extinction deficits may be part of the etiological factors of anxiety disorders and at the same time strengthening fear extinction could be a treatment modality for these conditions. In humans, fear extinction can be measured by physiological responses that occur during fear conditioning and extinction paradigms. Subjects with anxiety disorders have consistently been found to present increased fear conditioning as measured by startle responses (Orr et al.,2000). Neuroimaging studies of fear acquisition and extinction show that in subjects without psychopathology, fear acquisition is associated with increased amygdala response and recall of fear extinction is correlated with increased activity of the ventromedial prefrontal cortex (vmPFC) (Milad and Rauch, 2007). Similar neuroimaging studies show that patients with anxiety disorders show hyperresponsive amygdala activation during fear acquisition and decreased activity of the vmPFC (Milad and Rauch, 2007). These findings correlate well with functional and structural imaging of subjects with anxiety disorders which repeatedly show that these patients have alterations in the amygdala and prefrontal cortex areas such as the vmPFC (Rauch et al., 2003; Gilbertson et al., 2002). These same brain areas have been shown in animal and human studies to be related to fear learning and extinction. The ability to extinguish SCR responses to cues no longer paired with shock could predict a patient's response to exposure therapy (Kaplan et al., 2010; Hofmann, 2008), which is thought to be based on extinction mechanisms. Furthermore, the return of fear after extinction that is triggered by changes in context (renewal of fear) has been proposed as a risk factor for relapse after therapy (Boschen et al., 2009). Thus, being able to assess fear conditioning, extinction, and renewal in anxiety patients could help match specific therapeutic strategies to specific patients. It may not be practical, however, to routinely perform experimental fear conditioning in the clinic, because the necessary equipment and training is not readily accessible to most practitioners, especially in areas with limited resources. Alternatively, certain neuropsychological tests share common neuroanatomical substrates with fear leaning and extinction, and may be useful as predictors of conditioning, extinction, or renewal. Specific Aim #1: Can neuropsychological tests predict fear acquisition and extinction learning in normal subjects? Hypothesis: Scores on neuropsychological tests that activate areas of the brain such as the amygdala and vmPFC will be associated with the capacity of subjects to learn and to extinguish fear. We will be using two neuropsychological tests that have been shown to activate brain areas associated with fear circuitry. Functional MRI studies of subjects doing the Emotional Stroop Task (EST) show that brain areas very close to the vmPFC are activated in controls upon exposure to the threat words (Engels et al., 2007). Therefore we expect subjects with increased response times to the threat words to present with better extinction learning. The Multimodal Source Interference Test (MSIT) is a non-emotional form of stroop task that may not be related to fear learning. Specific Aim #2: Are associations between neuropsychological tests and fear learning also found in subjects with anxiety disorders? Hypothesis: Scores on these neuropsychological tests will also be associated with the capacity of subjects to learn and to extinguish fear but this association may be different in subjects with anxiety disorders due to fear extinction deficits that have been described in this population. fMRI studies of anxiety disorder patients doing the EST have found that they fail to activate the areas near vmPFC when exposed to threat words (Whalen et al., 2006). Therefore, we expect to find an association between these neuropsychological tests and fear learning but that it will be a different relationship as compared to the subjects without psychopathology.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 恐惧是对威胁刺激的正常反应。当恐惧以夸张的方式表达或在不适当的情况下表达恐惧时，就会出现焦虑症。数十年的研究描述了恐惧学习中涉及的大脑电路。更重要的是，近年来，各种研究提出了与恐惧灭绝有关的生物学过程。了解学习不恐惧（或恐惧灭绝）的大脑机制具有重要的临床意义。恐惧灭绝赤字可能是焦虑症的病因学因素的一部分，同时加强恐惧灭绝可能是 这些条件的治疗方式。在人类中，恐惧灭绝可以通过在恐惧调节和消光范式中发生的生理反应来衡量。 始终发现患有焦虑症的受试者表现出通过惊吓反应衡量的恐惧调节的增加（Orr等，2000）。神经影像学的恐惧获取和灭绝研究表明，在没有心理病理学的受试者中，恐惧获取与杏仁核反应的增加有关，恐惧灭绝的回忆与腹侧前额叶皮层的活动增加有关（Milad and Rauch，2007年）。相似的 神经影像学研究表明，焦虑症患者在恐惧获取过程中表现出高反应性杏仁核的激活，并减少了VMPFC的活性（Milad and Rauch，2007）。这些发现与患有焦虑症的受试者的功能和结构性成像很好地相关，这些受试者反复表明这些患者在杏仁核和前额叶皮层区域（例如VMPFC）有改变（Rauch等，2003； Gilbertson等，2002）。这些相同的大脑区域已在动物和人类研究中显示为 与恐惧学习和灭绝有关。熄灭SCR对线索的反应不再与冲击配对的能力可以预测患者对暴露疗法的反应（Kaplan等，2010； Hofmann，2008），这被认为是基于灭绝机制的。此外，灭绝后的恐惧返回 在上下文中的变化（更新恐惧）中触发的是治疗后复发的危险因素（Boschen等，2009）。因此，能够评估焦虑症患者的恐惧条件，灭绝和更新可以帮助将特定的治疗策略与特定患者相匹配。但是，在诊所中常规执行实验性恐惧调节可能是不切实际的，因为大多数从业者不容易获得必要的设备和培训，尤其是在资源有限的地区。另外，某些神经心理学测试具有恐惧和灭绝的常见神经解剖底物，并且可以作为调理，灭绝或更新的预测指标。 特定目的＃1：神经心理学测试能否预测正常受试者的恐惧习得和灭绝学习？ 假设：激活大脑区域（例如杏仁核和VMPFC）的神经心理学测试的评分将与受试者学习和消除恐惧的能力有关。 我们将使用两种已显示的神经心理学测试来激活与恐惧回路相关的大脑区域。对执行情感障碍任务的受试者（EST）的受试者的功能性MRI研究表明，在暴露于威胁词的情况下，在对照中激活了非常接近VMPFC的大脑区域（Engels等，2007）。 因此，我们期望对威胁词的响应时间增加的受试者通过更好的灭绝学习来表现。多模式源干扰测试（MSIT）是Stroop任务的一种非情感形式，可能与恐惧学习无关。 特定目标2：神经心理学测试与恐惧学习之间的关联是否在患有焦虑症的受试者中也存在？ 假设：这些神经心理学测试的分数也将与受试者学习和消除恐惧的能力有关，但是由于恐惧灭绝的赤字在该人群中已经描述了焦虑症的受试者，这种关联可能有所不同。 FMRI对焦虑症患者进行EST的研究发现，在接触威胁词时，他们无法激活VMPFC附近的区域（Whalen等，2006）。因此，我们希望在这些神经心理学测试和恐惧学习之间找到联系，但与没有精神病理学的受试者相比，这将是不同的关系。