The Psychophysiology Of Fear And Anxiety

我们的目标是确定防御机制和条件性恐惧的不同方面与人类正常和异常焦虑的特定形式的特征相关的程度。我们区分了两种形式的厌恶状态，恐惧和焦虑，特别关注焦虑。在操作上，恐惧被定义为由可识别的近端威胁引起的阶段性厌恶状态，而焦虑是一种更持续的反应形式，专注于无法明确识别的潜在远端或未来威胁。在动物身上的研究表明，这两种形式的厌恶状态可以分别通过线索和上下文条件反射来建模。 实验模型：我们专注于开发基于其假定的临床相关性的焦虑模型。在过去的几年里，我们使用虚拟现实来模拟线索和语境条件作用。在这个实验中，恐惧和焦虑是基于生理反应进行评估的。我们最近介绍了一项新的实验，一种模拟莫里斯水迷宫的虚拟现实。在这项任务中，焦虑是根据行为来衡量的。与上下文条件作用相比，莫里斯水任务也呈现出重要的程序差异。电击在情境条件作用下是不可控的，而应激源持续时间取决于受试者在Morris水迷宫中的行为(即到达隐藏的平台)。 精神药理学：我们已经证明，使用5-羟色胺能重摄取抑制剂(SSRI)西酞普兰的急性治疗会增加情景焦虑，而使用相同药物的两周治疗会减少情景焦虑。这些结果与SSRI治疗患者的效果是一致的。SSRI的抗焦虑作用依赖于长期给药。最初，SSRI在一些患者中可能会导致焦虑。我们最近研究了皮质醇在恐惧和焦虑中的作用。急性氢化可的松治疗被发现具有缓解焦虑的作用。这些结果意义重大，因为皮质醇对焦虑的影响被认为是通过它在巩固和恢复情感记忆方面的作用来实现的。我们的研究结果表明，这对焦虑情绪的表达有直接影响。一种可能性是皮质醇增强了应激激素促肾上腺皮质激素释放因子在边缘系统结构中的作用，如终纹床核。我们还发现，4天的治疗可以缓解焦虑。这种效果是意想不到的，但与皮质醇短期治疗可以改善情绪的观察结果并不矛盾。 对患者的行为研究：我们表明，患有恐慌症的人有更高的背景焦虑，但正常线索会导致恐惧。我们最近报告了创伤后应激障碍的类似反应模式，但在社交恐惧症中没有。这些结果表明，患有恐慌症和创伤后应激障碍的患者可能有一个共同的脆弱性，即传播背景威胁。他们还表明，焦虑的患者对不可预测的压力源过于敏感。虽然社交焦虑症患者对非特定应激源(如轻微电击)不太敏感，但他们倾向于与社会应激源形成厌恶的巴甫洛夫关联，这表明条件反射可能是这种疾病的一个病因。 神经成像：使用功能磁共振成像，我们证明了可预测和不可预测的厌恶事件激活了共同和不同的大脑区域。值得注意的是，杏仁核和前脑岛被这两种类型的威胁激活，而终纹的床核在不可预测的电击中被独特地激活，可能是因为不可预测的电击引起持续的焦虑状态。相反，亚膝体前扣带在可预见的条件下被激活。这种结构已经被证明在人类和动物的许多程序中调节对恐惧的抑制。因为可预测的电击比不可预测的电击压力小，与不可预测的情况相比，亚膝前扣带回可能参与了减少可预测条件下的焦虑。我们还在研究焦虑如何影响认知-注意力过程。定义焦虑的核心认知-注意变化可能会在大脑功能障碍和临床现象学之间提供重要的联系。例如，我们研究了无信号电击对反射性和控制性眼动反应(即支持和反对眼跳)的影响。我们的发现表明，焦虑促进了反射性反应，而牺牲了更多的控制性反应。

Our objective is to determine the extent to which different aspects of defense mechanisms and conditioned fear are relevant to features of particular forms of normal and abnormal anxiety in humans. We make a distinction between two forms of aversive states, fear and anxiety, with a particular focus on anxiety. Operationally, fear is defined as a phasic aversive state induced by a proximal and identifiable threat, whereas anxiety is a more sustained form of response focused on potential distal or future threats that are not clearly identifiable. Research in animals suggests that these two forms of aversive states can be modeled by cue and context conditioning, respectively. Experimental models: We focus on developing models of anxiety based on their presumed clinical relevance. In the last several years, we used virtual reality to model cue and context conditioning. In this experiment, fear and anxiety are assessed based on physiological responses. We recently introduced a new experiment, a virtual reality analogue of the Morris water maze. In this task, anxiety is measured based on behavior. The Morris water task also presents important procedural differences compared to context conditioning. The shock is uncontrollable in context conditioning, whereas stressor duration is contingent on subjects behavior (i.e., reaching the hidden platform) in the Morris water maze. Psychopharmacology: We have demonstrated that contextual anxiety is increased by acute treatment with the serotoninergic reuptake inhibitor (SSRI), citalopram, and reduced by 2-week treatment with the same drug. These results are consistent with the effects of SSRI treatment in patients. The anxiolytic effects of SSRI are dependent on a chronic administration of the drug. Initially, SSRI can be anxiogenic in some patients. We recently examined the role of cortisol in fear and anxiety. Acute hydrocortisone treatment was found to be anxiolytic. These results are significant because cortisol's effect on anxiety is believed to be mediated via its action on the consolidation and retrieval of emotional memories. Our results suggest a direct effect on the expression of anxiety. One possibility is that cortisol potentiates the effect of the stress hormone corticotrophin releasing factor in limbic system structures such as the bed nucleus of the stria terminalis. We also found that 4-day treatment is anxiolytic. This effect was unexpected, but is not inconsistent with observation that short-term treatments with cortisol can improve mood. Behavioral studies in patients: We showed that individuals with panic disorders have elevated contextual anxiety, but normal cued fear. We recently reported a similar pattern of responses in Posttraumatic stress disorder but not in social phobia. These results suggest that patients with panic disorder and PTSD may share a common vulnerability to diffuse contextual threats. They also suggest that anxious patients are overly sensitive to unpredictable stressors. While patients with social anxiety disorder are not overly sensitive to non-specific stressors (e.g. mild shocks), they tend to form aversive Pavlovian associations with social stressors, suggesting that conditioning may be an etiological factor in this disorder. Neuroimaging: Using functional Magnetic Resonance Imaging, we demonstrated that predictable and unpredictable aversive events activate common and distinct brain areas. Notably, the amygdala and anterior insula is activated by both types of threats, whereas the bed nucleus of the stria terminalis is activated uniquely during unpredictable shocks, probably because unpredictable shocks evoke a sustained state of anxiety. In contrast, the subgenual anterior cingulate is activated during the predictable condition. This structure has been shown to mediate inhibition of fear in a number of procedures in humans and animals. Because predictable shocks are less stressful than unpredictable shocks, the subgenual anterior cingulate may be involved in reducing anxiety in the predictable condition compared to the unpredictable condition. We are also studying how anxiety affects cognitive-attentional processes. Defining cognitive-attentional changes that are central to anxiety may provide important links between brain dysfunction and clinical phenomenology. For example, we examined the effect of unsignaled shocks on reflexive vs. controlled oculo-motor responses (i.e., pro- vs. anti-saccades). Our findings revealed that anxiety promoted reflexive responding at the expense of more controlled responding.