The Psychophysiology Of Fear And Anxiety

我们的目标是使用翻译方法来确定防御机制和条件性恐惧的各个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。过去的研究主要集中在恐惧和焦虑表达的潜在机制(获得、消退、概括)(1、4、8)，而受试者预计会受到不愉快的冲击。我们最近发起了一项研究，以检验诱导焦虑如何干扰我们的思想、感觉和行动(10)。定义焦虑的核心认知-注意交互作用可能提供脑功能障碍和临床现象学之间的重要联系，并可能为心理和精神药理学治疗提供靶点。 情感神经科学/神经成像：我们的实验集中在预期令人不快的冲击引发的恐惧/焦虑表达的潜在机制上。阐明特定症状在精神障碍整体病理中的作用的一种方法是在健康个体(或动物模型)中复制该症状，并检查其对情绪表达和任务表现的影响。焦虑会削弱思考和集中注意力的能力，但全神贯注于一项任务也可以减少焦虑。我们最近重点研究了情绪和认知之间的这种相互作用，因为它可能有助于阐明病理性焦虑的衰弱性质，也提供了关于认知机制如何帮助缓解焦虑的线索。使用参数调节认知负荷的言语n-back工作记忆(WM)任务，我们探讨了实验诱导的焦虑对任务绩效和惊吓反射的影响(10)。研究结果表明，在中等认知负荷和高认知负荷之间存在一个关键的转折点，在这个转折点上，资源从焦虑焦虑转向专注于任务需求。具体地说，我们证明了焦虑在低负荷下会损害表现，但当受试者从事一项占用执行资源的困难任务时，焦虑会减少。我们提出了一个焦虑的双成分模型，该模型描述了表现损害背后的认知机制和支持持续焦虑强化惊吓的自动反应。 我们现在已经开始了一系列的功能磁共振研究，以检查这些效应的神经基础(即，焦虑和工作负荷之间的相互作用)。初步结果表明：1)随着认知负荷的增加，焦虑相关区域(杏仁核、岛叶、背侧ACC)的激活减少；2)额背区同时被焦虑和认知激活，提示这些区域可能在临床上很重要；3)岛是唯一在高认知负荷下保持激活的焦虑相关区域，这表明该区域可能在维持焦虑的生理症状中起关键作用。 精神药理学：非肽催产素(OT)，被媒体称为道德或爱情分子，在不同物种中具有各种亲社会效应。对于这些复杂的影响，一个相对简单的解释是，OT可以缓解焦虑，从而间接促进信任、合作和其他附属行为。事实上，OT可以减少动物的焦虑行为。令人惊讶的是，OT还促进了对外部群体成员的领土、攻击性和其他防御行为，使任何对OTS社会情感影响的直接解释都变得复杂。我们最近的研究表明，加班不会减少不可预测的冲击引发的焦虑，反而会增加焦虑。这些结果意义重大，因为有人建议使用OT来治疗社会情绪障碍，如自闭症、精神分裂症和社交焦虑。然而，鉴于目前发现的抗焦虑作用，在我们更好地了解OT的非社会影响之前，推测OT的治疗效果可能为时过早。 临床研究：我们已经开始研究重度抑郁症(MDD)患者以及抑郁情绪的影响(7)，因为焦虑和抑郁之间的共病水平很高。虽然情感调节失调是MDD的一个标志，但这种调节失调的性质仍有待定性。有人认为，MDD的特征是不仅对积极刺激，而且可能更令人惊讶的是，对包括威胁性刺激在内的负面事件做出迟钝的情绪反应。这种情感上的迟钝被视为一种适应性反应，表明有必要脱离环境。然而，只有在使用假想威胁的实验中，如看令人不快的图片，才能证明MDD患者的情绪迟钝。此外，MDD显示，面对威胁时焦虑程度降低，这与抑郁症和焦虑症共享一个共同的痛苦因素--情感负性增强--的理论概念化不一致。这样的痛苦因素将预示着对厌恶刺激的夸大反应，而不是迟钝反应。我们已经用震惊的威胁来调查了这个问题。结果不支持MDD中情绪迟钝的观点。相反，与健康志愿者相比，MDD患者表现出更多的焦虑。这些结果表明，抑郁症可能与面对假设的和个人无关的威胁时迟钝的情绪反应有关，可能是因为情绪脱节。然而，当面对实际的身体威胁时，MDD患者表现出更强的焦虑。在动物和人类身上的研究开始确定与焦虑有关的精神药理学和神经机制。目前的实验范式是一个有价值的翻译工具，可以识别情绪和焦虑症中的大脑功能障碍，并可能有助于发现基于病理生理学的新治疗方法。

Our objective is to determine the extent to which various aspects of defense mechanisms and conditioned fear are relevant to features of particular forms of normal and abnormal anxiety in humans using a translational approach. Past works focused mainly on the mechanisms underlying the expression of fear and anxiety (acquisition, extinction, generalization) (1,4,8) while subjects anticipate unpleasant shocks. We recently initiated studies to examine how induced anxiety interferes with our thoughts, feelings, and actions (10). Defining cognitive-attentional interactions that are central to anxiety may provide important links between brain dysfunction and clinical phenomenology, and may provide target for psychological and psychopharmacological treatments. Affective neuroscience/neuroimaging: Our experiments focus on mechanisms underlying the expression of fear/anxiety evoked by anticipation of unpleasant shocks. One approach to clarifying the role of a given symptom in the overall pathology of a psychiatric disorder is to reproduce that symptom in healthy individuals (or animal models) and to examine its effect on emotional expression and task performance. Anxiety impairs the ability to think and concentrate, but being engaged in a task can also reduce anxiety. We have recently focused on this type of interaction between emotion and cognition as it may help elucidate the debilitating nature of pathological anxiety, but also provide clues about how cognitive mechanisms can help alleviate anxiety. Using a verbal n-back working memory (WM) task that parametrically modulated cognitive load, we explored the effect of experimentally induced anxiety on task performance and the startle reflex (10). Findings suggest there is a crucial inflection point between moderate and high cognitive load, where resources shift from anxious apprehension to focus on task demands. Specifically, we demonstrated that anxiety impairs performance under low load, but is reduced when subjects engage in a difficult task that occupies executive resources. We propose a two-component model of anxiety that describes a cognitive mechanism behind performance impairment and an automatic response that supports sustained anxiety-potentiated startle. We have now initiated a series of fMRI studies to examine the neural underpinning of these effects (i.e., interactions between anxiety and WM load). Preliminary results show that 1) as cognitive load increases, activation in anxiety-related areas (amygdala, insula, dorsal ACC) decreases, 2) dorsal frontal regions are activated by both anxiety and cognition, suggesting that these regions may be clinically important, and 3) the insula is the only anxiety-related area that remain activated at high cognitive load suggesting that this region may play a key role in the maintenance of the physiological symptoms of anxiety. Psychopharmacology: The nonapeptide oxytocin (OT), dubbed by the media as the moral or love molecule, has a variety of pro-social effects across species. A relatively simple explanation for these complex effects is that OT alleviates anxiety, thereby indirectly promoting trust, cooperation and other affiliative behaviors. Indeed, OT can reduce anxiety-like behavior in animals. Surprisingly, OT also promotes territoriality, aggression, and other defensive behaviors toward out-group members, complicating any straightforward interpretation of OTs socio-emotional effects. We recently showed that OT does not reduce but rather increases anxiety evoked by unpredictable shocks. These results are significant because it has been proposed that OT could be used to treat socio-emotional disorders such as autism, schizophrenia, and social anxiety. However, given the present finding of an anxiolytic effect, it may be premature to speculate on the therapeutic effect of OT before we have a better understanding of its non-social effects. Clinical studies: We have begun to study patients with major depression (MDD) as well as the effect of depressed mood (7) because of the high level of comorbidity between anxiety and depression. While dysregulated affect is a hallmark of MDD, the nature of such dysregulation remains to be characterized. It has been suggested that MDD is characterized by blunted emotional response not only to positive stimuli but, perhaps more surprisingly, to negative events, including threatening stimuli. This emotional blunting is seen as an adaptive response signaling the need to disengage from the environment. However, emotional blunting in MDD as been demonstrated only in experiments that use hypothetical threats such as looking at unpleasant pictures. In addition, that MDD shows reduced anxiety in the face of threat is inconsistent with the theoretical conceptualization that depression and anxiety disorders share a common distress factor of heightened affective negativity. Such a distress factor would predict exaggerated not blunted response to aversive stimuli. We have investigated this question using threat of shock. Results do not support the view of emotional blunting in MDD. Rather, MDD patients show increased anxiety compared to healthy volunteers. These results suggest that depression may be associated with blunted emotional responses when confronted with hypothetical and personally-irrelevant threats, probably because of emotional disengagement. However, when confronted with an actual physical threat, MDD patients exhibit enhanced anxiety. Studies in animals and in humans are beginning to identify psychopharmacological and neural mechanisms involved in anxiety. The current experimental paradigm is a valuable translational tool to identify brain dysfunction in mood and anxiety disorders and may help uncover novel pathophysiology-based treatments.