Neurocognitive Mechanisms of Trait Vulnerability to Human Anxiety

描述（申请人提供）：NIMH的两个关键目标涉及（a）发现可用于识别精神疾病风险个体的“标记物”和（B）开发预防性治疗措施，以预防这些个体的疾病发作。拟议的研究旨在进一步在焦虑症的背景下实现这些目标。它调查了神经认知机制，通过该机制赋予了对焦虑的特质脆弱性，并检查了认知和神经认知训练是否可以用于恢复受损区域的功能。此外，它还探讨了神经标记物是否可以用于识别那些最有可能从预防性认知训练干预中受益的焦虑症“高危”个体。功能性磁共振成像（fMRI）将被用来测试一个双重路线模型的特质脆弱性焦虑，争论是，至少有两个，很大程度上独立的，个体变异性来源赋予脆弱性焦虑症。我们的第一个具体目标是建立是否（i）贫困招聘的额叶控制机制和（ii）增强杏仁核反应的线索，信号威胁独立与特质脆弱性焦虑。注意力和恐惧条件反射功能磁共振成像实验将在具有不同水平特质焦虑的健康志愿者中进行。我们的目标是确定特质焦虑相关的额叶功能失调是否包括背外侧和腹内侧前额叶区域，干扰前者影响注意力的调节，干扰后者影响条件性恐惧的下调和消退。我们的第二个具体目标是确定是否特质焦虑的个人主要特点是额叶功能减退将受益于注意力和情绪调节训练在更大程度上比那些主要特点是杏仁核高反应。在这里，我们还将调查是否注意力和情绪调节训练的好处可以通过提供支持这些过程的额叶神经反馈来增强。我们将研究这些训练程序是否可以用来恢复贫困的背外侧和腹内侧前额叶功能，我们将调查这对持续的注意力和条件性恐惧的下调和灭绝的影响。

DESCRIPTION (provided by applicant): Two key NIMH objectives pertain to (a) the discovery of 'markers' that can be used to identify individuals at risk of psychiatric disease and (b) the development of preventative treatment measures to pre-empt the onset of disorder in these individuals. The proposed research seeks to further these objectives in the context of anxiety disorders. It investigates the neurocognitive mechanisms through which trait vulnerability to anxiety is conferred and examines whether cognitive and neurocognitive training can be used to restore function in areas of impairment. In addition, it explores whether neural markers can be used to identify those individuals 'at- risk' of anxiety disorders who are most likely to benefit from preventative cognitive training interventions. Functional magnetic resonance imaging (fMRI) will be used to test a dual route model of trait vulnerability to anxiety, the contention being that at least two, largely independent, sources of individual variability confer vulnerability to anxiety disorders. Our first specific aim is to establish whether (i) impoverished recruitment of frontal control mechanisms and (ii) enhanced amygdala responsivity to cues that signal threat are independently associated with trait vulnerability to anxiety. Both attention and fear conditioning fMRI experiments will be conducted in healthy volunteers with varying levels of trait anxiety. We aim to establish whether trait anxiety-related dysregulation of frontal function encompasses both dorsolateral and ventromedial prefrontal regions, with disruption to the former impacting the regulation of attention, and disruption to the latter impacting the down-regulation and extinction of conditioned fear. Our second specific aim is to establish whether trait anxious individuals primarily characterised by frontal hypo-activity will benefit from attention and emotion regulation training to a greater extent than those primarily characterised by amygdala hyper-responsivity. Here, we will also investigate whether the benefits of attention and emotion regulation training can be augmented by provision of neurofeedback from the frontal regions supporting these processes. We will examine whether these training procedures can be used to restore impoverished dorsolateral and ventromedial prefrontal function, and we will investigate the impact of this upon sustained attention and the down-regulation and extinction of conditioned fear.