Brain Mechanisms of Anticipatory Processing in Anxiety Disorders

描述(由申请人提供)：焦虑症是一种使人衰弱的精神疾病，影响许多人，并带来很高的社会和经济负担。这些障碍的一个中心特征是对潜在不良后果的过度预期。这位候选人和其他人的实验室中的大量研究发现，在对厌恶事件的预期过程中，会有多个大脑区域被激活。该应用程序的主要研究目标是探索焦虑症患者预期过程中的这些区域的异常，并检查不确定性和不可控性的影响，这些因素在焦虑中占有突出地位。这项计划中的研究还将评估已确定的大脑网络之间的功能关联和白质连接。为此，对功能和结构连接方法的培训是职业发展计划的主要重点。这些研究连通性的快速发展领域显然是候选人研究计划和职业发展的下一步，对于他继续努力为我们不断发展的关于焦虑状态下大脑功能的知识库做出贡献，将是至关重要的。该环境是追求这些研究和职业发展目标的理想环境，拥有出色的设施、合作者和资源，以及精神病学系和韦斯曼中心的高度支持。这项拟议的研究将使用候选人实验室在过去7年里设计和开发的图片范式来检验广泛性焦虑症和社交焦虑症的预期功能。这两种焦虑症与抑郁的高共病程度将通过纳入严重抑郁障碍的患者来系统地调查。预期过程中神经异常的发现应该会增加已经用于开发新的临床工具的工作，这些工具直接针对焦虑和抑郁的特定脑区，如经颅磁刺激、硬膜外皮质刺激和脑深部刺激。心理治疗客户可能受益于更多地关注与他们的症状相关的预期过程的干预策略。拟议项目的研究结果可能对确定哪些人可能从特定治疗中受益具有影响，这是基于候选人和他的同事最近的发现，即前扣带回更大的预期活动预示着对为期8周的药物试验的更好反应。

DESCRIPTION (provided by applicant): Anxiety disorders are a debilitating form of mental illness that affect many people and carry a high societal and economic burden. A central feature of these disorders is the excessive anticipation of potential adverse outcomes. Considerable work in the candidate's and others' labs has identified multiple brain areas recruited during the anticipation of aversive events. The primary research objectives of this application are to probe these areas for abnormalities during anticipation in anxiety disorder patients and to examine the impact of uncertainty and uncontrollability, which figure prominently in anxiety. The planned research will also assess functional associations and white matter connections among the brain networks identified. In service of that, training in functional and structural connectivity methods is the major focus of the career development plan. These rapidly developing areas examining connectivity are an obvious next step for the candidate's research program and career development and will be crucial in his efforts to continue contributing to our developing knowledge base about brain function in anxiety. The environment is ideal for the pursuit of these research and career development objectives, with outstanding facilities, collaborators, and resources as well as a high degree of support from both the Department of Psychiatry and the Waisman Center. The proposed research will examine anticipatory function in generalized anxiety disorder and social anxiety disorder using a picture paradigm designed and developed in the candidate's laboratory over the past 7 years. The high levels of comorbidity with depression for these two anxiety disorders will be systematically investigated by including patients with major depressive disorder. The discovery of neural abnormalities in anticipatory processes should add to the body of work already being used in developing new clinical tools for directly targeting specific brain regions in anxiety and depression, such as transcranial magnetic stimulation, epidural electrocortical stimulation, and deep brain stimulation. Psychotherapy clients may benefit from greater focus of intervention strategies on anticipatory processes relevant to their symptoms. Research findings from the proposed project might have implications for determining which individuals would be likely to benefit from a particular treatment, building on recent findings by the candidate and his colleagues that greater anticipatory activity in the anterior cingulate predicts better response to an 8-week medication trial.