Probing Amygdalo-Cortical Circuitry in Anxiety Disorders

描述（由申请人提供）：我们建议研究三种焦虑症的病理学：创伤后应激障碍（PTSD）恐慌症（PD）。和特定恐惧症（SP）。我们将使用认知激活范式和磁共振成像（MRI）来探讨相关杏仁核皮质回路的功能和结构。收敛数据表明杏仁核皮质回路与焦虑症的病理生理学有关。例如，PTSD 的一种模型假设杏仁核对威胁相关刺激的反应过度，以及特定皮质区域（包括前扣带皮层、胼胝体下皮质和海马体）对杏仁核反应的自上而下调节不足。尽管来自神经影像学研究的聚合数据支持该模型，但我们建议在几个方面扩展这一研究方向：1）使用一种能够表征杏仁核反应的习惯化/敏化的方法来研究这个时间维度。初步数据表明，PTSD 和 PD 的特征可能是杏仁核对威胁相关刺激的反应敏感化（相对于习惯化）。 2）测量同一受试者的膝周皮质和杏仁核功能，以定量评估这些大脑区域之间的关系。如果病理生理学或临床指标的相关性与区域间相互作用有关，则这种系统级方法是必要的。 3）研究大脑结构异常与功能异常之间的关系；我们计划使用现代皮质分割方法和测量皮质厚度的新技术。皮质厚度方法将使我们能够：A）分解体积差异以确定皮质厚度和皮质表面积的相对贡献，B）绘制观察到的功能和结构差异之间的地形一致性。 4）除了正常比较和遭受创伤的正常比较受试者之外，还研究精神病学比较组，以确定这些焦虑症中研究结果的特异性（与普遍性）。

DESCRIPTION (provided by applicant): We propose to investigate the pathoDhvsiology of three anxiety disorders: posttraumatic stress disorder (PTSD) panic disorder (PD). and specific phobia (SP). We will use cognitive activation paradigms and magnetic resonance imaging (MRI) to probe the function and structure of implicated amygdalo-cortical circuitry. Convergent data implicate amygdalo- cortical circuitry in the pathophysiology of anxiety disorders. For example, one model of PTSD posits exaggerated amygdala responsivity to threat-related stimuli as well as deficient top-down modulation of amygdala responses by specific cortical regions, including pregenual anterior cingulate cortex, subcallosal cortex, and hippocampus. Though convergent data from neuroimaging studies support this model, we propose to extend this line of research in several respects: 1) use an approach that enables the characterization of habituation/sensitization of amygdala response, to investigate this temporal dimension. Preliminary data suggest that both PTSD and PD may be characterized by sensitization (vs. habituation) of amygdala responses to threat-related stimuli. 2) measure perigenual cortical and amygdala function in the same subjects, to enable a quantitative assessment of the relationship between these brain regions. Such a systems level approach is necessary if pathophysiology or correlates of clinical indices are related to inter-regional interactions. 3) investigate the relationship between abnormal brain structure and abnormal function; we plan to use modern cortical parcellation methods and a new technique for measuring cortical thickness. The cortical thickness method will enable us to: A) decompose volumetric differences to determine the relative contributions of cortical thickness and cortical surface area, and B) map the topographic concordance between observed functional and structural differences. 4) study psychiatric comparison groups, in addition to normal comparison and trauma-exposed normal comparison subjects, in order to determine the specificity (vs. generalizability) of findings among these anxiety disorders.