Probing Amygdalo-Cortical Circuitry in Anxiety Disorders

探索焦虑症中的杏仁核皮质回路

• 批准号: 7029990
• 负责人: SCOTT L RAUCH
• 金额: $ 39.38万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7029990
• 关键词: amygdala; brain morphology; clinical research; corticofugal system; functional magnetic resonance imaging; habits; human subject; interview; neural information processing; neuropathology; panic disorder; patient oriented research; phobias; posttraumatic stress disorder; response generalization; visual stimulus

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.

描述（由申请人提供）：我们建议调查三种焦虑症的病理学：创伤后应激障碍（PTSD）和恐慌症（PD）。特殊恐惧症（Specific Phobia，SP）我们将使用认知激活范例和磁共振成像（MRI）来探测牵连杏仁皮质回路的功能和结构。聚合数据暗示杏仁核-皮质回路在焦虑症的病理生理学中。例如，PTSD的一个模型假定杏仁核对威胁相关刺激的反应过度，以及特定皮质区域（包括膝前扣带回前皮质、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。虽然来自神经影像学研究的收敛数据支持这一模型，但我们建议在几个方面扩展这一研究路线：1）使用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的特点可能是杏仁核对威胁相关刺激的敏感化（与习惯化）。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)研究异常脑结构和异常功能之间的关系;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，以及B）绘制观察到的功能和结构差异之间的地形一致性。4)除了正常对照和创伤暴露的正常对照受试者之外，还研究精神病对照组，以确定这些焦虑症中发现的特异性（与普遍性）。