Probing Amygdalo-Cortical Circuitry in Anxiety Disorders

探索焦虑症中的杏仁核皮质回路

• 批准号: 7163494
• 负责人: SCOTT L RAUCH
• 金额: $ 30.21万
• 依托单位: MCLEAN 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 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163494
• 关键词: Amygdaloid structure; Animal Phobia; Anterior; Anxiety Disorders; Area; Attenuated; Brain; Brain region; Clinical; Cognitive; Count; Data; Dimensions; Disease; Emotional; Exhibits; Face; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Hippocampus (Brain); Magnetic Resonance Imaging; Maps; Masks; Measures; Medial; Methods; Modeling; Names; Panic Disorder; Patients; Post-Traumatic Stress Disorders; Prefrontal Cortex; Principal Investigator; Relative (related person); Research; Sampling; Severities; Specific Phobia; Specificity; Stimulus; Structure; Structure-Activity Relationship; Surface; Symptoms; System; Techniques; Testing; Thick; Trauma; Traumatic Stress Disorders; cingulate cortex; comparison group; face mask; indexing; innovation; neuroimaging; programs; response

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）：我们建议研究三种焦虑障碍的病理生理学：创伤后应激障碍（PTSD）和恐慌障碍（PD）。和特殊恐惧症（SP）。我们将使用认知激活范式和磁共振成像（MRI）来探讨牵涉杏仁核-皮层回路的功能和结构。趋同的数据暗示杏仁核-皮层回路在焦虑障碍的病理生理中。例如，一种创伤后应激障碍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、胼胝体下皮层和海马体）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趋同数据支持这一模型，但我们建议在几个方面扩展这一研究路线：1)使用一种能够表征杏仁核反应的习惯化/敏化的方法，来研究这一时间维度。初步数据表明，PTSD和PD都可能以杏仁核对威胁相关刺激反应的敏化（与习惯化）为特征。2)测量同一受试者的下皮层和杏仁核功能，以便定量评估这些大脑区域之间的关系。如果病理生理学或相关的临床指标与区域间的相互作用有关，这种系统水平的方法是必要的。3)探讨脑结构异常与功能异常的关系；我们计划使用现代皮质包裹法和一种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)在正常对照和创伤暴露的正常对照对象之外，研究精神病学对照组，以确定这些焦虑症发现的特异性（与普遍性）。