Neural Probes of Respiratory Control and Interoception in Panic Disorder

描述（由申请人提供）：“恐慌障碍中呼吸控制和内感受的神经探针”，NIMH患者导向研究职业发展奖（K23）的申请。候选人已完成神经影像学奖学金培训，并寻求高级培训，以促进未来在情绪和焦虑症方面独立的神经影像学研究项目的目标。拟进行惊恐障碍患者呼吸内感受的神经影像学研究。惊恐障碍是一种严重的精神疾病，由于其在一般人群中的患病率为2-4%，以及治疗无反应和复发率高（50 - 50%），造成了重大的社会经济负担。恐慌症的病理生理基础尚不清楚，尽管主流模型反映了皮质边缘脑功能障碍和呼吸异常的作用。候选人建议测试一个新的皮质边缘/副边缘模型，重点关注岛皮质及其在内感受（身体生理状况的感觉）中的作用。完整的内感受作为体内平衡不平衡的警报对生存至关重要，并且被认为主要在岛叶皮层内进行处理。虽然岛叶皮层在之前的恐慌神经成像研究中有所涉及，但一个具有岛叶焦点的恐慌神经回路的统一模型尚未得到测试和解释。提出的神经回路模型将岛叶皮层的功能障碍归因于触发对身体症状（内感受性线索）的误解，进而导致最终共同恐慌回路中夸大的行为/恐惧反应。功能磁共振成像（fMRI）研究将用于测试候选人的恐慌障碍神经回路模型，以岛叶皮层为中心及其在间感受中的作用。酸/碱生理学和呼吸心理生理学的额外测试将补充神经影像学研究，以区分呼吸亚型的恐慌症，据报道占恐慌患者的50%以上。总的来说，这个项目代表了第一个对呼吸刺激和控制的恐慌症的综合神经系统研究。该项目将测试恐慌神经回路的统一模型，同时承诺为焦虑回路的一般模型提供信息。公共卫生相关性相关性：惊恐障碍（一种以频繁、自发惊恐发作为特征的疾病）的病因尚不清楚，目前的治疗不能使大多数患者缓解。目前的项目旨在描述与恐慌症有关的功能失调的大脑回路，以便开发出更好的治疗方法。

DESCRIPTION (provided by applicant): Neural Probes of Respiratory Control and Interoception in Panic Disorder," an application for an NIMH Patient Oriented Research Career Development Award (K23). The candidate has completed neuroimaging fellowship training and seeks advanced training to facilitate objectives for future independent neuroimaging research programs in the mood and anxiety disorders. A neuroimaging study of respiratory interoception in panic disorder will serve as the proposed project. Panic disorder is a serious psychiatric illness that imposes significant social-economic burden given its prevalence of 2-4% in the general population, and high rates (>50%) of treatment non-response and relapse. The pathophysiological basis of panic disorder is unknown, although prevailing models reflect roles for cortico-limbic brain dysfunction and abnormal respiration. The candidate proposes to test a new cortico-limbic/paralimbic model focused on the insularcortex and its role in interoception (the sense of the physiological condition of the body). Intact interoception is essential to survival as an alarm for homeostatic imbalance, and thought to be primarily processed within the insular cortex. While the insular cortex has been implicated in previous panic neuroimaging studies, a unified model for panic neural circuitry with an insular focus has yet to be tested and explained. The proposed neural circuit model attributes dysfunction within insular cortex to trigger the misinterpretation of physical symptoms (interoceptive cues), that in turn lead to exaggerated behavioral/fear responses along a final common panic circuitry. Functional magnetic resonance imaging (fMRI) studies during respiratory interoceptive provocation will be used to test the candidate's neural circuit model for panic disorder, centered on the insular cortex and its role in interoception. Additional tests of acid/base physiology and respiration psychophysiology will complement the neuroimaging studies in order to differentiate a respiratory subtype of panic disorder, reported to account for greater than 50% of panic patients. Taken together, the project represents the first integrated neural systems study of panic disorder with respiratory provocation and control. The project will test a unified model for panic neural circuitry while promising to inform general models of anxiety circuitry. PUBLIC HEALTH RELEVANCE RELEVANCE: The cause of panic disorder (a condition characterized by frequent, spontaneous panic attacks) is unknown and current treatments fail to keep most patients in remission. The current project aims to delineate the dysfunctional brain circuits involved in panic disorder so that better treatments may be developed.