Neural Probes of Respiratory Control and Interoception in Panic Disorder

描述（由申请人提供）：惊恐障碍中呼吸控制和内感受的神经探针，"NIMH面向患者的研究职业发展奖（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，以促进未来独立的情绪和焦虑症神经影像学研究项目的目标。本研究拟以呼吸内感受之影像学研究作为研究计画。恐慌症是一种严重的精神疾病，由于其在普通人群中的患病率为2 - 4%，并且治疗无反应和复发率很高（> 50%），因此会造成重大的社会经济负担。惊恐障碍的病理生理学基础尚不清楚，尽管流行的模型反映了皮质边缘脑功能障碍和呼吸异常的作用。候选人建议测试一种新的皮质边缘/边缘脑模型，重点是岛皮质及其在内感受（身体生理状况的感觉）中的作用。完整的内感受对于生存是必不可少的，作为稳态失衡的警报，并且被认为主要在岛叶皮层内处理。虽然岛叶皮层在以前的惊恐神经影像学研究中已经被发现，但一个统一的以岛叶为焦点的惊恐神经回路模型还有待检验和解释。所提出的神经回路模型将岛叶皮层内的功能障碍归因于触发对身体症状（内感受性线索）的误解，这反过来又导致沿着最终的共同恐慌回路的夸大的行为/恐惧反应沿着。呼吸内感受激发期间的功能性磁共振成像（fMRI）研究将用于测试候选人的惊恐障碍神经回路模型，该模型以岛叶皮层及其在内感受中的作用为中心。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，以区分惊恐障碍的呼吸亚型，据报道占惊恐患者的50%以上。总的来说，该项目代表了第一个对惊恐障碍与呼吸激发和控制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：惊恐障碍（一种以频繁的自发性惊恐发作为特征的疾病）的原因尚不清楚，目前的治疗方法无法使大多数患者缓解。目前的项目旨在描绘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.