Neural Probes of Respiratory Control and Interoception in Panic Disorder

描述(由申请者提供)：惊恐障碍中呼吸控制和内感的神经探针，“NIMH患者导向研究职业发展奖(K23)的申请书”。该候选人已经完成了神经成像研究员培训，并寻求高级培训，以促进未来情绪和焦虑症的独立神经成像研究项目的目标。一项惊恐障碍患者呼吸内感觉的神经成像研究将作为拟议的项目。恐慌症是一种严重的精神疾病，由于其在普通人群中的流行率为2%-4%，治疗无反应和复发率很高(50%)，因此造成了巨大的社会经济负担。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-边缘脑功能障碍和异常呼吸的作用。候选人建议测试一种新的皮质-边缘/边缘旁模型，重点研究大脑皮质及其在内感(对身体生理状况的感觉)中的作用。完整的内感觉对生存至关重要，因为它是体内平衡失衡的警报，被认为主要是在岛叶皮质内处理的。虽然岛叶皮质在以前的惊恐神经成像研究中有牵连，但关于岛叶病灶的惊恐神经回路的统一模型还没有得到测试和解释。提出的神经回路模型将岛叶皮质内的功能障碍归因于触发对身体症状(内感线索)的误解，这反过来又导致沿着最终常见的恐慌回路做出夸大的行为/恐惧反应。呼吸内感觉刺激期间的功能磁共振成像(FMRI)研究将被用来测试候选人针对惊恐障碍的神经电路模型，中心是岛叶皮质及其在内感觉中的作用。额外的酸/碱生理学和呼吸心理生理学测试将补充神经成像研究，以区分恐慌症的呼吸系统亚型，据报道，恐慌症患者中有50%以上。总而言之，该项目代表了第一个关于惊恐障碍与呼吸刺激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，同时承诺向一般模型提供焦虑回路的信息。与公共卫生相关：恐慌症(一种以频繁、自发的恐慌症为特征的疾病)的原因尚不清楚，目前的治疗方法未能使大多数患者得到缓解。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.