Amygdala modulation of volitional versus automatic breathing

项目总结 癫痫猝死(SUDEP)是难治性癫痫患者最常见的死亡原因 癫痫。SUDEP病例和癫痫诱发死亡动物模型的研究结果表明，中枢 呼吸暂停是SUDEP的关键。SUDEP中癫痫发作引起呼吸抑制的机制 并不清楚，因此，尚无已知的预防战略。候选人：布莱恩·德洛伊博士，医学博士 爱荷华大学的神经外科医生，他的临床实践侧重于癫痫的外科治疗。 这项提议对于他作为一名神经外科医生-科学家的持续发展至关重要。这项提议将 允许他的研究建立在他对杏仁核如何调节神经控制的兴趣之上 呼吸，将产生新的科学结果，并将为德洛伊博士提供关键培训。德洛伊医生的 最终目标是成为一名R01资助的学术神经外科医生-科学家，拥有独立研究 探索呼吸的神经控制的程序。环境：爱荷华大学提供丰富的培训 为德洛伊博士创造了良好的环境，他得到了卡弗医学院和他的 神经外科马修·霍华德医生。德洛伊博士组建了一支独特的导师团队， 每个人都是各自领域的领导者，并拥有对德洛伊博士的研究计划有帮助的专业知识： 杏仁核回路、呼吸的神经控制和人脑神经生理学。乔治·里切森博士是 呼吸神经生理学领域的专家；John Wemmie博士是杏仁核领域的领导者 神经生物学；马修·霍华德博士是人类电生理学专家。研究：使用颅内 在癫痫患者的记录中，德洛希博士先前发现，当癫痫发作蔓延到 杏仁核。电刺激杏仁核可导致与空气饥饿无关的呼吸暂停 (呼吸困难)或急于呼吸。在刺激性呼吸暂停期间，不存在对呼吸的意志控制； 受试者可以正常说话，并在提示下呼吸。潜在的神经机制， 杏仁核影响大脑的呼吸控制网络，以调节这些影响或调节正常 呼吸是未知的。这项建议旨在识别和表征杏仁核内的神经活动和 它与大脑呼吸控制部位的功能联系。德洛伊博士还将研究如何进行实验 杏仁核的神经调节影响自主呼吸与自动呼吸，以及对呼吸困难的感知。 这些目标将使用直接电生理记录和刺激的组合来实现 技术、电刺激和功能磁共振成像，以及呼吸生理学实验。建议数 科研计划，Richerson博士、Wemmie博士和Howard博士的优秀导师团队，以及 候选人所在机构和部门的热情支持将使德洛伊博士能够成功地推出 作为一名独立神经外科医生兼科学家的职业生涯。

PROJECT SUMMARY Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. Findings from SUDEP cases and from animal models of seizure-induced death suggest that central apnea is critical for SUDEP. The mechanisms underlying seizure-induced inhibition of breathing during SUDEP are unclear, and therefore, no known preventive strategies exist. Candidate: Dr. Brian Dlouhy, M.D. is a neurosurgeon at the University of Iowa whose clinical practice focuses on the surgical treatment of epilepsy. This proposal will be critical for his continued development as a neurosurgeon-scientist. This proposal will allow his research to build upon his established interest in how the amygdala modulates the neural control of respiration, will produce novel scientific results, and will provide critical training for Dr. Dlouhy. Dr. Dlouhy’s ultimate goal is to become an R01-funded academic neurosurgeon-scientist with an independent research program exploring neural control of respiration. Environment: The University of Iowa provides a rich training environment for Dr. Dlouhy, and he has the full support from the Carver College of Medicine and his Chair in the Department of Neurosurgery, Dr. Matthew Howard. Dr. Dlouhy has combined a unique team of mentors, each leaders of their respective fields and who possess expertise instrumental to Dr. Dlouhy’s research plan: amygdala circuitry, neural control of respiration, and human brain neurophysiology. Dr. George Richerson, is an expert in the field of respiratory neurophysiology; Dr. John Wemmie is a leader in the field of amygdala neurobiology; Dr. Matthew Howard is an expert in human electrophysiology. Research: Using intracranial recordings in epilepsy patients, Dr. Dlouhy previously found that apnea occurs when seizures propagate to the amygdala. Electrical stimulation of the amygdala can lead to apnea that is not associated with air hunger (dyspnea) or urge to breathe. Volitional control of respiration is spared during stimulation-induced apnea; subjects can speak normally and breathe when prompted. The underlying neural mechanisms by which the amygdala influences the brain’s respiratory control network to mediate these effects or regulate normal breathing are unknown. This proposal aims to identify and characterize neural activity within the amygdala and its functional connections with brain respiratory control sites. Dr. Dlouhy will also study how experimental neuromodulation of the amygdala affects volitional versus automatic breathing, and the perception of dyspnea. These aims will be accomplished using a combination of direct electrophysiological recording and stimulation techniques, electrical stimulation concurrent with fMRI, and respiratory physiology experiments. The proposed scientific research plan, the excellent mentorship team of Drs. Richerson, Wemmie, and Howard, and the enthusiastic support of the candidate’s institution and department will enable Dr. Dlouhy to launch a successful career as an independent neurosurgeon-scientist.