Amygdala modulation of volitional versus automatic breathing

项目摘要 癫痫猝死（SUDEP）是难治性癫痫患者最常见的死亡原因。 癫痫来自SUDEP病例和糖尿病诱导死亡的动物模型的发现表明， 呼吸暂停是SUDEP的关键。SUDEP时呼吸抑制的机制 目前尚不清楚，因此，没有已知的预防策略。候选人：Brian Dlouhy博士，医学博士是一 爱荷华州大学的神经外科医生，他的临床实践主要集中在癫痫的外科治疗上。 这一建议将是他作为一个神经外科医生科学家的持续发展的关键。这项建议会 让他的研究建立在他对杏仁核如何调节神经控制的既定兴趣之上， 呼吸，将产生新的科学成果，并将为Dlouhy博士提供关键培训。德劳希医生 最终目标是成为一名R 01资助的学术神经外科医生科学家，独立研究 探索呼吸的神经控制的项目环境：爱荷华州大学提供丰富的培训 Dlouhy博士的环境，他得到了卡弗医学院和他的椅子的全力支持， 神经外科马修霍华德医生Dlouhy博士结合了一个独特的导师团队， 他们各自领域的领导者，谁拥有的专业知识有助于Dlouhy博士的研究计划： 杏仁核回路、呼吸的神经控制和人脑神经生理学。乔治·理查德森医生 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 马修霍华德博士是人类电生理学方面的专家。研究：使用颅内 Dlouhy博士先前发现，当癫痫发作传播到大脑皮层时， 杏仁核杏仁核的电刺激会导致与空气饥饿无关的呼吸暂停 （呼吸困难）或迫切需要呼吸。在刺激诱导的呼吸暂停期间，呼吸的意志控制得以保留; 受试者可以正常说话并在提示时呼吸。大脑皮层的神经机制 杏仁核影响大脑的呼吸控制网络，以介导这些效应或调节正常的呼吸。 呼吸未知。该提案旨在识别和描述杏仁核内的神经活动， 它与大脑呼吸控制部位的功能联系。德劳希博士还将研究 杏仁核的神经调节影响自主呼吸和自主呼吸，以及呼吸困难的感觉。 这些目标将通过直接电生理记录和刺激相结合来实现 技术，电刺激与功能磁共振成像，呼吸生理学实验。拟议 科学研究计划，Richerson博士，Wemmie和霍华德的优秀导师团队，以及 候选人所在机构和部门的热情支持将使Dlouhy博士能够成功地开展 作为一名独立的神经外科医生和科学家。

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.