Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology

神经影像学呼吸和呼吸门控神经调节对人类类淋巴生理学的影响

• 批准号: 10214185
• 负责人: Laura Diane Lewis
• 金额: $ 68.98万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10214185
• 关键词: Alzheimer' s Disease; Arousal; Automobile Driving; Blood Vessels; Brain; Brain Stem; Breathing; Cell Nucleus; Cerebrospinal Fluid; Clinical; Clinical Research; Coupled; Coupling; Failure; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Future; Human; Image; Imaging Techniques; Intervention; Link; Maps; Measurement; Measures; Mediating; Metabolic; Nerve; Neurodegenerative Disorders; Neurodevelopmental Disorder; Outcome; Patient-Focused Outcomes; Periodicity; Physiology; Play; Population; Process; Resolution; Respiration; Rest; Role; Signal Transduction; Techniques; Testing; Tissues; Transcutaneous Electric Nerve Stimulation; Wakefulness; Waste Products; Work; afferent nerve; base; blood oxygen level dependent; brain health; cerebrospinal fluid flow; clinical investigation; design; fluid flow; glymphatic clearance; glymphatic system; hemodynamics; improved; locus ceruleus structure; neuroimaging; neuroregulation; noradrenergic; relating to nervous system; respiratory; spatiotemporal; temporal measurement; therapeutic evaluation; vagus nerve stimulation; wasting

Project summary: The flow of cerebrospinal fluid (CSF) through the brain is essential for maintaining brain health, and clears metabolic waste products through the glymphatic system. Disruption of this clearance process is associated with multiple neurodegenerative disorders, notably Alzheimer’s disease. Two key mechanisms underlying CSF flow in humans are the respiratory cycle, and coherent neural activity. This project aims to determine whether synergistic drive of respiration and neural activity enhances CSF flow in the human brain. We will test how spontaneous respiration is associated with CSF flow and test whether slower breathing drives higher flow. We will then use respiratory-gated transcutaneous vagal nerve stimulation, a noninvasive neuromodulation technique to stimulate neural activity, integrating both respiratory and neural activity to optimally drive CSF flow. Finally, we will test how respiration and respiratory-gated neurostimulation modulate flow both in the large ventricles, and in the tiny perivascular spaces that are essential for brain clearance, using a new fMRI-based imaging technique with high temporal resolution to measure rhythmic dynamics in perivascular flow. Together, these studies will establish how modulation of respiration and neural activity in concert drives CSF flow through the brain. This work will provide the foundation for future clinical investigations testing whether noninvasive stimulation integrating neural and respiratory rhythms can improve clinical outcomes and protect against development of neurological disorders such as Alzheimer’s disease.

项目概要： 脑脊液（CSF）通过大脑的流动对于维持大脑健康至关重要， 通过胶质淋巴系统清除代谢废物。破坏这一清除过程是 与多种神经退行性疾病相关，特别是阿尔茨海默病。两个关键机制 人体内潜在的CSF流动是呼吸循环和连贯的神经活动。该项目旨在 确定呼吸和神经活动的协同驱动是否增强了人脑中的CSF流动。 我们将测试自主呼吸如何与CSF流量相关，并测试呼吸减慢是否会导致 更高的流量然后，我们将使用非侵入性门控经皮迷走神经刺激， 神经调节技术刺激神经活动，整合呼吸和神经活动， 最佳地驱动CSF流动。最后，我们将测试呼吸和呼吸门控神经刺激如何调节 在大脑室和对大脑清除至关重要的微小血管周围空间中流动，使用 一种新的基于fMRI的成像技术，具有高时间分辨率，可测量 血管周围血流总之，这些研究将建立如何调制呼吸和神经活动， 音乐会推动脑脊液流经大脑这项工作将为今后的临床研究提供基础 测试整合神经和呼吸节律的非侵入性刺激是否可以改善临床 结果和防止神经系统疾病的发展，如阿尔茨海默氏病。