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

项目总结： 脑脊液(CSF)在大脑中的流动对维持大脑健康是必不可少的， 通过淋巴系统清除代谢废物。这一清关过程的中断是 与多种神经退行性疾病有关，特别是阿尔茨海默病。两个关键机制 人类脑脊液流动的基础是呼吸周期和连贯的神经活动。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脑脊液流动。 我们将测试自主呼吸如何与脑脊液流量相关，并测试呼吸速度是否较慢 更高的流量。然后我们将使用呼吸门控经皮迷走神经刺激，一种非侵入性的 神经调节技术，刺激神经活动，整合呼吸和神经活动，以 以最佳方式驱动脑脊液流动。最后，我们将测试呼吸和呼吸门控神经刺激是如何调节的。 在大脑室和微小的血管周围空间中流动，这是大脑清除所必需的，使用 一种新的基于fMRI的高时间分辨率心电节律动态成像技术 血管周围血流。总之，这些研究将确定呼吸和神经活动的调节是如何在 音乐会推动脑脊液在大脑中流动。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无创刺激是否能改善临床 结果和预防阿尔茨海默病等神经疾病的发展。

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.