Quantitation of Glymphatic Functioning in Sleep and Meditative States

睡眠和冥想状态下类淋巴功能的定量

基本信息

批准号：
10374920
负责人：
Daniel Oliver Claassen
金额：
$ 34.6万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374920
关键词：
Adult Awareness Behavioral Blood Circulation Brain Brain Drains Cerebrospinal Fluid Cerebrovascular Disorders Cerebrum Cervical lymph node group Cognitive Therapy Communication Communities Complement Conscious Descriptor Diffusion Disease Electroencephalography Enrollment Ependymal Cell Etiology Exercise Functional disorder Goals Health Health Benefit Human Image Individual Intercellular Fluid Laboratories Link Magnetic Resonance Imaging Measurement Measures Mediating Medical Meditation Meningeal Meningeal lymphatic system Mental Health Methods Nerve Degeneration Neuraxis Neurodegenerative Disorders Neurologic Pathway interactions Patients Perfusion Peripheral Personal Satisfaction Physiological Processes Physiology Population Proteins Reporting Role Sleep Structure of choroid plexus System Testing Therapeutic Time Tissues Toxin Training Wakefulness Waste Products Work aquaporin 4 brain parenchyma brain tissue cerebrospinal fluid flow cognitive change fluid flow glymphatic clearance glymphatic dysfunction glymphatic flow glymphatic function glymphatic system hemodynamics imaging modality improved insight lymph flow lymphatic circulation lymphatic dysfunction lymphatic vessel mindfulness meditation neuroimaging neuropathology neurophysiology non rapid eye movement non-invasive imaging novel quantitative imaging relating to nervous system tool wasting

项目摘要

ABSTRACT Brain network function and glymphatic system components vary with behavioral state, however non-invasive imaging methods have not been applied to quantify the impact of MM specifically on glymphatic flow. Here, we propose to extend our ongoing studies of glymphatic dysfunction in individuals with neurodegeneration to test fundamental hypotheses regarding the role of bulk and perivascular flow on behavioral state (wake, sleep, and MM) in health. Specifically, mindfulness meditation (MM) and associated contemplative exercises are fundamental to the mental health of a growing fraction of the population, however these practices are not widely accepted by all medical practitioners owing to a lack of objective, mechanistic evidence of how these therapies impact cerebral physiology. This issue is fundamental, as MM will not be widely accepted as a therapeutic tool until symptomatic changes are substantiated by quantitative, mechanistic descriptors. MM is hypothesized to be grounded in similar physiological processes as occur during sleep. Recent elegant work has demonstrated the role of a glymphatic waste clearance system, which is primarily active during sleep and serves to clear cerebral waste products. In this system, cerebrospinal fluid (CSF) and interstitial fluid efflux from periarterial to perivenous spaces acts in communication with potential meningeal and dural lymphatic channels to clear protein and waste products to cervical lymph nodes. Dysfunction of this system has recently been hypothesized to underlie a range of neurodegenerative disorders. However, glymphatic function remains incompletely characterized in humans, largely due to a lack of safe methods for quantifying system components routinely and across different behavioral states. Our work has focused on developing non-invasive magnetic resonance imaging methods to quantify (i) perivascular diffusion, indicative of glymphatic currents; (ii) cerebral and peripheral tissue hemodynamics and function; and (iii) bulk CSF flow velocity. These methods were first applied and validated in individuals with peripheral lymphatic or cerebrovascular dysfunction of known etiology and are now being used to evaluate how glymphatic and associated perivascular flow dysfunction may mediate neurodegenerative pathophysiology. Here, we propose to extend our ongoing studies of glymphatic dysfunction in individuals with neurodegeneration to test fundamental hypotheses regarding the role of bulk and perivascular CSF flow to Aim (1) quantify perivascular diffusion, indicative of glymphatic currents, during sleep and wakefulness; to quantify similarities between these measures of glymphatic flow, and Aim (2) for sleep and open awareness MM. Study findings are intended to inform the relevance of the traditional and well-characterized bulk CSF flow pathway, as well as more novel glymphatic pathway, on cerebral health during and following MM training. Study findings should inform the mechanism by which MM contributes to cognitive changes during active MM, as well as the potential of MM to be used as a cognitive therapy.

抽象的大脑网络功能和类淋巴系统组成随行为状态的不同而变化，然而，非侵入性成像方法尚未用于量化 MM 对类淋巴流量的具体影响。在这里，我们建议扩展我们正在进行的对神经退行性疾病个体的类淋巴功能障碍的研究，以测试关于大量和血管周围血流对健康行为状态（清醒、睡眠和MM）的作用的基本假设。具体来说，正念冥想（MM）和相关的沉思练习对于越来越多的人的心理健康至关重要，但由于缺乏客观、机械的证据来证明这些疗法如何影响，这些做法并未被所有医生广泛接受脑生理学。这个问题很重要，因为在症状变化得到定量、机制描述证实之前，MM 作为一种治疗工具不会被广泛接受。据推测，MM 的生理过程与睡眠期间发生的生理过程类似。最近的出色工作证明了类淋巴废物清除系统的作用，该系统主要在睡眠期间活跃，用于清除大脑废物。在这个系统中，脑脊液（CSF）和间质液从动脉周围流出到静脉周围空间，与潜在的脑膜和硬脑膜淋巴通道相通，以将蛋白质和废物清除到颈部淋巴结。最近有人假设该系统的功能障碍是一系列神经退行性疾病的基础。然而，人类的类淋巴功能仍然不完全表征，这主要是由于缺乏对不同行为状态下的系统组件进行常规量化的安全方法。我们的工作重点是开发非侵入性磁共振成像方法来量化（i）血管周围扩散，指示类淋巴电流； (ii) 大脑和周围组织的血流动力学和功能； (iii) 脑脊液总体流速。这些方法首先在具有已知病因的外周淋巴或脑血管功能障碍的个体中应用和验证，现在用于评估类淋巴和相关的血管周围血流功能障碍如何介导神经退行性病理生理学。在这里，我们建议扩展我们正在进行的神经退行性疾病个体的类淋巴功能障碍研究，以测试关于大量和血管周围脑脊液流向目标的作用的基本假设（1）量化血管周围扩散，指示睡眠和清醒期间的类淋巴电流；量化这些类淋巴流量测量与睡眠和开放意识 MM 的目标 (2) 之间的相似性。研究结果旨在揭示传统且特征明确的大量脑脊液流动通路以及更新颖的类淋巴通路与 MM 训练期间和之后的大脑健康的相关性。研究结果应揭示 MM 在活动性 MM 期间导致认知变化的机制，以及 MM 作为认知疗法的潜力。