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.

抽象的脑网络函数和胶状系统成分随行为状态而变化，但是尚未应用非侵入性成像方法来量化MM对胶状流的影响。在这里，我们建议扩展我们对神经变性个体的肾上腺功能障碍的持续研究，以检验有关散装和血管周流对行为状态（唤醒，睡眠和MM）健康作用的基本假设。具体而言，正念冥想（MM）和相关的沉思练习是越来越多的人群的心理健康的基础，但是由于缺乏这些疗法如何影响大脑生理学的客观，机械证据，所有医生都没有广泛接受这些实践。这个问题是基本的，因为MM不会被广泛接受为一种治疗工具，直到有症状的变化通过定量的机械描述符证实。假设MM在与睡眠过程中发生的类似生理过程中接地。最近的优雅作品展示了淋巴废物清除系统的作用，该系统主要在睡眠期间活跃，并且可以清除脑废物。在该系统中，脑脊液（CSF）和间质性液体从周期到周期空间的流出作用与潜在的脑膜和硬脑膜淋巴淋巴通道通信，以将蛋白质和废物清除到颈淋巴结中。该系统的功能障碍最近被认为是一系列神经退行性疾病的基础。然而，肾小球功能在人类中的表征仍然不完全，这主要是由于缺乏常规和跨不同行为状态量化系统组件的安全方法。我们的工作集中在开发非侵入性磁共振成像方法上来量化（i）周围的扩散，表明胶状电流。（ii）脑组织血液动力学和功能；（iii）大量CSF流速速度。这些方法首先是在已知病因的外周淋巴淋巴或脑血管功能障碍中应用和验证的，现在正在用于评估血浆和相关的血管周血流功能障碍如何介导神经退行性病理学病理学。在这里，我们建议将对神经退行性的个体的肾上腺功能障碍进行持续研究，以检验有关散装和血管周围CSF流动的作用的基本假设，以量化（1）量化血管周围的扩散，表明在睡眠和觉醒过程中，表明gllymphatic courrents；为了量化这些胶状流量的相似性，而目标（2）用于睡眠和开放意识mm。研究发现旨在为传统和良好的批量CSF流动途径以及更新颖的胶状途径提供有关在MM培训期间和之后的大脑健康的相关性。研究发现应告知MM在活性MM期间对认知变化有助于的机制，以及将MM用作认知疗法的潜力。