Sleep, Mindfulness and Glymphatics
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Meditative activities have emerged as a major component of wellbeing for a growing fraction of the population, yet the mechanisms by which these activities improve health are incompletely characterized; this issue is fundamental, as until mechanistic evidence demonstrating how these activities contribute to improved health are demonstrated, they will not be widely accepted by the medical community. It is logical that part of the wellness benefit arises from changes in a recently proposed glymphatic system in the brain, which serves to clear toxins and waste products and is over-active in states of sleep and altered consciousness, possibly including meditative states. We apply novel neuroimaging measurements of specific components of this system during different states (wakefulness, sleep, and during and following mindfulness meditation) to test fundamental hypotheses regarding the relevance of this system for explaining health benefits from mindful meditation.
Our manuscripts relevant to this work in sleep and mindfulness meditation:
More specifically, 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 quantify perivascular diffusion, indicative of glymphatic currents, during sleep and wakefulness; to quantify similarities between these measures of glymphatic flow, and 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.