15 Jul 2025
Teaching the brain to clean itself while sleeping; Meet the Grantee: Dr. Laura Lewis, MIT
Every night, while we sleep, our brain performs a vital task: clearing out the metabolic waste that builds up during waking hours. This natural cleanup process is essential for brain health, and disrupted sleep potentially contributes to diseases like Alzheimer’s.
Dr. Laura Lewis, a neuroscientist at MIT and a Corundum Convergence Institute research grantee, is studying how to keep this system working at its best. “I started down this path because I was fascinated by how our brains change during sleep,” she told us in our recent interview. Her research explores whether gentle sensory stimulation during sleep can boost the brain’s ability to clear waste, helping to protect memory and cognitive function. By better understanding how sleep and brain clearance are connected, her work could lead to new ways to prevent or even slow down neurological diseases.
The science behind the brain’s plumbing system
The brain is one of the most protected organs in the body, shielded by its own immune system and the highly selective blood-brain barrier (BBB). This barrier acts like a security checkpoint, letting in vital nutrients while keeping harmful substances out. Yet, some small molecules, metabolic byproducts, and toxins arise within the brain and, if not cleared, accumulate over time.
To tackle this, the brain relies on a sophisticated waste-clearing system, known as the Glymphatic System. This system, made up of a network of perivascular channels formed by astrocytes, functions much like the lymphatic system, but in the brain. Cerebrospinal fluid (CSF) moves through these channels to wash away metabolic waste, working just like a plumbing system. Unfortunately, this critical system doesn’t always function optimally. A recent paper in Nature highlights how the glymphatic flow slows in conditions like Alzheimer’s disease or after traumatic brain injury. This decline has sparked growing interest in how we might restore, or even enhance, this natural clearance mechanism. At MIT, Dr. Laura Lewis is one of the researchers tackling these very questions: how to measure and amplify brain fluid flow in real time, and what this could mean for preventing or slowing neurological disease.
Can this natural waste-clearing system be leveraged to prevent or even reverse brain disorders? Many biotech innovations aim to harness biological mechanisms for therapeutic purposes, and the glymphatic system could be the next big target. Unravelling the mysteries of how and when CSF moves through the brain could open the door to groundbreaking treatments for neurological diseases.
Sweep in your sleep: The role of sleep in brain clearance
The glymphatic system is most active during sleep, when synchronized neural activity generates rhythmic waves in CSF, facilitating waste clearance. Disrupting these waves hampers this process, but studies suggests that they can also be artificially stimulated. Another recent paper in Nature demonstrated that engaging the brain with non-invasive rhythmic sensory gamma stimulation significantly enhances CSF flow and amyloid clearance in Alzheimer’s mouse models.
The link between sleep and the glymphatic system is another active area of research. “I was surprised in the first place when we found CSF flow waves appearing in sleep!” says Dr. Lewis. In her research, she is studying how sleep deprivation disrupts CSF waves, impairing waste clearance and contributing to cognitive decline. With age, sleep quality diminishes, hinting that disturbed sleep could underlie changes in brain health across the lifespan. Dr. Lewis’s group is developing algorithms to enhance slow-wave sleep using sensory stimulation, aiming to improve CSF flow and brain health as we age.
Amplifying CSF Waves
In her research, Dr. Lewis uses closed-loop EEG-fMRI to measure the CSF-flow during sleep in real time. While this line of work is still early, the potential clinical implications are significant. “While EEG measures electrical activity with excellent temporal resolution,” Dr. Lewis explains, “it can't image other aspects of physiology in the brain, and it can't localize signals specifically in space, especially from deeper brain regions. We have been developing EEG-fMRI strategies to study sleep so that we can combine fast electrical measurements with imaging that captures a whole-brain view. This allows us to measure things like CSF flow, and also allows us to study deep brain regions that are critical for controlling sleep states.”
Her hypothesis is that if timed correctly, stimulation can nudge the system at just the right moment, similar to pushing a swing in rhythm, to boost the brain’s own waste-clearing mechanisms and potentially reduce risk of neurodegeneration. A critical challenge is developing a method that works in people of all ages, especially later in life. “One important change is that sleep itself changes in aging,” says Dr. Lewis. “People sleep less, and have fewer slow wave events in the EEG, which are coupled to CSF waves. Our current work is focusing on how to individualize stimulation in a way that takes into account individual spontaneous brain activity – for example, recognizing that slow waves are smaller in an older person, and redefining the stimulation targets accordingly.”
During non-REM sleep, CSF flows in rhythmic waves, aiding in the clearance of metabolic waste from the brain. This process is closely linked to synchronized neuronal activity and blood flow dynamics. As individuals age, there is a natural decline in slow-wave activity during sleep, which may lead to less efficient removal of neurotoxic waste products. This decline could contribute to cognitive impairments and an increased risk of neurodegenerative diseases. Individual variability is a major challenge in sleep research – what works for one person may not work for another. There are core differences in sleep patterns, neurophysiology, and CSF dynamics.
By tailoring closed-loop stimulation to each person’s unique sleep rhythms, Dr. Lewis aims to restore the slow-wave patterns that drive CSF clearance – and with them, the brain’s natural nightly reset. “I hope that we can develop the findings into a home device that patients could use to monitor, or even improve, their sleep,” says Dr. Lewis. “Since sleep is so strongly tied to health – neurological health, mental health, and chronic disease broadly – I’m excited for the potential of this project to be important for many different groups of patients, and in the long term hopefully improve outcomes in a wide array of clinical conditions.”
In future studies, Dr. Lewis hopes to identify the specific neural circuits that govern sleep and explore ways to optimize sleep medications. She also plans to investigate the close relationship between sleep and mood. The ultimate aim: a more precise and personalized toolkit for enhancing the brain’s own regenerative processes.
A window into prevention
Sleep remains one of the most accessible, yet underleveraged, entry points into brain health. Dr. Lewis’s work highlights the possibility of tuning intrinsic physiological rhythms, not with drugs or invasive devices, but with precise, personalized interventions rooted in the science of sleep. At the Corundum Convergence Institute, we support research like this because it opens entirely new categories of preventive care. By advancing tools to measure, modulate, and ultimately enhance the brain’s self-maintenance systems, Dr. Lewis’s work has the potential to shift how we age, how we intervene, and how we understand the relationship between rest and resilience.
The science behind the brain’s plumbing system
The brain is one of the most protected organs in the body, shielded by its own immune system and the highly selective blood-brain barrier (BBB). This barrier acts like a security checkpoint, letting in vital nutrients while keeping harmful substances out. Yet, some small molecules, metabolic byproducts, and toxins arise within the brain and, if not cleared, accumulate over time.
To tackle this, the brain relies on a sophisticated waste-clearing system, known as the Glymphatic System. This system, made up of a network of perivascular channels formed by astrocytes, functions much like the lymphatic system, but in the brain. Cerebrospinal fluid (CSF) moves through these channels to wash away metabolic waste, working just like a plumbing system. Unfortunately, this critical system doesn’t always function optimally. A recent paper in Nature highlights how the glymphatic flow slows in conditions like Alzheimer’s disease or after traumatic brain injury. This decline has sparked growing interest in how we might restore, or even enhance, this natural clearance mechanism. At MIT, Dr. Laura Lewis is one of the researchers tackling these very questions: how to measure and amplify brain fluid flow in real time, and what this could mean for preventing or slowing neurological disease.
Can this natural waste-clearing system be leveraged to prevent or even reverse brain disorders? Many biotech innovations aim to harness biological mechanisms for therapeutic purposes, and the glymphatic system could be the next big target. Unravelling the mysteries of how and when CSF moves through the brain could open the door to groundbreaking treatments for neurological diseases.
Sweep in your sleep: The role of sleep in brain clearance
The glymphatic system is most active during sleep, when synchronized neural activity generates rhythmic waves in CSF, facilitating waste clearance. Disrupting these waves hampers this process, but studies suggests that they can also be artificially stimulated. Another recent paper in Nature demonstrated that engaging the brain with non-invasive rhythmic sensory gamma stimulation significantly enhances CSF flow and amyloid clearance in Alzheimer’s mouse models.
The link between sleep and the glymphatic system is another active area of research. “I was surprised in the first place when we found CSF flow waves appearing in sleep!” says Dr. Lewis. In her research, she is studying how sleep deprivation disrupts CSF waves, impairing waste clearance and contributing to cognitive decline. With age, sleep quality diminishes, hinting that disturbed sleep could underlie changes in brain health across the lifespan. Dr. Lewis’s group is developing algorithms to enhance slow-wave sleep using sensory stimulation, aiming to improve CSF flow and brain health as we age.
Amplifying CSF Waves
In her research, Dr. Lewis uses closed-loop EEG-fMRI to measure the CSF-flow during sleep in real time. While this line of work is still early, the potential clinical implications are significant. “While EEG measures electrical activity with excellent temporal resolution,” Dr. Lewis explains, “it can't image other aspects of physiology in the brain, and it can't localize signals specifically in space, especially from deeper brain regions. We have been developing EEG-fMRI strategies to study sleep so that we can combine fast electrical measurements with imaging that captures a whole-brain view. This allows us to measure things like CSF flow, and also allows us to study deep brain regions that are critical for controlling sleep states.”
Her hypothesis is that if timed correctly, stimulation can nudge the system at just the right moment, similar to pushing a swing in rhythm, to boost the brain’s own waste-clearing mechanisms and potentially reduce risk of neurodegeneration. A critical challenge is developing a method that works in people of all ages, especially later in life. “One important change is that sleep itself changes in aging,” says Dr. Lewis. “People sleep less, and have fewer slow wave events in the EEG, which are coupled to CSF waves. Our current work is focusing on how to individualize stimulation in a way that takes into account individual spontaneous brain activity – for example, recognizing that slow waves are smaller in an older person, and redefining the stimulation targets accordingly.”
During non-REM sleep, CSF flows in rhythmic waves, aiding in the clearance of metabolic waste from the brain. This process is closely linked to synchronized neuronal activity and blood flow dynamics. As individuals age, there is a natural decline in slow-wave activity during sleep, which may lead to less efficient removal of neurotoxic waste products. This decline could contribute to cognitive impairments and an increased risk of neurodegenerative diseases. Individual variability is a major challenge in sleep research – what works for one person may not work for another. There are core differences in sleep patterns, neurophysiology, and CSF dynamics.
By tailoring closed-loop stimulation to each person’s unique sleep rhythms, Dr. Lewis aims to restore the slow-wave patterns that drive CSF clearance – and with them, the brain’s natural nightly reset. “I hope that we can develop the findings into a home device that patients could use to monitor, or even improve, their sleep,” says Dr. Lewis. “Since sleep is so strongly tied to health – neurological health, mental health, and chronic disease broadly – I’m excited for the potential of this project to be important for many different groups of patients, and in the long term hopefully improve outcomes in a wide array of clinical conditions.”
In future studies, Dr. Lewis hopes to identify the specific neural circuits that govern sleep and explore ways to optimize sleep medications. She also plans to investigate the close relationship between sleep and mood. The ultimate aim: a more precise and personalized toolkit for enhancing the brain’s own regenerative processes.
A window into prevention
Sleep remains one of the most accessible, yet underleveraged, entry points into brain health. Dr. Lewis’s work highlights the possibility of tuning intrinsic physiological rhythms, not with drugs or invasive devices, but with precise, personalized interventions rooted in the science of sleep. At the Corundum Convergence Institute, we support research like this because it opens entirely new categories of preventive care. By advancing tools to measure, modulate, and ultimately enhance the brain’s self-maintenance systems, Dr. Lewis’s work has the potential to shift how we age, how we intervene, and how we understand the relationship between rest and resilience.