Manipulating specific brain waves in sleep shifts balance between learning or forgetting a new skill
October 3, 2019
Science Daily/University of California - San Francisco
Distinct patterns of electrical activity in the sleeping brain may influence whether we remember or forget what we learned the previous day, according to a new study by UC San Francisco researchers. The scientists were able to influence how well rats learned a new skill by tweaking these brainwaves while animals slept, suggesting potential future applications in boosting human memory or forgetting traumatic experiences, the researchers say.
In the new study, published online October 3 in the journal Cell, a research team led by Karunesh Ganguly, MD, PhD, an associate professor of neurology and member of the UCSF Weill Institute for Neurosciences, used a technique called optogenetics to dampen specific types of brain activity in sleeping rats at will.
This allowed the researchers to determine that two distinct types of slow brain waves seen during sleep, called slow oscillations and delta waves, respectively strengthened or weakened the firing of specific brain cells involved in a newly learned skill -- in this case how to operate a water spout that the rats could control with their brains via a neural implant.
"We were astonished to find that we could make learning better or worse by dampening these distinct types of brain waves during sleep," Ganguly said. "In particular, delta waves are a big part of sleep, but they have been less studied, and nobody had ascribed a role to them. We believe these two types of slow waves compete during sleep to determine whether new information is consolidated and stored, or else forgotten."
"Linking a specific type of brain wave to forgetting is a new concept," Ganguly added. "More studies have been done on strengthening of memories, fewer on forgetting, and they tend to be studied in isolation from one another. What our data indicate is that there is a constant competition between the two -- it's the balance between them that determines what we remember."
Some Sleep to Remember, Others to Forget
Over the past two decades the centuries-old human hunch that sleep plays a role in the formation of memories has been increasingly supported by scientific studies. Animal studies show that the same neurons involved in forming the initial memory of a new task or experience are reactivated during sleep to consolidate these memory traces in the brain. Many scientists believe that forgetting is also an important function of sleep -- perhaps as a way of uncluttering the mind by eliminating unimportant information.
Slow oscillations and delta waves are hallmarks of so-called non-REM sleep, which -- in humans, at least -- makes up half or more of a night's sleep. There is evidence that these non-REM sleep stages play a role in consolidating various kinds of memory, including the learning of motor skills. In humans, researchers have found that time spent in the early stages of non-REM sleep is associated with better learning of a simple piano riff, for instance.
Ganguly's team began studying the role of sleep in learning as part of their ongoing efforts to develop neural implants that would allow people with paralysis to more reliably control robotic limbs with their brain. In early experiments in laboratory animals, he had noted that the biggest improvements in the animals' ability to operate these brain-computer interfaces occurred when they slept between training sessions.
"We realized that we needed to understand how learning and forgetting occur during sleep to understand how to truly integrate artificial systems into the brain," Ganguly said.
Brain Waves Compete to Determine Learning During Sleep
In the new study, a dozen rats were implanted with electrodes that monitor firing among a small group of selected neurons in their brains' motor cortex, which is involved in conceiving and executing voluntary movements. Producing a particular pattern of neural firing allowed the rats to control a water-dispensing tube in their cages. In essence, the rats were performing a kind of biofeedback -- each rat learned how to fire a small ensemble of neurons together in a unique new pattern in order to move the spigot and get the water.
Ganguly's team observed the same unique new firing pattern replaying in animals' brains as they slept. The strength of this reactivation during sleep determined how well rats were able to control the water spout the next day. But the researchers wanted to go further -- to understand how the brain controls whether rats learn or forget while they slumber.
To manipulate the effect of brain waves during non-REM sleep, the researchers genetically modified rat neurons to express a light-sensitive optogenetic control switch, allowing the team to use lasers and fiber optics to instantaneously dampen brain activity associated with the transmission of specific brain waves. With precise, millisecond timing of the laser, the scientists in separate experiments specifically dampened either slow oscillating waves or delta waves in a tiny patch of the brain around the new memory circuit.
Disruption of delta waves strengthened reactivation of the task-associated neural activity during sleep and was associated with better performance upon waking. Conversely, disruption of slow oscillations resulted in poor performance upon waking. "Slow oscillations seem to be protecting new patterns of neural firing after learning, while delta waves tend to erase them and promote forgetting," Ganguly said.
Further analysis showed that in order to protect learning, slow oscillations had to occur at the same time as a third, well-studied brain wave phenomenon, called sleep spindles. A sleep spindle is a high-frequency, short-duration burst of activity that originates in a region called the thalamus and then propagates to other parts of the brain. They have been linked to memory consolidation, and a lack of normal sleep spindles is associated with brain maladies including schizophrenia and developmental delay, and also with aging.
"Our work shows that there is a strong drive to forget during sleep," Ganguly said. "Very brief pairings of sleep spindles and slow oscillations can overcome delta wave-driven forgetting and preserve learning, but the balance is very delicate. Even small disturbances in these events lead to forgetting."
It's not yet known what tips the scales between delta wave-driven forgetting and slow oscillation-driven learning, but it's clear that better understanding the process could have profound impacts on the study of human learning and memory, Ganguly said. "Sleep is truly driving profound changes in the brain. Understanding these changes will be critical for brain integration of artificial interfaces and may one day allow us to modify neural circuits to aid in movement rehabilitation, such as after stroke, where previous studies have shown that sleep plays an important role in successful recovery."
Funding: The study was funded by the Department of Veterans Affairs, the National Institutes of Health, the National Research Foundation of Korea, and the Burroughs Wellcome Fund. Ganguly designed the study with postdoctoral fellows Jaekyung Kim and Tanuj Gulati, who conducted the experiments.
https://www.sciencedaily.com/releases/2019/10/191003114039.htm
Disrupted sleep in one's 50s, 60s raises risk of Alzheimer's disease
Protein tangles in the aging brain throw sleep rhythms out of sync, likely leading to memory loss
June 27, 2019
Science Daily/University of California - Berkeley
PET brain scans of healthy older adults show that those reporting lower sleep quality through their 50s and 60s have higher levels of tau protein, a risk factor for Alzheimer's disease. Previous studies link poor sleep to beta-amyloid tangles also, suggesting that protein tangles in the brain may cause some of the memory problems of AD and dementia. In addition, out-of-sync brain waves during sleep are associated with tau, providing a possible biomarker of dementia.
People who report a declining quality of sleep as they age from their 50s to their 60s have more protein tangles in their brain, putting them at higher risk of developing Alzheimer's disease later in life, according to a new study by psychologists at the University of California, Berkeley.
The new finding highlights the importance of sleep at every age to maintain a healthy brain into old age.
"Insufficient sleep across the lifespan is significantly predictive of your development of Alzheimer's disease pathology in the brain," said the study's senior author, Matthew Walker, a sleep researcher and professor of psychology. "Unfortunately, there is no decade of life that we were able to measure during which you can get away with less sleep. There is no Goldilocks decade during which you can say, 'This is when I get my chance to short sleep.'"
Walker and his colleagues, including graduate student and first author Joseph Winer, found that adults reporting a decline in sleep quality in their 40s and 50s had more beta-amyloid protein in their brains later in life, as measured by positron emission tomography, or PET. Those reporting a sleep decline in their 50s and 60s had more tau protein tangles. Both beta-amyloid and tau clusters are associated with a higher risk of developing dementia, though not everyone with protein tangles goes on to develop symptoms of dementia.
Based on the findings, the authors recommend that doctors ask older patients about changes in sleep patterns and intervene when necessary to improve sleep to help delay symptoms of dementia. This could include treatment for apnea, which leads to snoring and frequent halts in breathing that interrupt sleep, and cognitive behavioral therapy for insomnia (CBT-I), a highly effective way to develop healthy sleep habits. It may even include simple sleep counseling to convince patients to set aside time for a full eight hours of sleep and simple sleep hygiene tricks to accomplish that.
"The idea that there are distinct sleep windows across the lifespan is really exciting. It means that there might be high-opportunity periods when we could intervene with a treatment to improve people's sleep, such as using a cognitive behavioral therapy for insomnia," Winer said. "Beyond the scientific advance, our hope is that this study draws attention to the importance of getting more sleep and points us to the decades in life when intervention might be most effective."
The 95 subjects in the study were part of the Berkeley Aging Cohort Study (BACS), a group of healthy older adults -- some as old as 100 years of age -- who have had their brains scanned with PET, the only technique capable of detecting both beta-amyloid tangles and, very recently, tau tangles, in the brain.
Winer, Walker and their colleagues reported their results online last week in the Journal of Neuroscience.
Brain waves out of sync
The team also made a second discovery. They found that people with high levels of tau protein in the brain were more likely to lack the synchronized brain waves that are associated with a good night's sleep. The synchronization of slow brain waves throughout the cortex of the sleeping brain, in lockstep with bursts of fast brain waves called sleep spindles, takes place during deep or non-rapid eye movement (NREM) sleep. The team reported that the more tau protein older adults had, the less synchronized these brain waves were. This impaired electrical sleep signature may therefore act as a novel biomarker of tau protein in the human brain.
"There is something special about that synchrony," given the consequences of this tau protein disruption of sleep, Walker said. "We believe that the synchronization of these NREM brain waves provides a file-transfer mechanism that shifts memories from a short-term vulnerable reservoir to a more permanent long-term storage site within the brain, protecting those memories and making them safe. But when you lose that synchrony, that file-transfer mechanism becomes corrupt. Those memory packets don't get transferred, as well, so you wake up the next morning with forgetting rather than remembering."
Indeed, last year, Walker and his team demonstrated that synchronization of these brain oscillations helps consolidate memory, that is, hits the "save" button on new memories.
Several years ago, Walker and his colleagues initially showed that a dip in the amplitude of slow wave activity during deep NREM sleep was associated with higher amounts of beta-amyloid in the brain and memory impairment. Combined with these new findings, the results help identify possible biomarkers for later risk of dementia.
"It is increasingly clear that sleep disruption is an underappreciated factor contributing to Alzheimer's disease risk and the decline in memory associated with Alzheimer's," Walker said. "Certainly, there are other contributing factors: genetics, inflammation, blood pressure. All of these appear to increase your risk for Alzheimer's disease. But we are now starting to see a new player in this space, and that new player is called insufficient sleep."
The brain rhythms were recorded over a single eight-hour night in Walker's UC Berkeley sleep lab, during which most of the 31 subjects wore a cap studded with 19 electrodes that recorded a continual electroencephalogram (EEG). All had previously had brain scans to assess their burdens of tau and beta-amyloid that were done using a PET scanner at the Lawrence Berkeley National Laboratory and operated by study co-author William Jagust, professor of public health and a member of Berkeley's Helen Wills Neuroscience Institute.
Is sleep a biomarker for dementia?
Doctors have been searching for early markers of dementia for years, in hopes of intervening to stop the deterioration of the brain. Beta-amyloid and tau proteins are predictive markers, but only recently have they become detectable with expensive PET scans that are not widely accessible.
Yet, while both proteins escalate in the brain in old age and perhaps to a greater extent in those with dementia, it is still unknown why some people with large burdens of amyloid and tau do not develop symptoms of dementia.
"The leading hypothesis, the amyloid cascade hypothesis, is that amyloid is what happens first on the path to Alzheimer's disease. Then, in the presence of amyloid, tau begins to spread throughout the cortex, and if you have too much of that spread of tau, that can lead to impairment and dementia," Winer said.
Walker added that, "A lack of sleep across the lifespan may be one of the first fingers that flicks the domino cascade and contributes to the acceleration of amyloid and tau protein in the brain."
The hypothesis is supported, in part, by Jagust's PET studies, which have shown that higher levels of beta-amyloid and tau protein tangles in the brain are correlated with memory decline, tau more so than amyloid. Tau occurs naturally inside the brain's neurons, helping to stabilize their internal skeleton. With age, tau proteins seem to accumulate inside cells of the medial temporal lobe, including the hippocampus, the seat of short-term memory. Only later do they spread more widely throughout the cortex.
While Jagust has run PET scans on the brains of many healthy people, as well as those with dementia, many more subjects are needed to confirm the relationship between protein tangles and dementias like Alzheimer's disease. Because PET scanners are currently expensive and rare, and because they require injection of radioactive tracers, other biomarkers are needed, Walker said.
The new study suggests that sleep changes detectable in a simple overnight sleep study may be less intrusive biomarkers than a PET scan.
"As wearable technology improves, this need not be something you have to come to a sleep laboratory for," said Walker. "Our hope is that, in the future, a small head device could be worn by people at home and provide all the necessary sleep information we'd need to assess these Alzheimer's disease proteins. We may even be able to track the effectiveness of new drugs aimed at combating these brain proteins by assessing sleep."
"I think the message is very clear," Walker added. "If you are starting to struggle with sleep, then you should go and see your doctor and find ways, such as CBT-I, that can help you improve your sleep. The goal here is to decrease your chances of Alzheimer's disease."
https://www.sciencedaily.com/releases/2019/06/190627114105.htm