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

Sleep history predicts late-life Alzheimer's pathology

Findings suggest novel, sleep-based diagnosis and treatment methods

June 18, 2019

Science Daily/Society for Neuroscience

Sleep patterns can predict the accumulation of Alzheimer's pathology proteins later in life, according to a new study of older men and women published in JNeurosci. These findings could lead to new sleep-based early diagnosis and prevention measures in the treatment of Alzheimer's disease.

Alzheimer's disease is associated with disrupted sleep and the accumulation of tau and proteins in the brain, which can emerge long before characteristic memory impairments appear. Two types of hippocampal sleep waves, slow oscillations and sleep spindles, are synced in young individuals, but have been shown to become uncoordinated in old age.

Matthew Walker, Joseph Winer, and colleagues at the University of California, Berkeley found a decrease in slow oscillations/sleep spindle synchronization was associated with higher tau, while reduced slow-wave-activity amplitude was associated with higher ?-amyloid levels.

The researchers also found that a decrease in sleep quantity throughout aging, from the 50s through 70s, was associated with higher levels of ?-amyloid and tau later in life. This means that changes in brain activity during sleep and sleep quantity during these time frames could serve as a warning sign for Alzheimer's disease, allowing for early preventive care.

https://www.sciencedaily.com/releases/2019/06/190618102725.htm

Memories are strengthened via brainwaves produced during sleep

Researchers use medical imaging to map areas involved in recalling learned information while we slumber

May 15, 2019

Science Daily/Concordia University

Researchers have known about the close relationship between sleep and memory for decades. Now, a new study published in the journal NeuroImage looks at one important mechanism in that relationship. The research brings us closer to understanding how learned information turns into reliable memories during sleep.

The study was led by Thanh Dang-Vu, associate professor in the Department of Health, Kinesiology and Applied Physiology and Concordia University Research Chair in Sleep, Neuroimaging and Cognitive Health. In it, researchers studied how declarative information like facts and faces get stored after they have been learned. It has to do with brainwaves -- specifically, ones called sleep spindles, which are fast bursts of electrical activity produced by neurons mainly during Stage 2 sleep, prior to deep sleep.

Dang-Vu worked alongside Christophe Grova, associate professor in the Department of Physics, and researchers from the Cyclotron Research Centre at University of Liège in Belgium. Using medical imaging machines, they were able to assess brain activity related to these waves.

"It's hypothesized that sleep spindles play an important role in transferring information from the hippocampus to the neo-cortex," Dang-Vu says. "This has the effect of increasing the strength of memories."

To get the images they needed, Dang-Vu's team used both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). They applied these tools to a group of student volunteers during and after a lab-based face-sequencing task. The students were shown a series of faces and asked to identify the order in which they were shown. The researchers scanned them while they were learning the faces, while they were asleep and again when they woke up and had to recall the sequences.

Sleep spindles reactivated

 They then came back every day for a week and repeated the task without being scanned. After a week had elapsed, they had memorized the task, and were once again scanned during sleep and asked to recall the sequences.

"Our aim was to compare the sleep spindles from the night where the subjects learned the new information to the night where they didn't have any new information to learn but were exposed to the same stimulus with the same faces," Dang-Vu explains.

The researchers found that during spindles of the learning night, the regions of the brain that were instrumental in processing faces were reactivated. They also observed that the regions in the brain involved in memory -- especially the hippocampus -- were more active during spindles in the subjects who remembered the task better after sleep.

This reactivation during sleep spindles of the regions involved in learning and memory "falls in line with the theory that during sleep, you are strengthening memories by transferring information from the hippocampus to the regions of the cortex that are important for the consolidation of that specific type of information," he says.

Using non-invasive imaging to identify the mechanisms that strengthen memories can, he hopes, lead to improvements in our understanding of how memories work -- and can lead to improved interventions for people with sleep or memory issues.

https://www.sciencedaily.com/releases/2019/05/190515131750.htm