Brain wave stimulation may improve Alzheimer's symptoms

Noninvasive treatment improves memory and reduces amyloid plaques in mice

March 14, 2019

Science Daily/Massachusetts Institute of Technology

By exposing mice to a unique combination of light and sound, neuroscientists have shown they can improve cognitive and memory impairments similar to those seen in Alzheimer's patients.

This noninvasive treatment, which works by inducing brain waves known as gamma oscillations, also greatly reduced the number of amyloid plaques found in the brains of these mice. Plaques were cleared in large swaths of the brain, including areas critical for cognitive functions such as learning and memory.

"When we combine visual and auditory stimulation for a week, we see the engagement of the prefrontal cortex and a very dramatic reduction of amyloid," says Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the senior author of the study.

Further study will be needed, she says, to determine if this type of treatment will work in human patients. The researchers have already performed some preliminary safety tests of this type of stimulation in healthy human subjects.

MIT graduate student Anthony Martorell and Georgia Tech graduate student Abigail Paulson are the lead authors of the study, which appears in the March 14 issue of Cell.

Memory improvement

The brain's neurons generate electrical signals that synchronize to form brain waves in several different frequency ranges. Previous studies have suggested that Alzheimer's patients have impairments of their gamma-frequency oscillations, which range from 25 to 80 hertz (cycles per second) and are believed to contribute to brain functions such as attention, perception, and memory.

In 2016, Tsai and her colleagues first reported the beneficial effects of restoring gamma oscillations in the brains of mice that are genetically predisposed to develop Alzheimer's symptoms. In that study, the researchers used light flickering at 40 hertz, delivered for one hour a day. They found that this treatment reduced levels of beta amyloid plaques and another Alzheimer's-related pathogenic marker, phosphorylated tau protein. The treatment also stimulated the activity of debris-clearing immune cells known as microglia.

In that study, the improvements generated by flickering light were limited to the visual cortex. In their new study, the researchers set out to explore whether they could reach other brain regions, such as those needed for learning and memory, using sound stimuli. They found that exposure to one hour of 40-hertz tones per day, for seven days, dramatically reduced the amount of beta amyloid in the auditory cortex (which processes sound) as well as the hippocampus, a key memory site that is located near the auditory cortex.

"What we have demonstrated here is that we can use a totally different sensory modality to induce gamma oscillations in the brain. And secondly, this auditory-stimulation-induced gamma can reduce amyloid and Tau pathology in not just the sensory cortex but also in the hippocampus," says Tsai, who is a founding member of MIT's Aging Brain Initiative.

The researchers also tested the effect of auditory stimulation on the mice's cognitive abilities. They found that after one week of treatment, the mice performed much better when navigating a maze requiring them to remember key landmarks. They were also better able to recognize objects they had previously encountered.

They also found that auditory treatment induced changes in not only microglia, but also the blood vessels, possibly facilitating the clearance of amyloid.

Dramatic effect

The researchers then decided to try combining the visual and auditory stimulation, and to their surprise, they found that this dual treatment had an even greater effect than either one alone. Amyloid plaques were reduced throughout a much greater portion of the brain, including the prefrontal cortex, where higher cognitive functions take place. The microglia response was also much stronger.

"These microglia just pile on top of one another around the plaques," Tsai says. "It's very dramatic."

The researchers found that if they treated the mice for one week, then waited another week to perform the tests, many of the positive effects had faded, suggesting that the treatment would need to be given continually to maintain the benefits.

In an ongoing study, the researchers are now analyzing how gamma oscillations affect specific brain cell types, in hopes of discovering the molecular mechanisms behind the phenomena they have observed. Tsai says she also hopes to explore why the specific frequency they use, 40 hertz, has such a profound impact.

The combined visual and auditory treatment has already been tested in healthy volunteers, to assess its safety, and the researchers are now beginning to enroll patients with early-stage Alzheimer's to study its possible effects on the disease.

The research was funded, in part, by the Robert and Renee Belfer Family Foundation, the Halis Family Foundation, the JPB Foundation, the National Institutes of Health and the MIT Aging Brain Initiative. 

https://www.sciencedaily.com/releases/2019/03/190314111004.htm

Brainwave activity reveals potential biomarker for autism in children

October 26, 2018

Science Daily/Kanazawa University

Autism spectrum disorder (ASD) affects children's social and intellectual development. Conventional diagnostic methods for ASD rely on behavioral observation. Researchers have now identified a potential quantifiable biomarker for diagnosing ASD. Using magnetic brainwave imaging, they correlated altered gamma oscillation with the motor response of children with ASD, which is consistent with previous key hypotheses on ASD. The means of observation potentially offers a noninvasive, impartial form of early diagnosis of ASD.

Now, a team of researchers at Kanazawa University in Japan have made an important step towards identifying a biomarker based on motor-related brain activity. Their work followed on from the key hypothesis that autism results from an excitatory and inhibitory imbalance in the brain, which is associated with repetitive brainwaves called gamma oscillations. A reduction in this type of brain activity has been seen during visual, auditory, and tactile stimulation in individuals with ASD.

The researchers set out to further explore motor-induced gamma oscillations in children with ASD, and recently reported their findings in The Journal of Neuroscience.

They formed two groups of children who were 5-7 years old. Those in the first group were conventionally diagnosed with ASD, while the second group was made up of children classed as developing typically. The children each performed a video-game-like task where they had to press a button with their right finger, while in a relaxed environment. Magnetoencephalography, which records magnetic activity from neurons, was used to monitor the children's brainwaves during the task.

"We measured the button response time, motor-evoked magnetic fields, and motor-related gamma oscillations," study corresponding author Mitsuru Kikuchi says. "As found in other studies, the ASD children's response time was slightly slower and the amplitude in their magnetic fields was a bit decreased. The gamma oscillations were where we saw significant and interesting differences."

There was a considerably lower peak frequency of the gamma oscillations in the ASD group. A lower peak frequency of motor-related gamma oscillations also signaled low concentration of the inhibitory neurotransmitter GABA, which has also been found associated with ASD. The findings additionally suggest delayed development of motor control in young children with ASD. Collectively the behavioral performance and brainwave findings offer promise for ASD diagnosis.

"Early diagnosis of ASD is highly important so that we can actively manage the disorder as soon as possible," first author Kyung-min An says. "These findings may prove to be extremely useful in helping us understand the neurophysiological mechanism behind social and motor control development in children with ASD. Using magnetoencephalography in this way gives us a noninvasive and quantifiable biomarker, which is something we are in great need of."

https://www.sciencedaily.com/releases/2018/10/181026102712.htm