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Chemotherapy Brain Fog Cleared With Simple Light And Sound Treatment

If you or someone you know has gone through chemotherapy, you might be familiar with the side effect commonly called 'chemo brain.' Scientists have now demonstrated a simple way to protect brain cells from damage using flashing lights and sounds at a certain frequency.

Chemotherapy is one of our best treatments for many cancers, but unfortunately its effects are felt throughout the body, including the brain. Patients often report 'brain fog,' where they have trouble with memory, concentration and decision making, affecting their thinking and behavior. While it normally goes away after the chemotherapy finishes, it can be a frustrating interruption to everyday life for a few months.

But a new study by Massachusetts Institute of Technology (MIT) researchers might have uncovered a fairly simple treatment to counter those ill effects – and, best of all, it's less invasive than the chemo itself. All you have to do is look at some flashing lights and listen to some sounds daily.

Previous studies by the team have found that lights flickering at a frequency of 40 Hz, and sounds at the same pitch, can stimulate the brain to produce more gamma oscillations. These brain waves range from 25 to 80 Hz, and occur when you're highly alert, aiding things like focus and concentration. Since people with Alzheimer's disease seem to have problems with these gamma waves, the MIT team wondered whether this could form a simple treatment to improve their symptoms. And sure enough, experiments in mice showed reduced inflammation, lower levels of toxic proteins thought to contribute to neural degeneration, and improvements on cognitive tests after the light and sound therapy. For the new study, the MIT researchers turned their attention to a different ailment – chemo brain.

The team tested the treatment on mice with chemo brain, by giving them the common chemotherapy drug cisplatin for five days, then five days off, and five on again, mimicking the human dosage regime. Some received the 'gamma therapy,' involving an hour per day of exposure to 40-Hz light and sound, while the control group just had the chemo alone.

Three weeks later, the control mice showed many of the known brain effects of chemotherapy, including smaller brain volume, DNA damage, inflammation, and damage to myelin, the protective coating around neurons. Their populations of brain cells that produce myelin, called oligodendrocytes, were also reduced.

However, the mice that received daily gamma therapy for the duration of their chemotherapy showed significant reductions in all of these symptoms. They also performed much better on tests that measure the animals' memory and executive function. When the researchers analyzed gene expression, they found that genes linked to inflammation and cell death were suppressed in mice treated with gamma therapy.

"The treatment can reduce DNA damage, reduce inflammation, and increase the number of oligodendrocytes, which are the cells that produce myelin surrounding the axons," said Li-Huei Tsai, senior author of the study. "We also found that this treatment improved learning and memory, and enhanced executive function in the animals."

The benefits were found to persist, at least partially, for up to four months after treatment. Gamma therapy was found to work much better if administered at the same time as the chemotherapy, rather than starting it afterwards. Follow-up studies found similar positive effects in mice receiving a different chemo drug, methotrexate. While the mouse tests involved brain implants to directly deliver light and sound to neurons, previous human trials for Alzheimer's have shown similar benefits can be achieved using just a synchronized screen and speaker setup. If it works, this could become a standard part of administering chemotherapy to human patients, to make the life-saving treatment less uncomfortable.

The team also plans to test gamma therapy against other neurological diseases, like Parkinson's and multiple sclerosis. Clinical trials in human Alzheimer's patients are already underway.

The research was published in the journal Science Translational Medicine.

Source: MIT

A Noninvasive Treatment For 'chemo Brain'

Patients undergoing chemotherapy often experience cognitive effects such as memory impairment and difficulty concentrating -- a condition commonly known as "chemo brain."

MIT researchers have now shown that a noninvasive treatment that stimulates gamma frequency brain waves may hold promise for treating chemo brain. In a study of mice, they found that daily exposure to light and sound with a frequency of 40 hertz protected brain cells from chemotherapy-induced damage. The treatment also helped to prevent memory loss and impairment of other cognitive functions.

This treatment, which was originally developed as a way to treat Alzheimer's disease, appears to have widespread effects that could help with a variety of neurological disorders, the researchers say.

"The treatment can reduce DNA damage, reduce inflammation, and increase the number of oligodendrocytes, which are the cells that produce myelin surrounding the axons," says Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the Picower Professor in the MIT Department of Brain and Cognitive Sciences. "We also found that this treatment improved learning and memory, and enhanced executive function in the animals."

Tsai is the senior author of the new study, which appears today in Science Translational Medicine. The paper's lead author is TaeHyun Kim, an MIT postdoc.

Protective brain waves

Several years ago, Tsai and her colleagues began exploring the use of light flickering at 40 hertz (cycles per second) as a way to improve the cognitive symptoms of Alzheimer's disease. Previous work had suggested that Alzheimer's patients have impaired gamma oscillations -- brain waves that range from 25 to 80 hertz (cycles per second) and are believed to contribute to brain functions such as attention, perception, and memory.

Tsai's studies in mice have found that exposure to light flickering at 40 hertz or sounds with a pitch of 40 hertz can stimulate gamma waves in the brain, which has many protective effects, including preventing the formation of amyloid beta plaques. Using light and sound together provides even more significant protection. The treatment also appears promising in humans: Phase 1 clinical trials in people with early-stage Alzheimer's disease have found the treatment is safe and does offer some neurological and behavioral benefits.

In the new study, the researchers set out to see whether this treatment could also counteract the cognitive effects of chemotherapy treatment. Research has shown that these drugs can induce inflammation in the brain, as well as other detrimental effects such as loss of white matter -- the networks of nerve fibers that help different parts of the brain communicate with each other. Chemotherapy drugs also promote loss of myelin, the protective fatty coating that allows neurons to propagate electrical signals. Many of these effects are also seen in the brains of people with Alzheimer's.

"Chemo brain caught our attention because it is extremely common, and there is quite a lot of research on what the brain is like following chemotherapy treatment," Tsai says. "From our previous work, we know that this gamma sensory stimulation has anti-inflammatory effects, so we decided to use the chemo brain model to test whether sensory gamma stimulation can be beneficial."

As an experimental model, the researchers used mice that were given cisplatin, a chemotherapy drug often used to treat testicular, ovarian, and other cancers. The mice were given cisplatin for five days, then taken off of it for five days, then on again for five days. One group received chemotherapy only, while another group was also given 40-hertz light and sound therapy every day.

After three weeks, mice that received cisplatin but not gamma therapy showed many of the expected effects of chemotherapy: brain volume shrinkage, DNA damage, demyelination, and inflammation. These mice also had reduced populations of oligodendrocytes, the brain cells responsible for producing myelin.

However, mice that received gamma therapy along with cisplatin treatment showed significant reductions in all of those symptoms. The gamma therapy also had beneficial effects on behavior: Mice that received the therapy performed much better on tests designed to measure memory and executive function.

"A fundamental mechanism"

Using single-cell RNA sequencing, the researchers analyzed the gene expression changes that occurred in mice that received the gamma treatment. They found that in those mice, inflammation-linked genes and genes that trigger cell death were suppressed, especially in oligodendrocytes, the cells responsible for producing myelin.

In mice that received gamma treatment along with cisplatin, some of the beneficial effects could still be seen up to four months later. However, the gamma treatment was much less effective if it was started three months after the chemotherapy ended.

The researchers also showed that the gamma treatment improved the signs of chemo brain in mice that received a different chemotherapy drug, methotrexate, which is used to treat breast, lung, and other types of cancer.

"I think this is a very fundamental mechanism to improve myelination and to promote the integrity of oligodendrocytes. It seems that it's not specific to the agent that induces demyelination, be it chemotherapy or another source of demyelination," Tsai says.

Because of its widespread effects, Tsai's lab is also testing gamma treatment in mouse models of other neurological diseases, including Parkinson's disease and multiple sclerosis. Cognito Therapeutics, a company founded by Tsai and MIT Professor Edward Boyden, has finished a phase 2 trial of gamma therapy in Alzheimer's patients, and plans to begin a phase 3 trial this year.

"My lab's major focus now, in terms of clinical application, is Alzheimer's; but hopefully we can test this approach for a few other indications, too," Tsai says.

The research was funded by the JPB Foundation, the Ko Hahn Seed Fund, and the National Institutes of Health.

Gamma Brain Waves Might Prevent Cognitive Effects Of Chemotherapy

Caption:A noninvasive treatment may help to counter "chemo brain" impairment often seen in chemotherapy patients: Exposure to light and sound with a frequency of 40 hertz protected brain cells from chemotherapy-induced damage in mice, MIT researchers found.[Image courtesy of Christine Daniloff, MIT; iStock]

MIT researchers say a noninvasive treatment could stimulate gamma frequency brain waves and potentially help treat chemo brain.

In a study of mice, the researchers delivered daily exposure to light and sound with a frequency of 40 hertz. They found that this protected brain cells from chemotherapy-induced damage — also called chemo brain. The treatment also helped to prevent memory loss and the impairment of other cognitive functions.

Originally developed as a way to treat Alzheimer's disease, the team at MIT says this treatment could have more widespread effects capable of helping with a range of neurological disorders.

"The treatment can reduce DNA damage, reduce inflammation, and increase the number of oligodendrocytes, which are the cells that produce myelin surrounding the axons," Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the Picower Professor in the MIT Department of Brain and Cognitive Sciences, said in a post on the MIT website. "We also found that this treatment improved learning and memory, and enhanced executive function in the animals."

Tsai serves as the senior author of the new study, which appeared in Science Translational Medicine. The paper's lead author is TaeHyun Kim, an MIT postdoc.

The mice studies run by Tsai and her team found that exposure to light flickering at 40 hertz or sounds with a pitch of 40 hertz and stimulate gamma waves in the brain. This produces protective effects, including the prevention of the rotation of amyloid beta plaques. Using light and sound together provides even more significant protection, MIT says.

Phase 1 clinical trial results from humans with early-stage Alzheimer's also found the treatment safe with some neurological and behavioral benefits.

In the new study, the MIT team looked into whether the treatment could counteract the cognitive effects of chemotherapy treatment. Research showed that chemotherapy drugs can induce inflammation on the brain and other detrimental effects, like the loss of white matter. They also promote the loss of myelin, MIT says, and many of these effects are seen in Alzheimer's.

"Chemo brain caught our attention because it is extremely common, and there is quite a lot of research on what the brain is like following chemotherapy treatment," Tsai said. "From our previous work, we know that this gamma sensory stimulation has anti-inflammatory effects, so we decided to use the chemo brain model to test whether sensory gamma stimulation can be beneficial."

The researchers used mice given cisplatin, a chemotherapy drug commonly used to treat testicular, ovarian, and other cancers, over five days. They then took the mice off the drug for five days, then put them on again for five days. One group received chemotherapy only, while another received 40-hertz light and sound therapy every day.

After three weeks, mice that received cisplatin but not gamma therapy displayed many expected effects of chemotherapy. That included brain volume shrinkage, DNA damage, demyelination and inflammation. Those mice also had reduced populations of oligodendrocytes, the brain cells responsible for producing myelin.

On the other hand, mice that received gamma therapy with cisplatin showed significant reductions in all of these symptoms. Gamma therapy also had beneficial effects on behavior, MIT says. Mice that received this therapy performed "much better" on tests designed to measure memory and executive function.

Using single-cell RNA sequencing, the researchers looked at the gene expression changes that occurred in mice that received the gamma treatment. They saw that, in those mice, inflammation-linked genes and genes that trigger cell death were suppressed. This proved especially true in oligodendrocytes.

Mice that received gamma treatment with cisplatin still displayed some beneficial effects visible up to four months later. However, they found that the gamma treatment was much less effective when started three months after chemotherapy ended. They also saw that gamma treatment improved signs of chemo brain in mice that received methotrexate, a different chemotherapy drug. This drug often treats breast, lung and other kinds of cancer.

Tsai's lab now plans to test gamma treatment in mouse models of other neurological disease, including Parkinson's and multiple sclerosis. Cognito Therapeutics, founded by Tsai and MIT Professor Edward Boyden, completed a Phase 2 trial of gamma therapy in Alzheimer's patients and plans for a Phase 3 trial this year.

"My lab's major focus now, in terms of clinical application, is Alzheimer's; but hopefully we can test this approach for a few other indications, too," Tsai said.

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