Researchers at the Massachusetts Institute of Technology (MIT) report that the use of a noninvasive treatment that stimulates gamma frequency brainwaves could be an effective treatment against the cognitive side effects of chemotherapy, often referred to as “chemo brain.”
The research, published Wednesday in the journal Science Translational Medicine, could reduce the memory impairment and difficulty in concentrating that is common among patients receiving chemotherapy.
In their study, the investigators found that daily exposure to light and sound with a frequency of 40 hertz protected brain cells from chemotherapy-induced damage in mouse models. This treatment method, originally created as a way to treat Alzheimer’s disease (AD), may have widespread effects beyond these indications and could be used to treat a variety 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,” says senior author Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory. “We also found that this treatment improved learning and memory, and enhanced executive function in the animals.”
Tsai and colleagues have been studying for several years the effects of light flickering at 40 hertz to improve cognitive symptoms of AD. Prior work has shown that AD patients experience impaired gamma oscillations (brain waves in the range of 25 to 80 hertz), which are thought to support brain functions such as attention, perception, and memory.
Tsai’s work in this area has shown that exposure to light flickering at 40 hertz, or sounds at a pitch of 40 hertz, stimulate gamma waves in the brain with many beneficial effects, including the prevention of amyloid beta plaque formation. Combining light and sound at this frequency provides even broader protection, with early Phase I trials showing the treatment is safe and provides some benefits.
Leveraging this prior work, the MIT team sought to discover whether the beneficial effects of 40 hertz light and sound wave treatments could also address the cognitive effects associated with chemotherapy. This form of cancer treatment has many known deleterious effects including increased inflammation of the brain and the loss of white matter, the network of nerve fibers that help parts of the brain communicate with each other. Similar to AD, chemotherapy has also been shown to result in a loss of the myelin, the sheath of tissue that protects neurons.
“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 adds. “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.”
For their research, the investigators used the commonly prescribed chemotherapy drug cisplatin, providing it to their mouse models rotating between five days of receiving the drug, followed by five days off the drug. The control group received only chemotherapy, while another group received 40 hertz light and sound therapy every day in addition to chemotherapy.
When observed three weeks later, the mice that received cisplatin only exhibited many of the effects associated with chemo brain such as brain volume shrinkage, demyelination, inflammation, and DNA damage, while the mice on the gamma therapy showed significantly lower levels of these symptoms. The gamma therapy also provided other benefits on behavior including better performance on tests that measure memory and executive function.
Single-cell RNAseq revealed some of the reasons for these benefits. The gamma therapy mice showed gene expression changes that suppressed inflammation-linked genes and other genes that trigger cell death. This was especially true in myelin producing cells called oligodendrocytes.
The timing of the treatment was an important variable in producing positive results. Gamma therapy that didn’t start until three months after the start of chemotherapy was much less effective, but if started early, the benefits were still seen for up to four months.
The team also produced similar results using a different chemotherapy agent, methotrexate, which is often prescribed for the treatment of breast 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.
