Stimulating Brain Waves May Protect Against “Chemobrain”

A method to stimulate gamma brain waves could pave the way for a non-invasive treatment for so-called “chemobrain”, the side effects of chemotherapy on cognitive skills. That’s according to Massachusetts Institute of Technology (MIT) researchers whose new study in Science Translational Medicine showed promising early results in chemotherapy-treated mice.

Cognitive deficits after chemotherapy

Chemobrain is experienced by some cancer patients as a side effect of their cancer treatment. It leads to a host of symptoms such as short-term memory loss, attention problems and chronic fatigue that can last for many years after treatment.

“While we do not fully understand the detailed mechanism of chemobrain, the key pathological features are DNA damage, oxidative stress-related cellular damage and chronic inflammatory reaction in the brain,” Dr. Li-Huei Tsai, a professor of neuroscience at MIT and senior author of the study, told Technology Networks.

Tsai’s lab has demonstrated promising results for Alzheimer’s disease (AD) by stimulating gamma waves in the brain – something that they hypothesized could also provide benefits for chemobrain, given its shared characteristics with neurodegenerative diseases.

The treatment is known as gamma entrainment using sensory stimuli, or GENUS. It uses pulses of light and/or sound at a frequency of 40 Hz to induce gamma oscillations in the brain.

Studies using mouse models of AD as well as small pilot studies of human AD patients found GENUS was safe and may provide some neurological benefits. Tsai’s lab investigated if GENUS could also counteract the cognitive effects of chemobrain using mouse models.

Positive results in mouse study

The animals in Tsai’s study were treated with the common chemotherapy drug cisplatin in a short cycle of five days on, five days off and a final five days on. One group received chemotherapy only while the other also underwent GENUS treatment during and after receiving chemotherapy.

“The treatment itself is a very simple and non-invasive method,” Tsai explained. “Animals are exposed to LED light flickering and sound pulsating at 40 Hz for 1 hour every day.”

Mice that did not receive GENUS therapy had brain volume shrinkage, DNA damage and inflammation, as well as reduced numbers of oligodendrocytes – the brain cells that produce myelin – and demyelination. Meanwhile, mice that received both chemotherapy and GENUS had significant reductions in these findings and also performed better on cognitive tests.

“We found this treatment increases expression of genes involved in DNA damage repair and resistance to oxidative stress and apoptosis,” Tsai added.

GENUS also had similar effects in mice treated with methotrexate, another chemotherapy drug that works in a different way to cisplatin.

“We believe these responses in the brain protect the brain cells and reduce inflammatory response in chemobrain and neurodegenerative diseases,” said Tsai.

However, though the mice received chemotherapy, they did not have cancer – something Tsai seeks to address in further studies. “It should be tested [to see] if GENUS treatment would be safe and have the same effect we observed on chemobrain pathology in animals with cancer,” she added.

The findings suggest that timing is important for GENUS treatment, as it was less effective when started three months after the last chemotherapy treatment compared to during chemotherapy.

Focus remains on neurodegenerative disease

“We believe that our study provides a result with high potential for clinical use as GENUS has already been shown to be safe in clinical trials for Alzheimer’s,” Tsai explained. “Also, this study demonstrated that GENUS could prevent the loss of oligodendrocytes and rescue demyelination, which is often observed in neurodegenerative diseases.”

“Moreover, we observed similar effects of GENUS on neurons and glial cells in the brain with chemobrain mouse model and Alzheimer's disease mouse models. This suggests that GENUS might be a viable treatment for other neurodegenerative diseases with similar pathologies.”

The current focus of Tsai’s work is whether GENUS is effective in treating and improving pathologies in neurodegenerative diseases.

Reference: Kim T, James BT, Kahn MC et al. Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice. Sci Trans Med. 2024. doi: 10.1126/scitranslmed.adf4601

Dr. Li-Huei Tsai was speaking to Dr. Sarah Whelan, Science Writer for Technology Networks.

About the interviewee:

Dr. Li-Huei Tsai is the director of the Picower Institute for Learning and Memory at MIT, and a professor of neuroscience in MIT’s Department of Brain and Cognitive Sciences. She earned her PhD from the University of Texas Southwest Medical Center, and her research focuses on using multi-disciplinary approaches to investigate the mechanisms underlying neurological disorders that impact learning and memory.