In a lab in MIT’s Picower Institute for Learning and Memory, cohorts of mice with artificially-induced Alzheimer’s have been getting an unusual new treatment: Confined to a dark room, they’re exposed to visual stimulation in the form of rapidly-flashing white LED strips.
The blinking lights, which run at 40 hertz, or 40 times a second, are less reminiscent of a strobe in a club, and more like the twinkling of stars, says Li-Huei Tsai, author of the study, which appeared in Nature. These mice, divided into groups for different types of therapy and controls, show improvement in Alzheimer’s-related symptoms—specifically the reduction of beta amyloid plaque associated with the disease.
Though the relationship between the disease and the cause of the plaque in the brain is not entirely clear, and though the experiment was conducted on mice that were genetically programmed to have the disease, the research could indicate both a new understanding of the process behind the disease and a non-invasive treatment for it.
The idea behind the study was to influence gamma oscillations, a measure of rhythmic activity among neurons that ranges from 25 to 80 hertz. Tsai, who is a professor of neuroscience at MIT, and her lab tried pulses from 20 to 80 Hz and found that 40 was the sweet spot.
“I think this is the first study, not just showing that gamma oscillation has an effect on beta amyloid levels, but really it’s the first study to even think about gamma oscillations and molecular and cellular changes in the brain,” says Tsai.
It’s not the first study to look at gamma oscillations in general, though. Way back in 1989, in Nature, Wolf Singer and his lab also showed evidence that 40 Hz was an important rate. “What it does is it causes high synchronicity,” says Singer, comparing it to a pacemaker.
Singer found that visually induced gamma oscillations could spread across the brain, synching different parts to the same rhythm, which he believes explains how our brain coordinates itself. In the decades since, the field has been controversial and frequently studied, often by implanting electrons on the scalp or brain to induce oscillations. It’s been shown to affect memory, attention, consciousness, and even schizophrenia, but Tsai’s application of using lights to influence it in Alzheimer’s is new.
“What they did is, they reversed the causality, they said, maybe it’s the disturbed temporal dynamics of the system that causes the diseased state,” says Singer. Though it has been shown previously that gamma oscillations are impaired in people with Alzheimer’s, it was this inspection of the timeline that led Tsai to her experiment.
“We initially wanted to know, how early does this impairment happen?” says Tsai. “If it happens late, simultaneously with memory impairment and other damage that happens, then the impaired oscillations could just be one of the consequences of the disease. But if it occurs early, it has the potential to contribute to the manifestation of the disease.”
It isn’t entirely clear why induced gamma oscillations seem to lead to less plaque, but Tsai has a couple of ideas. First, the generation of the plaque itself seems to be suppressed. This is particularly surprising, says Tsai, because of the magnitude—they saw a 50 percent reduction—and because no direct relationship has been shown between gamma oscillations and beta amyloid plaque.
Another noted feature seen in Alzheimer’s is the dysfunction of microglia cells. Normally considered the immune cells of the brain, clearing toxic materials and debris, they fail to operate, or can even cause inflammation in Alzheimer’s patients. “Their normal function is to clear toxic materials and debris around the brain, and keep everybody happy,” says Tsai. As the study showed increased microglia cell function under the treatment, the researchers reasoned that this may be one of the ways—along with preventing the genesis of new plaque—that the oscillations contribute to a reduction in plaque.
Because the oscillations are induced visually, the plaque reduction seen by the study is limited to the visual cortex of the brain, and seems to wear off in about a day. Other upcoming research includes increasing the duration of the experiment, to see if the effects will last longer and spread throughout the brain, as results from Singer’s research suggested. It may even be useful in other diseases that show abnormal gamma oscillations, such as autism and psychiatric disorders, says Tsai. She has founded a company called Cognito Therapeutics to work toward human trials.