Neuroscientists could use brain waves to spur immune cells into action against the disease — but the process is almost too fantastic to believe.
Quanta Magazine said:Discoveries that transcend boundaries are among the greatest delights of scientific research, but such leaps are often overlooked because they outstrip conventional thinking. Take, for example, a new discovery for treating dementia that defies received wisdom by combining two formerly unrelated areas of research: brain waves and the brain’s immune cells, called microglia. It’s an important finding, but it still requires the buy-in and understanding of researchers to achieve its true potential. The history of brain waves shows why.
In 1887, Richard Caton announced his discovery of brain waves at a scientific meeting. “Read my paper on the electrical currents of the brain,” he wrote in his personal diary. “It was well received but not understood by most of the audience.” Even though Caton’s observations of brain waves were correct, his thinking was too unorthodox for others to take seriously. Faced with such a lack of interest, he abandoned his research and the discovery was forgotten for decades.
Flash forward to October 2019. At a gathering of scientists that I helped organize at the annual meeting of the Society for Neuroscience in Chicago, I asked if anyone knew of recent research by neuroscientists at the Massachusetts Institute of Technology who had found a new way to treat Alzheimer’s disease by manipulating microglia and brain waves. No one replied.
I understood: Scientists must specialize to succeed. Biologists studying microglia don’t tend to read papers about brain waves, and brain wave researchers are generally unaware of glial research. A study that bridges these two traditionally separate disciplines may fail to gain traction. But this study needed attention: Incredible as it may sound, the researchers improved the brains of animals with Alzheimer’s simply by using LED lights that flashed 40 times a second. Even sound played at this charmed frequency, 40 hertz, had a similar effect.
Today, brain waves are a vital part of neuroscience research and medical diagnosis, though doctors have never manipulated them to treat degenerative disease before now. These oscillating electromagnetic fields are produced by neurons in the cerebral cortex firing electrical impulses as they process information. Much as people clapping their hands in synchrony generate thunderous rhythmic applause, the combined activity of thousands of neurons firing together produces brain waves.
These waves come in various forms and in many different frequencies. Alpha waves, for example, oscillate at frequencies of 8 to 12 hertz. They surge when we close our eyes and shut out external stimulation that energizes higher-frequency brain wave activity. Rapidly oscillating gamma waves, which reverberate at frequencies of 30 to 120 hertz, are of particular interest in Alzheimer’s research, because their period of oscillation is well matched to the hundredth-of-a-second time frame of synaptic signaling in neural circuits. Brain waves are important in information processing because they can influence neuronal firing. Neurons fire an electrical impulse when the voltage difference between the inside and outside of the neuron reaches a certain trigger point. The peaks and troughs of voltage oscillations in brain waves nudge the neuron closer to the trigger point or farther away from it, thereby boosting or inhibiting its tendency to fire. The rhythmic voltage surging also groups neurons together, making them fire in synchrony as they “ride” on different frequencies of brain waves.
I already knew that much, so to better understand the new work and its origins, I sought out Li-Huei Tsai, a neuroscientist at MIT. She said the idea of using one of these frequencies to treat Alzheimer’s came from a curious observation. “We had noticed in our own data, and in that of other groups, that 40-hertz rhythm power and synchrony are reduced in mouse models of Alzheimer’s disease,” she said, as well as in patients with the disease. Apparently, if you have Alzheimer’s, your brain doesn’t produce strong brain waves in that particular frequency. In 2016, her graduate student Hannah Iaccarino reasoned that perhaps boosting the power of these weakened gamma waves would be helpful in treating this severe and irreversible dementia.
To increase gamma wave power, the team turned to optogenetic stimulation, a novel technique that allows researchers to control how and when individual neurons fire by shining lasers directly into them, via fiber-optic cables implanted in the brain. Tsai’s team stimulated neurons in the visual cortex of mice with Alzheimer’s, making them fire impulses at 40 hertz. The results, published in 2016 in Nature, showed a marked reduction in amyloid plaques, a hallmark of the disease.
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