Hello, everyone. It is a tremendous pleasure to be here to share with you my story.
You’ve all heard of brainwaves. For a long time, neuroscientists didn't know what they meant. But we slowly come to understand their purpose. The brain generates waves with different paces or frequencies to transmit information and thoughts by coordinating the activity of nerve cells. These waves are a little like the effect of the orchestra conductor waving a baton to keep the musicians synchronized.
I'm going to talk today about the waves that have the so-called gamma frequency. These gamma waves are particularly important for synchronizing brain activity to process new information from the senses and for learning and memory. You might be surprised to learn that when these gamma waves are weaker than they should be, this may contribute to Alzheimer's disease. Indeed, my laboratory and others have shown that in people with Alzheimer's and in laboratory mice that model the disease, gamma waves at the frequency of 40 hertz have reduced power and synchrony than they should be.
So back in 2015, we got an idea. What if we artificially boosted these waves? Would that affect Alzheimer's disease? We have to know the answer because we are an aging society. As we have made progress in treating many other health problems, we've begun living long enough to develop others. In the last 20 years, the Alzheimer's Association estimates deaths from heart disease declined by about seven percent. But the number of deaths from Alzheimer's disease increased 145 percent. One in three seniors in the US dies [from] Alzheimer’s disease or another dementia, they say. And more than 11 million people provide unpaid care for their loved ones with Alzheimer's.
So this means that probably most of us in this room have known and loved someone with Alzheimer's. I am no exception. One day when I was four, I went out with my grandmother. And when I looked up to her to say, "Let's go home," She said, "Home. Where is home?"
So to see if we could treat Alzheimer's disease by changing brainwaves, we tried out different approaches. By working with my colleagues, Emery Brown and Ed Boyden at MIT, we figured out that we could entrain or stimulate increased gamma waves by simply showing mice lights blinking at that frequency. This really works. Showing mice 40-hertz flickering light -- and we demonstrated later, placing of 40-hertz buzzing sound -- creates a 40-hertz disco that increases the power and synchrony of these waves across the brain. The effect reaches key parts of the brain, such as the prefrontal cortex, where we do planning and reasoning and the hippocampus where we create memories.
So the light and sound stimulation approach seems cool and flashy. Literally. But what amazes the most is that it produced profound and widespread benefits in mice engineered to model this disease. Mice exposed to gamma light and sound stimulation had major reductions in protein build-ups, amyloid plaques and tau tangles that are hallmarks of Alzheimer's progression. The stimulation preserved more of the connections or synapses that bind nerve cells into circuits. More cells survived, so the brain decayed less. The brain naturally has open spaces known as ventricles. And in the brain of mice left untreated, these ventricles became very big. But in the brain of mice exposed to gamma-wave stimulation, these ventricles are closer to the size of healthy mice. And consistent with all of these physical differences, Alzheimer's mice exposed to light and sound stimulation show better performance on learning and memory tests than untreated mice did.
We are still studying why stimulating gamma waves works. But we have made some key observations. The brain has immune cells known as microglia that are supposed to maintain health by removing waste. These cells change their form and activity following gamma wave stimulation. We've also seen that the blood vessels in the brain respond to the stimulation. These vessels widen their diameters to increase blood flow, for instance. This improved circulation may play a key role in flushing out waste as well.
So, mice are nice. But people are the point. So my group and others have begun testing gamma light and sound stimulation in humans. We've developed a delivery device that our volunteers can use in their homes. It’s a poster-sized light box with a speaker underneath to produce synchronized 40-hertz sensory stimulation. A little tablet in the middle allows them to play videos when they are getting stimulated.
Recently, we have begun to see data emerge from these pilot clinical studies. Annabelle Singer, a former member of our MIT team and now a professor at Georgia Tech, recently published encouraging results showing that gamma light and sound stimulation entrains stronger gamma waves in people. And their brains show increased connectivity and synchrony. My group has made some similar findings, including signs of preservation of brain volume and cognitive improvement. A private company we co-founded, Cognito Therapeutics, has also seen benefits in human testing, including reduced brain atrophy and improvement in mental functioning. While we still have more work to do to determine the full clinical efficacy, we have provided a lot of evidence that this approach appears safe. Our participants use their devices consistently and tolerate gamma wave stimulation well. Unlike a drug, this stimulation is completely non-invasive and has minimal side effects, which could make this approach very accessible.
We are now working to launch a new study of whether gamma-wave stimulation can effectively delay the incidence of Alzheimer's disease. Given the prevalence of Alzheimer’s disease in our aging population and how safe this gamma light and sound stimulation approach appears to be, I sometimes dream of a gamma society where we integrate gamma wave stimulation into our daily environment through our lighting or even our video entertainment. Maybe we will have a better world and a brighter future if we can keep our brainwaves, and therefore our mind and memory, well stimulated.
Thank you.
(Applause)
Chris Anderson: Thank you so very much. I actually would have so many questions, but the clock is not our friend. I'm going to ask you one. The cause of Alzheimer's, like, the implication of what you're saying, is that it's possible that an actual causal factor is this falloff in the gamma brainwaves. Is that how you see it or what is the picture?
Li-Huei Tsai: You know, obviously, the causes for Alzheimer's disease are very complex. There are a lot of genetic factors and environmental factors. But one thing is that this compromise of the gamma waves happens very early in the course of the disease. And you know, as I alluded to earlier, it has tremendous effects on many different cell types, many different functions in the brain. So it is very likely that these impaired gamma waves leads to the build up of the protein aggregates and pathology. But I would also like to mention that this impairment of these other cell types and other processes in the brain can also impact the strength of the gamma waves.
So if you think about the pathophysiology of the disease, it's like a runaway train that eventually crashes. So I think that this light and sound approach, what it does is to give a break of this process and give the brain an opportunity to heal.
CA: So you are not necessarily arguing that gamma-ray therapy would be a complete prevention of Alzheimer's, but that it could, in combination with other things it could play an absolutely critical role.
LHT: It depends on when do you start the treatment. So if you start early -- so that’s why we are now testing whether this approach can delay the incidence of the disease.
CA: If you start early enough, you really believe, that alone could delay materially the onset of Alzheimer's.
LHT: We'll see, we're starting a clinical trial.
CA: Thank you so much, thank you for your work.
(Applause)
