9UNP0440SD_Yuri_Danilov 

- Thank you for joining me for Wednesday Nite @ the Lab at UW-Madison Biotechnology Center. Tonight we welcome Dr. Yuri Danilov, hope I said that correct, I forgot to ask you, from the Department of Orthopedics, correct, at UW-Madison. Dr. Yuri Danilov is a neuroscientist with over 35 years of experience in research on brain function and the special senses, including vision, taste, hearing, proprioception and balance. Dr. Danilov is the lead discoverer of the balancer tension effect, lead development of the specific training regiments, and continues to identify potential clinical and non-clinical applications of neuromodulation and sensory substitution technology. So all of that, a lot of jargon and hopefully he will explain some of this, and as I can tell, there's certainly great interest. Dr. Danilov received his MS degree in biophysics from St. 

Petersburg University in Russia, and his PhD in neuroscience from the Pavlov Institute of Physiology, Russian Academy of Science. He is the senior scientist and director of clinical research at -- where he oversaw both conceptual development for the brain port system, as well as its clinical testing. He's currently the senior scientist in the department of orthopedics and rehabilitation medicine. And his interests in research lie in neuroplasticity, neurorehabilitation, human performance, and human sensory systems. So please join me in welcoming Dr. Yuri Danilov to Wednesday Nite @ the Lab.
(applause)

- Danilov: Thank you very much. Months ago, when another sent me email with request to give a lecture, what we're doing, she requested me to do as simple as possible. And that makes me laugh, and now I understand why. So when in the beginning of the '50s, group of scientists decided to create science with name "cybernetics," you probably heard about it. 

So first thing's first, they separated all known systems in the three categories. Simple, complex, and supercomplex. Simple system is a car, computer. Complex system is like weather in a planet biosphere. Hypercomplex system, we know only two. Universe and the brain. Ironically, and it's true, both systems have 10 to power 12 known elements. Okay, so you can imagine the level of complexity. So when you start to talk about the brain, another important feature that we have to emphasize, that a major unit of the brain, if you ask yourself, what's the first coming in your mind? It's a neuron. 

So scientists study cells of the neuron, cells of the brain, called neurons and glia. So neurons considered the most important element of the brain for many, many years. In the last ten years, exponentially growing science showing that glial cells, what people consider supportive cells for the neuron, actually have a lot of important function. They also compacting signals and glia actually can modify -- the neuron. Then, if you go deeper inside of the cell, there is a branch of scientists studying the intracellular organization, nucleus, Golgi apparatus, synthesis of peptides. If you go deeper you go on a molecular level, there are a bunch of scientists who are studying the proteins, DNA, RNA. And a separate branch of the molecular science are people who study genes, because a lot of disease, we know to be linked to the malfunctioning of the gene activity. So if you go above the neurons, neurons never work alone. They always work together with someone. They grouped and unified together in cell population, in structures, in the systems, let's say visual systems, motor systems. 

As a result of these systems and the brain itself, we have a behavior and we have a branch of science that studies brain activity using behavior. We have psychology, looking on activity of the brain on a psychological level. And you know the psychology, psychiatry, psychophysiology, neuropsychology, a bunch of scientists who are studying brain from that angle. And finally, believe me or not, there was a science, neurosociology. That's saying that the social activity of the human might be very tied with normal activity of the brain, or abnormal activity of the brain. And actually, all these stairs have to be linked in a circle and I will do it later to explain why. So we have at least in this picture nine levels of the complexity of the brain. In each level, it's a focal attention for many, many different sciences. You usually can split it into 50 if you start to look in separate disciplines, inside of each level of organization. So let's talk a little bit about neurons. 

The neuron is the most sophisticated cell in the human body. It's the largest cell in the human body, because the axons, the branch of the cell that acts as the synaptic connection with the body, might be even in a human easily more than one meter long. The small spot on the left panel, it's blood cell size. And the neuron you see is 100 times larger. The glial cells that look like chocolate chip cookie there, so the chocolate chips will be neurons and dough outside it will be glial cells. Very important especially in some topics that we're going to discuss today. Okay, so one of the important features that we're going to discuss today, let's say the disease multiple sclerosis. When the glial cells is a major target of disease. And on the blue wire down in the panel, it's sheaths of the glial cell that isolate the neuron's axons and actually make the human nerves. So it's multiple layers of glial cells surrounding the axons. 

Now, when we talk about the problem or disease, we also can -- of complexity. So if you have a splinter in the finger, it's painful, give or taking, but you know exactly what the problem is and you know exactly what to do. You take a forceps and remove the splinter, it's a surgery, right? So if you have a headache, you have no idea where it's coming from, but it's really painful. You go to the doctor, doctor give you the pill, painkiller, you remove the system. That's a pharmaceutical approach, for simplicity. But let's go to the problem like Parkinson's disease. We know that some structure in the brain stops releasing dopamine. It's very important for systems that organize our movements. We know-- doctors know, scientists know-- that there are approximately five, six, seven targets involved in this process. 

But yeah, decoding the disease there are four major symptoms. It's tremor, hand shaking. It's bradykinesia, people cannot move correctly. It's plasticity, the muscles get really tense and people cannot move their hands. And balance, posture, and gait, people cannot walk and stand steady, because of the disease. Well, the surgery will definitely not help, because you don't know what to remove. Pharmaceutical approach, possibly. People invented some drugs like Levodopa that emulate the dopamine in the brain and help sometimes some patients. The radical treatment, when this is getting really serious and people cannot move at all, it's put electrodes in the brain, in one of the structures, and doctor have to be careful selecting target, and produce electrical stimulation on the structure. Again, sometimes it's helping, sometimes it's not. 

But usually it's creating great relief for tremor, a little bit for bradykinesia, almost nothing for the balance, posture, and gait. So what to do in this situation? Next situation is even more complex. Traumatic brain injury, stroke, multiple sclerosis, viral infection, and many others that can create the piece of dead tissue, -- for example. So you have the area of the brain that's dead. And if you're lucky, you can see it on the imaging and doctor can approximately say where the damage is located. But you cannot see in any existing technology tissue that looks healthy but is not functioning because connections are broken. All tissue surrounding the damage is also not working properly. Even worse, sometimes the pathways are just coming through this area and you break this connection with a function located somewhere else, but you cannot find where. Symptoms usually associated with this kind of trauma are like speech problems, cognitive disorders, memory loss, attention deficit, depression, post-traumatic stress disorders, it's very hard to define. 

So now you don't know where the problem happened and you don't know how to treat it. So one of the ways how people try to handle the situation, that gives a patient tens and tens of different drugs. Because usually each doctor working with, let's say, balance, gives one set of drugs. If it's a bladder control issue, another set of drugs. If it's a memory issue, a third set of drugs. Sometimes I have a patient who uses 50, 60 pills a day. Even if we know, and everybody knows, it was published, that more than five different pills creates unpredictable side effects. Nevertheless, it's only options for the patients. Now, surgery is not working, pharmaceutical approach, pretty weak, what to do? Ironically you, if you look on yourself, if you have a small cut, you're not going to the doctor, you know the body will heal itself, right? 

So it's self-healing. Well, now the body can't do that. And for people who have a really hard and very difficult situation, another option is to stimulate the self-healing, self-recovery. Because pretty often, let's say, you have a hard stroke and usually people have three weeks of rehab, therapy after the hospital. Then they're going home and during the years, slowly, slowly, they recover more. Not much, but to some extent. So obviously, everybody for many centuries, wants to find a way how we can stimulate the self-recovery. So now, let's create some clarity, I hope, in an area of neurostimulation and neuromodulation. If you open literature or look on the web, you'll see a lot of terminology that quite makes you dizzy. And you're really confused. 

What is what? What is this for? So let's try to make a clarification. All the main methods, therapies, related to recovery of missing or affected neural functions is called "neurorehabilitation." Obviously the most known way, do nothing, and wait until the body recovers itself. You can use physical therapy or occupational therapy to reinforce the physical performance and improve the quality of -- or mobility of the joints. You can go to neuropharmaceutical approach, but there is actually nothing really serious in this domain. People want to create some drugs for that, but because they don't have a target, it's very hard to design special drugs if you don't know what for. And finally, there is a branch they call "neuro engineering." It's a combination of all possible ways of physical inference on the brain. 

And that also can separate right now into three different branches. One is neuroregeneration. People using the physical, chemical method to stimulate recovery of the broken axons, for example. Or the traumatized spinal cord. Another very popular way is simple neural repair. It's basically stem cells injection in the area affected by disease and by trauma. I don't want to talk about the positive and negative sides of it, I go to the third part, called neuro technology. And that's an area that we are working in. It also can separate in a few different domains. Let's say if I say about neural stimulation, everybody knows about heart pacemaker. 

It was one of the first devices to use this approach in modern medicine. Right now we have a full family of different devices that people implant in the body to stimulate peripheral nerves, spinal cord --, to eliminate lower back pain, headaches, and so on. There is a non-invasive method. If you go to chiropractor office, you know the machine that stimulates your muscles. But all of these methods only end up on the body. What about the brain? So in 1863, Luigi Galvani first discovered that electricity applied to the right tissue can produce movement. And if you stimulate a piece of the -- the leg muscles will contract. So right now, in the beginning of 21st century, you have a bunch of devices that people implanted in the human body to stimulate the different nerves. Sciatic nerves, nerves that control the bladder, the nerves that control the lower back to eliminate pain. 

The upper one is movement for stroke patients. And if device stimulates your nerves, whether you want it or not, your hand will move in a very specific manner. Again, does it help the brain? Not exactly, because it -- from the neural system to the muscles. But if you think that stimulation of the brain with electricity is something new, think again. 1,000 years ago in the Roman Empire, doctors recommend to apply electrical fish to the head, if you have a headache or gout. Until 16th century people used this approach to help with migraines, epileptic seizures, and depression. Well, right now the most popular way to stimulate the brain is called transcranial magnetic stimulation. It's a sharp change of electrical field that induced in the neurons below the skull some sort of activity. But there is a drawback of this stimulation. 

So I call it "shaking the box." So if you remember analog TV, if something is going wrong, what's the first approach? You shake the box.
(laughter)

Right? It's about the same approach to the brain. And the reason why I call it so is because you never control what are you stimulating. You're stimulating volume of the tissue, millions and millions of neurons at the same time. It's not natural --. If you like you can create stimulation and you can contract the muscles, but the method is very sensitive to orientation of the magnet. That's first. 

And second, in the brain, different branches of neurons and different populations of the cells are oriented in space in a different way. So only specifically oriented neurons are excited. So another way to put electrodes from the side of the skull and do the direct -- stimulation. People assume that this is low intensity. -- can change the threshold to the neurons and help work against depression or epileptic seizures. Another way. Implant the epidural plate or the matrix of the electrodes that stimulate the surface of the brain, next to the stroke-affected area. The results so far were not very convincing. Finally, two methods that are widely used in a hospital, in a clinic, that are both invasive. One of them, deep brain stimulation, when the electrode's implanted in deep structure of the brain, with a Parkinson's patient, for example. 

Or Vagus Nerve stimulation. It's only nerve that immigrate in internal organs and have a massive input to the brain from the body. So the people implanted the pacemaker below the clavicle bone, hooked to the left Vagus Nerve and stimulate once in 50 seconds, feel impulses, assuming that it changes activity of the brain against depression and epileptic seizures. So if you look on the map of this method for electrical stimulation of the brain, again you can see invasive or noninvasive technologies. Our technology, we call it --. Why a strange name? Because all of these on the left side of the diagram, it's a noninvasive neuromodulation. And to distinct our approach from others, we added two letters, CN. It means "cranial nerves." Because the human body, an invasion of the human body may be going through the spinal cord. 

And on the 12 nerves going from the brain directly, and ten of them going to the brain stem, we're stimulating two of them. Trigeminal nerve and facial nerve, nerve number 7 and nerve number 5. Again, if you think that we are the only people who are doing that, I can show you example of Minneapolis and one of the company developed a device to stimulate the optical nerve against glaucoma and macular degeneration. In San Francisco people also use trigeminal nerve but in other branches. The trigeminal is a huge nerve located right here, it's -- and then -- the face. And it has three branches, first, second, and third. So this group stimulates the first and second against epileptic seizures. We are stimulating the lower branch of trigeminal nerve. 
-- nerve. 

So summarizing all these approaches, so majority of the peripheral nerve stimulation going from the body to the peripheral muscles. 

The transcranial magnetic stimulation is basically on the cortex and -- cortical structures. Our technology stimulates very specific area of the brain. It's brain stem and cerebellum, it's the yellow panel here. So why is that important? Oh, okay, it's another summary of what we're doing. So if we have a problem with central nervous system, as we already mentioned, there are many different approaches, different points of view on the brain. And let's say the stem cells approach the problem from the cellular level. People inject a group of cells and look how it integrate in the structures of the brain. Pharmaceutical approach, using mainly molecular level, genetic level, sometimes intracellular structures. Our technology approaching to the same problem from the point of view systems. 

So what we're doing is stimulation of the different systems in the brain and structures. So all work based on ideological background of the father of the neuroplasticity, Professor Paul Bach-y-Rita, who was chairman of orthopedic department at this university and for many, many years he was the only person to find that brain is not rigid, the brain is plastic. And he -- the three major concepts. That one of the sensory substitution, that you can replace, affect the sensory system with another working system. Nonsynaptic transmission, that brain communicates with different parts of the brain, not only through the neurons, but also from extra-neuronal space. And we know now, everybody agreed, that the glial cells, glial network, is a huge part of the brain function that we just start to discover. Last part, late brain plasticity. So most, how I say...? Not accepted by everybody now. Because its conventional view, people think that kids have a very plastic brain and the older you are the less sensitive you are for changes. 

You're not as plastic as a kid. It's not true. And that's what I want to show you. So talking about sensory substitution, just a few words. So when I talk about prosthetic device, that's the first coming in mind. Okay, wooden leg, hook in the hand. That's a prosthetic device. But if you think that sensory substitution is something new, think again. Because cane in the hand of a blind person, that's a substitution device. And what we designed, instead of one cane, we give the person 400 canes. 

But they're connected through the tongue. And if you open the web and try to look at the vision through the tongue, that's the picture that's coming right now from every pages because in December, "Scientific American" published article about this technology and around the globe people are discussing right now this approach. In the United States and England they test it on the veterans who came from Iraq and Afghanistan. Now, everybody asking about the tongue. But because we start from the vision, that was the point. Because if you want to replace the vision you have to find sensory system with maximal spatial resolution. Smell and taste is not working, it's the chemical senses. But closest one to vision is the tactile sensation, and the highest density of tactile receptors in the human body is on the tip of the tongue, so that was simple logic. Technologically, it's much more easy to stimulate the tongue, for example, than chin, because it's a constant wet environment, very electro-conductive constant. Acidity. 

Constant chemical, constant temperature, and so on. So it's easy to stimulate. But then when we proved that it's working on the blind people, and by itself it's a separate lecture, we decided to try something else. Can we prove that we can substitute missing sense other than vision? And that was our starting point 11 years ago. So we invited patient who had so-called -- reaction. About 5% of population is very sensitive to antibiotic --. And if by some reason they put IV with antibiotics, next morning you are losing your sensory system. You're losing your balance permanently, period, no recovery. So from this point of view for us as a model, it was ideal because in these patients only sensory receptors were damaged. 

And the hair cells... what's happening, the --, when it's in the blood, is going to the lympha, and what it's doing, it's actually dissolved the hairs on the hair cells. And they stick together and cells die. So the human body is losing ability to sense the movement, observation, more important, sensation of gravity. Because for us it's natural, we can move the body many different angles, but we always know what vertical means, so we can reorient our body along verticality. If you lose the sensation, you --. Period. Now, so we designed a device that includes -- that measures deviation of the head from the verticality. And transfers the signal to the tongue, because we know that's a very good interface. So the idea was that when a patient feels the way it's moving, left, right, forward, back, he can correct the body, and the goal is just to keep the signal in the center of the tongue. 

Well, you can see on the left panel the trajectory of the head of one of the patients, the first patient, who was standing with closing eyes. You can see the sways. It looks like body continues to look for the reference point, where the verticality is, but he cannot find it. The proprioception, when the muscles react, that's very slow, so that's why he cannot keep the balance precise. But as soon as you provide the feedback, and they start to feel where the center is, they immediately reorient the body. It takes a few minutes, just to learn how to use the device, can they stabilize the body. And they were happy to stay hours in this position because for many years they don't feel sensation of centering and stability. Well, at his point we decided, fine, we did our job, let's go to another project. But... A few things was very suspicious because the patient was so stable, so we decided to remove device and see how long they can stay without device. 

And that's what happened. So on the left panel you can see 100, 200, 300 second stabilization with device. Then you remove device from the mouth, and what was surprise? The period of stability marked by dotted line, increased depending how long you stabilize a patient. And even right now, ten years later, it's one of the most intriguing slides. Because nobody can explain what's happened in the period of stability when we remove device. Because there was no natural receptors, there were no artificial receptors. Why are they steady? And it took some time until the wobbling starts to develop. Well, the maximum time up here was five minutes, so when we go to 20 minutes, results were amazing. 

So that's the most wobbling patient before. Then we did 20 minutes stabilization, and patient was steady for four and a half hours after that. And when I'm saying "steady," it was absolutely normal in any sense. The patient was not supposed to even stay straight, was capable of riding bicycle, walking a beam, jump rope, you will see in a minute. So that's what was that. And that was a key point of our new discovery, that we did something to the brain. Once again, I repeated a few times during the lecture, we're not doing surgery, we're not even doing the drugs and pills. All resources are inside of the patient's brain. And we did something that switched some hidden button that opened the box with the hidden resources. Now, just give you a brief review. 

Okay, so the patient cannot stand with closed eyes, she's falling. Look at the way how she's walking. So it's protruded head, wide stance, cane, extra weight to keep the balance. Few weeks later, the same patient. That's Paul Bach-y-Rita.
(laughter)

Well, second patient. Patient number 2. Just show you example, what 20 minutes can do. So before stimulation, we asked him to walk on the parking lot that's slightly bended. Again, you see the wide stance. 

They have to look where they're stepping, where their feet are, because if they're not looking, they're falling. So we asked this guy to stand 20 minutes with stance stimulation. And he was brave, on purpose he wasn't looking down, he was looking up. Now, next patient was even worse. It was amputation of both legs at knee level because of diabetes, and during surgery they introduced the Gentamycin. He lost his -- system. Even with a cane, he couldn't walk straight unassisted. After five days of stimulation, the same person. Now, finally, the idiopathic patient. Nobody knows what's wrong, but 17 years, continually year by year, person lost balance. 

He came to us in this condition. He cannot walk, use a cane, -- slightly bended. Stairs, that's a typical feature, they have to use both hands to walk on the stairs up and down. The tests that we asked him to perform, to stand with closed eyes, he cannot stand. He's falling a lot, but he's almost not reacting. Again, we did it twice a day, 20 minutes stimulation. You see he is not perfect, but he's not falling. The body starts to react. Somehow we switched the mechanism to control the posture. He walked down the stairs without assistance, and walking on the same parking lot, five days later. 

And that was really inspiring. So after that, we tested it on many different patients and to summarize what we discovered on the balance affected patients. If we can help with any peripheral disorders that we tested, many of them, we can help people with central -- disorders and then we decided, okay, what we can do on the people who lose balance as a secondary to something, like traumatic brain injury, Parkinson's, multiple sclerosis. Yes, it's worked in everybody. So what we discovered, that not only balance and gait, but many other functions improving. Like muscular tone, speech, sleep, the number of falls decreased, depression decreased, migraines, pain sometimes going away during the training time, fatigue, a very interesting symptom. Nobody knew what to do with that. Also saw improvement in abnormal eye movement and tinnitus, the abnormal noise in the ears. All symptoms getting better. Even more intriguing, we figured out that it's not depending on aging. 

In the 40s, in the 80s, improvement after the same period of time is about the same. So the oldest patient that worked in this project was about 86, I think. Now, usually people ask five magic questions. First, how it's possible that buzzing of the tongue can help so many symptoms. Second, why it's the same buzzing can help different disease, different symptoms. Another question that nobody asks directly, but usually afterwards, if there are any negative effects. And the last one, how we can get this device.
(laughter)

So that's the five typical questions. I try to answer all of them. Well, answer as I mentioned before, it's a picture that painted by a patient in the anatomy textbook, and the name of this picture, "Brain Stem." 

So that's an answer of many questions that we're talking. The brain stem is part of the brain that connects the spinal cord with the brain. And it's not just a connection unit. It's a very difficult, complex, difficult built and complex structure. Why? Because if you remember Jurassic Park, you probably were amazed how smart were dinosaurs, right? Yeah, but dinosaurs had only brain stem. The reptiles don't have anything besides a brain stem, so it means that all functions that you can imagine exist in the brain stem. In the human brain, when we developed a few more stages above this, brain stem is still there and the circuitry that connects brain stem with all parts of the brain, and -- possible functions still there. It's like a NASA control center, because what's the brain stem do? 

It transfers the program that major brain designs to spinal cord to execute, so basically it's executive brain. Cerebellum, it's brain that's specifically involved in the movement control. It's also has a very tight link with the brain stem. Cranial nerves, ten out of 12 connect in the brain through the brain stem. And finally, the purple substance in the center that is called reticular formation of the brain, responsible for -- unite and actually control our sleep and level of activity. So now the tongue, anatomically, is connected to the brain stem through two major cables, two major nerves. Lingual nerve, give you idea of texture of the food, and taste nerve, a branch of facial nerve that is responsible for taste. But 30% of taste nerve also includes the terma fibers that feel temperature, pain, and tactile sensation. So you have two massive inputs in the brain stem through the tongue. When we apply the matrix of our electrodes on the tongue surface, we're pumping in the brain like air in a flat tire, from 5 to 45 million impulses that come into the brain stem and start to do something. 

Basically what the neurons do, they spike, they start to send activity in the different circuitries. Now, if you look at anatomy textbook, just one trigeminal nerve spreading all along the brain stem from the spinal cord to mid-brain. And the two structures, let's say you ask, what's the name between tip of the tongue and -- system, because here they are outside and far away from each other. But in the next step, in the brain stem, all structures link together. But if you make a cross-section, so this part of the brain stem, it's the trigeminal --, a projection of lingual nerve, solitary --, projection of the facial nerve, and vestibular --. So now, two years ago we did FMRI research to prove. What I said before was a theory. But two years ago we did FMRI research and compared brain activity before and after one week of our training, and figured out that major changes in activity, long-lasting. The measurement was done next day after last therapy, but you still see the changes in activity in the pons, the center of the brain stem, cerebellum, and medulla. And medulla, it's interesting point, because a lot of descending pathways that control the spinal cord and actually control the human body movement, -- the medulla. 

So we equally well, I assume, help with spinal cord injury and brain injury because activation that we provide the brain stem is going both ways. It's interesting, a picture from the article that was published in 2005, -- involvement of these three structures, trigeminal nucleus, the solitary nuclei and vestibular nuclei, in a different human function. It's interesting in this picture that all links, arrows here, they exist, they're proved anatomically. But what mainly is this picture saying, that stimulation or activity of the three nuclei responsible for trigeminal vascular reflex, indeed, on every patient we're seeing, when stimulation actually is reaching the brain, facial expression start to change, skin changes color, sweating appears, sometimes tears. People have dry eyes and are extremely happy about that. Now, vestibular reflex, eye movement, head movement, that we are curing in every patient who has a balance problem. Automatic responses. We just recently discovered working with multiple sclerosis patient that, say, bladder control, bowel control, GI control is improving. And it's directly proved, this schematic. Endocrine response, we never had the time or ability to test. 

But the cognitive function, and here we have my colleague --, who is actually right now testing this on her patients, their cognitive functions like memory, attention, executive function, multitasking, decision making, all cognitive function also improving. And that's just this corner of the picture. Now in a part of the experiment with the biomedical engineering department, we also found the stimulation of the tongue very quickly activated the whole brain. Well, from one point of view it's very good, because if you remember problem about traumatic brain injury, the problem identifying where it's located. And if we're stimulating the whole brain it doesn't matter, because we're stimulating everything, right? So we're not missing anything. Drawback of the situation, how to focus on what you want to get? And the answer is very simple. It's exercises. With the most efficient application of this technology, it's a combination of the brain stimulation and exercises. 

Exercises, physical if you have a balance problem, or mental if you have a cognitive issue or other thing. And it makes no sense to stimulate the brain if body's not connected, it makes no sense to stimulate the body if brain is not connected. Only together, body and brain stimulation, give the maximum effect. What kind of effect? So just to show you a few examples.
(man singing)
This patient lost ability to sing 28 years ago. Last six years, he even couldn't speak. On the second day of our treatment, he start to sing.
(singing)

He was opera singer, so it's not we teach them.
(laughter)

You still see that he has a problem, but it's a completely different story. 

As a matter of fact, on the end of this treatment, he showed me the tap dance he did on the Broadway. And he came to us with standing touching the wall. Now, another example, also one of the most amazing we have, the patient came here after car incident, whiplash injury five years ago. She has a balance problem, movement control problem, vision was shifted in 30 degrees, she was wearing two pairs of glasses because she had to -- the vision and body sensation. She had headaches, supersensitivy to red light, fluorescent light, and so on, a whole bunch of problems. When she came, I said, "Oh." It wasn't on my list, because what I worked in specifically at that moment was the balance, posture, and gait. And now you see the tests that we're applying to each patient, we have to evaluate their performance during the walking. So they're asked just to walk straight. And this next, we asked her to increase speed. 

She can't, because acceleration, it's not with the body falling, she cannot accelerate the gait. We decided to stop the test and do the one session. 48 minutes later, the same patient. No problem. What you can change in 20 minutes. Rhetorical question, I don't know answer, either. But one test showed a deficiency. When she put the head down, headaches start, it's a -- reflex, pretty well known, but instead of usual four hours, in a few minutes she continued test and was so excited... Look at that.
(laughter)

Of course I have to test more. 

Well, effect continued five hours. In five hours she returned to original condition. But after five days of treatment, she was by all tests absolutely normal person. In this moment, we didn't have the portable device, so we had to send her home without device. And all effects faded away in about six weeks. One year later, she desperately want to come back, and she fell during this time, she fell a few times, and feels actually initially much worse than she did the first time. So you can see this time I have to control her, because I didn't allow her to walk without support. I wasn't sure that she would not fall. Well, the big problem for me in this moment was, like, you cannot count the same river twice, right? So the question was, can we repeat the same results? 

You see she also cannot walk, only touching the walls. Yes, the answer is yes. One week later, so she again regained ability to walk normally. So we repeated on the same patient twice, the same effect. So now she gets device, came home, and continued improving. Well, next patient. Multiple sclerosis. So this is a woman, 27 years progressively getting worse. The body bended, she's not relying on the left foot, you see she use the left foot to throw over the obstacles. Another test, stairs. 

If people using the rail or not. Because she had to use it. And very slow and carefully walking down. Now, two weeks in the lab and three months at home, the same patient. You see the body realigned? Now when she's stepping over, she uses the left leg to stand on. So she recovered the confidence in the left leg. Stairs, no rails. And the final challenge. She didn't do it for 27 years. 

Kids are grown up in about 18 years, so obviously never saw their mother can jump. Now she can. Another example, also secondary progressive multiple sclerosis. Very quickly person loses ability to move. He came with his walker. Right hand, the last three years before that, he lost the ability to control the fingers. If you look on the right hand, the hand is moving, and actually move the walker away. 12 days later, the same person. Not perfect, but you see the difference. Before that, he refused to walk on the stairs. 

He tried to do it using both hands and then he refused. So now you see, he starts moving again, and you see the right hand start to grab the rail, fingers start to move. So when we noticed that, we asked him to perform another task. This one. He didn't do it for two years. Okay? But we didn't train him for the hand. What we trained, the balance, posture, and gait. Why the hand is improving? Okay, it looks like the stimulation reinforced not one, but many systems involved or affected by disease. 

So the last one is a recent one. 40 years diagnosis with Parkinson's. Patient is 80 years old. And 40 years progressively decreasing the functions. It's usually small steps, very slow, the request to turn the head creates a dis-balance. Walking over the obstacles, a typical thing. So it's a delay before they step over. And pause after that. Then she continued walking. Again, small steps. 

Slow steps on the stairs, again touching the rail. Very careful steps. Now, two weeks in the lab, two months at home. You see the lengths of the steps changed? Tremor in the right hand decreased. Changing the speed, no problem. Turn the head, no dis-balance anymore. Stepping over the obstacles, no delay, easy. Stairs, no rails. Left hand still has a tremor, but she wasn't capable to prepare food for herself, but right now she can. 

Make a sandwich and put the tea in the pot. Well, summarizing what I am saying. So, what you saw so far. We can separate four different kinds of plasticity that we are observing. So one of them is a functional plasticity, definitely. In 20 minutes, you cannot change anything anatomically or physiological. Well, a little bit physiologically, but what you can do, it's like I tried to find the right analogy. Try to imagine you have a radio with a station. So it's slightly offset, you hear nothing, or noise, but you change a little bit tuning and signal is getting stronger. Approximately something like that happening with the people who show effects in about 20 minutes. 

It means the functions are there, it's not just tuned enough. And somehow our stimulation helps the re-tune, readjust the tuning. Because that's how you can explain the effects that you can observe in a minute. Then there is a bunch of effects that develop days and weeks. So in the literature, newer science, there is a full branch starting from '70s they call "long-term excitation and long-term potentiation." So this effect on animals and the -- of the brain, show about exactly the same dynamic. High-frequency stimulation, that's exactly what we're using, in 20 or more minutes, produced long-lasting changes along the neuronal change. Neurons start to grow this number of synaptical endings, increase the size of synaptical endings, increase the efficiency of synaptical conduction, to make the circuitry work more efficiently or more noise-resistant. The third kind of phenomena, I didn't show it here because that's effects that develop a few months, a year, or more. We have a patient from Baraboo, 30 years after car incident, was half paralytic body, who started to show improvement of the balance and posture in the regular time. 

But what was intriguing, that after about 15 months, he almost completely regained ability to move on the paralytic side. And after 21 months he regained the ability to sense the paralytic side. And since the sensitivity starts to move from the bottom of the foot up, every week until it comes to the point of the trauma. So these effects definitely show that neurosystems start to reconnect the parts of the body. But to develop these processes, you need a few months or maybe years, depending on how difficult and how severe the trauma of the brain. And finally, unfortunately, I don't see Cheryl. That's my first patient. That's example of the systemic plasticity. Because after a few years, in her case about two and a half years she used the device, now she's not using it at all. And we have about six patients who are not using device after a few years of using it. 

So they consider it completely recovered. They don't use the device anymore. Now, if you look on the burden of the neurological disease on society, so it's about, in United States only, it's about $1 trillion a year. On the list of diseases that you can find in the government sources. And if you can see the green cross, it's disease that we proved that we can help. The yellow stars that we have very high confidence or some occasional observations that we can help. So from this list you see that it's only schizophrenia that we didn't touch. But we didn't touch on purpose because it's too much --. So the mental disorders so far are not on our list. But the rest of it, we completely developed the protocol for the stability and balance disorder. 

This year we're going to finish multiple sclerosis, the regiment of treatment that we're ready to transfer to the clinic. We start to work with Parkinson's disease. Next month with cerebral palsy. Maybe this fall with autism. That's something on our immediate list of interest. Thank you very much.
(applause)