 Good evening. I'm Eric Barker. I'm Dean of the Purdue College of Pharmacy and it's my pleasure to welcome you to this Ideas Festival event as part of the 150 years of giant leaps celebration here at Purdue University. Tonight we welcome Dr. Walter Korschitz, Director of the National Institute of Neurological Disorders and Stroke. Dr. Korschitz joined NINDS in 2007 as Deputy Director and then was named Director of NINDS in 2015. A native of Brooklyn, New York, Dr. Korschitz graduated from Georgetown University and received his medical degree from the University of Chicago. Before joining NINDS, Dr. Korschitz held positions at the Massachusetts General Hospital and Harvard Medical School. A major focus of his research career was to develop measures particularly brain imaging techniques for patients that reflect the underlying biology of their conditions. Guided by a variety of brain imaging tools, he pioneered acute clot removal for stroke patients with large artery occlusion which is now a procedure practiced at comprehensive stroke centers across the country. Tonight Dr. Korschitz will share some thoughts on the future of brain research with the Ideas Festival question what if we could control the brain for better health. Following his remarks I'll be back to begin a dialogue with him and then we'll have time at the end of the presentation to take questions from you our audience. So with that please join me in welcoming to Purdue Dr. Walter Korschitz. Thanks everyone. It's a great pleasure for me to come to you today to talk to at this Ideas Festival because I'm going to talk to you about where ideas come from between your ears. So again as was mentioned I'm one of the directors at the National Institutes of Health. I'm the director of the Neurologic Institute but there are multiple other institutes all with their own separate missions and we try to cover the entire spectrum of health problems and advance the science behind each of these problems to develop solutions for patients. The NIH is the world's largest research funding agency and we are indebted to all of you who pay your taxes on April 15th every year for your generous donations. But truthfully it is a testimony to the generosity and wisdom of the US taxpayer to put this kind of investment into biomedical research. Now I'm in the Neurologic Institute. I'm one of multiple other institutes that are involved in neuroscience funding. We'll talk about some of them. The point of this slide is that if one looks at the leading causes of disability in the United States the brain disorders are the leading in those categories. If you combine the neuro, mental health and substance abuse disorders as all disorders of the brain they are the leading cause of disability in the US and in fact at NIH they lead in the funding category. So there is more funding going into neuroscience than any other area of research from the NIH budget. Now the challenges that we face in devising solutions for the neurological disorders, the mental health disorders, substance abuse disorders are really quite striking in their complexity, the nuances and the tragedies that they cause which is what it's illustrated in these pictures. In our society being able to pull a plow is not going to ensure success in life. Our contributions to society depend heavily upon the ability of our brain to communicate, create ideas, devise contributions to society in general and is really at the basis of living a fulfilling life. Many people don't have that opportunity because of say rare genetic disorders that they're born with. There's also conditions that concur out of the blue, traumatic brain injury, falling off your bike, stroke, sudden occlusion of an artery or bleed into the brain. So there's acquired, there's genetic and there are disorders we really don't understand. There causes many of the psychiatric disorders would fall into that category. So trying to devise solutions for these patients requires a knowledge of how the brain and nervous system work. And although we have had some successes, we've had many more failures and we've had successes and the failures are due to the fact that there are huge gaps of knowledge. We understand something and we think we can go from that understanding to a treatment. We fail and that's because there's a gigantic gap between what we know and what's needed to be known before those solutions are really going to take effect. I've used the analogy of trying to cross a river where you can see there's stones across the river, but from one side of the bank of the river, you can't tell how far apart those stones are. You start jumping across them until you reach the point where you realize I'm not going to make it to that next stone. That's really the problem that we face in trying to develop solutions for many of these problems. Now our institute is one, as I said, of 27 institutes and probably about 13 institutes are doing neuroscience. And so we're all a little bit different. So take that, what I say with a grain of salt in terms of generalizing across NIH. But in general, it's true that we invest in basic research, translational research and clinical research. Translational research is the research that's needed to bring discoveries from the bench to the bedside. Clinical research is usually, I'd say, clinical trials. The basic research falls in two categories. And in our institute, 25% of the budget goes to basic neuroscience research that's disease agnostic. About 40 to 50% of the research goes to basic research on disease mechanisms. So the major component in our institute is what we call basic research. Most of it is investigator-initiator research. So it's not top-down telling people what to do, but it's people have the ability in our system to submit a grant, have it reviewed by peer review, they get a score, we pay the best scores until we run out of money. And the system is not perfect. The review committees, it's a review by jury of your peers. I always say that 30% of the time, they get it completely wrong. But if you look around the world, there is no better system that people have devised. Many of the countries suffer heavily from grants that go to people who know somebody who's in position of power. In the United States, it's a much more American system based on this idea of meritocracy and jury by your peers, but in no means is it a perfect system at all. We are very interested in training because we know that many of the problems that are facing us are not going to be solved by the current generation. But as the tools development, we'll talk a lot about tools, the promise that future generations of scientists will solve these problems looks to us to be incredibly attractive. So I think it's a great time, particularly to enter neuroscience. And we'll be talking a lot about tools and resources, and that's something we think about. But particularly in neuroscience, the brain initiative is focused heavily on the development of neurotechnologies and therefore relies heavily on places like this to produce engineers, material scientists, computational bioinformatics folks to work on problems of neuroscience. So as I mentioned, we're one of multiple institutes that fund neuroscience and the other ones are seen here. We're 100% neuroscience. Many of them are a percentage of neuroscience. But again, the budget ballooned to $8.12 billion in neuroscience research in 2018. In our institute, as I mentioned, we fund across these three areas. Our translational program is somewhat unique and probably of interest to some of the people in the audience and at Purdue in the sense that we have been able to recruit people from industry who are very knowledgeable about the process of moving drugs or biologics or devices through the process of get FDA approval and then to go into patients. So we have what's kind of like a virtual pharmaceutical company. But the purpose of that is not to actually make drugs or devices and market them as a company would, but instead our purpose is to build the case for a device or a biologic or a drug to the point where a drug company or a device company will say, it's not so risky as I thought, and I'll pick that up. And so we are very interested in moving things that we are able to hand them off to industry, so-called de-risking. And that's actually been very successful so far. It's important we think that we engage in this because many of the conditions that we deal with are considered too risky by the industry. And many of the industry, especially the big companies, have moved out of CNS-type research because of the high risk. So that's the purpose behind that program. But it's a special interest, particularly in a place like this, where there are so many innovative ideas that could come to the forefront and have the chance to move into patients at some point. So that's kind of a general overview of the Institute and what we do. And I'll be happy to answer further questions about it. I'm going to spend the rest of the time talking about a very special project called the Brain Initiative. And the Brain Initiative is, it's actually about the brain, but it's actually an acronym for brain research through advancing innovative neurotechnologies. So if you, that spells out brain. And so that interesting title, that was actually devised by the White House. And this program came from the Office of Scientific Affairs at the White House in 2013. And it was the result of the White House group coming to NIH and talking to many different folks around the country to try and understand what investment the country could make to advance neuroscience. And the answer was to focus on understanding circuits and to do that and enable that by developing the neurotechnologies to see circuits to manipulate circuits. And this is what the Brain Initiative is about. So I use the word the three M's when describing the Brain Initiative for people to remember it. First is for maps. You're trying to understand circuits, you need a circuit map. That involves the different cell types, how they're connected together, which is easier said than done because of the complexity of the spatial scales that are involved in the circuitry of the brain. With 85 billion neurons and about a couple of trillion connections. So the mapping is probably without that comprehensive mapping of the human brain is probably not something within our grasp, at least in my generation, potentially in the future generations. The next M is for monitoring. So we have made great progress in structural imaging of the brain. But we don't actually have the ability to see activity going through those circuits. And that's actually been a big problem which we'll talk about. And the last M is for modulation, modulating circuits for health. So the three M's I asked you to think about. So the Brain Initiative is again has a singular focus on circuits. So it's, it's a portion of the neuroscience budget. It's not even close to a major portion of the neuroscience budget. But it's got this singular focus on understanding how brain circuits control how we move, plan, execute actions, remember, think, a moat, and how to monitor and manipulate circuits for improved function. And when you think about people who have the disorders I described, whether they're mental health disorders, neurological disorders, or substance abuse disorders, the patient's disability comes from not actually what's in the brain but how it disturbs the circuits in the brain. In many neurological disorders, we're able to look inside the brain after someone dies. And we can see an area of abnormality. And we assume that that abnormality is affecting a circuit that's involved in say motoric function or cognitive function. But that's a supposition. And oftentimes it's wrong. But we had no way of testing it because we had no way of interrogating those circuits to find out what is wrong with them. And the hope is that with the Brain Initiative, we'll be able to get at that. And that will become the diagnostic criteria for different brain disorders as opposed to a symptom complex, which we think is related to some circuit abnormality, but we're basically guessing. We could be precise about what circuits are disordered would be incredibly important to help us to diagnose these disorders, particularly before they become intractable to treatments. And then modulating the circuits. So if you think about someone who has manic depressive illness, lithium for some reason, no one really understands is quite effective at preventing these kind of fluctuations into mania. It must be affecting a particular circuit. There's such a it's such a unique characteristic switch that occurs in people with manic depressive illness. We don't know what that circuit abnormality is. The drug actually works for but we have no idea how that happened. Think how better we could be in devising precise therapeutics if we could measure the circuit abnormality and then screen that circuit abnormality against drugs to actually improve the circuit function. And there are examples where although this sounds, you know, like it's very far in the future, we have this example in Parkinson's disease, where a deep brain stimulator put into a particular area of the brain that's been identified as a region that's important in the motoric abnormality of Parkinson's. When you turn on the stimulator, a patient can go from frozen and shaking to actually normal. Within a second, you turn off the stimulator and seconds later, they're back in that terribly disabled state. So it's an attractive goal to be able to do that not just for Parkinson's, but for other disorders in neurology and particularly in psychiatry. Now the brain initiative luckily has considerable funding behind it. So Congress has appropriated two types of funding in the blue is funding that goes to the base of the institutes. That funding generally is there on a almost permanent base permanent as anything else is in the government, which is not saying much, but it's it does it, it has been true in the past. And then the green is money that's been appropriated through the 21st Century Cures Act. But it brings the the actual expected budget for the brain initiative to $4.9 billion over 10 years. And we're at about the halfway point now. And so how do we basically go after this problem with the resources we have? And I use this quote from Freeman Dyson, who was a mathematician at Harvard, and philosopher who said that new directions and science are launched by new tools much more often than by new concepts. The effect of a concept driven revolution is to explain old things in new ways. The effect of a tool driven revolution is discover new things that have yet to be explained. And that is where we really are in the brain initiative. There is so much that we don't understand because we haven't had the ability to monitor modulate circuits in the past. But with this new ability comes a chance to actually discover something new. And what the new thing is in my mind is the language of the brain. How does the brain process information? We know there are action potentials and that transmitters are released at the axon and they go over to the dendrite and they excite the next neuron or inhibit the next neuron. So we understand kind of the alphabet. We have no idea how the alphabet fits together to be words or how the words fit together to be sentences or the sentences to be paragraphs or the paragraphs to be chapters or the book to be written. And that is the kind of fundamental information processing fundamentals that are completely opaque to us now. That with the ability to monitor circuits we'll be able to get the data and then really smart people will mathematically computational talented folks may be able to kind of eke out what are these kind of grammatical rules which are being followed in information processing the brain. Now I mentioned that structural imaging has improved considerably when I came out of medical school in the mid 70s. This was the first CT scan of a human person and we were very excited by seeing mush. There's really no information here except for we can see how big the ventricles are which are the black fluid filled area but very little to understand it's going to help you understand the brain. But look what technology has done in 2019 with advanced high field MRI one can get almost histological images of the brain. And this has had a tremendous influence on how we practice neurology. My job often as a training director was to prevent the trainees from seeing the images until they saw the patient because once they saw the images they felt they knew everything and they didn't have to talk to the patient. That was wrong but they could get by because the imaging became so powerful. Now what we haven't been able to do is to actually see the circuit connections so the map of the brain and how to do this is quite because of what I mentioned about the number of cells and the number of connections is really quite complicated. But there have been some new techniques that allow us to do this. And so here I think there's been a big emphasis on developing astronauts who can move into space. I think this is really the big challenge is moving into the space between your ears as the new frontier. It's very similar to a Star Trek movie for instance going out to seeing new planets. So the connections are complex but they're intriguing and we have technologies like this one Clarity which takes the lipid out of the brain makes it translucent. So if you have stained this in this case the neuron with a particular fluorescent dye you can see all the connections that those neurons are making. These are not all the neurons is sparsely labeled cells but gives you an example of a technique that allows you to get a 3D connections in the brain. We'll get back to this with some further technology that's advanced this even further. I should say we're not the only agency going after the Brain Initiative. The National Science Foundation DARPA and the FDA and IARPA have been also strong partners along with multiple private groups the Cavalry Foundation the Allen Institute the Simons Foundation and IEEE. Now to explain the Brain Initiative we have basically separated out we meaning the science community and NIH taking their call from them into seven high priority areas. The first one is is the cell census trying to understand all the different cell types in the brain we call discovering diversity. The second one is developing the maps at multiple scales. So the nanometer scale we're basically proteins are interacting with receptors. The scale of synapse is interacting the pre and the postsynaptic junction. Nerve cells in a nucleus interacting together and then nerve cells with with nuclei all over the brain distributed interacting with themselves. So the spatial resolution is really tremendous. There's also a spatial scale. There's also a developmental scale that's also incredible that you start out in an early developmental stage and this this amazing computer is is basically manufactured every time a new person is born and that those scales over time are tremendous. And then the brain circuits are plastic so they're changing all the time. And so when we learn something we learn we went to school we don't know math we come out of school we know math circuit in the brain change to allow us to do that. So experience is also changing the brain so the experience is another area of complexity. And to understand this we'd like to see the brain in action we'd like to see activity going on when we think when we talk. And and this now is possible. We have technology to come through that I'll show you that allow us to actually record neural activity from thousands if not a million neurons at a time in an animal as the animal is performing a particular task. That's something that we could not do before the brain initiative. We can also manipulate the circuits in a way in which we could never do before. Some of these use electrical techniques. Some of these use optical steering techniques to turn on or turn off certain cells in an image up to 20 at a time to manipulate a circuit. The idea being if you can manipulate a circuit. If you have a model of what the circuit's doing you manipulate it you should be able to predict the change in behavior. If you think that that network activity was the driving cause of the behavior. And now I should say that the cell census project is is essential to these two main components because the cell census doesn't just give you a list of different cell types but the cell census project got off to a tremendous start when there was an explosion the ability to single cell transcriptomics. So when now we have a program going on now to get all the different cell types in the mouse brain 8.5 billion cells to by determine all the different cell types and with each of these transcriptomics cell signatures you get cell type specific enhancers or promoters that you can then hook up to the your gene of interest put it into a mouse either transgenic or with a virus and you can now specifically turn on or turn off these cell types in a precise manner. The best example the one that is hitting my brain the most is an experiment out of Stanford where they found a cell group in the amygdala where if they turn the cells off the animals responded to pain normally in terms of moving away from the pain but they didn't seem to care there was no kind of negative emotion to the pain so when you think about trying to develop a treatment for people who are suffering with chronic pain that's exactly what you would want you don't want to take all the pain away because they'll bump their head they'll burn their tongue but you'd like to take away that suffering that's associated with the pain and that this experiment you know it's not you know it's not nailed in stone but it gets you to the point that maybe there are cells that you can do that to if you just figure out where they are and in this experiment they did think they figured it out they turn them off and they get this incredible behavioral response and that gets you the idea of causality it's not just looking at network activity correlating its behavior but it's actually intervening and changing behavior but with all that what we as I mentioned in the beginning the idea is that with this type of data we'll understand the language of the brain these fundamental principles that are require people really skilled in theory mathematics to put these principles out in front for testing and of course we're all the purpose at NIH is not just for discovery for the sake of discovery but the discovery for the sake of patients so moving this into human neuroscience and understanding how all these brain circuits allow us to do what we we can do now I wanted to just stop there and say we have made lots of progress and I'll show you some but we have a lot of big problems still out there so we can record from neurons but we're limited to the coverage area the brain that we can do so figuring out how to get better coverage of brain you can only look at one tiny region you're going to be limited what you can do optical techniques have exploded the challenge though is that they're great for things on the surface of the brain but because of the light scattering getting deeper than a millimeter into the brain seems daunting if not impossible and that is clearly a huge challenge so other ways of getting signals out of the brain that get around this problem of light scattering would be incredibly important the computational theory challenge I mentioned and then a lot of the work has been done in mouse for us to make this available you know to understand movement into humans we really need to go into larger brains at some stage so the scaling is is incredibly challenging on how to do this okay now this is school that prides itself on its engineering and I would say that we also are desperate for engineers to enter the brain initiative and we have a number of them out here that I'll mention but this is just as an example at the brain initiative meeting which is held every year there were more engineers than there were any other group they're all interested in neuroscience but it was highly highly populated by engineers now the outcomes were so as I mentioned the mouse brain project is often running and we're hoping to get what we call a Google map of the brain of the mouse with all the different cell types where they're located where they're connected to but that's kind of like a scaffold based on the transcriptomics and the location we need to fill that scaffold in with the morphology the intricate intricacies of the different connections the physiology the different type of cells their molecular makeup the proteomics for instance and so we're just starting this project but we think we can build the scaffold for an entire mouse brain the big question in front of us is can we do something like that for the human brain within the time frame of the brain initiative and that is our plan so this is seen we know how we what our aspirations are is to put considerable effort into the mouse brain and then start the human brain project with that type of knowledge and then keep that going even past the 2026 mark now this one is a movie and I think you guys have to hit this one yeah so this is just you know a tiny speck of brain I think it's less than a millimeter if I remember right and it's basically a serial electron microscopy through this tiny section and it's then been a sterile stitched together so all the connections between the different em sections were stitched together to just indicate the kind of complexity and again this is a tiny speck of brain what you'd like to do is to have this for an entire brain and that is a challenge that people are thinking about particularly on the mouse side it's been done in the Drosophila brain but but I just wanted to show it to you to to give you a sense of what the complexity is at the spatial spale so that's not even connecting it to all different other parts of the brain one progress that's been made in this area which is ingenious there we go is Ed Boyden at MIT who developed along with called Deseroth this clarity technique you take the lipid out of the brain but then he replaced it with a polymer and this polymer expands in water but doesn't distort the structure of the brain so basically you start with a small brain and you when you put the polymer in put in water the brain expands to nine times the original size without losing its structure what that allows you to do is to actually you can use a fluorescent marker on one side of the synapse first of the other side which you would need an electron microscope to resolve but now when it when it's pulled apart with the expansion microscopy you can do this with light microscopy so he teamed up with Eric Betzig at Janelia who won the Nobel Prize for super resolution microscopy techniques and they have this technique now that you can do the entire Drosophila brain or the entire mouse cortex in two days electron microscopy of the Drosophila brain takes many many months to do by electron microscopy now this offers the opportunity to do something like this in human brain I should also say that one fallout of the cell sensors project was that a lot of the information that was coming from the transcriptome in the cytoplasm that we used to to classify different cell types that same information is in the nucleus in the RNA in the nucleus so you can actually do a very good classification of cell types based on nuclear RNA or actually the chromatin pattern in the nucleus why I mentioned that is because you can't dissociate the cytoplasm in human brain tissue but you can dissociate the nuclei in human brain tissue so we actually have the ability to do the cell sensors project in human autopsy tissue using the nucleus as opposed to the cytoplasm so this is just an example of the ability to measure neural activity during an awake behaving mouse and so this is using optical techniques where the gene is put into the mouse so that when calcium flows into the cell the cell lights up so instead of sticking electrodes and recording from one or two neurons at a time now you can see thousands of neurons at a time in the wake behaving animal collect the data and try and develop the correlation of what the network activity how it is generating the behavior seem to be stuck there we go and people here at Purdue have been very much engaged this is Meng Sui's work developing a new imaging technique that expands the field of view so we can see more of the surface of the brain in terms of recording from cells and another paper from their lab actually trying to get us to be able to look deeper into the brain tissue using adaptive optics and a an ultrasound driven scanning system so the problems that we're facing are really engineering problems and and these the barriers are the physical structures of brain tissue and so the folks who can solve these problems are really the folks in this room and the folks at Purdue and they have been there are also technologies now to develop sensors so not just when the calcium flows in but when dopamine binds to a cell there are artificial genes have been put in that the cell lights up and people here at Purdue this is Matt Tantema if I got it right pronounce it right Matt Tantema's lab developed an ATP sensor so when ATP is released from cells binds to the cell surface the cell lights up around the surface so we have now optical sensors very high temporal resolution to actually see chemical events going on the brain as well as the electrical events now how this is going to get into people we can turn on or turn off cells with light there are people who have developed nanoparticles injected into the brain that will turn on or turn off adjacent cells when there's electric magnetic radiation from the surface of the brain or focused ultrasound from the surface of the brain but tried in true way is to give somebody a medicine and so this technology called dread technology puts in artificial genes that are totally inactive until a chemical is given to the person or the animal in this instance that chemical binds to the to the artificial receptor and that turns on it turns off the cell so this would give us the ability I think this will go into people first the reason is because if you have a problem you just don't give them the chemical anymore so it's controlled manipulation of the cell type but you can do this in an animal now you can pick and actually the example I told you before about those pain neurons being turned off that was done with this technology so they give the animal the chemical and that turned off the cells and then the animal was no longer bothered by a painful stimulus we are doing work in the human although most of the work has been done in the animals but people particularly in the neurosurgical space have the ability to record from human brain and this is people who have epilepsy and come in for epilepsy monitoring you need to find out where the epilepsy activity is coming from but you can also recruit these patients at the trials and this trial that you are seeking is sign millable in moves it's recording over the speech area you are seeking is not available in books that sends signals to the larynx and pharynx you are seeking is sign millable in moves so what they've been able to do is actually decode what someone is saying in this process from the neural activity they record over the brain and this would potentially enable someone who has ALS to actually talk through a computer because they can activate their motor cortex but they can't activate the muscles and this takes the activity from the motor cortex directly and creates sound another example later perotian implanted the device made by second sight over the visual cortex in Jason's brain the Orion device converts images from a tiny video camera on a pair of sunglasses into a series of electrical pulses those pulses stimuli electrodes in Jason's brain that let him see patterns of light that act as visual cues we basically have the video camera in the video processing unit functioning or performing the functions of what the eye normally does and we go directly back to the brain so in this case the patient is not seeing images he's seeing just dots of light and you would think well that's not too useful but you know he's trying to crossing the street and if there's a car coming the dots of light start coming up and he knows the car coming and the funny thing he said was when his wife's mad at him she doesn't say anything so he doesn't know where she is but now he can find her so so there are it's amazing when people have these disabilities how a little bit of technology makes a huge amount of difference so I'm going to end by just saying that the technologies I talked to you about have tremendous potential to improve health I think got a couple examples of that but you can easily imagine how these technologies could be used for other purposes and so in the brain initiative right from the beginning we've been very cognizant of the ethical issues that are inherent to the ability to record electrical activity in someone's brain or manipulate activity in someone's brain and so we have had a group that's been advising us all along they develop got general guidelines for our investigators we have groups in our program that talk to the investigators about these ethical issues should they come up and we feel very confident that we can manage these in the health space how they're used in someone who's blind or someone who can't talk there are issues but there seem solvable for a greater society we are not so secure that these technologies will be used in the appropriate manner and we're not sure that anybody knows what the appropriate manner to use these technologies really is one can start and say well why would you manipulate someone's brain well we do it every day the best example is the school you were in a university people come here to have their brains changed they learn you know differential equations they didn't have circuits to do different equations when they came but they do when they leave if they're in math that's a circuit how how you learn is going to be how you change a circuit we don't know how you do that we will know how you do that and then the question is are there technologies that should be applied to the brain to enable better education just an example more threatening potentially are technologies that are put in military people so that they can you know much more efficiently drive a fighter jet you don't have to use their hands activity goes right from the brain right to the right to the jet lots of other science fiction type things one can think about and their society is really going to have to have a really strong considered discussion about where these things should go and that's something I'm happy to talk to you about I don't have the answers but I hope people will be cognizant of this as you go forward so with that I'd like just like to say if people go to the Society for Neuroscience meeting we have a couple of things regarding to the brain initiative one is a seminar on about six different technologies that have been produced and available for others to use and then we have tools and technology more informal session at a social hosted by the Cavley Foundation on Sunday so hopefully we see you there so thanks very much and appreciate your attention yeah so Dr. Korschitz and I are going to have a very brief dialogue I will remind you that in a bit we'll invite you audience members if you have questions to ask those questions of Dr. Korschitz and there are microphones here in the front we'll invite you front and center I do want to start out you mentioned engineers and physicists and obviously Purdue is a place that's well known for engineering as well as the other sciences that are here but if you could pick just one or two things that are of highest priority for engineers and biomedical scientists to work together on that would impact the brain initiative what would those one or two things be well I'd say first of all which you know in advising particularly young people I'd say what you want to do is to look at a field and find out what you're passionate about and go for that so don't let anybody tell you what to do that being said I think what you should do is that being said you know the things I mentioned our biggest problem I think that I don't we don't know if there is a solution is how to get information deeper in the brain out of the brain and so on two aspects even in the animal models going deep into the brain is a big problem but if we want to translate to humans we need to develop ways of getting these kind of signals you know non-invasively out of the brain through the skull so develop so that I think is the biggest problem is depth and particularly when you get the bigger brains it gets to be a tremendous problem so that would be the thing I hope people could focus on. As we think about decoding the brain and you showed the slide of the epilepsy patient where we're decoding circuits and you think about taking new technologies that further and further refine our ability to decode brain circuits and correlate that with individuals thoughts you really start to talk about the science fiction realm of almost reading minds and suddenly now you and you mentioned some of the ethics of this but let's talk a little bit about what the ethical implications are as we begin to map and decode these brain circuits how is a society can we prepare for that? Well I think that's that's kind of the big question I tried to end on I think what we do which is we have this luxury of being in this medical space so we can say you know you know this is what you can do with the data and that's all you can do and that's got to be in the consent form and the patient has to know about it so and and also the patient has to know what that data is being used for so in the epilepsy monitoring unit people have these electrodes on the surface of their skull for weeks at a time so there's lots of things that are happening to them in that time period that they may not want somebody to decode and so that is something that the investigators have an agreement with the patient now as I mentioned the thing that I'm more concerned about is if these technologies get out into into space where for instance they're used for you know driving a car how do we know that the company that put this in is not also you know knowing what else you're thinking besides you know maybe I left there in the right turn and that's where I think those kind of things we haven't had to face before but those are coming and I think society is going to have to put you know establish the rules of the game in that in those spaces and those I don't think I don't think there's any real good precedence there you wouldn't be suggesting that there's companies out there spying on us would you as our iPhones are listening yeah well we've heard that but but then they only hear what we say and not what we think exactly yeah so as we think about brain disorders and there's certainly numerous brain disorders that are still very much seeking treatments often times in my world of pharmacy we think about medications but there are clear examples where there are devices and technologies that are coming forward that can have a major impact and so maybe in addition to maybe a few of the things that you showed what other kinds of devices or technologies are out there that you've seen on the forefront that would be available to treat brain disorders right so so I think the most powerful one to follow the brain initiative is going to be the ability to introduce genes that allow you to turn on a turn off particular neuron such types and so if you think about Parkinson's disease you want to turn on the dopamine neurons that's totally doable now in an animal but if we could find the circuits for manic depressive switching or pain emotion I think that that's still I think that the first step is going to be this design this combination between the gene in the neuron specific neuron type and a drug that then interacts with that that particular artificial receptor and so developing those chemicals I'm actually the chemical that's used now in animals is Closapine which you don't want to use in people that's an anti-psychotic so we need better better medicinal chemistry for this new age of gene directed cell specific therapy you have a chance in your job to sort of see again things that are on the forefront what's the boldest or biggest idea that you've heard of anyone that's out there you know we the science fiction of 20 years ago is the reality of today and I'm thinking what's 20 or 30 years down the road and you've heard people dream about what they'd love to see be able to do scientists around the country and you would probably right now say there's no way that's possible but what what's right well that actually happened already so the thing that I thought was impossible what's happened was the nods zest on it yell figured out a way to reperfuse the brain in pigs four hours after it was decapitated now that's supposed to be impossible but he did it and not only do that but he showed that metasabilism returned into the brain and he showed that in slices of the brain taken you know 24 hours later there was activity so that is you know that for us was a major ethical challenge to deal with and but on the other hand it allows us to actually do some of these technologies to map the human brain that we can never do before so it preserves the tissue it could if we did this in a human in an ethical manner it would preserve the tissue so we could actually get the connections which you can't do once the tissue is no longer you know sending proteins here and there to do this say the connectomics for instance so that I think that that was if you I mean the answer the question is no one thought that was possible it already happened yeah wow well as a university and this is actually going to be my last question so if you do have a question for Dr. Korschitz I will invite you up in just a moment but as a university how should we be thinking about educating and training and to prepare that next generation of neuroscientist clinicians and basic scientists in the brain related disciplines right so so I think I think the strength here is the weakness at many other places so I always play your strengths you know you better go and write and she'd write go right if you get a chance so I would say that you know the computational the engineering the material science folks particularly in the brain initiative are really the people who are who really bring you to the next level and that involves you know it can't it's not going to happen automatically involves you know a real kind of scientific discussion between the neuroscientist in the in the brain space and and the people in the physical or engineering sciences and but the the great lesson for me in the brain initiative was that NIH was not investing in technology sufficiently and the brain initiative opened the doors to folks from these different areas so what is a neuroscientist you can train there are so many ways you can train to to be able to contribute to neuroscience and diversity is what we need as opposed to you know someone who's in you know a singular track so I think that we're doing what you're I think you're doing the right thing here and just to build those opportunities for folks to to get engaged in the neuroscience problems I think would be great well we do want to open the floor up for questions from the audience I would invite you to please come to the microphones in the front and if you would if introduce yourself if you're a student tell us what discipline you're from if you're a faculty member perhaps what department you're from so that we have a sense of who's asking questions but at this time we'll invite you to ask questions of Dr. Coreshitz and if you don't ask questions I'll ask you questions there we go hello Dr. Coreshitz I thank you for your talk today I thought it was very interesting this is something I'm very curious about I just wanted to ask you if you believe that this work or this research done at the NIH and with the brain initiative will lead to a better understanding about consciousness within the human brain that's a really interesting question so I would say let me correct you the the work is not being done at NIH is we're funding in this being done all over the country but so so it's interesting you brought this up because there's a big battle between the two advisory groups that we had the neuroethics group said that we that a moonshot project is we should try and understand the neuro circuitry and the consciousness and the hardcore scientists said we're not ready to do that so I don't know the answer to the question but then I would say so I'm a neurologist and and if one thinks about you know simplified issues the big problem for us was we would have people would have had injury and they would be in coma so they have no consciousness and we had no good way of telling the family whether that person was going to return to consciousness and some people did and it would take sometimes six months to a year some people didn't so it offers the opportunity and people are taking this to try and study those patients to try and see what brain circuits are destroyed in people who never return to consciousness and also what brain circuits start to come online over time as someone does return to consciousness and so if you think of consciousness as something at that level you know either have it or you don't then I think it's something we can we can approach and then potentially give it insights into the neural circuits that are involved in the bigger consciousness issue but that's that's how I see it at this point okay thank you I should probably introduce myself I'm Chris I'm a I'm in chemical engineering and biochemistry I'm an undergrad student I'm a senior thank you thank you hi hello I'm Muriel I'm from medicinal chemistry and molecular pharmacology I'm a third-year PhD and I had a question more about animal usage do you ever see the way the directions are going decreasing the use of animal models and more towards organoids and human-based models like stem cells very good so we there has there has been tremendous advances in the use of induced polypotein stem cells in the nervous system and and so the lot of activity now has shifted from searching for targets in animal models and move towards human cells particularly because in many of the animal models the targets didn't actually help us get to treatments and so particularly the industry the drug industry is very interested in this as well so a lot of work has shifted to IPS cells in terms of organoids again these are again IPS cells that are then or their their yeah induced polypone stem cells that are then allowed to grow divide and organize themselves and it's really quite remarkable in the early stages how this actually happens and it seems to recapitulate development very faithfully and so I think it's a great model to understand the brain development now if you get to questions like you know how to animals communicate then I it's hard to imagine that we can answer or even get close to answers in those questions without animal experimentation and in actual fact I think that in many of the issues that we've been struggling with in diseases part of the problem is that the mouse is is so different from the human that it's let us down the wrong pathway so we actually have to think about moving back out of the mouse into larger and maybe non-human primates as well for the disease work and for these complicated circuits that don't exist in the mouse which doesn't have much say in the way of frontal court prefrontal cortex you really will have to move even into non-human primates to be able to just to analyze those circuits so it's a little bit of both thank you yeah other questions for Dr. Korschitz well I'll ask one last question probably on the minds of many are treatments or even cures for two of our diseases of aging and it falls somewhat in the NINDS mission and it falls a little bit out but certainly Parkinson's and dementia are two conditions that I know are on the forefront of many in our society's minds and kind of tell us where you think we are in terms of treatments and cures from what you see from where you sit okay well so that the neurodegenerative diseases there as you could as you hinted there are real tragedies for folks and their families and so the question is is there you know a straight line path where we think we can really make a big difference and so again you know as I said in the beginning we know a little bit and then we know there's a lot we don't know you know the question is can we use what little we know to make a difference most of the money now is on this idea that each of these neurodegenerative disease associated with aggregates of protein inside the cells and it's tau and Alzheimer's tau and progressive super nuclear palsy and some of the frontal dementias and snuclein and Lewy body disease Parkinson multiple system atrophy and so can we if we figured a way to prevent these aggregates from occurring with that basically stop the disease from progressing and we also know that these aggregates are spreading from one nerve cell to the other so can we prevent the spread because each of these diseases start locally and then they spread through different brain areas so if we can prevent the spread of these aggregates well that kind of stop the disease in its tracks so that's where most of the money is right now but again it's a lot of this is what we know so this looks good but until you know until you try it and you fail you there's a lot you don't know so I think one big example has been the clearance of amyloid from people who have Alzheimer's disease has so far been successful in clearing amyloid but it has not had any clinical effect on patients so that was clearly a lot of people surprised a lot of people and there may be explanations for that but it's just an example when you you think you know exactly what the problem is nature sometimes just hits you right in the face and says you're wrong and that is probably a good place for us to stop the balance for the future the brain is certain certainly and still a lot to discover as you said it's sort of where no one has gone before so to speak and we look forward to the discoveries that continue to occur here at places like Purdue and we appreciate the continued support from the National Institutes of Health would you please join me in thanking Dr. Korsch it's for spending the evening with us we do have a small thank you thank you gift there's something to remember Purdue by black and so it is we'll be black and gold back in Bethesda so thank you all for being with us this evening enjoy your evening