Chapters Transcript Video Touch-and-go: Sensorimotor Processing in Neurotypical and Clinical Populations Jeffrey M. Yau, Ph.D. presents at the Johns Hopkins Department of PM&R’s Grand Rounds on February 18, 2020. Okay, thanks, gorilla. Thank you all. Uh, it's as Gabriella said, this is Hopkins is kind of home to me because I basically did my PhD and postdoc training here. And so even just driving, flying into B. W. I. Driving into the city, there's really this overwhelming nostalgia. And so I can say once you leave here you kind of a little bit of Baltimore goes with you, which may not be a good thing, but we'll see. Okay, so, uh, let me assure you, I will not go long today because I understand that talks that go longer, not all that pleasant. Um, and I mean, thank you in advance for your attention. So, as Gabrielle said in my lab, and my research has focused on somatic sensation. So how we perceive information by touch and also how that contributes to the way that we can interact with the world. And so today I'm gonna be telling you a little bit about sort of a high level overview of touch, how we can behave and maybe some things that you may not know about, Things that could affect touch. And hopefully the big picture is how can maybe, you know, we all sort of incorporate this into the way that we think about intervening for patients who have sensory motor deficits or just sort of high level type of takeovers from this. Okay, so before we get into the details again, say that why is touch important? So I think everyone recognizes that touch is important because you want to use that to perceive your environment. We're sensing the environment, we're sense uh, things that are touching us, We sense things that we're touching. So this is my daughter being born and immediately she's touching my hand and I can have this sort of immediate contact. So there's a sense of even social communication. What I also want to make the point of is that without touch we would really have a hard time interacting with the world, right? So it's sort of really critical for guiding and shaping our interactions with our environment through tools through through our limbs. My research has looked at basically different aspects of touch, including how we combine somatic sensory information over the body, over our hands, how we have other sensory modalities like vision and hearing that may shape the way you feel your touch. Uh and then trying to understand how are the parts of your nervous system that are dedicated to perceiving information on your body? How are they shaped? How are they patterned? How might they change? Uh And just a very important note that I have no disclosures to declare and I am not a rich person in any way. Okay, so again, I think I need to stay some objectives. So the objectives from today will be that by the end of my hopefully engaging talk, we'll all be able to recognize how the brain is organized. Support sensory motor functions. Hopefully everyone can identify how sensory motor processing is then modulated by things like attention and multi sensory influences. And again, this is where I want to already put as not a challenge. But for you to think about in all of your work, how might these principles apply in some way? Uh and then I'll end with some work that we've done recently with amputees to see how does the nervous system maybe change or perhaps stay the same in people who have lost their limbs. And I would say we can keep this casual. So throughout the talk, if there's something that you have a question about, please feel free to interrupt. Okay, and now I'm gonna lead with the take home message. So if anyone wants to sort of black out for the next 30 minutes, you can do so take home message is one successful and dexterous behavior requires sensory motor control networks that can be more distributed and possibly more complex than what our textbooks tell us. So, the textbook says, I'm going to go through, you have sensory motor cortex up here, sort of straight up above your ears and sort of this, you're right, part of your body is in the left hemisphere and vice versa. I'm going to talk about some evidence that supports that, and also some evidence that says it's a little bit more complicated than that second part, which is despite the fact that the brain is really organized in this really modular way. Again, you learn your textbooks, you have sensory motor cortex here, you have visual cortex back here. You have auditory cortex down here. In fact the brain is much more interconnected in a functional manner. And so it almost doesn't make sense in my mind to think about these different sensory domains as unique and independent. And then lastly, I'm going to emphasize how the way that we perceive and process sensory motor information can be very adaptable, although also sort of, you know, maybe where the rigidly pattern to recognize that that seems like a self contradiction. So clarify what I mean by that. Okay, uh, and again, my goal and my hope is that we can, y'all can sort of think about this. I should also say I moved to texas six years ago. I grew up in the East coast my entire life. And then now I say, y'all uh, but let me also point out that y'all is a very efficient use of words and also very gender neutral. So I feel like it's a good thing. Okay, uh, why is the matter sensation important? This is one of those things where a bunch of people who are interested in matters sensation are walking in now. So clearly it's important. All right, this is something that actually when I lecture medical students, I sort of start with this example because I think everyone in the room can maybe appreciate what happens if you lose your sense of vision if you're blind or maybe everyone has a sense of what happens if you lose your sense of hearing, but I don't know how many people actually know what it means to lose your sense of touch. So I want to give everyone sort of a clear example of this. So in this video on the left you see a woman who's got a very simple job. Her task is to just pick up a match and light it. Okay, so this is very obvious that she can do this, she can see it, she can do it very easily. Now on the right, you have the same exact woman who now you already know can do this, but the only difference is her hand has been anesthetized by a local nerve block, so she has no sensory information coming in through her hands. And what you can clearly see is despite the fact that she demonstrated expertise on this, she has sight of her hands so she can use vision to guide this. She could barely pick up the match, you can barely position it properly and hold it tightly in her hand. And now you're like please like this, don't burn yourself. Got it right. And so what I want to emphasize and hopefully what's very clear is that without sensory information, even if you have other sensory modalities to guide your interactions, even if you have fine dexterity of your hands, you really lose the ability to have coordinated behaviors. Okay? And so beyond just this very artificial situation where you have your hand magically anesthetized, why else is this important? Well, as technology is evolving as people are working on things like brain machine interfaces, Right? This is where the idea of understanding what the principles that underlie touch are important, because we want to be able to incorporate sensory feedback into these brain machine interfaces. So here is a patient who is a quadriplegic. So he is sitting in his power vulture here, he's controlling this robot arm with electrodes that are implanted into the sensory motor cortex. Right? So that by itself is pretty amazing. This is science fiction. He already that he can just sort of think about doing this and then he can reach over, pick this thing up, drop it over. But what I also want to point out, sort of moving beyond this marvel is if I were to ask any of you to go pick up a block and move it over, you'd be like, boom, boom, give me another boom, boom, where does this go? Let me juggle these. Right. And this guy is like, he's got these online computer systems that are also doing a lot of signal processing for him. Right? And so the point is without sensory feedback while we can do motor things, then we're still doing this in a very labored manner that's a very uncoordinated manner. And so, understanding touch then allows us to start to build uh neural prosthetic devices that can now generate artificial sensations. Right? So here is rob gone from Pittsburgh who is now stimulating mechanically and I don't know if you can hear this right? So now he's touching this robotic hand. Yeah, index. And the quadriplegic participant now is able to identify which of the hands on the which are the fingers on the artificial hand is being touched because now there's sensors on the hands that are being touched that then generates electrical signals that are now being injected into the brain as electrical currents to parts of somatic sensory cortex. Index. Okay, so again, pretty cool stuff. Okay, okay, okay, so that technology works in part because we can exploit what has already been long known and really made famous by Penfield where we have in central motor cortex was called this clear body map homunculus. So everyone I think understands that in the medial part of the brain you have your lower limb representations as you start to wrap around and get more lateral, you now are going to traverse through a large hand representation, You can kind of resolve fingers in that and then now get into a large face and mouth representation. This is highly conserved across species. This is highly conservative cross individuals, although there's a lot of individual differences as well and this is mirrored both in motor cortex which is more interior and then in somatic sensory cortex which is more posterior and I already want to make the point that you know our brains evolved to do stuff in efficient ways. Right? And so the fact that again your sense of touch is really, really intimately tied into your ability to do stuff right? Your motor side. It kind of makes sense that the brain would have these two representations right next to each other mapped in this very systematic and clear analogy which is organized by the body map. And so these brain machine interfaces at this point to say I felt touched on one finger or I felt touch on a different finger. It works because we have this organization, the somatic copy that's there. Okay, so we can leverage that. But now what other information does the brain process for touching? Although I say that I'm not really going to get into the details of that other than to sort of highlight some fun little things that we could talk about. Okay, so I think one again textbook principle that we know and we teach is that at least in primary sensory areas you have this contra lateral bias in the representation of the limbs in cortex. So how do we know that? That's true. Well, I'm going to tell you a little bit very quickly of a study that my lab has done which again sort of hits just some fun little tools that we can use and they are also used in the clinic. So I think many of you are likely familiar with transcranial magnetic stimulation. And so the principle here is you have some electro magnet once you create this turn on and off this magnet very quickly you have magnetic flux. And so that flux is going to induce electrical current cortical tissue that's underneath the quo. And so if you have different arrangements of the quos, you can have different profiles of the electrical, of the magnetic field that you're generating. And this is happening very very fast. Okay, so how can we use this in a research environment and also how can we use this in a clinical environment? So we can use this for example to non invasively activate and and drive activity and populations of neurons. And so if you were to stimulate over primary motor cortex you would engage in these upper motor neurons. They would then send their information decades it go down synapse onto these lower motor neurons and then that would drive muscle activity. And so here you can see me applying stimulation to my postdocs brain. And so you can see he twitched every single time. This thing little flashes he's twitching because now words were directly engaging his hand representation in his brain, causing his muscles to contract as much as he would want to resist as he cannot because we have brain control in my lab. Um And so in the clinic this is a useful tool because now you can use this as a noninvasive probe to map what is the function in different parts of the brain. So that's one way. And then what I'm not going to talk about today is the fact that you can also use this type of stimulation and other forms of non invasive stimulation to create persistent changes in the brain through neuromodulation. So that's something FADA in 2008 approved TMS as intervention for drug resistant depression for example. Okay, so we've used this very simply just ask basic questions right? So I'm not going to get to the sort of finer grained details of this study that we published a few years ago. But the point of this that I'm talking about today is we can use this to test how contra lateral is the representation of the hand in your brain, right? So we have subjects to a very basic task where they were either going to feel touch on their left hand or on the right hand on both hands or on neither hands. So they know this and we say now did you feel touched, where did you feel? Right? So that we call this the urban test right, there's four alternative answers. And so without tms participants are basically perfect at this, they can reliably tell us when the only one hand is touched, where both hands are touched or when there's no touch. When we apply tms to pride. All cortex on the left side we found that the behavior would be changed and what we found was on the left hand. So it's a lateral to the side. We're stimulating their performance is still nearly perfect. But on the right hand now they started to miss touches. They would not be able to feel when their hand was being touched despite the fact that everything was the same. And when they were not responding, they're actually saying nothing happened. So this is almost like you're creating this temporary numbness of the hand. They just don't detect this similarly in the by manual conditions. Now they would miss them but now when they missed they would actually say I only felt something that left hand. So again it tells us that it's selectively affecting the perception of the right hand when we stimulate over left cortex. So this is consistent with the textbook view that we have sensory when you do it. There's no. Yeah. Right, right, that's right. So with the motor side you're evoking some sort of output on the century side. We don't create phantom sensations. So there's not sort of the equivalent of sort of a phosphene that we can generate in touch with tms. Mostly we can just create this almost like an equivalent of a scat toma. But in touch. Okay, so we can just quantify again this is just showing the point that I made which is you're selectively disrupting perception on the contra lateral hand And this is just to make the point that this is almost in nearly every one of the 30 subjects that we tested on an individual basis we can see this effect. So again this is not some slate of hand of averaging over a large group and that's showing something this is on an individual basis, we can see this. Okay so that's the textbook view and now when I'm going to transition into again in a very sort of high level summary is some functional M. R. I. Experiments that my lab has been running where we want to see what parts of the brain are responding to left hand stimulation and this is now vibration stimulation on the fingers. So it's left hand or right hand only or both hands being stimulated simultaneously. Again the details of this study I'm not going to get into. So the way that we think about this is basically you have some vibrations that happened on the hand that we're measuring both signal changes measured with functional M. R. I. And then now we can say what is the amount of signal change that we see for different left hand conditions, different right hand conditions or when the both hands being stimulated in unison. So this is just showing an example subject where we get significant modulation of the bolts and go in essentially across any of these conditions on average there's some kind of change and what we can see is with vibrations in particular. We're getting a lot of activations in these lateral parietal cortex areas or more posterior parietal but not really too much in primary sensory cortex. So I'm gonna bring that up again a little bit. But again this is just to see what parts of the brain respond to touch. And again we can look at this at an individual subject level to avoid group averaging and there's pretty consistent patterns across our subjects. So the more interesting question is now can we take an individual Vauxhall which is two millimeters Aisa tropic of the brain which again contains, let's say millions of neurons. So in terms of spatial specificity we're not really getting into these fine grained neuroscience questions but simply want to say if we have a two millimeter chunk of the brain, how much does it respond to either hand alone or both hands together. And so we can quantify that in a very simple way, which is just sort of the average absolute change in the signal. So now each Vauxhall is described by three points or three values. We can then look at all the different boxes and you see there's a range of different type of response patterns, right? So some respond a lot to the left hand, some respond a lot to the right, some do combinations of those. Then we can just apply a clustering algorithm and of this chaos, this structure pops out and we can see that there's actually some really consistent types of responses that you see. And it turns out that there are some boxers. Again that only respond when the left hand is touched, others that only respond when the right hand is touched. Yeah. Others that respond only when both hands are touched together. Right? This set of officers response to either this hand or this hand, but not when they're together. And then there's this other little group that's when both hands are together touched or just the right. So the point here is that there are these consistent response motifs that can be found in these hemispheres of sensory motor cortex. Yeah, actually decreasing. Great. So yes, they're meaningful in this talk. I'm not going to get into the details of that, but this afternoon we can talk about that. And so here are index is simply how much does the signal change by touch? Regardless regardless of the direction. Okay, so I think the important question that I want to highlight now and really everyone should be thinking is these different types of classes of responses. How are they distributed over the brain? Do we see this lateral bias or contra lateral bias as one would suspect? And it turns out we don't with this data. So if we look at this, we actually see that these different classes are sort of scattered in what I'll call more of a salt and pepper type of organization, right? It's not that we see left Chemistry are primarily response to the right hand. The right chemistry of primary response to the left hand. All these different types of responses are really mixed up in lateral parietal cortex. Right. And so again this is the point that I want to make that depending on the way that we think about our data. Maybe because we're thinking about the negative changes in the response in addition to the positive changes, then that shows that the brain is actually responding in these more complex ways that are less organized in the simple contra lateral bias that we typically expect. Okay, okay, so that's the first part. Everyone take a little breath. I'm gonna take a little breath and take a sip and I think the rest of this is going to hopefully be a little bit less data heavy. I don't know, maybe not. Okay, so Right. So the second part then is about modularity. Right? And this is again moving away from just touch and motor behavior and really think about what else influences the way that we can behave and sense through touch. So I just talked about sensorimotor representations of the hands and again, I made the point that motor cortex sensory cortex there also right next to each other straight up here. Visual is back here auditory is back here. They seem like they're pretty dissociated from each other. But the point that I want to make in the next part of this slide is that they're really not independent and they're always almost systematically influenced by other senses. I'm not going to get into the details. I'm just gonna plug my body of resource, shown what you hear will systematically influence the way that you perceive vibrations, right? So feel and you do that. It's going to change the way you feel that it's going to bias it towards the sound. All right, that's his first part. We've also shown that there are many, many parts of the brain that respond both to sounds and to touch in ways that are very, very specific and reflect this interaction. And then we've also used some of the brain stimulation technologies to show that we can actually stimulate some medicine, sorry, cortex and then disrupt auditory perception the way that you hear sounds. So I'm not gonna get into any more of that, but I will highlight that. Why is this important beyond just sort of interesting little parlor tricks where you get to make sounds and talk, right, it's important because to the extent that the brain is integrating touch and hearing information. Then again, from a clinical perspective, we might be able to leverage these multisensory relationships, for example, in cochlear implant patients as your giving them an implant. The brain doesn't really know how to use that peripheral signal, but if you have touched that is also engaging in those same cortical circuits. You can think of touch as sort of training wheels that trains the brain to say when you hear this, this is what that means. Right? So this is one way to think about that. Or you can maybe engage in cortical hearing circuits for tinnitus now shape the auditory cortex activity using vibrations or accessing the same representations. Okay, what I will talk a little bit more about is just how our vision can influence touch. So again, rather than just thinking about how do you do stuff on your hands? But now what are you looking at? How does that potentially going to change even if it has nothing to do with the behavior that is at hand? Literally. Okay, so we had a very simple question that we just want to say, even if it's not about perception on your hand. In fact let's not even worry about doing anything with the hand. Let's just look at stuff near our hand. How does simply directing your visual attention near your hand change the way that sensory motor cortex is processing motor stuff. The excitability of motor cortex, the way that we did this then is we had subjects either have to do a visual task that would require them attending in the space near their hand or attending away from where their hand is two possible locations. And we basically said in a block of trials, the visual thing is going to happen here close to your hand, respond anytime that that happens. Right. And so most of the time during that would happen there 80% of the time, but 20% of the time it would actually happen on the other side and they would also have to respond. Okay, so their job is just to detect when does this visual thing happen In the second block that we can tell them attend over here, this is where it's more likely to happen. And again, 80% of the time the light would happen there, 20% of the time it would happen over here. Right? So this is the way that we can direct their spatial attention to regions close to their hand or away from their right hand. And we can then confirm that they're doing this because behaviorally the idea would be if they're attending to the location that the light appears, they're gonna be faster responding to that as opposed to if they're attending here in the light flashes over here, they're going to be able to do that, it's going to be slightly slower. The prediction is the response times is going to be our readout that they're attending where we want them to attend. The more interesting question is, now, what happens if we tms over motor cortex and we measure 80 mg of the FBI muscle on the right hand? And the prediction here that we had was if you're attending to this space, you're going to automatically increase cortical excitability to the muscles that are in that space. Right? So then the prediction is when you're attending to this hand or this space near the right hand, you're gonna have larger mbps when you tms motor cortex and you cause that twitch compared to if you tell them attend to this side and we tms motor cortex, they're gonna have a smaller M. E. P. That we measure. They gotta want to emphasize that that their task has nothing to do with the hands, simply the hand is there and it's just how does attention happen to do something near it? So what do we show in nearly every single subject? We confirm that when you are attending towards the hand, that the light appears or the side that you're pairing, you respond faster than when the light appears on the other side. So this is the first prediction. This proves that subjects are attending where we are telling them to attend. And what we also see then is when you're attending to the space near the right hand, when you tms motor cortex on the left, I'm sure you get a larger muscle activity than when you tms motor cortex and you're attending away from this hand. So again this is telling us that they don't need to do anything with the hand, but just by simply looking near their hand, that's changing how motor cortex is responding to their hand. Good question. They're responding with foot pedal presses so we make sure that their hands are not involved at all. That's right. So we did not do the right hand side. But sometimes we figured you could direct attention both sides. We had a follow up where actually we have in some subjects and recordings on both sides. So we can see that is specific to the side still. I mean it's not the contra lot otms but we can at least show that baseline E M. G. And sort of spontaneous minis are not different. Okay. Uh let me just skip that last little bit. Okay, and so what this suggests is that, you know, So why is this important? Why should anyone think about this? So one possibility is that simply looking at things and having something flash near your hand? Your brain has this reflexive ability to say I need to do something. Right? So then you're already preparing your brain in some automatic way to say visual information that happens near my hand dynamically is going to require some sort of behavioral intervention on my such and then my hands are always in a prepared state. Okay, so that's on visual influences on motor. Now this is visual influences and a tactile perception. So, recall that I described that urban task before. Right. Did you feel on the left hand on the right hand or both hands were none here we titrate ID. That the amplitude is a little bit. So performances Leslie's by our unbiased without any sort of uh visual information. But we also played this little trick where we said you're going to have a little flashy lights on your fingers. Just ignore those. They don't matter to you only report when you feel touch on your left hand, on your right hand on both hands or if you don't feel touched at all. And what we found is despite that instruction for the participants to ignore light, they were unable to. And so when we crossed this behavior with light that flashed on the left side, all of their tactile performances then became biased towards the left side, right, there are more likely to report left when it appeared on left only. And when it was on both hands, they were now also more likely to report that was on the on the left right. So this tells us that a little flash of light is going to even change the way that your experience touch on your hands. And so we then could see if we had left a bright light on one hand, a dim light on the other hand, behavior gets bias towards the bright side when it's bright, it's flashed alone, behavior gets by us to the dim side. When the dim side is flash alone. When the bright and dim are both flash. Now behaviors bias towards the brighter side. So there's actually this competition between the visual cues that are occurring at the same time. There's a brighter one, there's more sand than the demo that brighter one captures your behavior more. And so we can quantify that bias by just saying for every single subject positive numbers means you're biased towards the bright negative numbers says you're biased at the dim and we can see that in these different conditions you see the strength of these biases. Alright. The last little thing that was kind of interesting for us and that I think it's a little bit more puzzling but potentially something that again, think about in more of a clinic patient rehab setting which is even the experience of lights was able to bias behavior subsequent to that have offline effects. So what do I mean by that when we were inter leaving these flashy trials, there were also trials where no light was presented. But even on those trials, we found that after people have been exposed to this bright light on one side, their behavior started to be biased towards a brighter side. So that tells you that your brain is again almost like a statistical learning machine and it says whatever is happening, whatever is important to me or whatever may be important to me. I'm going to learn that I'm gonna use that and incorporate that into my behaviors. And so the question that is, is there some way to now think about again these multisensory relationships, multi sensory functions and the leverage that as you're trying to now treat maybe things that we normally would think of as more isolated impairments or deficits, how long last? Yeah. Right. Good question. So, don't have an answer for you only in our block. And we now have studies to see what the sort of unlearning of this might be. Okay, so, last part that we're going to move into sort of this adaptability of sensorimotor process. So, what I just actually described in the previous slide is the way that we perceive information, the way that we use our hands can change very quickly, right? So that seems like it's a very adaptable system, and the example was you can recalibrate localization on your hands. But now the question is other things like the Samata toppy, right. The body map that, you know in your textbook, is that also adaptable? So this is where we're gonna ask this question. Where in amputees or individuals who have lost their limbs, what happens to this homunculus map? Right? And so again, here's the body map. If we just take able bodied individuals who have all their limbs, and we say, as we're scanning them with M. R. I. We say just move your left ankle, right, So we tell them sort of rotate, you can't see this, I'm not going to demonstrate, but you kind of rotate your ankle, right? This is the consistent part of the brain that is active with FMR, that we can measure, which is corresponding to this lower limb representation. Right? So now a number of things can happen that would lead to amputation of the lower limb. So, you have some trauma, you could have cancer, you give diabetes that leads to a cascading series events that would ultimately lead to amputation. And so, in individuals who are now missing part of their lower limb, what happens to this Samantha topic representation? And so, again, we can do this with Fmri. So, we did a very simple experiment where in different blocks, we just had our participants move different parts of the body. So, for these 12 seconds, they would move their left ankle for these 12 seconds, then remove their right hand right ankle lips, left hand, and so on. So, very simple block design. And with our amputees, it turns out, even if they're missing their limbs, almost every single amputee is able to experience phantom limbs, so they still experience as though they had a limb is just clearly not there, and they know this, and the cool thing is, you can actually control your phantom limb. So, we can ask our amputees during this block, when it says left ankle, rotate your phantom left ankle, they're like, what it's like, yeah, just move your left ankle control as though you had it, not just visualize it, but control it. And so that is the instruction. And so, when we look at our amputees now, this is the 18 amputees that we tested, and what you can see, is again. in, essentially, nearly every one of these amputees when they're moving their phantom ankle. This part of the brain that is part of the lower limb representation continues to be active. All right. Some of these amputees lost their legs 47 years part of our experiment, right? So what that tells us is that the structure that is in the brain is not going away, it's not like you don't have a limit, so the brain is going to reorganize to do other things right here. It's clearly still doing stuff that it had been doing many, many, many years before. So we can even look more systematically and say, is there a contra lateral bias in the amputees? In fact, we see that when you look in the one hemisphere there's greater response to the contra lateral limb, the other hemisphere greater response to the contra lateral limb. This is true both in the unilateral amputees and in the bilateral amputees. Now, the sort of uh Holy grail would be, does this activity in some way predict their phantom pain experience or a chronic pain experience, because if it does, then we know we should be targeting this in some way. Maybe we can go and intervene, change this pattern of activity that might lead to sort of amelioration of the pain in our hands. The data is not consistent with this idea that central motor cortex responses when they're moving the phantom relates to anything related to phantom pain magnitude, or the phantom sensation magnitude. Or the sort of vividness of the phantom limb movements. It's also not related to depression is not related to their ambulance in scores measured by the plus M but the only thing that we saw there are some statistical relationship was this thing called the Suez which is spontaneous use of imagery scale. And so these individuals are the ones that turn out that in sort of other behaviors are better able to sort of visualize things and users sort of the mental I right to say. And so I think this is somewhat disappointing for us but such as life so that the phantom response magnitude that is really not in our hands, sort of something that ties directly to this pain response. Okay. And so I'm going to wrap up here just by again hitting the take home message is what I've hopefully conveyed to you today. Is that successful? Dextrous behavior really requires this integration of sense and movements of multiple systems and that can be distributed and more complex than what the textbooks tell you also that despite the modularity of the brain organizing different sort of cortical systems, those are highly interactive. And then also while we can have this sort of very quick fine scale adaptation, there's also evidence that some of the things that are in our brain basically stay that way for possibly ever. And with that let me just sort of thank my lab from three years ago funding and then thank you for your attention. Yes. Question. Mm. Good question. So yes. Great question. What happened to the cerebellum? You did not see activations of the cerebellum because the way I was depicting the data was with the surface models of the brain that were inflated. So that's why they did not resemble the brains that you would see normally. And those don't include the cerebellum. We actually do have activations in the cerebellum. Uh They are localized in regions of the cerebellum that are also consistent with a body map. And so I just did not show those. Yeah. Yeah. Hotel sensory processing near developmental disorders. And some of the slides presented there, you showed that your videos special attention modulates. Good to see. You think the sensory abnormalities really just pinned down has been when they've been. Right. So the question is the sensory, the atypical sensory processes that are observed in neurodevelopmental disorders, how much of that can be attributed to things like attention, right? Or just sort of other. So I would say attention, things like working memory capacity. Those are all cognitive functions that may not be specific to the perceptual systems but certainly would impact your ability to judge those. I think that's a great question. That's one that as far as I know, there's not a really clear way to disentangle those. Right. Unless you're starting to look at different modalities and that you compare performance across that. And then it turns out that in populations like those with ASD, uh there could be individuals that show tactile abnormalities but not auditory or visual and vice versa. Right? So then you wind up realizing that in that case it might not be attention, it might not be these higher order cognitive things, they might be sensory specific. And there are other hypotheses than of what underlies those. So, for example, there's recent work that suggests at a very fundamental sort of neuro circuit level their operations like divisive normalization, that is just maybe not working in the way that it normally does. And so then the way that information is being represented is already being shaped at sort of a population level. Yeah. So with your laterally studies, have you ever looked at any other body parts besides waiting hands? Only because for motor representations, you actually have a different amount of sort of like contra lateral the area. So like hands, for example, we have a but like swallowing muscles, you actually had representation. So I was wondering if that might follow suit also. Yeah. Yeah. So four hours. So the question is, have we looked at other body parts that may be less lateral? Ized? Uh not on the sensory stimulation side, but on the motor behavior. Right. We had the sort of lip movement to contrast with the hand movements and the ankle movements. I mean, I think it's clear that it's hard to move half of your lips, right, your right side versus your left. Um and so there, so I guess that's a short way to say, we don't have a good way to look at that because they're often yoked. But I would say that in sometimes the hands ought to be the most lateral eyes because in sometimes we use those most independently and again we see evidence from both its lateral ized and it's also highly intermixed. Yeah, Yeah. Treatment. We tend to focus on the but your data and other data showing that plantation. Yeah. That a lot of manual but reinstate the central. Yeah, I think Absolutely. Right. Thank you for that. Because I think that if there's any kind of take home from what I've said, I think that that really articulates that well, which is again, rather than focusing on only one, you know, limb or organ system or modality, really sort of leveraging the fact that the brain is really functionally interconnected and so leveraging everything that you can, that provides redundant or systematically related information will likely help. I think, yeah, yep, measure that you can like. Yeah. Motor. Our union. Mm hmm. Thanks. Mhm. One right. Yeah. Yeah. So, I think that is a good question. And I think that's a good idea in many ways. I feel like that relates already to the way that we're right. We're basically saying when this thing comes on, if we can pass this is when you stop feeling that right? So now you're just saying if you have a continuous background would you actually feel that switch off? My prediction is you would but it'll be less easy to detect that switch off. But my prediction is that you would and I should say other people have reported. And I think that this is a sort of bad data or at least noisy data that there are sometimes people who can perceive as though their hands are moving when U. T. M. S. One. Um My one possibility is that in that case it's actually engaging sort of motor circuits as well. Right? I mean because another dirty little secret is when you tms are part of the brain you're activating more than just that part of the brain right? You're engaging in this distributed network. And so this is where I think while tms is a powerful tool to sort of start messing around with people's brains is not such a localized thing. Yeah. Point that's right. I think that's true too. Yeah. Have you done much work trying to improve it? Just sensory perception? I have not. So there are some, right so I mentioned that with neuromodulation there are some protocols that exist that can change cortical excitability. Other groups have used Tms. Uh or T. D. C. S. Now growing to use focused ultrasounds tying back to the first thing that we talked about today to actually modulate actually we use T. D. C. S. In one study. Not over somatosensory cortex but over visual cortex and auditory cortex. And that showed selective interactions with touch. So yes that's right. So we can improve spatial perception on your fingers by stimulating visual cortex. And so we and this is sort of following up on some other stuff with TMS as well. Uh And then if you targeted more lateral areas more over the auditory system then you can improve sort of vibration perception because of the auditory area some sense. Yeah So uh the relationship between audition and touch is very similar in the frequency domain and vibrations. Right? So I think that you can think of the auditory cortex as being really good at processing frequency information or spectral information. And then you will be recruiting many of those circuits when you're feeling touch and using that same information. Just so people know the way that you feel textures right? You hear that that feels different then, right? Because the vibrations that you generate in your skin when you interact with these surfaces are very very different. So what you hear there's a different pattern of sounds just like when you move your fingers is a different pattern of complex vibrations. And so your brain is basically doing the same type of spectral analysis of those to figure out what is the surface in the same way that if you hear your voice saying what is the spectral cues for speech? Right. Yeah, yeah. Yeah. You are able stimulate both of fields different sense. Really? That's right yeah. Things we're vibration where station auditory audition generated by that. That's right. So we do see that the interaction. So if you have subjects feeling vibrations and judging what the frequency of it is and you play sounds the sounds of bias again, the way that they perceive those and the degree to that they bias each other though is related in part to how similar the frequencies are. So there is evidence for that potentially like let's say morning different. Yes. Yes, exactly. Should learn it better. That's right. Even very different in fact. So it's hypothesized it has not been I would say demonstrated in such an explicit learning study. Yeah. And this and this is exactly the logic that was describing for how when with cochlear implants. This is where if you play vibrations that are matching the sounds that the implants should be no representing then this is a way you sort of leverage that shared representation suggest that types of different impairments. Gloria. Mhm. Story. That's right. Percent shared three. All right. So what? Much quicker. Perfect. I could not have said that better. That's another. Take home from this. Yes. Yeah, yep. We I guess of course. Center. Oh yeah. Sense. Right. So uh are there representations of the phantoms in central cortex that you can access to now affect and modulate pain again, that's I think one of those Holy Grail type of things, it's to date people have tried to do that. Uh it's not obvious that there is, it's actually not obvious how you engage in a century representation of a phantom limb right? Alone. Right. So when we have them move their phantom limb that's actually getting motor cortex and sensory cortex, it's hard to stimulate a century. Right. I mean you can maybe tell them imagine you're touched on your phantom limb but but that type of imagery I think is much weaker than imagine you're moving something. This dynamic kinesthetic thing I think is really driving that response. So people are trying to stimulate sensory cortex to modulate chronic pain phantom pain, I think it's not clear how the evidence is showing the efficacy at that at this point. So people are also doing that. That's right. So, so I think this gets into the broader question of when you have phantom pain or if you have chronic pain that's due to some sort of injury, where is what is the origin of that that pain signal? Right. And so you have you know, pain that can originate from the damage the nerve itself or you can have central central pain where now there's plasticity in the deceptive system at the level of the spinal cord, at the level of the brain stem and cortex. So I think it's hard to really, if it were only localized in one part then you can tap into that. But I think there's so many levels of the, your axis that's affected by pain and, and representing the pain that, that I don't know that. Again, the sort of mixed results everywhere, yep. Yeah, we're cramping, right? Yeah, that's a good question. We should have asked that in our offline interviews, we spoke with them once we realized that our questionnaire was kind of useless. And so we, you know, we could ask things like, how many years have you felt this? How, what is the scale of this? But, but it turns out that there's a lot of different experiences of phantom pains, right? And there's actually another thing that some of, y'all might find interesting, y'all. Again, uh, there's phantom numbness and it's kind of aware that you would be like, you don't have a limb, you're talking about a phantom limb, but yet it feels numb to you. Like, what does that even mean? So that was kind of a cool thing that we realized anecdotally. And then also this other thing that was kind of cool. And again, I don't know how many of you have experienced or not experiences, but sort of encountered this, there seems to be a tendency for, in the case of trauma, when someone loses their limb due to trauma, their phantom is oftentimes in the same posture that their limb was in at the time of the trauma. Right. So we talked to someone who lost their limb in a boating accident, like the propeller basically hit them in their leg in a way. And so when he experiences his phantom limb, he feels as though his leg is sort of back as though he were swimming still in that posture. Right? There's also these anecdotes and some medical books where there's this guy who reports he lost his hand because he was shooting a grenade launcher. So don't play with grenade launchers. That thing blew up in his hand. And so he lost his hand. But now his phantom is always in the sense that he's holding a trigger. Right? So there's this really interesting sort of history of trauma that's maintained in that representation. Again, all very anecdotal. Okay, yep, soon. All right, great. What do you think of this company? It's called a halo. Hmm. We did just The Big Brother. So it came up basically like headphones were basically stimulation and they claim to increase learning ability, precision as well as modern frank. What do you think of that? Thanks. Ah again, notice that I have no conflict of interest declarations. I think that the jury is still out on many many of those types of devices in a very controlled research settings. Transcranial stimulation is already sort of a mixed bag. Right. So, I think to the extent that companies are now trying to leverage that and say buy this thing is gonna make you learn something faster or make you a better gamer, right? I mean this is actually the gaming industry has sort of really connected with this. I would say I'm not spending money on that and I'm also not recommending that. Yeah. Okay. Action I deserve like just I want when you was. Mhm. So you can do it well. Tms not Like two, but we're pretty. Mhm. Mhm. Mhm. Yeah. I mean with a lot of these transparent electrical current stimulations, you know the idea is like 50% of the current is shunted at the scalp already, right? So what is even reaching your brain is not really obvious and you might feel this little tingling, you're like yeah something is awesome is happening, I feel so smart. Uh Yeah. Okay well thank you for your great questions. Created by
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