WEBVTT 00:00:03.557 --> 00:00:10.517 This is the Convergent Science Network podcast. Leading researchers in the domain 00:00:10.517 --> 00:00:16.737 of neuroscience, brain theory and technology are interviewed by Paul Verschoor and Tony Prescott. 00:00:19.677 --> 00:00:24.657 This is Paul Verschoor with Convergent Science Network and I'm here with my 00:00:24.657 --> 00:00:32.017 colleague Tony Prescott and with our guest, the speaker of our summer school, John Kass, 00:00:32.857 --> 00:00:36.957 the great anatomist with whom we already did a podcast, I think that was two 00:00:36.957 --> 00:00:37.957 years ago, if I'm correct. 00:00:39.557 --> 00:00:43.717 Where we focused at that time very much on the evolution of the brain. 00:00:44.757 --> 00:00:50.137 In your talk today, I mean, two years ago, your talk was so fantastic, 00:00:50.277 --> 00:00:54.077 we definitely wanted you to come back. you expanded much more on the work you 00:00:54.077 --> 00:00:59.357 actually started to do about two years ago on the organization of the motor system. 00:01:00.457 --> 00:01:07.397 So what brought you to looking at motor function in more detail? 00:01:07.637 --> 00:01:09.077 What got you to that point? 00:01:10.117 --> 00:01:17.457 Actually, it was on a visit to give a talk at Princeton, and an investigator 00:01:17.457 --> 00:01:23.717 there had an electrode and motor cortex and he stimulated for a half a second. 00:01:23.877 --> 00:01:29.097 And every time he did that, there was a macaque monkey looking around completely bored. 00:01:29.337 --> 00:01:32.977 And whenever he did that, the monkey put its hand to its mouth. 00:01:33.317 --> 00:01:36.697 And I thought this was the most fantastic thing ever. 00:01:37.457 --> 00:01:41.077 And then I thought, I've got to try this when I get home. 00:01:42.097 --> 00:01:47.577 And we simplified because it takes a long time to put a chamber on a monkey and do everything. 00:01:47.577 --> 00:01:52.837 So we had an anesthetized prosimian primate, a Gallagher, and we put electrodes 00:01:52.837 --> 00:01:57.717 down in the motor cortex and premotor cortex and posterior parietal cortex. 00:01:57.897 --> 00:02:05.277 We got movements with the long-term stimulation, half-second electrical pulses in all these places. 00:02:05.397 --> 00:02:09.537 And we can see that they were related to one another, and we started to get a plan. 00:02:10.237 --> 00:02:13.257 So why did you pick the Gallagher for that? 00:02:13.657 --> 00:02:19.557 The reason wasn't very deep. We had a colony of about 50 of them, 00:02:19.597 --> 00:02:20.797 and they were right there. 00:02:21.237 --> 00:02:24.817 And I didn't have to order any animals or do anything like that. 00:02:24.977 --> 00:02:28.097 And actually, I thought it would never work. 00:02:28.457 --> 00:02:30.657 I thought it was not a macaque monkey. 00:02:31.457 --> 00:02:34.937 It's anesthetized. That's enough. And it won't work. 00:02:34.997 --> 00:02:40.537 But when it worked, then I saw it must be what's— and they didn't know the complete 00:02:40.537 --> 00:02:42.437 story for macaque monkeys. Yeah. 00:02:43.897 --> 00:02:45.797 Graziano was an investigator and 00:02:45.797 --> 00:02:49.817 he was just looking at motor cortex and a little bit in premotor cortex. 00:02:50.077 --> 00:02:55.417 And actually, he gave up this line of research due to lack of funding. 00:02:55.557 --> 00:02:59.617 And we had funding problems initially as well. 00:03:00.777 --> 00:03:06.697 And then it started to emerge. We decided we can do, we did next macaque monkeys, 00:03:07.077 --> 00:03:12.337 and we did a very limited study on macaques because it was expensive and hard to do. 00:03:13.537 --> 00:03:17.717 And then we switched back to New World monkeys, and we did two different species 00:03:17.717 --> 00:03:25.417 of New World monkeys, and we got such similar results from prosimia and galagos, New World monkeys, 00:03:25.537 --> 00:03:31.477 and our limited studies in macaque that I thought, this is something that's 00:03:31.477 --> 00:03:33.697 going to be true for all primates from this. 00:03:34.117 --> 00:03:39.397 Because what you found seemed to, in some sense, contradict, 00:03:39.557 --> 00:03:44.997 if you want, our standard interpretation of how brain and motor systems are organized, 00:03:45.637 --> 00:03:50.697 in the sense that often there's a view of a very hierarchical kind of structure 00:03:50.697 --> 00:03:52.997 where things all are converging onto, let's say, 00:03:53.097 --> 00:03:55.937 a motor area like M1, on and then from 00:03:55.937 --> 00:03:59.257 there action is executed right and also in the 00:03:59.257 --> 00:04:02.037 standard interpretation well then the encoding of a motor 00:04:02.037 --> 00:04:04.877 command at level is fairly primitive right but 00:04:04.877 --> 00:04:08.917 you actually what you found was rather different so how would you describe the 00:04:08.917 --> 00:04:14.137 functional consequence of these results so we would agree on one part of that 00:04:14.137 --> 00:04:20.077 and that's the part that it is fairly hierarchical because if you You cool any 00:04:20.077 --> 00:04:23.657 part of motor cortex that causes a movement when you stimulate. 00:04:23.897 --> 00:04:28.677 You can't get the movement anymore from stimulating premotor or posterior parietal cortex. 00:04:28.917 --> 00:04:34.497 So it depends on that cortex being intact for the stimulation to work. 00:04:34.937 --> 00:04:40.997 So our view is that the posterior parietal cortex is activating at the same 00:04:40.997 --> 00:04:43.117 time motor and premotor cortex. 00:04:43.117 --> 00:04:48.257 And premotor cortex is activating at the same time when you're simulating posterior 00:04:48.257 --> 00:04:50.297 parietal, for example, motor cortex. 00:04:50.517 --> 00:04:55.797 So it's a series that jumps ahead in the sense it's not completely serial. 00:04:55.937 --> 00:05:00.737 It also jumps ahead to motor cortex directly from posterior parietal cortex. 00:05:00.997 --> 00:05:07.057 And that's pretty common in cystic cysts. But wait, would this mean that you 00:05:07.057 --> 00:05:10.317 would get this result anywhere where you were stimulating cortex, 00:05:10.697 --> 00:05:14.877 or it's more to restricted areas where you would see this effect? 00:05:15.097 --> 00:05:19.557 So it's a small area that we would get hand coming to mouth, 00:05:19.717 --> 00:05:25.737 but it's a small region in posterior parietal cortex. It's a small region in 00:05:25.737 --> 00:05:28.717 premotor cortex, and it's a small region in motor cortex. 00:05:29.457 --> 00:05:34.197 A defensive movement protecting the head from a blow would be in all three areas. 00:05:35.257 --> 00:05:41.237 Reaching would be in all three areas. eye movements would be in all three, except. 00:05:42.782 --> 00:05:47.602 Eye movements are hard to get actually from motor cortex to get from frontal eye field. 00:05:48.102 --> 00:05:53.882 But you get this posterior parietal cortex going to premotor cortex to motor 00:05:53.882 --> 00:05:56.242 cortex for all these different things. 00:05:56.302 --> 00:06:02.402 They all involve small regions that we think are in competition with one another 00:06:02.402 --> 00:06:05.862 locally within the overall region, posterior parietal cortex, 00:06:06.122 --> 00:06:08.362 premotor cortex, or motor cortex. 00:06:09.162 --> 00:06:12.102 So you found these results in monkeys. 00:06:12.782 --> 00:06:18.662 And you said in your lecture that there was a difference here from non-primate 00:06:18.662 --> 00:06:22.202 mammals and something that it seems to have changed in evolution, 00:06:22.442 --> 00:06:24.002 in the evolution of primates. 00:06:24.162 --> 00:06:29.842 Two things, yeah, you can say. One is that posterior parietal cortex in tree 00:06:29.842 --> 00:06:33.722 shoes or mice or squirrels or rabbits, 00:06:34.602 --> 00:06:39.342 a lot of those kind of animals, posterior parietal cortex, if we try to define 00:06:39.342 --> 00:06:43.622 it in the same way, is a small part of the brain. It's the narrowest triple cortex. 00:06:44.102 --> 00:06:49.542 There's not much distance between primary visual cortex and primary sensory 00:06:49.542 --> 00:06:51.402 cortex in those animals. 00:06:51.542 --> 00:06:53.922 Pretty close together. There's not much room there. 00:06:54.342 --> 00:07:00.162 But in primates, it's a big expansive region, and it's even more so in the human 00:07:00.162 --> 00:07:04.442 brain than it would be in the galagal brain. It's a large region. 00:07:05.862 --> 00:07:09.242 We also have evidence from other 00:07:09.242 --> 00:07:12.062 people's studies that it's the part of the human 00:07:12.062 --> 00:07:15.462 brain that expands the most in development 00:07:15.462 --> 00:07:21.282 so we think it expands in evolution in primate evolution and then and it's late 00:07:21.282 --> 00:07:28.982 developing in in the formation of the brain part of this cortex is non-responsive 00:07:28.982 --> 00:07:32.922 to electrical stimulation you stimulate there for a half a second at any level 00:07:32.922 --> 00:07:34.262 of current you get nothing. 00:07:34.662 --> 00:07:40.862 That's the most posterior part of posterior panthrointics. Then you get into the movement part. 00:07:41.762 --> 00:07:46.842 The part that doesn't initiate movements actually projects to the part that does. 00:07:47.042 --> 00:07:51.182 So it's a feed-in of higher-order visual information, basically. 00:07:52.162 --> 00:07:57.482 A lot of these areas also get direct visual input from identified visual areas. 00:07:58.062 --> 00:08:03.842 So you have areas, yes, I can say this is V3 or this is the amorosome identified, 00:08:03.942 --> 00:08:08.422 and it's projecting to areas that cause movement. 00:08:08.622 --> 00:08:15.542 But most of the original input is from a higher level that goes in there. It's indirect. 00:08:16.122 --> 00:08:20.702 So it's already fairly analyzed visual information. There's a lot of somatosensory 00:08:20.702 --> 00:08:25.622 information, a lot less somatosensory information for reaching, 00:08:25.842 --> 00:08:28.622 and a lot more for grasping and manipulation. 00:08:28.622 --> 00:08:35.222 And it makes sense what kind of information you need to initiate this behavior. 00:08:36.589 --> 00:08:39.589 So that means what you're identifying is 00:08:39.589 --> 00:08:42.729 let's say a subsystem that could 00:08:42.729 --> 00:08:46.649 control if you want goal-oriented behavior and you call it that yeah it's not 00:08:46.649 --> 00:08:51.509 reflexes really right yeah we call it some systems yes it would be a goal-oriented 00:08:51.509 --> 00:08:57.609 behavior or is that provided would it be these are different possible goal-oriented 00:08:57.609 --> 00:09:01.489 movements and we think that they're basic the primate behavior, 00:09:01.649 --> 00:09:05.109 or a lot of animals behavior, you think a lot of. 00:09:07.229 --> 00:09:10.349 Say, rodents don't need all these steps. 00:09:10.869 --> 00:09:16.089 They do have motor cortex and premotor cortex. A lot of this behavior might 00:09:16.089 --> 00:09:22.349 be in a modular form or a domain form in motor cortex and even in premotor cortex. 00:09:22.529 --> 00:09:27.769 There's some evidence already for this, but they don't have the full repertoire. core. 00:09:28.969 --> 00:09:34.249 And a lot of these behaviors would be just controlled subcortically, 00:09:34.309 --> 00:09:38.389 and subcortical centers will contribute in primates as well. 00:09:38.509 --> 00:09:44.629 For example, you might get protective reflexes by electrically stimulating the superior follicles, 00:09:44.909 --> 00:09:48.969 because you have visual information coming in, and you have access to motor 00:09:48.969 --> 00:09:55.349 movements that would not just be eyes, but moving of arms and head to avoid a blow. 00:09:55.749 --> 00:09:58.969 So subcortical areas could be involved. 00:09:59.149 --> 00:10:03.369 But now it looks to us like we're 00:10:03.369 --> 00:10:09.189 getting more cortical control over basic behaviors that all animals need. 00:10:09.529 --> 00:10:16.009 To various extents, animals might reach for food or they might use their face and reach for food. 00:10:16.349 --> 00:10:19.929 But primates are going to reach with their hand for food a lot. 00:10:20.069 --> 00:10:24.189 These are things to pick them up and bring to their mouth or manipulate them 00:10:24.189 --> 00:10:25.689 or do something like that. 00:10:25.789 --> 00:10:32.369 So that's more developed in primates. But we think that now three stages are 00:10:32.369 --> 00:10:33.949 well-developed in all primates. 00:10:37.084 --> 00:10:43.504 Posterior parietal stage is probably more developed and more expansive in humans 00:10:43.504 --> 00:10:47.024 by far than it would be in prosimian primates. 00:10:47.064 --> 00:10:49.884 And it's more in a macaque monkey by far. 00:10:49.964 --> 00:10:57.184 And I would say it's expanded out so that it has more satellite information coming in. 00:10:57.344 --> 00:11:02.624 The cortex right around the domain where you get the movement is also involved. 00:11:03.864 --> 00:11:07.684 And we know it's involved for two reasons. 00:11:07.964 --> 00:11:11.424 Say you have a grass barrier where you're stimulating and you get grasping movements 00:11:11.424 --> 00:11:14.584 or you might say manipulation on something. 00:11:16.324 --> 00:11:19.564 If you go just outside that region where you're getting the grass, 00:11:20.384 --> 00:11:23.524 you won't get grasped by electrically stimulating anymore but if you record 00:11:23.524 --> 00:11:26.084 from the neurons they're active during this. 00:11:26.404 --> 00:11:31.304 So they might be and they are interconnected directly with the grass domain. 00:11:31.444 --> 00:11:37.844 So they're involved in the grass behavior as well. So that extra cortex that's 00:11:37.844 --> 00:11:44.444 involved in it, it occupies, we think, more of the brain in the macaque monkey than in the calico. 00:11:44.764 --> 00:11:50.504 It gives more options, more ways of modifying that behavior through, we think, learning. 00:11:50.704 --> 00:11:54.544 Mm-hmm. There are two aspects to this, I mean, there are many aspects, 00:11:54.644 --> 00:11:58.024 but two that I would like to ask you about. 00:11:59.599 --> 00:12:03.159 So, let's look at this region, right? So, we have, let's say, 00:12:03.179 --> 00:12:06.759 now a subset of brain areas. 00:12:07.159 --> 00:12:10.779 So, on the one hand, we have this posterior parietal area with M1, 00:12:10.839 --> 00:12:12.439 and then we have a prefrontal area. 00:12:13.879 --> 00:12:17.839 Okay, we might want to draw borders around that, but maybe we can have you on that later. 00:12:18.399 --> 00:12:24.339 But these are sort of like now three interconnected stages of the control of behavioral patterns. 00:12:24.699 --> 00:12:29.419 So this posterior parietal area is more, let's say, perceptual. 00:12:31.179 --> 00:12:37.639 Would you say purely visual or multimodal? Multimodal, but depending on the behavior. 00:12:37.939 --> 00:12:42.359 A behavior that doesn't need much somatosensory and probably doesn't need auditory 00:12:42.359 --> 00:12:45.099 at all, which would be reaching to a target. 00:12:45.159 --> 00:12:47.659 The target is identified by visual information. 00:12:48.079 --> 00:12:50.319 So reaching to a target is going 00:12:50.319 --> 00:12:54.439 to be almost mostly exclusively added vibrational information. Right. 00:12:54.939 --> 00:12:59.479 Manipulation of something will have a lot of tactile information and proprioceptive 00:12:59.479 --> 00:13:02.079 information added to that. Cell visual. 00:13:02.839 --> 00:13:07.559 Okay. And then we have in the, so this is, let's say if you want the sensory 00:13:07.559 --> 00:13:11.039 component, perception component, like you said earlier, it's fairly high level. 00:13:11.159 --> 00:13:13.919 It's not really at the level of the signals coming from a retina. 00:13:14.099 --> 00:13:17.039 It's really a process signal as a percept we're dealing with, 00:13:17.159 --> 00:13:20.699 you know, like an object. And then we would have this prefrontal area, 00:13:20.839 --> 00:13:26.939 which would supposedly be more executive, decision-oriented, I would presume. 00:13:27.419 --> 00:13:30.119 And then you'd have the motor area, which is then more with, 00:13:30.279 --> 00:13:34.659 let's say, fine-tuning or programming the action itself. 00:13:34.899 --> 00:13:38.459 Would that be a decomposition you would agree with? Yes, and I would add, 00:13:38.599 --> 00:13:45.339 besides fine-tuning to motor cortex, the connection with premotor areas that 00:13:45.339 --> 00:13:48.999 we haven't talked about much would be the supplementary motor area, 00:13:49.079 --> 00:13:52.459 the pre-supplementary area, and three-singular motor areas. 00:13:53.239 --> 00:13:58.879 And some of these will have to do with reward expectancies. 00:13:59.439 --> 00:14:06.019 Some of these will have to do with error correction, like that was a wrong movement. 00:14:06.019 --> 00:14:10.039 And some general motivation, levels of motivation. 00:14:10.119 --> 00:14:14.139 So that all impinges on primary motor cortex. 00:14:14.879 --> 00:14:18.659 Okay, so that would mean there would then be a fourth zone that you haven't 00:14:18.659 --> 00:14:21.319 really identified yet, dealing more with valuation. 00:14:22.479 --> 00:14:27.919 That's input that comes into the motor cortex, and that's the last step at the 00:14:27.919 --> 00:14:30.019 cortical processing that you're sending out. 00:14:30.159 --> 00:14:34.099 We've already sent out some cortical information from premotor cortex, 00:14:34.099 --> 00:14:38.739 even from posterior viral cortex but the critical output is from motor cortex 00:14:38.739 --> 00:14:44.579 you take that away these other areas at least if you take it away immediately 00:14:44.579 --> 00:14:50.699 like in cooling or immediately after a lesion the other areas now don't function 00:14:50.699 --> 00:14:52.159 they don't give movements anymore, 00:14:53.208 --> 00:14:58.988 We haven't looked at what the long-term consequences of a lesion might be. 00:14:59.128 --> 00:15:04.628 Because my guess is, if you do a lesion, you don't get the movement from other areas. 00:15:04.908 --> 00:15:10.308 I would bet in a month's time, you would, maybe less. I mean, two weeks, three weeks. 00:15:11.608 --> 00:15:16.368 Because there's a lot of plasticity, and you can take over functions and reinforce 00:15:16.368 --> 00:15:20.908 connections that were not strong enough before, but become strong enough to 00:15:20.908 --> 00:15:22.408 elicit the behaviors. years. 00:15:22.688 --> 00:15:27.368 But that'll be another whole chapter. The plasticity and the ability to take 00:15:27.368 --> 00:15:32.328 hormone and make up for lesions will be another whole chapter in this kind of 00:15:32.328 --> 00:15:33.988 research. Not started yet. 00:15:34.228 --> 00:15:38.468 But now the consequence of this is a bit tuition. On the one hand, 00:15:38.508 --> 00:15:40.628 we can pose the question, okay, how 00:15:40.628 --> 00:15:46.288 does it really then sit with standard interpretations of motor control? 00:15:46.288 --> 00:15:50.728 And on the other hand we can also ask how does, 00:15:51.648 --> 00:15:56.808 this three layered control system of behavior relate to the subcortical control 00:15:56.808 --> 00:16:00.528 so on the one hand if you look at more, 00:16:01.408 --> 00:16:06.108 common ideas of motor control the granularity is already very different I'm 00:16:06.108 --> 00:16:12.428 thinking of the standard idea of M1 being encoding action along population vectors 00:16:12.428 --> 00:16:17.608 where every neuron would encode very very discreet movement directions and amplitudes. 00:16:17.868 --> 00:16:22.448 And then if you would sample across large populations, then the common response 00:16:22.448 --> 00:16:23.928 would give you a direction of movement. 00:16:25.428 --> 00:16:30.868 But this is a much lower granularity of organization than the one you're describing. 00:16:31.408 --> 00:16:37.088 So do you see this as a conflict, or can these two views be made compatible? 00:16:37.108 --> 00:16:42.948 I don't see it as a conflict, and I think it will be our job to try to fit them together. 00:16:43.148 --> 00:16:46.128 But it's not fitting together. just yet. 00:16:48.008 --> 00:16:53.848 If you electrically stimulate and you get that particular movement by reaching 00:16:53.848 --> 00:16:59.468 and you start stimulating around and moving the electrode, you'll eventually, 00:16:59.728 --> 00:17:05.248 in a short few millimeters or less, move out of that territory into another 00:17:05.248 --> 00:17:06.888 territory where you get another movement. 00:17:07.028 --> 00:17:10.728 Or you might move out where you get no movement and then you move a little further 00:17:10.728 --> 00:17:12.528 and you start getting another movement. 00:17:13.428 --> 00:17:16.148 This is also the model you proposed, right? That's the model. 00:17:16.248 --> 00:17:20.168 But the movement, as you move the electrode, isn't exactly the same. 00:17:20.328 --> 00:17:25.368 So it may be that you're getting somewhat different sets of neurons activated. 00:17:27.908 --> 00:17:33.588 When you look at the connection pattern, say in posterior parietal cortex, 00:17:33.788 --> 00:17:41.448 because we have that posterior parietal cortex, one region will connect widely to all other modules or 00:17:41.668 --> 00:17:43.568 domains that I've been talking about. 00:17:45.196 --> 00:17:49.636 If you turn this around now and optically image while you're doing that, 00:17:49.776 --> 00:17:51.636 you get a totally different picture. 00:17:52.276 --> 00:17:56.416 Optical imaging is where you would activate neurons high enough to recover a 00:17:56.416 --> 00:17:59.196 threshold. So it's not whether there's any activation. 00:17:59.596 --> 00:18:03.976 It's whether you change the ongoing activity to a higher level. 00:18:05.316 --> 00:18:09.336 And there you see a much different picture. You'll see around the electrode 00:18:09.336 --> 00:18:13.716 stimulation, neurons are activated at a higher level over a very short distance. 00:18:13.716 --> 00:18:20.176 And then you'll see patches around that domain that are activated, 00:18:20.416 --> 00:18:24.616 and more distantly you see nothing, although the connections are there. 00:18:25.596 --> 00:18:31.476 So our interpretation of that is that the connections are largely connecting 00:18:31.476 --> 00:18:36.836 inhibitory neurons, and those inhibitory neurons are downregulating the activity. 00:18:36.836 --> 00:18:41.796 If you add a negative image, like it can have an fMRI, but not so easily an 00:18:41.796 --> 00:18:46.576 optical imaging, because you're going over a threshold new set. 00:18:46.996 --> 00:18:51.776 If you look at functional imaging, I would predict in there that you would get 00:18:51.776 --> 00:18:56.696 a down regulation and less activity than if you're doing an optical and nose region. 00:18:57.036 --> 00:19:01.216 So you're saying, and this is how you showed it, right, that actually there's 00:19:01.216 --> 00:19:06.056 a very clean organization of these behavioral zones, if you want. 00:19:06.056 --> 00:19:10.676 And your idea would be that they are quietly excitatory coupled across these 00:19:10.676 --> 00:19:16.036 three pages of the control system, but then they are tightly, 00:19:16.196 --> 00:19:19.376 let's say they're competing with each other through inhibition. Yes. 00:19:19.576 --> 00:19:23.256 But inhibition regulated through cortical-cortical connections. 00:19:23.716 --> 00:19:28.316 Right. Okay. So you don't see a role in this kind of, let's say, 00:19:28.356 --> 00:19:33.536 competition and action selection for subcortical structures such as basal ganglia. 00:19:34.136 --> 00:19:37.856 When you see this play out as a pure cortical problem? We don't know the role 00:19:37.856 --> 00:19:45.636 of subcortical structures yet, but we know that if we inject tracers in free-reach 00:19:45.636 --> 00:19:48.056 zones, for example, one in posterior paracortex, 00:19:48.316 --> 00:19:51.236 one in premotor cortex, and one in motor cortex, 00:19:51.536 --> 00:19:55.956 and we have a medical student working on this project just right now, 00:19:57.656 --> 00:20:01.376 the connections, interconnections are to the same part. 00:20:01.376 --> 00:20:05.556 They're all overlapping completely in the basal ganglia. 00:20:05.616 --> 00:20:11.736 If you go to a reach and a defense area in the same region of cortex or in different 00:20:11.736 --> 00:20:14.676 regions, they'll be in different parts of the basal ganglia. 00:20:14.856 --> 00:20:17.676 So the basal ganglia has a chance of having. 00:20:19.387 --> 00:20:24.087 Information coming from all three areas at once and feeding back, 00:20:24.307 --> 00:20:27.387 ultimately, to all three areas. 00:20:27.807 --> 00:20:34.107 So what the basal ganglia might be contributing, we don't know yet. 00:20:34.187 --> 00:20:39.287 But it's intriguing knowing that basal ganglia are essential for heaven formation. 00:20:39.487 --> 00:20:45.727 I think that this is a place where that kind of learning can alter the functioning 00:20:45.727 --> 00:20:47.407 of these cortical ligaments. 00:20:47.407 --> 00:20:56.267 So our understanding is at a very primitive level you have to get how to not 00:20:56.267 --> 00:21:00.767 only how to standard behaviors come about but how do you vary these behaviors 00:21:00.767 --> 00:21:03.227 how do you how do you unite them how do you, 00:21:03.767 --> 00:21:07.407 get learning sequences of behavior coming 00:21:07.407 --> 00:21:14.907 about and we're not there yet but we want to go there eventually sure the example 00:21:14.907 --> 00:21:21.267 you described is sort of basically guided region graph in primates and so it's 00:21:21.267 --> 00:21:26.707 easy to imagine in the evolution of primate that uh. 00:21:28.461 --> 00:21:33.561 We moved from being animals that essentially use their mouth as their main effector 00:21:33.561 --> 00:21:37.101 to being animals that would use their hands as their main effector. 00:21:37.161 --> 00:21:40.941 And our eyes start to face forward and we do stereo. 00:21:41.241 --> 00:21:46.441 And we were able to then really precisely control the movements of the arm and 00:21:46.441 --> 00:21:47.901 hand, which wasn't possible before. 00:21:48.361 --> 00:21:55.001 And perhaps this posterior parietal cortex, therefore, evolved to fit this need 00:21:55.001 --> 00:21:56.861 of visiting guidance of reach. 00:21:56.861 --> 00:22:01.281 But would you say that it's more general than that, that it's involved in other 00:22:01.281 --> 00:22:05.321 aspects of motor control, or is it particularly for those kind of movements? 00:22:06.021 --> 00:22:13.301 When we go most new, we get movements, combined movements of forelimbs and hindlimbs. 00:22:14.021 --> 00:22:19.301 We've only done this in anesthetized animals, and so we don't know what that 00:22:19.301 --> 00:22:21.721 means, but it looks like it's running or climbing. 00:22:22.101 --> 00:22:26.201 Okay. So… So, but it could be involved in regulating pain? There could be something 00:22:26.201 --> 00:22:30.941 for initiating climbing or running escape behaviors or whatever. I don't know. 00:22:31.541 --> 00:22:34.841 But it's promising to go in that direction and try to figure that out. 00:22:35.261 --> 00:22:41.321 Have you looked in non-primate animals that maybe have good vision and grasp 00:22:41.321 --> 00:22:45.861 to see if they have anything similar to this development? 00:22:46.261 --> 00:22:52.621 I don't think you would get in posterior parietal cortex because the stripping cortex is so small. 00:22:52.621 --> 00:22:59.941 And actually you get a lot of visual inputs directly to premotor cortex and 00:22:59.941 --> 00:23:03.881 even motor cortex in rodents and free shoes and a lot of other animals. 00:23:04.081 --> 00:23:12.821 They're not adding this extra step in there and that means you've lost the connection as well. 00:23:13.501 --> 00:23:20.481 You're gaining a large expanse of posterior parietal cortex and you're not having 00:23:20.481 --> 00:23:24.901 these direct visual connections to motor and sensory areas. 00:23:26.521 --> 00:23:32.001 But now the, you could, so this is, and this is a pretty clean scheme, right? 00:23:32.061 --> 00:23:35.961 Because you would say, look, at the level of prior motor cortex, 00:23:36.341 --> 00:23:41.221 you would have, let's say, clusters that control different joints of the body. 00:23:41.281 --> 00:23:42.781 This is the motor of the mind, right? 00:23:42.901 --> 00:23:47.481 And they are again grouped together in a, if you want, a zone that controls 00:23:47.481 --> 00:23:49.501 a specific behavioral pattern. 00:23:50.061 --> 00:23:53.621 And they're linked together They had an executive and had perceptual systems. 00:23:54.021 --> 00:23:58.201 And then you could argue within that behavioral zone, you might find something 00:23:58.201 --> 00:24:02.841 like a population response, but collectively they really control the whole behavioral pattern. 00:24:03.021 --> 00:24:05.681 This would be roughly the picture, right? 00:24:05.881 --> 00:24:10.861 But one challenge here is, of course, that you could argue if you now want to 00:24:10.861 --> 00:24:15.241 scale up towards, let's say, macaque performance or human performance, Mm-hmm. 00:24:16.452 --> 00:24:22.792 One thing that characterizes us, if you want, is that we actually are less dominated 00:24:22.792 --> 00:24:24.512 by stereotype behavioral patterns. 00:24:24.772 --> 00:24:27.732 And in our case, we can play musical instruments, we can generate, 00:24:27.832 --> 00:24:30.532 let's say, and control arbitrary behavioral patterns. 00:24:30.672 --> 00:24:35.392 So, and also using the Gallagher, you could say, well, there's still a fairly primitive brain. 00:24:35.772 --> 00:24:41.472 And maybe what you see is more the behavioral organization of a primitive brain 00:24:41.472 --> 00:24:43.832 as opposed to one of a more advanced brain. 00:24:44.052 --> 00:24:48.172 That is, that you look at the control of stereotype behavioral patterns that 00:24:48.172 --> 00:24:53.732 are very much brainstem dependent, but that in the end the organization of arbitrary 00:24:53.732 --> 00:24:57.312 behavioral patterns as we kept producing them would follow different principles. 00:24:58.232 --> 00:25:03.672 How would you look upon that challenge? I would speculate, and we don't know 00:25:03.672 --> 00:25:08.792 much about human brains in this, or we don't I don't know very much about macaque cranes yet. 00:25:09.552 --> 00:25:15.852 But we would speculate that exactly the expansions in the direction you're going. 00:25:15.892 --> 00:25:20.352 So we have a primitive system that is important for all these primates, 00:25:20.552 --> 00:25:23.172 new world monkeys, old world monkeys, pursuing primates. 00:25:23.412 --> 00:25:28.792 We don't know how chimpanzees might be or humans might be, but there's a lot 00:25:28.792 --> 00:25:35.832 of reason to suspect these basic modules have been retained across all these animals. 00:25:36.472 --> 00:25:39.752 But they would also be built upon. 00:25:40.132 --> 00:25:47.552 And especially, say, from grasping to being able to do grasping in all sorts of different ways. 00:25:48.332 --> 00:25:54.972 And of course, most of what we do with grasping is not in conscious awareness. 00:25:55.512 --> 00:26:02.252 Then you reach out and you do the appropriate position of all the fingers for 00:26:02.252 --> 00:26:03.212 whatever you're going to do. 00:26:03.212 --> 00:26:08.872 And it's been pointed out, I don't know if this has been studied in macaques 00:26:08.872 --> 00:26:15.492 to any extent, but in humans, you not only reach the best grass if you're just 00:26:15.492 --> 00:26:16.932 going to pull a twidge or something, 00:26:17.072 --> 00:26:19.132 but if you're going to do something next, 00:26:19.292 --> 00:26:24.312 like turn it upside down, then you do a different grass for turning upside down. 00:26:26.732 --> 00:26:31.272 So there's the potential for a lot more going on than what we're seeing. 00:26:31.272 --> 00:26:34.172 And how does that occur and where does that occur? 00:26:34.652 --> 00:26:40.372 We don't know. We don't know. But I suspect a lot of that is due to circuits 00:26:40.372 --> 00:26:41.872 in posterior parietal cortex, 00:26:42.092 --> 00:26:48.532 where instead of a small grasp area, you have a huge region involved for manipulation, 00:26:49.072 --> 00:26:50.332 grasping and manipulation. 00:26:50.912 --> 00:26:55.072 And maybe only part of that will give you a simple grasp. 00:26:55.192 --> 00:27:00.412 And other things all combine in different ways to add complexities to this. 00:27:00.412 --> 00:27:07.872 And then you think you have to know what you're going to do more than one step 00:27:07.872 --> 00:27:11.292 in advance to do a lot of this and yeah so, 00:27:12.330 --> 00:27:16.950 The challenges are great. But there's something interesting about scaling this. 00:27:17.070 --> 00:27:20.190 If you scale up, because I think we're going to hit the bottleneck. 00:27:20.810 --> 00:27:26.010 Because you could argue, okay, if we now scale up this Gallagher brain that you're investigating, 00:27:26.730 --> 00:27:30.170 then if the same principle would hold for a human brain, 00:27:30.430 --> 00:27:34.550 which is, let's say, much more diverse in its behavioral output, 00:27:34.570 --> 00:27:39.670 almost arbitrary in what it can do, you would say, well, that would mean that 00:27:39.670 --> 00:27:40.970 instead of having, let's say, 00:27:40.970 --> 00:27:44.890 eight of these behavioral zones that you've seen to go, like defensive, 00:27:45.210 --> 00:27:46.770 grasping. 00:27:48.350 --> 00:27:53.510 Stereotype behaviors you identified, now I have, let's say, a large thousands 00:27:53.510 --> 00:28:00.990 of these three-staged controllers that define very specific behavioral patterns. 00:28:01.290 --> 00:28:05.190 Would that be the scaling up that you envision? That's one possibility. 00:28:05.630 --> 00:28:08.510 That's one possibility. It might not be. That's the way it goes. 00:28:08.870 --> 00:28:17.470 Maybe what happens is individually variable according to learning experience 00:28:17.470 --> 00:28:23.190 and modifications in the circuits that come from the learning experiences and 00:28:23.190 --> 00:28:26.190 may depend more on basal ganglia. 00:28:26.190 --> 00:28:30.530 It might depend more on different parts of the whole complex system. 00:28:31.770 --> 00:28:37.750 We don't know that. But if you start to think about other parts of the brain, 00:28:38.610 --> 00:28:44.750 premotor cortex looks pretty simple in the Gallagher goal and fairly enlarged 00:28:44.750 --> 00:28:46.650 and complex in a macaque monkey array. 00:28:47.010 --> 00:28:53.670 And then you think of the complexities. Where did speech come from? 00:28:53.750 --> 00:28:55.850 The motor circuits for speech and so on. 00:28:56.190 --> 00:29:01.390 How did that get elaborated? We actually have no animal model. 00:29:01.450 --> 00:29:06.670 It's partway there that we can look at. You have to learn from humans how this 00:29:06.670 --> 00:29:09.630 happened and what circuits are involved in. So... 00:29:10.880 --> 00:29:15.340 Big jumps, there may be big jumps. We're so far away from macaque monkeys, 00:29:15.400 --> 00:29:20.200 they use them and say, this is what, we're just scaling this up for human brain. 00:29:21.580 --> 00:29:28.200 I'm thinking that's probably not going to be the case. And so we're going to see a budding off. 00:29:28.960 --> 00:29:33.720 Grass barrier will have functional subdivisions and there'll be some that'll be standard. 00:29:35.400 --> 00:29:43.040 And that means a lot of different grass behaviors will be there for every human child. 00:29:43.600 --> 00:29:48.240 And then there will be a lot of things that will be acquired and acquired on 00:29:48.240 --> 00:29:49.160 the basis of experience. 00:29:49.280 --> 00:29:54.700 But the cortex will be there that can be modified for other parts of the brain. 00:29:54.760 --> 00:29:55.820 It doesn't have to be cortex. 00:29:56.080 --> 00:29:59.520 It can be modified according to the learning experience and, 00:29:59.560 --> 00:30:02.040 you know, sort of making stone tools or whatever. 00:30:02.600 --> 00:30:05.480 You're not going to do that well the first day you're doing it. 00:30:05.520 --> 00:30:13.560 But there's some things that you have to do well on the first time avoid a bullet to the head. Right. 00:30:15.620 --> 00:30:23.460 Reaching out and a newborn human baby doesn't have to do very much to survive. 00:30:24.680 --> 00:30:29.760 But a lot of primates are very good at grasping and holding on and reaching out. 00:30:30.260 --> 00:30:35.400 As newborn infants, their visual system has functioned. They can do that. 00:30:36.620 --> 00:30:42.980 So So a lot of experience is needed for some of these behaviors. 00:30:43.060 --> 00:30:46.940 And even if they're late developing or emerging in humans postnatally, 00:30:47.620 --> 00:30:51.400 I'm not sure that experience is an important thing. 00:30:51.600 --> 00:30:54.420 It's just the maturation of the system. 00:30:54.700 --> 00:31:00.720 So it's sort of like the old studies of children crawling upstairs and you don't 00:31:00.720 --> 00:31:01.620 let them crawl upstairs. 00:31:01.860 --> 00:31:05.100 It doesn't make any difference if they have the experience or not. 00:31:05.260 --> 00:31:08.920 At a certain age, they do it. but now. 00:31:10.890 --> 00:31:19.070 So if we take the scaling up question, one bottleneck I would see is how can 00:31:19.070 --> 00:31:24.030 I build my decision-making system, my executive functions of prefrontal? 00:31:24.030 --> 00:31:28.130 Because, for instance, in the perceptual case, you would argue, 00:31:28.170 --> 00:31:32.390 well, this is convergent because I have a number of objects. 00:31:33.270 --> 00:31:37.790 Objects afford certain actions. So you can already see that there's some sort 00:31:37.790 --> 00:31:40.510 of mapping there, which is not completely arbitrary, right? 00:31:40.890 --> 00:31:47.370 And not objects most objects don't afford an infinite amount of of radically different actions, 00:31:47.950 --> 00:31:50.690 at the action side it's highly convergent you have to go to 00:31:50.690 --> 00:31:53.990 your skeletal muscle systems it's very constraint with a 00:31:53.990 --> 00:31:56.710 level of executive control where you have to if 00:31:56.710 --> 00:31:59.530 you want to now these actions to the rules that you find 00:31:59.530 --> 00:32:03.190 in your environment that's almost open-ended right environment 00:32:03.190 --> 00:32:06.350 also for the color goal in theory environments can change 00:32:06.350 --> 00:32:10.430 dramatically and they still have to adapt to that so wouldn't 00:32:10.430 --> 00:32:13.810 would dare not be a bottleneck for 00:32:13.810 --> 00:32:16.690 this idea of very strict zones because that would 00:32:16.690 --> 00:32:20.590 also mean that the information you can now use of capturing 00:32:20.590 --> 00:32:24.190 the rules of your environment the opponent rules your environment is 00:32:24.190 --> 00:32:28.230 actually very limited now because i i'm tied to a certain set of connections 00:32:28.230 --> 00:32:35.690 in a very small zone to pick up an arbitrary set of rules right So don't you 00:32:35.690 --> 00:32:43.310 think that there we need a bit more access to memory than your model would predict? 00:32:44.891 --> 00:32:49.511 You need access to memory, and where memory comes in isn't so clear, 00:32:49.631 --> 00:32:56.631 but you can start to tease this apart by looking at humans with perispherian injuries, 00:32:56.791 --> 00:33:03.691 but it also can be done more productively, I think, with primates where you 00:33:03.691 --> 00:33:08.691 can do selective cooling or inactivation on parts of surface and see what happens. 00:33:09.451 --> 00:33:14.651 But I would, you know, just as an example, say, well, one of the hard things 00:33:14.651 --> 00:33:22.691 for, and I tell you, the frontal cortex develops enough is to inhibit a natural movement. 00:33:22.811 --> 00:33:26.391 So if something moves in the visual field and you look at it, 00:33:26.491 --> 00:33:30.591 but you can tell a person not to do that. Don't look. 00:33:30.751 --> 00:33:35.671 And that would be a command that they understand the rule and they argue. you. 00:33:37.151 --> 00:33:42.471 But a person with frontal lobe damage might have a hard time not looking. 00:33:43.131 --> 00:33:48.271 And so that suggests that the interaction is in the frontal lobe. 00:33:48.291 --> 00:33:55.471 Things that are from the frontal cortex, prefrontal cortex, are important in that decision. 00:33:55.631 --> 00:33:58.011 Otherwise, it's more sensory crib. Right. 00:33:58.271 --> 00:34:03.231 But anatomically, you have not found any evidence for this more, 00:34:03.271 --> 00:34:04.891 let's say, broader other accent of memory. 00:34:05.531 --> 00:34:07.751 Anatomically, you find very sort 00:34:07.751 --> 00:34:11.691 of restricted, zone-like organization is called a vertical projection. 00:34:11.911 --> 00:34:16.531 So we don't know where that happens, but we'd say in short term, 00:34:17.311 --> 00:34:19.991 it's just that short term thing, that working memory. 00:34:22.971 --> 00:34:27.651 Coleman and Ritchie would say prefrontal cortex. Long term memory, 00:34:27.811 --> 00:34:33.331 which certainly if you told me not to look, I wouldn't have to keep that in, 00:34:33.891 --> 00:34:38.471 a short-term memory because I'd remember that the next day saying, 00:34:38.551 --> 00:34:39.751 well, I'm in this situation. 00:34:39.931 --> 00:34:44.431 I'm not supposed to look. I'll just look straight ahead. So how does that, 00:34:45.486 --> 00:34:48.866 Where does that access to that memory, how does that get retrieved? 00:34:49.286 --> 00:34:56.606 And then it gets harder. Okay, but this might imply that there's a fifth zone you should consider. 00:34:56.686 --> 00:34:59.286 Because although there's a fourth zone dealing with value and effect, 00:34:59.546 --> 00:35:04.826 which must be still identified, but maybe there's a fifth zone that is more 00:35:04.826 --> 00:35:07.226 a broader cognitive memory system. 00:35:07.366 --> 00:35:11.346 That is, if you're playing this piano of these zones, these behavioral zones 00:35:11.346 --> 00:35:13.586 you have identified, would that be reasonable as an intervention? 00:35:14.106 --> 00:35:21.966 Yes, absolutely. So we have to think of both understanding what the rules of the game are. 00:35:22.726 --> 00:35:27.226 And we can pick that up verbally very easily. But the problem would be for a 00:35:27.226 --> 00:35:28.466 monkey to understand rules. 00:35:28.606 --> 00:35:33.606 They have to understand by the training procedure that they now are getting 00:35:33.606 --> 00:35:35.126 the idea of how to solve the problem. 00:35:36.446 --> 00:35:39.386 But then you have to know all sorts of other things. 00:35:39.466 --> 00:35:42.106 You have to know if there's a reward if you're doing the right thing. 00:35:42.166 --> 00:35:46.506 What's the value of the reward? And the value of the award would not be consistent 00:35:46.506 --> 00:35:50.026 if it's a food reward because you're hungry or less hungry. 00:35:51.466 --> 00:35:57.986 So if it's a punishment, what's the value of that? And all that information has to be there. 00:35:59.186 --> 00:36:05.166 So it's a huge task to try to explain these complex behaviors. 00:36:06.326 --> 00:36:10.326 So I think we're at the very early stages of trying to do that. 00:36:10.326 --> 00:36:13.006 And looking at basic components. 00:36:13.846 --> 00:36:19.566 And maybe you're right. Maybe the basic components could fade into the woodwork 00:36:19.566 --> 00:36:21.506 as you get a more complicated system. 00:36:23.186 --> 00:36:27.786 But my analogy is one that I'll steal from John Ullman in his little book that 00:36:27.786 --> 00:36:31.506 he wrote on the evolution of quinnets because I used to work with him. 00:36:31.686 --> 00:36:37.086 And he said he went to the power station in Los Angeles and said, 00:36:38.248 --> 00:36:42.308 They have some of the most ancient equipment in there and some of the most modern. 00:36:42.588 --> 00:36:46.128 And the reason that they have both is that they never can shut down the power 00:36:46.128 --> 00:36:50.068 system because they have to keep it running all the time. So they add to it. 00:36:50.968 --> 00:36:55.828 And brains are like that in evolution in the sense that it has to keep working 00:36:55.828 --> 00:37:00.428 all the time and you can start to modify it and tinker with it. 00:37:00.588 --> 00:37:04.868 But you can't shut it down and redesign and say, I have a much better design. 00:37:05.568 --> 00:37:10.908 That's maybe pushing it too far because maybe the new additions make some of 00:37:10.908 --> 00:37:17.028 the older components less necessary and they might fade or disappear if it's 00:37:17.028 --> 00:37:19.108 possible. But it might be a different system. 00:37:19.408 --> 00:37:27.628 But my bias is that we're going to see this primitive system, 00:37:27.808 --> 00:37:32.108 which isn't so primitive because it's new with primates as opposed to a trial 00:37:32.108 --> 00:37:33.088 organization. and fish. 00:37:33.248 --> 00:37:39.788 That premise is since preserved in all primates, but greatly modified in the 00:37:39.788 --> 00:37:40.488 human brain especially. 00:37:40.908 --> 00:37:47.868 But also we think macaques will be modified considerably from prosimian primates. Right. 00:37:49.048 --> 00:37:55.928 So you mentioned the possibility of using neuropsychology or cooling to tease 00:37:55.928 --> 00:37:57.548 out some of these questions. 00:37:57.708 --> 00:38:03.068 Do we have evidence from that already maybe of the impact for instance, 00:38:03.228 --> 00:38:08.648 of stroke on posterior to parietal cortex. What does that show us? 00:38:09.708 --> 00:38:15.648 So when Randy Nuda made small lesions on part of the hand cortex, 00:38:15.968 --> 00:38:19.548 he wasn't looking at specific modules or domains. 00:38:19.988 --> 00:38:23.468 He was just doing, this is hand cortex, Randy, sum of this out. 00:38:24.448 --> 00:38:31.568 With a little experience in three or four weeks, you couldn't tell the animal unless it's cortex. 00:38:32.568 --> 00:38:35.748 So Leah Kruitzer has done this in posterior parietal cortex, 00:38:35.788 --> 00:38:39.468 making a small lesion of an area involved in grass behavior. 00:38:39.688 --> 00:38:43.268 And in three days, you can't tell. 00:38:45.621 --> 00:38:52.581 So the reason we want to look at cooling is that we realize that the brain has 00:38:52.581 --> 00:38:56.541 enough plasticity and is going to change the strengths of connections and modify 00:38:56.541 --> 00:38:58.641 actually where the connections are, 00:38:59.661 --> 00:39:04.561 even over short periods of time, that it's a moving target. 00:39:04.721 --> 00:39:06.461 You can't figure out what the 00:39:06.461 --> 00:39:10.361 machinery is doing if it's modifying itself while you're looking at it. 00:39:10.881 --> 00:39:15.381 So cooling will give us a chance to look. look, we're going to change the machinery 00:39:15.381 --> 00:39:20.321 for a short period of time and we're going to restore its original organization. 00:39:20.541 --> 00:39:27.501 And hopefully there aren't permanent changes in the machinery by doing that. 00:39:27.541 --> 00:39:30.481 There might be. You might not ever be able to go back. 00:39:32.781 --> 00:39:36.461 So we're both interested in the plasticity and the ability of the machinery 00:39:36.461 --> 00:39:42.281 to adjust and change because that's going to be important in the learning and 00:39:42.281 --> 00:39:44.721 experience component of everything we do. 00:39:46.241 --> 00:39:51.861 But that's going to be a harder task. You know, the robotic studies would suggest 00:39:51.861 --> 00:39:55.681 that there needs to be, for the control of reach and grasp, 00:39:55.801 --> 00:40:01.981 an area that analyzes the visual affordance of an object or grasp and decides 00:40:01.981 --> 00:40:04.881 then, okay, these are the alternative graphs I might do. 00:40:05.141 --> 00:40:10.901 And then that would go downstream towards the motor system, which would perhaps plan a specific graph. 00:40:11.201 --> 00:40:16.061 And when we write proposals to try to get funding, I'd say one of the criticisms 00:40:16.061 --> 00:40:19.721 we're getting is from older people saying, you're not doing the right experiments. 00:40:20.101 --> 00:40:26.821 For example, when an animal in your setting, some part of the brain is reaching 00:40:26.821 --> 00:40:30.061 and grasping, why don't you put weights on the hand and see what happens then? 00:40:31.221 --> 00:40:37.741 So, but we already know that the animal will compensate for that weight and still do the test. 00:40:37.941 --> 00:40:44.401 How does it do that? That's an interesting question that is, 00:40:44.601 --> 00:40:51.041 in our future, not the immediate thing to understand because we don't understand 00:40:51.041 --> 00:40:53.041 things that come before that. 00:40:53.141 --> 00:40:57.821 I think that's an advanced question, a part of the immediate adjustments of 00:40:57.821 --> 00:40:59.921 circuits so you can accomplish something. 00:41:00.161 --> 00:41:05.401 But already you can do a lot in the spinal cord, as in frogs or whatever, 00:41:05.641 --> 00:41:08.321 that beats anything that's revealed. 00:41:09.001 --> 00:41:12.881 That wherever the limb is, it'll come to a particular position. 00:41:14.481 --> 00:41:21.181 Those circuits are really very elegant at that level for doing something to a specific goal. 00:41:22.461 --> 00:41:24.901 But now with respect to the plasticity effect you mentioned earlier, 00:41:26.222 --> 00:41:30.202 Are you with that saying that these ideas of Lashley from the 30s, 00:41:30.202 --> 00:41:34.142 of mass action, equipotentiality, actually hold? 00:41:34.202 --> 00:41:38.742 That means function of the brain results from the collective activity of many 00:41:38.742 --> 00:41:45.762 of its neural units, and single neurons can basically take on a plurality of 00:41:45.762 --> 00:41:47.862 functions dependent on the context they're in. 00:41:48.602 --> 00:41:54.402 Do you see that confirmed by your... I think that's true, but I wouldn't agree 00:41:54.402 --> 00:41:57.382 with everything that Lashley would say. 00:41:57.482 --> 00:42:02.222 For example, he said that you can do everything with one-sixtieth of primary visual cortex. 00:42:02.942 --> 00:42:08.802 You could, if you imagine doing everything by looking through a peephole, then I'd say yes. 00:42:08.842 --> 00:42:14.182 You have all the machinery for analyzing a small little bit of visual space, 00:42:14.402 --> 00:42:19.202 because you're doing all these different bits of space somewhat in parallel, 00:42:19.382 --> 00:42:23.902 not completely, because there are horizontal connections that are interacting 00:42:23.902 --> 00:42:25.522 and feedback that are interacting. 00:42:25.802 --> 00:42:31.282 The rat would lose that in its 60s, but it still could do a lot in that little people. 00:42:31.482 --> 00:42:36.722 And you would be fooled to think that the rat is fairly normal if you didn't 00:42:36.722 --> 00:42:39.182 pay attention to how it was using vision. 00:42:41.002 --> 00:42:46.522 And that's where Lashley went, of course, you take any part of the brain out, 00:42:46.582 --> 00:42:49.502 you're degrading the function of the machine. 00:42:50.302 --> 00:42:56.842 But the ability to compensate for loss is tremendous. That's what's so... 00:42:58.369 --> 00:43:02.589 Would be so unexpected for people 20 years ago. 00:43:02.849 --> 00:43:08.289 Although any physician that saw somebody with a lesion would say, 00:43:08.429 --> 00:43:12.769 of course they get better. 00:43:14.369 --> 00:43:19.329 It's just that imagining how the brain can change to recover. 00:43:20.509 --> 00:43:25.469 People said, well, once you develop a brain, it's fixed. That was the view I was raised on. 00:43:25.549 --> 00:43:29.929 It's developmental capability can change. Once it's developed, it's fixed. 00:43:30.669 --> 00:43:33.509 Now we have so much evidence that it's not there. 00:43:33.929 --> 00:43:38.729 But now, what's so surprising about this result that we've now been discussing, 00:43:38.789 --> 00:43:42.709 as well as we've paid so much attention to it, is that after, let's say, 00:43:42.849 --> 00:43:49.749 what, 150 years or so of motor system neurophysiology, 00:43:51.209 --> 00:43:56.129 why did it take us so long to stumble on to this idea about the organization, 00:43:57.309 --> 00:44:02.549 of motor control in this sort of, let's say, multi-layered architecture. 00:44:04.389 --> 00:44:11.209 Why did no one stumble into that earlier? I think early on, there was a lot 00:44:11.209 --> 00:44:14.869 of evidence that you can simulate widely in the brain and get behaviors. 00:44:15.929 --> 00:44:21.289 And then that was forgotten as soon as we said we have a motor cortex and this 00:44:21.289 --> 00:44:22.409 is where it's really happening. 00:44:22.689 --> 00:44:31.069 And we can focus on that. but also single-unit, single-none recordings became the focus. 00:44:31.329 --> 00:44:37.589 And if you look at where in the macaque monkey you can evoke grasping behavior 00:44:37.589 --> 00:44:42.629 by electrical stimulation, it's only part of a much larger area where neurons 00:44:42.629 --> 00:44:45.709 are active, very active during grasping. 00:44:46.629 --> 00:44:52.929 Those neurons are all contributing in some way, but we don't know how they're contributing. 00:44:52.929 --> 00:44:58.749 So this correlation of being active during a behavior is a good start, 00:44:58.929 --> 00:45:04.129 but it doesn't tell you their role in the behavior yet. 00:45:04.169 --> 00:45:08.889 And of course, you could lose a lot of them and the behavior still would either 00:45:08.889 --> 00:45:10.309 be there or would recover. 00:45:10.549 --> 00:45:12.709 And it doesn't tell you how that happens. 00:45:14.339 --> 00:45:20.879 Now, one contradiction that I have, or that I have to resolve for myself, 00:45:21.059 --> 00:45:27.319 is that if I look to your work, on the one hand, you do make a point, 00:45:27.419 --> 00:45:28.719 also supported by a lot of anatomy, 00:45:29.099 --> 00:45:34.319 that actually we should not interpret sensory modalities as being really so 00:45:34.319 --> 00:45:36.239 specialized as single modalities. 00:45:36.959 --> 00:45:41.999 There's a lot of, let's say, cross-modal responses that you find in, 00:45:42.039 --> 00:45:45.619 let's say, primaries, in the primary sensory, some of the sensory area might 00:45:45.619 --> 00:45:49.279 find response that led to motor actions or you might find, let's say, 00:45:49.339 --> 00:45:50.099 visual response, whatever. 00:45:50.319 --> 00:45:52.419 So it's much more, let's say, a mixed bag. 00:45:52.739 --> 00:45:54.139 There's specialization, but 00:45:54.139 --> 00:45:58.659 not strict boundaries. It depends on what sensory information is needed. 00:45:59.199 --> 00:46:10.179 Yeah. And, of course, you know, Sixty years ago, Wellesley was saying that we 00:46:10.179 --> 00:46:12.299 shouldn't call something motor cortex. 00:46:12.379 --> 00:46:15.799 It's motor sensory or sensory motor. 00:46:15.999 --> 00:46:20.939 And the second word means it's the reduced part. What's the dominant part? 00:46:20.999 --> 00:46:23.759 You put motor or sensory. But they're all sensory motor. 00:46:24.019 --> 00:46:29.419 Right. But now in your interpretation of the functional organization, 00:46:30.039 --> 00:46:37.239 you seem to segregate very specifically from perceptual, executive, and mode. 00:46:38.719 --> 00:46:42.719 So should we really put strict borders around that now? 00:46:42.919 --> 00:46:48.139 Or do we also face, let's say, a challenge that maybe, let's say, 00:46:48.179 --> 00:46:53.759 executive is not solely executive in that way or perceptual neither? 00:46:54.559 --> 00:47:01.219 Yeah, I see what you're getting at. Part of the problem is that you would say, let's say. 00:47:03.456 --> 00:47:07.536 Because I have someone in my department working on frontal light field. 00:47:08.256 --> 00:47:12.296 And he would say that frontal light field. 00:47:13.336 --> 00:47:19.816 If you ask an animal to move to a target, and the target has to be a red square 00:47:19.816 --> 00:47:24.116 against green ovals, or it could be shape, 00:47:24.176 --> 00:47:30.196 it can be color, it can be anything that you can change in the visual system, The animal will move, 00:47:30.276 --> 00:47:37.696 and the neurons in the frontal eye field will be activated by more by the red 00:47:37.696 --> 00:47:40.796 square than the green oval or whatever dimension you want. 00:47:40.936 --> 00:47:47.256 So you could claim now that those neurons are sensory neurons that are selective 00:47:47.256 --> 00:47:50.956 for whatever attribute you wanted to make up. 00:47:51.676 --> 00:47:56.576 But in another test, they can be selective for any other visual attribute. view. 00:47:56.916 --> 00:48:02.136 So I would say they're visual, but not in the same sense that we have a visual 00:48:02.136 --> 00:48:06.116 processing hearing that's trying to extract bits of information. 00:48:06.376 --> 00:48:11.716 That information has already been extracted, and now there has to be some mechanism 00:48:11.716 --> 00:48:15.596 of having frontal eye field know what the rules are. 00:48:15.696 --> 00:48:21.576 And only get excited when the cue is coming that means that you'll get water 00:48:21.576 --> 00:48:27.916 or juice or some reward if you move your eye to there, then those neurons won't be activated. 00:48:28.216 --> 00:48:31.456 So is that a sensory input or not? 00:48:31.536 --> 00:48:37.376 It's probably an executive input that also has the sensory information and so on. 00:48:38.036 --> 00:48:43.756 And when the red color in the square is there, go for it. 00:48:45.056 --> 00:48:51.396 But that's hard, I think, to start to specify exactly how that's accomplished 00:48:51.396 --> 00:48:54.836 in a mile. Mm-hmm, right. 00:48:56.821 --> 00:49:00.561 So the theme of this week is about the evolution and development, 00:49:00.701 --> 00:49:02.921 the evo-gevo of behavior. 00:49:03.321 --> 00:49:12.121 And I wonder what ideas you might have about how this relatively reorganized 00:49:12.121 --> 00:49:15.401 system emerges with early primates. 00:49:15.441 --> 00:49:19.481 Sort of what are the combination of different things which are giving rise to 00:49:19.481 --> 00:49:23.641 this, a lot of developmental mechanisms that are perhaps allowing the brain 00:49:23.641 --> 00:49:29.661 to reorganize of this important esthetic parietal cortex area that can, 00:49:31.221 --> 00:49:34.381 give you much more control over visually guided vision of rats. 00:49:34.661 --> 00:49:42.681 So I think in early mammals the behaviors that were species specific and necessary 00:49:42.681 --> 00:49:47.141 are largely subcortical under control. That's somewhat limiting. 00:49:49.101 --> 00:49:55.041 In mammals without a motor or primal cortex which we would judge to be marsupials, 00:49:56.021 --> 00:49:57.261 Most of them or all of them. 00:49:59.901 --> 00:50:04.761 Somatosensory cortex is heavily involved in providing sensory information about 00:50:04.761 --> 00:50:12.221 where touch is, where proprioceptive, and so on, to a largely subcortical motor system. 00:50:14.961 --> 00:50:21.181 So a lot of behaviors can be evoked by stimulating subcortical stations or visual 00:50:21.181 --> 00:50:26.321 avoidance. A lot of this can be done by deep layers of the spirit colliculus, for example. 00:50:26.541 --> 00:50:30.081 We don't know how that's involved in this behavior that I'm talking about, 00:50:30.241 --> 00:50:32.701 but it's certainly part of the possibility. 00:50:33.301 --> 00:50:38.141 How this is done by extra-parietal system, for example, not so clear. 00:50:38.981 --> 00:50:45.841 But with the advent of a separate motor cortex and what I would call the fracture 00:50:45.841 --> 00:50:52.721 or modular organization of motor cortex, That seems to be, when you have a primary motor cortex, 00:50:52.921 --> 00:50:55.321 it has these jumps. 00:50:55.461 --> 00:50:58.501 It's not completely cemented topi. It's jumbled. 00:50:59.641 --> 00:51:05.081 And the cerebellum, where you're dealing with a jazzing, using sensory information 00:51:05.081 --> 00:51:10.001 to correct errors in motor behavior, is jumbled as well. 00:51:10.081 --> 00:51:12.741 Why is it fractured in this way? 00:51:12.841 --> 00:51:17.621 You have different body parts next to one another. probably for the same reason. 00:51:17.741 --> 00:51:21.961 You have to have different combinations locally, so you have to repeat the same 00:51:21.961 --> 00:51:27.841 inputs several times in different ways so that you can have a modular kind of organization. 00:51:28.121 --> 00:51:32.041 So we think this already happens in motor cortex. 00:51:32.141 --> 00:51:37.201 So one way of looking at motor cortex is to say motor cortex is just the general 00:51:37.201 --> 00:51:42.801 purpose motor region, and its organizing feature is somatotopy, 00:51:42.881 --> 00:51:46.421 goes from foot down to tongue. Tale to Pond. 00:51:47.666 --> 00:51:50.606 That's the crude organization within those big blocks. 00:51:51.186 --> 00:51:57.066 You'll see all kinds of mixtures, and this will be true of any motor cortex, rat, whatever. 00:51:58.686 --> 00:52:03.406 So already, I think there's a sign that it's modulately organized in terms of 00:52:03.406 --> 00:52:04.626 certain specific behaviors. 00:52:05.746 --> 00:52:10.026 Once you set up that organization that would match with the information that's 00:52:10.026 --> 00:52:11.646 coming from the cerebellum, 00:52:11.646 --> 00:52:19.646 then that means that premotor cortex should follow that suit or posterior parietal 00:52:19.646 --> 00:52:24.126 cortex should follow that suit if it's going to interact with it in a meaningful 00:52:24.126 --> 00:52:29.746 manner and so these are steps added on older cortex first, 00:52:30.866 --> 00:52:39.346 posterior parietal is more on the perceptual side of the beginning of this motor hierarchy in a way, 00:52:40.226 --> 00:52:46.566 I wouldn't necessarily say so much on the perceptual side because what if the 00:52:46.566 --> 00:52:51.226 sensory information is used in a non-conscious way where you're not aware of 00:52:51.226 --> 00:52:53.766 how the sensory information is being used? 00:52:54.506 --> 00:52:58.606 Right, it would still be perceptual, no? It would be sensory, 00:52:58.746 --> 00:53:01.186 but perceptual implies an awareness. 00:53:01.686 --> 00:53:10.346 I mean, you are aware of the visual scene, but you might not be aware of how you crawl motor behave, 00:53:11.446 --> 00:53:16.146 well I'm not sure if we really have to bring in awareness for to talk about 00:53:16.146 --> 00:53:18.086 perception perception maybe. 00:53:19.506 --> 00:53:24.966 Perception essentially means that you rely on categories right that knowledge 00:53:24.966 --> 00:53:33.206 is imposed in defining what a visual scene or what a sensory scene comprises of, 00:53:34.166 --> 00:53:36.686 So, I'm not sure whether we have to…, 00:53:37.686 --> 00:53:43.906 So, I'll try to make the distinction in how I think about it and see if we have some agreement. 00:53:44.046 --> 00:53:48.146 But I would say that if an area of the brain is involved in perception, 00:53:48.346 --> 00:53:52.146 when you electrically stimulate, you should have a perception. 00:53:54.920 --> 00:53:59.340 And if you electrically simulate a motor cortex you might not have any perception 00:53:59.340 --> 00:54:05.960 you might I move but I don't know why okay yeah I would I would I would disentangle 00:54:05.960 --> 00:54:09.200 these two because I think a percept as such can be, 00:54:09.900 --> 00:54:14.520 a representation you use to classify states, 00:54:15.240 --> 00:54:19.380 but these states don't you don't need to enter awareness we don't need to couple 00:54:19.380 --> 00:54:23.960 this automatically to awareness but of course we can make on definitions right but 00:54:24.220 --> 00:54:30.820 But to bring it to the finish line, so here you are with this enormous experience 00:54:30.820 --> 00:54:33.980 in brain research and evolution of the brain. 00:54:34.280 --> 00:54:36.820 So how many more years do we need to really understand the brain? 00:54:38.260 --> 00:54:42.480 I hope five more years. Because I have five years of funding. 00:54:44.080 --> 00:54:47.080 Well, here you are. But I think it's 00:54:47.080 --> 00:54:53.720 an endless task in the sense that our understanding is very crude now. 00:54:53.720 --> 00:55:01.900 I feel, but much better than it was at the time I showed you the Thompson textbook pictures of cortex. 00:55:02.120 --> 00:55:07.780 And now people are labeling functions or areas all over the place and saying, 00:55:07.900 --> 00:55:11.420 well, this area is involved in eye movements. Well, that's pretty good. 00:55:12.280 --> 00:55:17.300 But why would you have an area that people call LIP, which we see in all these 00:55:17.300 --> 00:55:20.380 primates now that we can get the eye movements from posterior parietal cortex 00:55:20.380 --> 00:55:25.120 in the region that I think is LIP that you define in humans or mechanics. 00:55:25.400 --> 00:55:29.340 Why would you have an eye movement in there? Also another eye movement in the 00:55:29.340 --> 00:55:32.080 frontal lobe. And then a supplementary eye. 00:55:33.440 --> 00:55:38.500 Why all these steps? Unless each step has a different role. 00:55:39.540 --> 00:55:45.560 And that's the heart of what I'm thinking about. And so the role of posterior 00:55:45.560 --> 00:55:52.240 paracortex is sensory-dominated. to make the best of what the sensory information is. 00:55:53.640 --> 00:55:59.000 And that's perception. It's perception. But I don't necessarily think that the 00:55:59.000 --> 00:56:05.520 person, the observer, has to be aware of the perceptual decisions or the sensory decisions. 00:56:06.080 --> 00:56:09.080 They could be or they might not be. I'm not sure. 00:56:09.200 --> 00:56:14.440 But really, if you were designing a robot, it wouldn't make any difference, right? 00:56:15.360 --> 00:56:17.460 What's the function of consciousness? 00:56:19.877 --> 00:56:23.377 That's to add the executive decisions to the whole thing. 00:56:24.937 --> 00:56:30.817 But a lot could be totally automated where consciousness is not an important component. 00:56:31.217 --> 00:56:35.197 Right. I think, I mean, a perhaps interesting analogy, 00:56:35.737 --> 00:56:42.037 that we might consider in robotics, you know, until maybe 10 years ago, 00:56:42.137 --> 00:56:47.637 we were really struggling with vision for robots to do even elementary scene analysis. 00:56:48.177 --> 00:56:54.517 And then suddenly, people did have stereo algorithms, but it was difficult to piece it all together. 00:56:54.817 --> 00:56:59.177 And then Microsoft came out with the Kinect and it delivered to you a 3D analysis 00:56:59.177 --> 00:57:01.937 of the scene, which is really quite detailed. 00:57:02.197 --> 00:57:06.477 And suddenly we can do all sorts of new things really quite easily and quickly 00:57:06.477 --> 00:57:08.277 that were very difficult before. 00:57:08.577 --> 00:57:15.137 So perhaps in primate vision, we have something similar is that the visual system reorganized itself 00:57:15.417 --> 00:57:18.117 to give us good stereo because i think in a lot 00:57:18.117 --> 00:57:21.177 of these other animals it's really a defense system and it's 00:57:21.177 --> 00:57:23.937 not fusing it's not giving you depth it's certainly not 00:57:23.937 --> 00:57:27.017 as you were saying in your talk giving you a high detail 00:57:27.017 --> 00:57:35.237 so once you have this nice depth analysis of the visual world the brain can 00:57:35.237 --> 00:57:39.597 maybe reorganize itself to make use of that in some way and that would be interesting 00:57:39.597 --> 00:57:43.537 to try and understand whether that was one of the things that is giving rise 00:57:43.537 --> 00:57:45.177 to this new capacity They probably have. 00:57:46.377 --> 00:57:49.977 And what's surprising to me, even though I've studied plasticity for a long 00:57:49.977 --> 00:57:55.177 time, is how quickly a new feature can be useful. 00:57:55.397 --> 00:58:00.957 And the best example is adding a third cone to a squirrel monkey's eye. 00:58:01.057 --> 00:58:06.877 Officially, everybody knows about that research, where you add a new gene to 00:58:06.877 --> 00:58:11.177 something to coincide in the retina so that you have a third pigment. 00:58:11.177 --> 00:58:14.837 And their color vision immediately changes. 00:58:16.097 --> 00:58:18.577 The whole system adjusts to something new. 00:58:20.257 --> 00:58:23.317 Would anybody ever have guessed that in advance? 00:58:23.697 --> 00:58:30.997 I mean, I'm stunned by that, but it shows us that at least the developmental 00:58:30.997 --> 00:58:35.117 plasticity is fantastic in adjusting to change. 00:58:35.297 --> 00:58:41.837 And so a little change anywhere can be built. will affect the brain widely. Right. 00:58:42.817 --> 00:58:46.597 Although I want to be careful with Tony's suggestion that the primate brain 00:58:46.597 --> 00:58:49.377 might have been based on Microsoft architecture. 00:58:50.577 --> 00:58:52.997 So the other thing is, so now. 00:58:55.337 --> 00:59:01.697 What's the kind of prediction you would like to make today about the work that you're pushing now? 00:59:01.897 --> 00:59:04.457 So you have five more years, you were telling us, funding. 00:59:05.237 --> 00:59:07.877 What are we going to see at the end of these five years? What's the prediction 00:59:07.877 --> 00:59:08.917 that you're really testing there? 00:59:09.797 --> 00:59:18.437 Well, we hope to do several things. I want to demonstrate that it can be put 00:59:18.437 --> 00:59:21.577 into a model of how posterior parietal cortex, 00:59:21.577 --> 00:59:24.837 seven or eight functional zones interact and 00:59:24.837 --> 00:59:28.317 how they interact and do 00:59:28.317 --> 00:59:31.917 the same for motor cortex and premotor cortex if anything 00:59:31.917 --> 00:59:38.497 more than that comes out of it I'll be delighted and the one way to do this 00:59:38.497 --> 00:59:44.217 is I want to know what are the inhibitory connections and what are the excitatory 00:59:44.217 --> 00:59:50.597 connections we have a prediction and the prediction is that there will be, 00:59:51.577 --> 00:59:56.837 excitatory connections to excitatory neurons in a very specific local pattern. 00:59:57.857 --> 01:00:00.957 And then the other ones will be excitatory to inhibitory neurons, 01:00:01.157 --> 01:00:07.217 but in posterior parietal cortex, there will be mutual conflict between the 01:00:07.217 --> 01:00:11.457 areas, and they'll be fighting on the basis of inputs to win out. 01:00:12.877 --> 01:00:20.957 Those connections can be demonstrated now by selectively labeling connections 01:00:20.957 --> 01:00:25.517 to inhibitory neurons and seeing which neurons go to inhibitory neurons and 01:00:25.517 --> 01:00:27.497 which ones go to excitatory neurons. 01:00:27.617 --> 01:00:31.157 That's possible through genetic manipulation techniques. 01:00:34.461 --> 01:00:37.921 We haven't done that. The things that have been done in that area are not very 01:00:37.921 --> 01:00:39.741 far along yet, but we can do it. 01:00:40.101 --> 01:00:43.661 If I have the right collaborators, we can do it. Right. 01:00:44.481 --> 01:00:50.021 And then, so how long have you been active in neuroscience now? 01:00:50.121 --> 01:00:51.921 How many years are we talking about here? 01:00:52.281 --> 01:01:04.261 Well, I started graduate school in late, I finished in early 60s. 01:01:04.461 --> 01:01:08.781 Undergraduate, and then I was in graduate school, and so I would say I was involved 01:01:08.781 --> 01:01:13.701 in it from the 60s, and late 60s, pretty well involved in it, 01:01:13.821 --> 01:01:19.601 and so it's really a long career, longer than most people ever get to enjoy, 01:01:19.861 --> 01:01:26.441 and so I'm delighted to be still here doing this thing, having this fun, 01:01:26.601 --> 01:01:27.621 because it's really fun. 01:01:27.621 --> 01:01:32.081 But now, based on this experience, in the study of the brain, 01:01:32.301 --> 01:01:36.261 what is the John Kass law that we should all follow? 01:01:38.241 --> 01:01:42.301 I'm not sure I understand your question. Well, there's like a norm that you 01:01:42.301 --> 01:01:48.081 would like to sort of, if you want, impose upon all of us interested in the brain, a heuristic, 01:01:48.301 --> 01:01:54.041 a rule that we should adhere to in order to make progress, to really gain understanding in the brain. 01:01:56.001 --> 01:02:01.141 Everybody gets it understanding and in their own ways and so i wouldn't hesitate 01:02:01.141 --> 01:02:05.821 to say this is the way i don't know the way i'm i'm learning new ways all the 01:02:05.821 --> 01:02:09.441 all of the time and and uh i would, 01:02:10.721 --> 01:02:13.501 after working on plasticity for a long time i 01:02:13.501 --> 01:02:16.501 didn't intend to work on plasticity and developing think they're 01:02:16.501 --> 01:02:22.641 dull brains but there it was and you couldn't avoid it so i guess all of us 01:02:22.641 --> 01:02:28.401 should be open to different ways of thinking about surprises that we didn't 01:02:28.401 --> 01:02:33.861 anticipate and then incorporating them into our thinking and um, 01:02:35.163 --> 01:02:40.543 I think it's very hard to ever change your mind on something when you get committed 01:02:40.543 --> 01:02:42.323 emotionally to a line of thinking. 01:02:42.723 --> 01:02:45.523 But if we could do that more easily, it would be helpful. 01:02:48.103 --> 01:02:52.563 One example is I was on sabbatical on the way, and my graduate student was working 01:02:52.563 --> 01:02:58.563 on something that would provide really compelling evidence for a view I had 01:02:58.563 --> 01:02:59.663 about the visual system. 01:03:00.203 --> 01:03:05.623 And he said, the evidence is just the opposite. and argues that you were wrong 01:03:05.623 --> 01:03:07.683 about how you thought the visual system. 01:03:07.743 --> 01:03:12.063 He thought he was first hesitant to tell me about this because I was on sabbatical. 01:03:12.123 --> 01:03:13.943 I wasn't seeing how things were happening at home. 01:03:14.523 --> 01:03:19.683 And I thought, this is great. It's much better to announce the mistake ourselves 01:03:19.683 --> 01:03:21.603 than have somebody tell us we were wrong. 01:03:23.603 --> 01:03:27.843 But the evidence was so convincing that I flipped over right away. 01:03:28.123 --> 01:03:32.083 And now I have a person that's now working with me, a crew that's there, 01:03:32.083 --> 01:03:36.563 And she's telling me, you're wrong in another way. You have to incorporate that in your thing. 01:03:36.763 --> 01:03:40.243 And I teased her and I said, no, that can't be right. She went away in a postdoc, 01:03:40.323 --> 01:03:42.763 still thinking I disagree with her completely. 01:03:43.163 --> 01:03:46.463 But I'm going to send her a paper that I want her to be a co-author on, 01:03:46.483 --> 01:03:49.903 which I agree with her completely. It'll be a surprise to her. 01:03:51.123 --> 01:03:54.543 But maybe it's because I've had now a couple of years to think it over. 01:03:55.203 --> 01:04:00.563 But she didn't have a strong bias in going in. And she just looked at the data 01:04:00.563 --> 01:04:02.223 and she came to a different view. 01:04:02.383 --> 01:04:06.743 My other graduate student didn't have a strong bias. I had the strong biases. 01:04:07.283 --> 01:04:12.023 It's my view that had to be changed. Theirs was easy to change because they 01:04:12.023 --> 01:04:14.903 didn't have a strong one. So, John's law, we keep an open mind. 01:04:15.803 --> 01:04:19.423 Keep new investigators around you. Right, exactly. 01:04:19.963 --> 01:04:23.823 A lot of surprise. That's fantastic. So, they'll tell you where you're going. 01:04:24.403 --> 01:04:27.163 Exactly. Well, John, thank you very much for this conversation. 01:04:29.563 --> 01:04:35.363 The CSN podcast was produced by the Convergent Science Network of Biometrics 01:04:35.363 --> 01:04:42.123 and Biohybrid Systems, a project funded by the European 7th Research Framework Programme. 01:04:43.323 --> 01:04:48.643 For more interviews, recorded lectures or upcoming conferences in the field 01:04:48.643 --> 01:04:54.863 of biometrics and biohybrid systems, go to csnnetwork.eu. 01:04:54.960 --> 01:05:03.760 Music.