WEBVTT 00:00:03.637 --> 00:00:09.057 This is the Convergent Science Network podcast. All right, we're running. 00:00:09.057 --> 00:00:13.057 Leading researchers in the domain of neuroscience, brain theory and technology 00:00:13.057 --> 00:00:16.737 are interviewed by Paul Verschure and Tony Prescott. 00:00:16.997 --> 00:00:20.317 This is Paul Verschure for the Convergent Science Network podcast, 00:00:21.337 --> 00:00:23.377 together with my colleague Tony Prescott. 00:00:23.417 --> 00:00:29.657 And we're here at our BCBT Summer School of 2015 with Ranulfo Romo. 00:00:29.677 --> 00:00:37.037 Ranulfo, you came here from Mexico to share with us your incredible work and 00:00:37.037 --> 00:00:40.417 also this long tradition of work that you've been engaged in and understanding 00:00:40.417 --> 00:00:41.777 decision-making in the brain. 00:00:42.597 --> 00:00:45.337 So what's so special about decision-making? 00:00:47.737 --> 00:00:57.917 I think decision-making is the crown of brain function because sooner or later 00:00:57.917 --> 00:01:02.377 you have to make a decision whether it's conscious or whether it's unconscious. 00:01:03.417 --> 00:01:07.117 Habits, I think, for example, require decision-making. 00:01:08.077 --> 00:01:13.877 They probably are below our conscience. When I walk in some way, 00:01:14.997 --> 00:01:22.517 I have an apparatus in my spinal cord together in concert with my brain, 00:01:22.517 --> 00:01:26.817 allows me to move, I don't have to be very conscious. 00:01:26.957 --> 00:01:32.017 But from time to time, I'm conscious of where I'm going and what direction, 00:01:32.137 --> 00:01:35.457 where my steps are, etc., etc. 00:01:35.777 --> 00:01:40.557 But there are decisions. I think we are talking about decision-making in the 00:01:40.557 --> 00:01:43.597 way in which we can think about. 00:01:44.377 --> 00:01:52.217 For example, if my girlfriends ask me to marry, I can reflexively say, yes. 00:01:52.937 --> 00:01:56.177 I can say, listen, why don't we talk in a week? 00:01:56.497 --> 00:02:04.277 Or, for example, in a month, I have a friend that has delayed a decision for eight years. 00:02:06.106 --> 00:02:13.106 No kidding. But now you have actually looked at this problem of decision-making 00:02:13.106 --> 00:02:20.506 with respect to marriage in a much more compressed way, in a much more controlled way. 00:02:20.726 --> 00:02:26.326 You reduce it down to somatosensory decision-making, where you really have to 00:02:26.326 --> 00:02:32.546 combine signals from different modalities and sort of extract a meaning from 00:02:32.546 --> 00:02:35.066 them relative to your goals and then act accordingly. 00:02:35.066 --> 00:02:41.406 Okay, so why did you choose somatosensory decision-making? 00:02:41.826 --> 00:02:48.106 For various reasons. The first one is because I was trained in a very long tradition, 00:02:48.326 --> 00:02:57.226 coming from Philip Barr at Johns Hopkins in the 1920s of the past century, 00:02:57.406 --> 00:03:00.326 and then continued by Vernon Mountcastle. 00:03:00.326 --> 00:03:09.506 And third, because, believe me or not, but the reward signals were discovered 00:03:09.506 --> 00:03:14.006 using somatosensory signals in Freiburg with Wolfram Schultz. 00:03:14.326 --> 00:03:22.866 And then, trying to think about, I discovered that behind this there was a fundamental 00:03:22.866 --> 00:03:26.726 problem, at least for me in that time when I was young with the Bernoull-Montcastle, 00:03:26.926 --> 00:03:28.706 the representational problem. 00:03:28.706 --> 00:03:34.566 One question is how the brain represents, brain cells represent sensory inputs, 00:03:34.686 --> 00:03:36.666 no matter what is the sensory modality. 00:03:36.946 --> 00:03:42.506 Somehow, you have to generate a neural copy of the external world. 00:03:42.946 --> 00:03:47.126 You don't feel with your fingertips. You don't see with your eyes. 00:03:47.366 --> 00:03:57.386 You don't hear with your ear. You do all these sensory functions with your brain, and the question is, 00:03:57.646 --> 00:04:04.366 well, how does the brain manage to generate a representation of the external world? 00:04:04.426 --> 00:04:09.346 Just to begin, as a prelude to decision-making, perceptual decision-making. 00:04:09.346 --> 00:04:16.866 So then, the question is, once you start to generate sensory representations. 00:04:17.546 --> 00:04:21.606 You are training your network in such a way you generate experience. 00:04:22.146 --> 00:04:26.926 And when you generate that, you treat sensory inputs in a different way than 00:04:26.926 --> 00:04:28.826 if you were a naive organism. 00:04:29.486 --> 00:04:33.666 When you have that, you have to think about what is experience, 00:04:33.966 --> 00:04:41.986 which is memory, whatever you label it, whether long-term or short-term memory. 00:04:43.026 --> 00:04:52.066 So the question is, how do we store sensory input information in our brain that makes what we are? 00:04:53.206 --> 00:05:03.186 So that's one of my general questions. So at the end, we want to understand how these big problems, 00:05:03.786 --> 00:05:10.366 sensory representations and internal representation combine together to generate 00:05:10.366 --> 00:05:11.866 perceptual decision-making. 00:05:11.866 --> 00:05:18.266 But you can have only perception decisions alone with little experience if you 00:05:18.266 --> 00:05:20.046 were a very low organism animal. 00:05:20.226 --> 00:05:26.166 Or you can make, in your case, you use your internal experience in order to 00:05:26.166 --> 00:05:28.626 make decisions. You don't need sensory input sometimes. 00:05:29.506 --> 00:05:36.186 But now when I might move my eyes, right, to have a differential response to 00:05:36.186 --> 00:05:42.186 stimuli in the world, I might push a button, or I might decide to get married eight years from now. 00:05:42.606 --> 00:05:46.626 So these are all forms of decisions. So do you think that decisions in that 00:05:46.626 --> 00:05:52.006 sense are hierarchically structured, or are they really situated at a specific 00:05:52.006 --> 00:05:56.606 level in, let's say, a hierarchy of perceptual cognitive operations? 00:05:57.126 --> 00:06:02.386 If you are an eclectic man, you have to think that it happens all around us. 00:06:02.386 --> 00:06:06.226 It can be a hierarchical processing, different situation. 00:06:07.286 --> 00:06:14.426 And I think what is important in our brain functioning is that we depend a lot on context. 00:06:14.766 --> 00:06:20.846 So our brain adapts to the context every time. 00:06:20.926 --> 00:06:27.846 Context situations in such a way that one decision at this moment can be, 00:06:27.846 --> 00:06:33.006 Even if it's exactly the same, the same operation in another context, 00:06:33.226 --> 00:06:36.666 it's what's going on. We are context dependent. 00:06:36.986 --> 00:06:38.966 We are no more than that, I think. 00:06:39.666 --> 00:06:43.246 But then, so if we put it so broadly, 00:06:43.606 --> 00:06:50.166 so now it's decision making is very much helping us to transform, 00:06:50.486 --> 00:06:55.506 let's say, sensory states into an action in the service of our goals. 00:06:55.506 --> 00:07:00.106 So, what we have to bring together is sensory states, our motivations and goals, 00:07:00.226 --> 00:07:04.686 and our action repertoire in the end to produce this one output that will drive 00:07:04.686 --> 00:07:05.926 our skeletal muscle system. 00:07:06.106 --> 00:07:09.646 And given that we only have one skeletal muscle system, it better be one action. 00:07:11.126 --> 00:07:16.226 So, there's this funnel we have to go through to get sensory states into action. 00:07:16.386 --> 00:07:19.666 And this funnel is modulated by different things, goals, memory, actions. 00:07:19.686 --> 00:07:25.306 Yes. But now, at the beginning of this funnel stands the sensory process. 00:07:25.886 --> 00:07:30.966 And there, what I found interesting, in some sense, you take a very extreme perspective, 00:07:31.146 --> 00:07:37.886 in my opinion, on sensory processing as really insisting that a primary sensory 00:07:37.886 --> 00:07:43.286 area is really primary in the sense that it's uniquely dedicated to the modality 00:07:43.286 --> 00:07:45.426 that the thalamus dictates to it. 00:07:46.046 --> 00:07:51.006 So you really believe that to be the case? I do believe. and and uh. 00:07:52.171 --> 00:07:58.811 It's not that I believe, I think, because it depends on hypothesis and results 00:07:58.811 --> 00:08:02.051 and interpretation and challenging that hypothesis. 00:08:02.131 --> 00:08:08.231 In fact, I cannot say that I have lost more than 10 years doing experiments 00:08:08.231 --> 00:08:14.911 in order not to convince myself, because no matter what is the result, it's fine to me. 00:08:14.911 --> 00:08:21.151 For example, in one stream, many colleagues say that early sensory cortices, 00:08:21.311 --> 00:08:27.331 the earliest stage of processing in our cerebral cortex, is multimodal. 00:08:27.631 --> 00:08:35.631 In the other stream, which is almost a dogma, is that early sensory cortices are unimodal. 00:08:35.651 --> 00:08:40.351 They have only one capacity to process, only one modality. 00:08:40.351 --> 00:08:47.731 Just, let's say, visual cortex is visual cortex because it does receive an input 00:08:47.731 --> 00:08:52.151 coming from the retina going through the thalamus, and the thalamus dictates 00:08:52.151 --> 00:08:54.431 that territory to be visual. 00:08:54.691 --> 00:08:58.991 And for the auditory cortex, exactly the same, and for the somatosensory cortex. 00:08:59.071 --> 00:09:06.031 But there, in science, it's very important to insist and to challenge dogma, 00:09:06.051 --> 00:09:10.651 even if we lose time, In the sense that we lose money, 00:09:10.791 --> 00:09:17.211 we invest many hours in something that does not produce something positive, 00:09:17.431 --> 00:09:18.491 a positive result. 00:09:18.971 --> 00:09:23.951 It might be a negative one, but it's very important in order to allow hypothesis 00:09:23.951 --> 00:09:29.151 or interpretation of something, a fact, that is true or not true. 00:09:29.151 --> 00:09:35.711 So, in fact, over the last 10 years, I've been insisting and trying to document 00:09:35.711 --> 00:09:41.271 whether unimodal, whether multimodal, at the moment it wins unimodal. 00:09:41.871 --> 00:09:45.931 So, what was the key piece of data that convinced you that it was unimodal? 00:09:46.071 --> 00:09:56.271 I'm relying on a very simple signal that I think comes from the Cajal tradition. 00:09:57.960 --> 00:10:01.520 The neural doctrine in the sense that neurons 00:10:01.520 --> 00:10:04.780 that the brain is made of pieces of individual 00:10:04.780 --> 00:10:12.800 neurons that are connected together by a tiny space called synapses and that 00:10:12.800 --> 00:10:18.900 all the territories of our brain at least for the sensory and perceptive territories 00:10:18.900 --> 00:10:23.340 and dictated by our sensory lamina let's say for For example, 00:10:24.060 --> 00:10:27.100 somatosensory cortex is somatosensory 00:10:27.100 --> 00:10:31.060 because it's connected to our receptors in our skin, our body, 00:10:31.800 --> 00:10:37.080 in such a way that our brain makes a map of our body surface. 00:10:38.040 --> 00:10:43.720 And the visual cortex is visual because it's very reliant to the retina in such 00:10:43.720 --> 00:10:49.380 a way that the retina can be mapped out in that part of the cerebral cortex. 00:10:49.380 --> 00:10:52.820 And the same for the auditory cortex. 00:10:53.720 --> 00:11:04.700 So, in the beginning, in the mid-19th century, there was a big effort by physicists in Germany, 00:11:04.900 --> 00:11:09.440 Helmholtz, something that started to set out the basis of the action potential. 00:11:10.560 --> 00:11:14.640 That there was a transmission of signal from the skin up to the brain. 00:11:14.640 --> 00:11:25.260 And they were able, in the beginning of the 1920s or something like that, the English school, 00:11:25.360 --> 00:11:30.020 to discover the basis of the transmission. 00:11:32.889 --> 00:11:36.549 That the signal that uses our brain is a signal, signals. 00:11:36.909 --> 00:11:40.129 And Cajal had already settled out the neural doctrine. 00:11:40.429 --> 00:11:47.109 So I'm using a very tiny signal from this old tradition in order to map out 00:11:47.109 --> 00:11:51.029 the responsive properties of brain cells. 00:11:51.429 --> 00:11:54.709 Not only responsive properties, but once the stimulus is gone, 00:11:55.449 --> 00:12:00.929 something in our brain is working at this moment, and in fact I'm talking about, out. 00:12:01.029 --> 00:12:03.569 It's internally generated by my brain. 00:12:05.609 --> 00:12:12.229 You're looking at the S1 cortex particularly, and there are other somatosensory areas. 00:12:13.549 --> 00:12:18.509 Have you looked into those too to see whether there would be multimodal cells there? 00:12:18.669 --> 00:12:21.869 Because there are other projections, certainly I would know in the rat, 00:12:22.089 --> 00:12:28.809 where the sensory input comes in from the periphery, but may mix in in primarily 00:12:28.809 --> 00:12:32.129 sensory areas, perhaps more cross-modally. 00:12:35.029 --> 00:12:44.589 It was clear to me for about 30 years when I was working with Wolfram Schulz, a very dear colleague, 00:12:45.409 --> 00:12:55.929 that in order to understand the function in our brain, we have to go across cortical areas. 00:12:57.009 --> 00:13:01.329 So, when I started to work out in Mexico City, 00:13:01.529 --> 00:13:09.569 I decided to use exactly the same input and see the transformation across the 00:13:09.569 --> 00:13:12.129 system, which is something very important. 00:13:12.249 --> 00:13:14.669 It's like, for example, if I tell you something. 00:13:16.640 --> 00:13:22.860 You interpret it, and then you tell something to Paul, not in front of me, 00:13:22.900 --> 00:13:25.660 and then Paul tells to some others, something like that. 00:13:25.780 --> 00:13:30.880 It's like I'm passing to you directly the information, and then you treat this 00:13:30.880 --> 00:13:35.220 information in a different way and pass that information to Paul. 00:13:35.440 --> 00:13:37.740 But Paul never spoke to me. 00:13:38.040 --> 00:13:43.000 So it's more or less what's going on in the brain. It's a metaphor that is like 00:13:43.000 --> 00:13:46.220 in Spanish, which is chismoso. 00:13:46.960 --> 00:13:55.660 It's not a liar, but what Paul interprets from me is through you. 00:13:56.000 --> 00:13:59.260 It's what I'm trying to do myself across the brain, 00:13:59.360 --> 00:14:07.280 trying to understand what kind of representation receives a very downstream 00:14:07.280 --> 00:14:13.380 area outside the sensory representation, 00:14:13.660 --> 00:14:14.500 for example. 00:14:14.540 --> 00:14:18.760 Something like that. So I think that's the major contribution of my work, 00:14:18.900 --> 00:14:25.760 going in this direction, in which it tries to see what's going on across the brain. 00:14:25.880 --> 00:14:34.200 Because I think, at the end, what Paul says is the true representation for Paul. 00:14:34.320 --> 00:14:36.580 And when you say your true representation, 00:14:36.780 --> 00:14:40.400 and not necessarily exactly the same, I share with myself too. 00:14:42.480 --> 00:14:45.860 So I understand you're trying to do a very pure experiment. 00:14:45.900 --> 00:14:53.120 You're going to try to simplify it as much as you can to get at this basic process of decision-making. 00:14:53.580 --> 00:14:57.120 But the criticism that I guess people can make, and you already said this in 00:14:57.120 --> 00:15:01.220 your lecture, is that this isn't what happens in daily life. 00:15:01.560 --> 00:15:08.880 So much of the time, the stimuli coming from multiple modalities that are telling 00:15:08.880 --> 00:15:13.740 us similar information and it pays greatly to pay attention to them together. 00:15:14.320 --> 00:15:18.220 And also, even in the touch system, which you're describing, 00:15:18.880 --> 00:15:23.500 most of the time we are actively controlling the way that, for instance, 00:15:23.640 --> 00:15:25.080 the fingertip is moving on a surface. 00:15:25.320 --> 00:15:30.220 And that's going to have a huge impact on how we process that signal upstream. 00:15:30.560 --> 00:15:34.700 So when you're in your experiment, you essentially stimulate a passive, 00:15:34.700 --> 00:15:38.620 the fingertip is a passive receptor surface perhaps 00:15:38.620 --> 00:15:41.520 you're missing something about what 00:15:41.520 --> 00:15:44.540 was more common for the for the that sensory 00:15:44.540 --> 00:15:48.200 system to be doing which is to be actively controlled in 00:15:48.200 --> 00:15:52.740 finding useful information so the information is being given here there's no 00:15:52.740 --> 00:15:57.560 sense that i have to look it out well you're right and you're not right as always 00:15:57.560 --> 00:16:05.560 first yes i'm dealing with basically with the touch system and use it as a model of. 00:16:06.558 --> 00:16:13.578 Processing, because the general question is how a sensory representation, unimodal as you like. 00:16:14.578 --> 00:16:19.838 Is transformed up to Paul or something like that, and produce a function, 00:16:20.038 --> 00:16:21.938 which is a very complex issue. 00:16:22.718 --> 00:16:28.438 The second issue is, and you raise, which is very good, is that a criticism 00:16:28.438 --> 00:16:31.918 is very welcome. It's a passively delivered stimulus. 00:16:32.238 --> 00:16:38.498 And normally, for example, I am squeezing my fingers across the surface in order to get information. 00:16:39.918 --> 00:16:46.498 But that's the way science works. We would like to have an experiment in natural 00:16:46.498 --> 00:16:53.638 condition, but this is almost impossible because it's very difficult to control our variables. 00:16:53.638 --> 00:17:00.918 And you can dribbly, grongly in some direction because there are many cues, 00:17:01.198 --> 00:17:08.658 many things that must take you in a very different direction. 00:17:08.878 --> 00:17:15.938 And myself, I had decided to control as much as I can where I deliver the stimulus. 00:17:16.018 --> 00:17:19.018 Exactly the same as the people work in the visual system. 00:17:19.198 --> 00:17:22.798 What people in the visual system do is very simple. Normally, 00:17:22.918 --> 00:17:28.638 we are moving the eyes, but we have to bring the fovea in a given moment to deliver the steam. 00:17:28.718 --> 00:17:35.058 Otherwise, it can be in different ways and make sense of sensory processing. 00:17:35.238 --> 00:17:37.418 Visual processing will be very difficult. 00:17:37.638 --> 00:17:42.578 So that is a decision that I made because I made it. 00:17:42.778 --> 00:17:47.778 Of course, I can be wrong, but it provided some pieces of evidence. 00:17:47.778 --> 00:17:57.658 Of course, it's not telling to you how the sensory motor loop works. I do not pretend it. 00:17:58.138 --> 00:18:07.218 I do not pretend even to show intentionality from the active point of view. 00:18:07.298 --> 00:18:12.178 Because if I want my wish, which I do not know what is a wish. 00:18:12.318 --> 00:18:15.638 For example, my desire to do something, where does it come? 00:18:15.738 --> 00:18:20.078 I do not know. But eventually, if you know, you can move your hand, 00:18:20.198 --> 00:18:25.438 you can move your finger, you can walk, you can think about something like that, 00:18:25.518 --> 00:18:28.478 and then use your senses actively. 00:18:28.478 --> 00:18:31.618 So in my case, I do not pretend to do that. 00:18:31.638 --> 00:18:34.558 I tend to do it in the opposite way. 00:18:34.718 --> 00:18:39.998 I just simply want to see in a very, in Spanish, which is a castiza way, 00:18:40.198 --> 00:18:49.298 how a sensory input is represented by brain cells and bring a big network of 00:18:49.298 --> 00:18:53.558 our brain to thinking and deciding and using, 00:18:53.678 --> 00:18:56.538 if you like, the motor apparatus afterward. word. 00:18:56.718 --> 00:19:01.518 In other words, I'm very interested to know how is, what is. 00:19:02.939 --> 00:19:10.859 Behind a decision report. So let's say we convince Tony, okay, 00:19:10.939 --> 00:19:14.679 and the sensory stimulus is sort of ecologically valid, 00:19:14.919 --> 00:19:21.859 and we can discuss details of that later, then the real decision-making doesn't 00:19:21.859 --> 00:19:22.999 take place at that stage. 00:19:23.219 --> 00:19:29.279 The real decision-making takes place in areas that are sort of in frontal areas of the neocortex. 00:19:29.279 --> 00:19:32.259 Cortex um so what kind of network now 00:19:32.259 --> 00:19:37.019 gets engaged so here i have my two stimuli they might be frequency modulated 00:19:37.019 --> 00:19:40.959 in some way my primary visual cell metasensory areas are responding they're 00:19:40.959 --> 00:19:45.299 now transducing this stimulus to a prefrontal network that's going to make the 00:19:45.299 --> 00:19:49.179 decision so what's happening there what's going to happen in this is a very 00:19:49.179 --> 00:19:50.959 important question because at the end. 00:19:52.479 --> 00:19:59.319 Thinking early in the morning when I am alone in the dark, my dark room, or I close. 00:19:59.819 --> 00:20:04.819 And the other day I was thinking about what is the point of this? 00:20:05.459 --> 00:20:11.119 Of course, I many years ago discovered that I was not a somatosensory man. 00:20:11.999 --> 00:20:18.779 As the people say, I'm a visual man. I'm not visual. I'm using a model to understand something. 00:20:19.299 --> 00:20:24.459 So at the end, I can simplify my thinking about this. 00:20:24.679 --> 00:20:29.199 For example, your organism, we, 00:20:29.399 --> 00:20:37.319 and animals, even the lowest animal, you need to map out something which is 00:20:37.319 --> 00:20:41.619 happening in the external world, transform energies in something. 00:20:42.859 --> 00:20:50.119 And the current money to transmit something is the action potential, electrical signals. 00:20:50.959 --> 00:20:55.639 But there had to be receptive areas, even if in the lower levels, 00:20:55.799 --> 00:21:02.039 that very quickly take these signals and then do a response. 00:21:02.279 --> 00:21:09.559 Those are very fast systems, even the sensory ones that go up to the cerebral cortex in ourselves. 00:21:10.539 --> 00:21:15.079 So that takes 25 milliseconds in the somatosensory system. 00:21:15.379 --> 00:21:19.019 And if you think about the spinal cord, it's 10 milliseconds. 00:21:20.959 --> 00:21:22.779 That's exactly what happened in a war. 00:21:24.839 --> 00:21:30.359 But fast, and then fast responses from the motor side. You have to do bah! 00:21:30.599 --> 00:21:38.799 In our cases, it can be, you can treat the signals and store it in some way. 00:21:39.819 --> 00:21:44.299 Those are slow systems. The working memory ones, for example, 00:21:44.359 --> 00:21:47.719 allow you to think about. And... 00:21:49.418 --> 00:21:56.198 So there, those are very slow systems that depend on some other kind of transmissions, 00:21:56.838 --> 00:22:02.418 molecules differently to the ones associated to sensory and motor output systems. 00:22:03.018 --> 00:22:08.258 And there are the dopamine system, cholinergic, noradrenergic, 00:22:08.398 --> 00:22:10.118 serotonergic, or something like that. 00:22:10.118 --> 00:22:18.938 That not special cells, but are localized in such a way that can add something 00:22:18.938 --> 00:22:23.818 to this fast transmission and more or less slow transmission. 00:22:24.098 --> 00:22:25.878 So at the end, you have a trio there. 00:22:26.798 --> 00:22:31.238 Fast sensory input, fast motor output, and something in between. 00:22:31.698 --> 00:22:35.718 And you can put many things, memory, motivation, motivation, 00:22:35.838 --> 00:22:40.598 decision-making, subjectivity, and something like that. 00:22:40.698 --> 00:22:45.698 And when something is a mess out of this, then you have frustration, 00:22:45.878 --> 00:22:50.598 you have psychiatric problems, memory problems, et cetera, et cetera. 00:22:51.738 --> 00:22:58.078 But I can put in troubles. If I cut the sensory inputs, the rest doesn't work. 00:22:58.218 --> 00:23:00.218 If I cut the motor output, too. 00:23:00.378 --> 00:23:05.958 So there is something in between, extremely important. And that's the one I 00:23:05.958 --> 00:23:07.258 want to understand myself. 00:23:07.818 --> 00:23:14.118 But now, do you see this as one monolithic system that always converges onto 00:23:14.118 --> 00:23:19.358 then the same decision, evaluating the same information, or do you see this 00:23:19.358 --> 00:23:21.478 as competing subsystems? 00:23:21.698 --> 00:23:28.358 Absolutely, I think. For example, if I were a Martian, if I go and see Paul 00:23:28.358 --> 00:23:35.618 lying in the bed, if I were a neurologist, I would say it has some other problem. 00:23:35.958 --> 00:23:40.358 But eventually, you are in depression. 00:23:40.958 --> 00:23:44.118 You don't want to move. I call you, Paul. 00:23:44.618 --> 00:23:48.558 Paul, good morning. And you don't move. And I can say, well, 00:23:48.778 --> 00:23:53.718 it's a sensory deficit. Or secondly, you don't move, it's a motor deficit, 00:23:53.978 --> 00:23:58.978 but simple, you are out, you don't want to hear, you don't want to move. 00:23:59.318 --> 00:24:03.458 Those are the systems who are in troubles in between. 00:24:03.898 --> 00:24:10.298 A Parkinsonian person, for example, I'm sorry if I use this, 00:24:10.438 --> 00:24:18.818 but if Miss Universe crosses in the field it doesn't move it doesn't care. 00:24:20.118 --> 00:24:25.038 Something because it doesn't care probably the sensory input is there. 00:24:27.516 --> 00:24:33.856 There is no more motivation. There is no, there is nothing. It's an empty brain. 00:24:35.156 --> 00:24:40.856 So now we have the decision-making system, or however we want to call it, 00:24:40.896 --> 00:24:43.716 because maybe this is now more than just a decision-making system, right? 00:24:43.756 --> 00:24:48.136 We have a perceptual system with the motor system, and then there's the something in between. 00:24:48.716 --> 00:24:52.136 We're going to call that the decision-making system, or we're going to give it a different name? 00:24:52.356 --> 00:24:59.016 No, I think it's just, Because whatever you do in life is always decision-making. 00:24:59.196 --> 00:25:06.596 But decision-making needs to be expressed through a voluntary action. It's not a reflex. 00:25:08.216 --> 00:25:12.396 So, for example, you do not move. You can think about. 00:25:14.356 --> 00:25:18.556 You can even, we have a paper called postpone decision. 00:25:18.556 --> 00:25:25.416 For example, when you go to a bar or restaurant and the waiter comes to you 00:25:25.416 --> 00:25:29.656 and gives you the menu, and you say, I don't know whether to take this or that. 00:25:29.996 --> 00:25:34.096 Then comes the waiter in a minute and says, have you decided? 00:25:35.216 --> 00:25:40.476 Give me a minute, normally we say. And then, finally, you are under pressure 00:25:40.476 --> 00:25:43.456 and come the waiter, have you decided? And you decide. 00:25:43.516 --> 00:25:47.196 And then when the waiter goes, you say, why did I decide this? 00:25:47.196 --> 00:25:50.776 You know, so decision-making is something like that. 00:25:51.276 --> 00:25:57.196 When you are allowed to make a pos- a postponed decision, which is always I 00:25:57.196 --> 00:26:02.976 do myself, and it's called post-crastination, which is, um, 00:26:03.616 --> 00:26:10.016 um, a true mental problem that I have myself, for example, I do receive an email 00:26:10.016 --> 00:26:15.236 and I know what is my decision, but I postpone it for, I will do it tomorrow. 00:26:16.327 --> 00:26:20.627 And when tomorrow comes, I say, I will do it tomorrow. And at the end, 00:26:20.707 --> 00:26:22.867 I say to myself, what's going on with me? 00:26:22.927 --> 00:26:25.647 I have to make a decision. My decision was made before. 00:26:25.967 --> 00:26:30.907 I don't know what that. There is a colleague in Israel which is doing a modeling 00:26:30.907 --> 00:26:32.947 about this. It's a fantastic work. 00:26:33.187 --> 00:26:41.847 And I think there are some mental diseases which are not taken by certain in the society. 00:26:42.187 --> 00:26:47.827 But I have that problem myself. It's proscultination, not now, that. 00:26:48.187 --> 00:26:54.767 Right. And as we do have many memory problems, which are perfectly adaptable 00:26:54.767 --> 00:27:01.267 to what people can think is normal, but it's not normal if you make a simple test. Right. 00:27:01.807 --> 00:27:07.687 So, well, I'm quite a specialist myself in procrastination. You're not alone, I can assure you. 00:27:07.947 --> 00:27:12.547 But now, so, okay, we have the sensory signals. They are sort of, 00:27:12.547 --> 00:27:16.907 we have strongly stimulus-locked responses in the sensory areas. 00:27:17.127 --> 00:27:24.387 They converge over a number of steps into a premotor area like PMC. 00:27:24.447 --> 00:27:27.207 You pointed to a number of areas. 00:27:27.627 --> 00:27:32.427 So is this information reaching that area simultaneously? 00:27:32.627 --> 00:27:35.667 Is there any kind of coordination across these signals? 00:27:36.367 --> 00:27:44.047 Let's say primary somatosensory area is just in distance closer to frontal areas, 00:27:44.167 --> 00:27:46.887 PMC, as might be a visual signal. 00:27:47.187 --> 00:27:53.867 So do these areas care at all about latency matching of these areas that project to them? Of course. 00:27:54.367 --> 00:28:02.907 For example, the sensory input, which you can quantify in the stimulus parameters 00:28:02.907 --> 00:28:07.107 there, takes about 25 milliseconds, the beginning. 00:28:07.987 --> 00:28:13.187 You can have a very faithful representation of, at least for this stimulus. 00:28:13.187 --> 00:28:23.827 When you go to the frontal lobe areas that treat the stimulus in a different way, but this is... 00:28:25.608 --> 00:28:30.228 You can directly decode the information there. It's about 180 milliseconds. 00:28:30.948 --> 00:28:39.548 So there is a time, a delay time, between that sensor representation and what you see there. 00:28:40.048 --> 00:28:46.828 Of course, if you fill the gap between the two, you can find out some areas, 00:28:46.948 --> 00:28:51.568 60 milliseconds, 100 milliseconds or something, which is a time. 00:28:52.668 --> 00:28:55.888 And I don't know why. Why? Why it is not directly, for example, 00:28:55.888 --> 00:29:00.468 from the skin to the MPC, to the frontal lobe. It needs to be treated. 00:29:01.488 --> 00:29:07.748 And that reminds me Benjamin Leavitt, who was very much engaged in trying to 00:29:07.748 --> 00:29:12.208 understand the time it takes to make conscious something. 00:29:13.308 --> 00:29:19.128 A sensory input, for example. He always referred to about 500 milliseconds in men. 00:29:20.008 --> 00:29:26.548 But his techniques were not perfect at the time. It probably is about 200 milliseconds. 00:29:26.708 --> 00:29:31.608 No matter what is the sensory input I have spoken with people working in the auditory system, 00:29:31.808 --> 00:29:36.328 in decision-making in the visual system, some of the sensory system in my case, 00:29:36.448 --> 00:29:43.048 it takes about a signal which is consistent with the period in which you make 00:29:43.048 --> 00:29:46.548 the decision, which is about 180, 200 milliseconds. 00:29:46.548 --> 00:29:53.188 But that's, in Libet's case, he's talking about the conscious awareness of the decision. 00:29:53.608 --> 00:29:58.008 So you believe that for the monkey, it's a comparable kind of process. 00:29:58.588 --> 00:30:03.008 There may be some differences in the timing. Sure, but qualitatively, 00:30:03.008 --> 00:30:05.588 it would play out in the same way that we would have. 00:30:05.808 --> 00:30:11.508 I do think so. Okay. Yes. Of course. So now we have, so your opinion, 00:30:11.568 --> 00:30:17.488 the decision-making we're talking about, just to sort of finish up the Libet aspect, 00:30:17.988 --> 00:30:23.128 also decision-making is always engaging conscious awareness. 00:30:23.848 --> 00:30:28.088 Not necessarily. Okay. For example, when you drive your car. 00:30:29.308 --> 00:30:36.428 You may be aware once you make the decision, you know, but in other cases, 00:30:36.628 --> 00:30:42.888 if you give me time, which is not always possible because you have, 00:30:43.048 --> 00:30:45.908 it depends, it's a very adaptable operation. 00:30:45.908 --> 00:30:52.568 It depends on the time constraints and what beneficial is to make a decision, 00:30:52.848 --> 00:30:57.128 whether you need to think about or whether you have to make a decision. 00:30:57.568 --> 00:31:03.768 Not in a very reflexive way, because you have brain circuits that allow you 00:31:03.768 --> 00:31:09.728 to think about below your conscious awareness. 00:31:10.268 --> 00:31:17.848 Sometimes you are conscious on that, and then you say, why did I do that? Oh, I did quite well. 00:31:18.608 --> 00:31:22.708 Your experiment is a little bit unusual in that respect, because you have something 00:31:22.708 --> 00:31:28.628 which is highly practiced, but at the same time is always intrinsically unpredictable, 00:31:29.008 --> 00:31:31.188 because you don't know what the next stimulus is going to be, 00:31:31.208 --> 00:31:33.108 but you know it's going to be one of two things. 00:31:33.788 --> 00:31:40.968 So you have something there, I guess you would say, why you cannot use a habit 00:31:40.968 --> 00:31:44.548 system because you always have to make a choice. Yes. 00:31:44.968 --> 00:31:47.168 And therefore, it would come into consciousness. 00:31:47.728 --> 00:31:52.788 It was made by purpose from the beginning. I thought a lot about this because 00:31:52.788 --> 00:31:56.968 I was trained by a very incredible man, 00:31:57.228 --> 00:32:05.088 Vernon Mountcastle, who laid out many of the ideas we use right now, believe me or not. 00:32:05.088 --> 00:32:09.808 And when I was working with him, in some way we treated this problem, 00:32:09.888 --> 00:32:16.048 and I discovered that he was doing, at least from my perspective, in a wrong way. 00:32:17.272 --> 00:32:21.992 Of course, he had, I thought about him, had more flexibility. 00:32:22.952 --> 00:32:28.432 Because he was older than me, I was eager. So everything was left. 00:32:28.872 --> 00:32:33.732 And then when I went back to Mexico, I said, why didn't it work? And I discovered why. 00:32:34.412 --> 00:32:41.832 So I made by purpose, in which in a very artificial way, I could recreate the different steps. 00:32:41.832 --> 00:32:47.172 Steps, you know, one without being contaminated by the next one, 00:32:47.352 --> 00:32:53.512 but being sure that to pass from one to two, you have to go through this step. 00:32:53.692 --> 00:32:58.012 Otherwise, you will be wrong at the end with simply guessing. 00:32:58.372 --> 00:33:02.652 So it's very, if you like, it's artificial, but everything is artificial, 00:33:02.932 --> 00:33:09.412 even CERN in Geneva, in order to prove the molecule, God molecule. 00:33:09.832 --> 00:33:17.972 So it's made by purpose. But I had to make clear that we had to have both inputs, 00:33:18.252 --> 00:33:22.292 a central input, an output, and then be combined. 00:33:22.632 --> 00:33:28.892 And I had to be able to look at both, not in a very different way, 00:33:29.012 --> 00:33:30.772 just simple, hard to capacity, 00:33:31.072 --> 00:33:37.812 with a very simple statistical technique coming from engineering and physics, 00:33:37.912 --> 00:33:41.612 just to the code and have them both in my hands. 00:33:41.832 --> 00:33:47.272 So it's a very peculiar way of doing science. 00:33:47.512 --> 00:33:51.092 A very simple way is pedestrian, frankly. 00:33:52.292 --> 00:34:00.852 But now, so what you found is that neurons in MPC, if you look at how these 00:34:00.852 --> 00:34:02.812 neurons respond to the task properties. 00:34:03.092 --> 00:34:08.852 Now, in this case, we have these frequency-modulated visual or tactile stimulation, 00:34:09.172 --> 00:34:15.592 and now dependent on the frequency and the difference, like before the waiting 00:34:15.592 --> 00:34:20.992 period and after the waiting period, the monkey has to choose for one action or the other. 00:34:21.312 --> 00:34:25.992 So what you show, however, is in this waiting period of up to three seconds, 00:34:26.292 --> 00:34:28.052 something very peculiar happens. 00:34:28.192 --> 00:34:34.272 And that it looks like the response of these neurons sort of also at the offset 00:34:34.272 --> 00:34:40.152 of the the first stimulus pair, they slowly ramp up their activity or exceed it, might vary, 00:34:40.872 --> 00:34:46.392 but still reflecting the key feature that should inform this decision, which is frequency. 00:34:47.612 --> 00:34:50.832 Okay. So, but why would that be a ramping activity? 00:34:51.132 --> 00:34:56.132 Why don't you just latch on to a certain representation of that frequency and 00:34:56.132 --> 00:34:58.152 just keep it there? What's the ramping all about? 00:34:58.332 --> 00:35:04.012 Let me say something that somebody today asked me about, he was posing to me 00:35:04.012 --> 00:35:05.152 a philosophical question. 00:35:05.512 --> 00:35:12.912 I admire Democritus, but recently I discovered Epicurus. 00:35:14.140 --> 00:35:20.240 Epicurus precedes Democritus in the ideas that there has to be a representation 00:35:20.240 --> 00:35:22.100 of something in the brain. 00:35:23.500 --> 00:35:30.740 Democritus was talking about molecules, atoms, that everything in our external 00:35:30.740 --> 00:35:37.200 world was made by atoms that entered through our eyes, our ears, our fingers. 00:35:37.540 --> 00:35:41.600 And these atoms move up to the brain. 00:35:41.600 --> 00:35:48.060 He said that, and in the brain, these molecules gather together and give an 00:35:48.060 --> 00:35:53.180 iso, in the case of the form, an object, they generate the form. 00:35:53.560 --> 00:35:59.140 And that that representation was important for learning, memory, 00:35:59.420 --> 00:36:02.340 voluntary action, and decision making. 00:36:02.940 --> 00:36:08.500 Democritus said that 200 and 300 years ago, 2,300 years ago. 00:36:08.500 --> 00:36:13.500 So, if you like, I'm a continuator of Democritus. 00:36:14.720 --> 00:36:19.920 So, if you like, the atoms are the action potential right now in the modern view. 00:36:20.460 --> 00:36:27.940 And those action potentials are how cells generate electrical signals, tiny electric. 00:36:28.220 --> 00:36:33.520 If you put together, you can generate the form of an image. 00:36:33.520 --> 00:36:43.840 In fact, Otto Creufield used this idea to study the form of visual inputs in 00:36:43.840 --> 00:36:45.200 the visual cortex in the cat. 00:36:46.480 --> 00:36:50.660 Myself, I'm using a more simple stimulus, vibration in the fingers, 00:36:50.860 --> 00:36:55.460 and you can see that it's not isomorphic. 00:36:55.520 --> 00:37:03.320 This is isometric representation. So I wanted to have something that I can see 00:37:03.320 --> 00:37:05.100 directly from the spikes. 00:37:05.480 --> 00:37:13.720 And the idea is, to me, the AC test was, what is left when the stimulus is gone? 00:37:14.600 --> 00:37:17.760 And I wanted to find out that. 00:37:17.920 --> 00:37:23.300 And with very simple statistical methods, we see that the stimulus parameter is there. 00:37:23.300 --> 00:37:28.840 Of course, neurons are like humans, have different ways of representing, 00:37:29.000 --> 00:37:35.200 but at the end it's exactly the same neural code, a parametric code, in different times. 00:37:35.520 --> 00:37:40.020 And I want to believe that neurons, thousands of neurons, millions of neurons, 00:37:40.080 --> 00:37:43.400 gather effort in order to represent something. 00:37:44.380 --> 00:37:49.440 And this is what is shown. Sorry, so what is Epicurus that's different from 00:37:49.440 --> 00:37:54.320 Democritus? No, it's the way, no, Epicurus added something. 00:37:55.180 --> 00:38:04.440 Democritus was more from the physical side, like a journalistic person would think right now. 00:38:04.840 --> 00:38:11.220 As, for example, very often the students say, what do you think of this paper, I always say. 00:38:12.385 --> 00:38:16.425 Well, this paper is not very good because it's very qualitative. 00:38:17.505 --> 00:38:22.945 And I always tell them, listen, if somebody is able to show qualitative properties 00:38:22.945 --> 00:38:25.105 of something, it's because he solved everything. 00:38:25.885 --> 00:38:29.385 Because they always criticize. It's not very quantitative. 00:38:29.905 --> 00:38:37.825 So, what Epicurus added is precisely the other, the qualitative thing. 00:38:37.885 --> 00:38:39.265 He thought about that. 00:38:40.005 --> 00:38:46.425 For what for is that? For example, many years when I discovered that isometric 00:38:46.425 --> 00:38:50.405 representation of the stimulus, I wanted to know whether it served for something, 00:38:50.705 --> 00:38:54.445 whether it was an artifact. So I did the reverse experiment. 00:38:54.745 --> 00:38:58.425 I activated artificially brain cells. 00:38:58.645 --> 00:39:04.725 And what happens is that the monkey or the subject had the capacity to generate 00:39:04.725 --> 00:39:11.945 something which is very consistent with what I observed with the natural steam. 00:39:12.145 --> 00:39:21.005 So there was a very causal confirmation that that representation was useful for decision-making. 00:39:22.545 --> 00:39:27.165 But now, so we have this slowly ramping activity. 00:39:28.305 --> 00:39:33.765 And for you, the key point here is that what these neurons do is sort of they 00:39:33.765 --> 00:39:37.645 throw away information that really doesn't matter for the decision making. 00:39:37.825 --> 00:39:42.245 And they conserve the information that is sort of modality independent and relevant, 00:39:42.485 --> 00:39:45.405 which in this case is the frequency of the modulation. Right? 00:39:45.805 --> 00:39:54.745 So how does that process play out? So here we have two, we have an auditory and a tactile stimulus. 00:39:55.005 --> 00:39:59.045 They might have a different kind of frequency response, right? 00:39:59.565 --> 00:40:04.025 Converging on any of these frontal areas. And now during the, 00:40:04.185 --> 00:40:09.985 what you showed, which is interesting, is that during the wait period where the stimulus is gone. 00:40:11.085 --> 00:40:16.565 The system, these frontal areas that you investigated are still modulating that signal. 00:40:16.565 --> 00:40:22.485 Is it only this sort of frequency-specific response starts to emerge, 00:40:22.905 --> 00:40:27.885 is most pronounced towards the end of the waiting period, just before the decision is made? 00:40:28.205 --> 00:40:34.825 So how do you see this incremental sharpening of the task-relevant information in the response? 00:40:35.445 --> 00:40:42.745 This is science. We have no answer for everything, but it's a fact that happens there. 00:40:43.005 --> 00:40:45.925 And once you have it, then you can think about it. 00:40:46.565 --> 00:40:52.725 The first thing which strikes me is that this is the way that happens in the brain. 00:40:52.845 --> 00:41:01.105 Secondly, I'm very impressed that for that cells in a very downstream area, 00:41:01.245 --> 00:41:04.945 far away from the sensory representation, um. 00:41:07.623 --> 00:41:11.023 Do that, have that neural code in that moment. 00:41:11.283 --> 00:41:16.423 And so it might tell you something fundamental about that. 00:41:16.823 --> 00:41:25.443 So the question is here, is that you are thinking about underrepresentation 00:41:25.443 --> 00:41:31.683 on a stimulus parameter for different modalities in the same way. 00:41:31.903 --> 00:41:36.963 It's an abstract, it's a supramodal, a modal if you like, but it's there. 00:41:37.623 --> 00:41:42.623 What is the strike the most to me? So we can think right now in models, 00:41:42.903 --> 00:41:50.443 in one stream trying to model and implement model and think about and do experiments 00:41:50.443 --> 00:41:56.903 in order to find out the biophysical basis and the architecture, 00:41:57.223 --> 00:41:59.163 neural architecture, which is there. 00:41:59.163 --> 00:42:02.403 There, no doubt that, and makes this. 00:42:02.543 --> 00:42:06.583 To me, the most important contribution of this, 00:42:06.823 --> 00:42:13.663 I'm trying to think that my work has something worth in life, 00:42:13.823 --> 00:42:24.183 is that I think we were the first to show in the tactile modality a way our 00:42:24.183 --> 00:42:28.103 brain cells store, represent information during working memory. 00:42:28.103 --> 00:42:34.983 Because in the case of my colleague, Goldman Rakeesh, it was always contaminated by eye movements. 00:42:37.343 --> 00:42:43.863 And, but it's a very, the physical space, if we want to think, is there, is there. 00:42:44.263 --> 00:42:46.723 But in our case, it's something learned. 00:42:48.163 --> 00:42:54.283 It's something, play cells are there. But the monkeys don't have to think about vibrotactile. 00:42:54.383 --> 00:42:57.323 Why? or by acoustic repetition. 00:42:58.900 --> 00:43:03.780 It's exactly the same when you go, you study medicine, your brain is not made 00:43:03.780 --> 00:43:06.640 to do medicine or engineering. 00:43:06.960 --> 00:43:11.520 You have to be trained. So this is something forged by experience, 00:43:11.960 --> 00:43:18.320 which means that your brain circuits can be modified by experience, 00:43:18.880 --> 00:43:24.740 can store information, experience, and can use it for the best or for the worst. 00:43:25.240 --> 00:43:28.960 That's, to me, the contribution. vision. But now in your analysis, 00:43:29.220 --> 00:43:32.900 you look at these cells as being either unimodal. So we look at PMC, 00:43:33.020 --> 00:43:33.820 right? The frontal area. 00:43:34.200 --> 00:43:38.780 You looked at whether these neurons were tuned unimodal or bimodal, right? 00:43:39.120 --> 00:43:42.480 And then what we see is that over the three seconds, initially, 00:43:42.560 --> 00:43:45.980 actually, they're not that strongly committed to anything. 00:43:46.440 --> 00:43:50.400 And in the end, we see a very strong, what you call bimodal response. 00:43:50.680 --> 00:43:53.520 However, would it not be then more appropriate, actually, 00:43:53.580 --> 00:43:56.600 as you said said earlier to call it a modal yes because 00:43:56.600 --> 00:43:59.700 what they care about is just that bit let's 00:43:59.700 --> 00:44:03.060 say they care about the semantics of the task the frequency is 00:44:03.060 --> 00:44:07.320 telling you something important forget the rest which you would you be happy 00:44:07.320 --> 00:44:12.440 with that interpretation absolutely okay good in fact i i had a i spent a lot 00:44:12.440 --> 00:44:17.740 of time thinking about this to me it was the most simple paper in my life to 00:44:17.740 --> 00:44:19.920 report but when When I started to write, 00:44:20.140 --> 00:44:26.020 I was confronting literature that there was nothing. 00:44:26.720 --> 00:44:30.000 Or the people used to say they had already discovered. 00:44:30.240 --> 00:44:36.160 But how to say that? How to confront the community to tell them there is nothing? 00:44:36.860 --> 00:44:40.040 And how to say I'm a pioneer really in this? 00:44:40.260 --> 00:44:49.280 So at the end, I have to think about and be very polite, and sometimes say supramodal, 00:44:49.340 --> 00:44:54.140 and sometimes a modal, sometimes bimodal. 00:44:54.260 --> 00:44:56.340 But at the end, what happens? 00:44:57.920 --> 00:45:02.540 We discovered very few cells unimodal, and I think it's a statistical issue. 00:45:03.940 --> 00:45:09.480 The network is basically more than 85, almost 90% bimodal. 00:45:10.540 --> 00:45:13.720 And I've been thinking, you don't have to think about... 00:45:16.905 --> 00:45:21.105 The brain doesn't care when once, there are circuits that treat the stimulus 00:45:21.105 --> 00:45:26.065 parameter, but at the end is the goal, is to treat something. 00:45:26.265 --> 00:45:30.585 What is fundamental here is the frequency, and the cells don't care whether 00:45:30.585 --> 00:45:33.925 it's acoustic, whether it's tactile, or whether it's visual. 00:45:34.085 --> 00:45:38.785 I think this is very, very physiologic, very natural, this. 00:45:39.345 --> 00:45:46.345 Yeah, Tony, go ahead. Are you able to show that these neurons are getting their 00:45:46.345 --> 00:45:51.785 input directly from the unimodal cells and that they're integrating? 00:45:51.985 --> 00:45:58.305 Or could there be some other site of integration that's perhaps viewed more 00:45:58.305 --> 00:46:03.145 as a sensory area so that the integration happens sooner or elsewhere and you haven't seen that yet? 00:46:03.185 --> 00:46:07.745 These cells are very far away from the sensory input where you see the stimulus 00:46:07.745 --> 00:46:18.125 parameter. There are many areas in between, and you can see the gradual contribution of these areas. 00:46:18.525 --> 00:46:26.565 In this, what I show, I simply wanted to contrast input and what you get there. 00:46:26.745 --> 00:46:29.525 But in between, it's already done the experiments. 00:46:29.785 --> 00:46:35.145 I can tell you there is a gradual transformation. For example, circuits, 00:46:35.605 --> 00:46:41.305 neurons from circuits, which are in between this area and the sensory input, 00:46:41.545 --> 00:46:49.665 that treat the most the responses in the sensory input in the two ways, opposite way. 00:46:50.105 --> 00:46:56.445 They share correlated noise, which is something common thing, 00:46:56.765 --> 00:46:59.105 synaptic input, something like that. Right. 00:47:01.916 --> 00:47:05.436 Populations of neurons, we are only in the early components, 00:47:05.616 --> 00:47:07.516 some others which are more delay. 00:47:09.696 --> 00:47:16.296 Some ones, we respond the most during the second one, which is the right moment 00:47:16.296 --> 00:47:19.836 in which we have to combine two different modalities. 00:47:19.916 --> 00:47:23.516 For example, the first is acoustic that has to be stored in working memory, 00:47:23.616 --> 00:47:24.516 and the second is tactile. 00:47:24.516 --> 00:47:30.616 Somehow, there have to be some gears in your brain that shift gears in a very 00:47:30.616 --> 00:47:32.496 efficient way in order to compare, 00:47:32.696 --> 00:47:37.576 to treat in the same way to this different sensory input coming for different 00:47:37.576 --> 00:47:39.976 representation in your brain. 00:47:40.056 --> 00:47:47.476 So that requires tremendous, it's very simple, but to analytically, 00:47:47.756 --> 00:47:51.096 statistically to prove a modeling is another issue. 00:47:51.096 --> 00:47:55.256 So there's several steps on the path to the premotor cortex. 00:47:55.456 --> 00:48:01.036 What about signals coming back? Are there signals from PMC which could be modulating 00:48:01.036 --> 00:48:02.356 the primary sensory areas? 00:48:02.576 --> 00:48:07.316 Yeah, we haven't discovered that. But I was surprised in another experiment 00:48:07.316 --> 00:48:11.476 in 2005 that we… No, no, that was 2002, 00:48:11.876 --> 00:48:19.516 that reported in Nature, during which we discover decision-making in downstream 00:48:19.516 --> 00:48:25.696 area immediately after S1 sensory primary somatosensory cortex. 00:48:25.756 --> 00:48:29.036 This is called secondary somatosensory cortex. 00:48:30.116 --> 00:48:35.916 So everybody would expect that this area is very somatosensory. 00:48:36.856 --> 00:48:39.576 But we discovered that it was associated to decision-making. 00:48:39.576 --> 00:48:48.116 They have also working memory cells and combine the working plus the sensory input. 00:48:49.176 --> 00:48:58.216 So when I got the beginning of the decision-making process, it happens that it was delaying. 00:48:59.117 --> 00:49:02.617 With respect to the media promoter cortex. 00:49:02.897 --> 00:49:08.937 It's like it's the frontal lobe sent back a copy. Listen, do you agree that 00:49:08.937 --> 00:49:09.917 I made the right decision? 00:49:10.237 --> 00:49:16.877 So the beginning of the decision signal was in the MPC, and then a secondary 00:49:16.877 --> 00:49:19.357 somatosensory. I had thought in the opposite way. 00:49:19.657 --> 00:49:24.197 The secondary, because it was very close to the sensory, had to be the beginner. No. 00:49:24.637 --> 00:49:28.677 So that showed that there has to be a feedback projection 00:49:28.677 --> 00:49:33.417 rejection with nobody knows okay but 00:49:33.417 --> 00:49:36.497 now so the data on which we base basis 00:49:36.497 --> 00:49:42.077 interpretation is sort of the number of neurons that are responsive in the waiting 00:49:42.077 --> 00:49:47.937 period to either um unimodal or the bimodal aspect of the stimulus so i guess 00:49:47.937 --> 00:49:51.777 you you reveal that by probe trials right that way where there's there's no 00:49:51.777 --> 00:49:55.657 specific reward to be gotten by the animal but we just present either one, 00:49:55.697 --> 00:49:58.377 the tactile stimulus or the auditory stimulus, 00:49:58.537 --> 00:50:01.097 and we see which neuron responds or not. 00:50:01.237 --> 00:50:07.117 How do you exactly get, how can you tell me, how can we figure out how many 00:50:07.117 --> 00:50:11.817 neurons are responsive to a certain modality in this time? Because we have to 00:50:11.817 --> 00:50:12.917 threshold something somewhere. 00:50:13.277 --> 00:50:18.477 Well, we don't make any assumption, except that we know that this area has the 00:50:18.477 --> 00:50:23.717 capacity because we had already shown in the TAC-TAC protocol. 00:50:24.137 --> 00:50:30.397 So we simply wanted to add whether the acoustic stimulus was treated in the 00:50:30.397 --> 00:50:33.417 same way, whether those neurons had or not the capacity. 00:50:33.857 --> 00:50:40.497 And the second hypothesis was whether we wanted to test whether it were if that 00:50:40.497 --> 00:50:47.657 area, the neuron had that capacity, were intermingled, many unimodal or were bimodal. 00:50:47.657 --> 00:50:52.157 So, the only thing we did was to insert the microelectrodes. 00:50:52.217 --> 00:50:58.997 We insert the wires, is there, leave them to recuperate the tissue because we believe. 00:50:59.981 --> 00:51:04.421 We perturbate the environment of brain cells. 00:51:05.481 --> 00:51:09.141 We let the monkey to do the task that there is no problem. 00:51:09.841 --> 00:51:16.361 We don't have any statistical bias. We simple, whatever is there, we pick it. 00:51:16.881 --> 00:51:21.321 And that's it. The only thing we require is that the neurons are there. 00:51:21.881 --> 00:51:29.581 That we don't lose the cells across trials, not to have statistical problems. 00:51:29.981 --> 00:51:35.721 So cells, they have to be stable from the beginning up to the end of the test. 00:51:36.081 --> 00:51:39.601 And that's it. We don't make any assumptions. So, of course, 00:51:39.721 --> 00:51:46.301 we would like to have the through populations, but nobody can make it. 00:51:46.741 --> 00:51:53.921 Even the people that think that they have massive recordings, 00:51:54.401 --> 00:51:58.941 EEGs, magnetoencephalographic or fMRI, that's not true. 00:51:59.881 --> 00:52:06.381 This is the way we are running the experiment in 2015, and there is no more, 00:52:06.501 --> 00:52:08.121 and we have to rely on that. 00:52:08.701 --> 00:52:12.801 There will be new techniques in the future, which are not available, 00:52:12.981 --> 00:52:17.361 even calcium signals, because they have to destroy a little bit the brain. 00:52:18.241 --> 00:52:22.661 In very small animals, which sometimes I think they are not doing what the people 00:52:22.661 --> 00:52:29.341 claim, and they are sampling only some layers, and that's it. 00:52:29.521 --> 00:52:33.181 So here is what we have, no more than that. Right. 00:52:33.921 --> 00:52:39.361 So now a traditional approach or model to think about decision-making is what's 00:52:39.361 --> 00:52:41.821 called drift diffusion in psychology. 00:52:42.061 --> 00:52:47.761 It has been popular for many years and now it has been picked up in neuroscience as well. 00:52:48.041 --> 00:52:54.001 And people are sort of, you know, singing that tune quite loudly nowadays that 00:52:54.001 --> 00:52:57.161 everything is about integration of these kinds of simple signals. 00:52:57.161 --> 00:53:04.321 So now in your model, you show that the number of cells that now respond to 00:53:04.321 --> 00:53:08.161 the decision-making variable is increasing over time in a delay period. 00:53:08.341 --> 00:53:11.901 So I could say, well, isn't that suggestive of a drift-diffusion model? 00:53:11.981 --> 00:53:15.521 Because now I have just another neuron that must read out this whole population. 00:53:15.801 --> 00:53:20.121 The more neurons respond to the frequency, the higher the rate it will get until 00:53:20.121 --> 00:53:21.861 it reaches its decision threshold. 00:53:22.041 --> 00:53:25.001 And there we go. Is this how you think about it? 00:53:25.061 --> 00:53:31.661 No. In fact, I have followed a very different way myself, thinking that having 00:53:31.661 --> 00:53:38.601 hypothesis, having, but in fact, every time we do a statistic, we use a model. 00:53:39.481 --> 00:53:42.501 But I'm not married with any model. 00:53:44.041 --> 00:53:48.661 Intuitively, it's very nice that there is an accumulation model. No doubt that. 00:53:49.101 --> 00:53:55.121 But it's true and it's not true. It depends how you treat it. and uh, 00:53:56.318 --> 00:53:59.358 Accumulation can be done by the population, 00:53:59.718 --> 00:54:07.538 and in my case, I show that the signals is more represented, 00:54:07.778 --> 00:54:11.318 the numerosity increases, and the quality too. 00:54:11.398 --> 00:54:17.298 Because it's coming very soon, the right moment in which it's like when you 00:54:17.298 --> 00:54:21.458 are running the 100 meters. 00:54:21.458 --> 00:54:26.198 When you are sitting just to listen to the ball, 00:54:26.438 --> 00:54:31.458 the cue signals that trigger the beginning of the 100 meters, 00:54:31.638 --> 00:54:38.438 your brain brings you, comes to a state in such a way that sensory input treated 00:54:38.438 --> 00:54:41.718 very differently in other situations. 00:54:42.298 --> 00:54:45.858 Sensory inputs are not treated in the same way every time. 00:54:46.418 --> 00:54:48.258 It's exactly the same what happens 00:54:48.258 --> 00:54:53.498 in this case. is coming, the second stimulus, and the monkey knows. 00:54:53.838 --> 00:54:59.358 And in fact, there is a timing signal superimposed on this working memory and the numerosity. 00:54:59.678 --> 00:55:03.778 And I want to believe that the number of neurons matters in order to do a function. 00:55:07.158 --> 00:55:12.918 So, but still, there must be some thresholding and comparison going on because 00:55:12.918 --> 00:55:17.658 all what we look at now is a decision, is there's the neurons in this premotor 00:55:17.658 --> 00:55:20.118 network that you measure from are saying, yes, 00:55:20.318 --> 00:55:24.838 the frequency is there that tells me that we should do A, let's say. 00:55:25.018 --> 00:55:27.038 I have to move my eyes to the left. 00:55:27.318 --> 00:55:32.138 So now we have the evidence, but how do we get it then transformed into actually 00:55:32.138 --> 00:55:33.938 executing that one action? 00:55:34.618 --> 00:55:36.938 This is what I like to understand. 00:55:37.738 --> 00:55:42.738 For example, in fact, one other issue, if I can speculate here, 00:55:42.838 --> 00:55:46.958 because I'm not doing an experiment, simply speaking, is that, 00:55:47.818 --> 00:55:52.958 out of the number of neurons and decoding directly, 00:55:54.818 --> 00:56:01.638 something from brain cells, I would like to understand how subjectivity emerges. 00:56:03.598 --> 00:56:05.438 From the activity of brain cells. 00:56:05.778 --> 00:56:11.278 I frankly have no idea. I know it emerges, but how? 00:56:11.518 --> 00:56:20.238 It's the most difficult problem in science And if we manage once to discover 00:56:20.238 --> 00:56:26.298 this, that could be probably the most important discovery in science for the rest of the humanity. 00:56:27.772 --> 00:56:34.772 I agree with you. So you come out of a tradition, if you want, 00:56:34.812 --> 00:56:36.532 the giants of neuroscience, right? 00:56:36.612 --> 00:56:39.512 We're in the Mount Castle as your mentor. 00:56:41.412 --> 00:56:46.592 Also, you've been delving into the brain deeply and also you have very deep 00:56:46.592 --> 00:56:47.492 thoughts about the brain. 00:56:47.492 --> 00:56:53.612 So if we want to follow that tradition, what is Ranulfo's law that we should 00:56:53.612 --> 00:56:58.532 now spray paint on the wall and sort of imprint in our brains every day in order 00:56:58.532 --> 00:57:00.632 to understand the brain? I have many mentors. 00:57:00.912 --> 00:57:03.712 One also could be Wolfram Schultz. 00:57:04.032 --> 00:57:10.512 In fact, he and I were so young that when we entered into the field, 00:57:10.612 --> 00:57:14.112 we didn't know, because we didn't know how to study the motor system, 00:57:14.592 --> 00:57:19.852 we didn't know that we were dealing with reward, which probably was one of the 00:57:19.852 --> 00:57:29.112 most important functions of our brain, which is subjectivity, how to treat things. 00:57:29.452 --> 00:57:33.672 I don't think so that I have a law. 00:57:34.412 --> 00:57:39.572 I think it's a particular way of treating in doing the way do science. 00:57:39.832 --> 00:57:47.992 And probably one of the last ones is right now science is becoming like industry 00:57:47.992 --> 00:57:53.312 and bureaucracy dominates politics or something like that. 00:57:54.482 --> 00:57:59.162 I do not know whether there will be something left by me, but at the moment, 00:57:59.282 --> 00:58:01.082 I'm quite happy with what I'm doing. 00:58:01.262 --> 00:58:07.622 My subjectivity is largely recompensated, rewarded by what I do. 00:58:08.002 --> 00:58:11.882 There might be something which is important. 00:58:12.202 --> 00:58:17.482 I have dealt with two problems. For example, how the physical work is represented 00:58:17.482 --> 00:58:23.942 in the brain and track the signals to make decisions together with working men or something. 00:58:23.942 --> 00:58:27.622 And the other one, I want to believe, together with Wolfram Schultz, 00:58:27.642 --> 00:58:32.502 that we'll deal with something which is very different. 00:58:33.202 --> 00:58:39.742 It's not a physical parameter. It's something that is generated by brain cells, the reward business. 00:58:40.302 --> 00:58:46.602 But in spite of that, we were able to call something. So, we're dealing in these 00:58:46.602 --> 00:58:53.922 two works, the physical representation in brain cells and the subjectivity represented in the brain. 00:58:54.142 --> 00:58:59.702 And if you like, that could be my contribution, but I have no big hypothesis yet. 00:59:00.442 --> 00:59:04.522 Okay. So, it's like embrace subjectivity. Would that be a good law for Renulfo? 00:59:05.582 --> 00:59:09.482 Or at least respect subjectivity? Of course. Yes. Yes. 00:59:09.722 --> 00:59:14.342 But now, so the other thing, Tony likes traveling. He wants to go to Mexico 00:59:14.342 --> 00:59:15.642 City. He's never been there yet. 00:59:16.382 --> 00:59:19.982 So five years from now, he's going to come to your doorstep with a piece of 00:59:19.982 --> 00:59:22.702 paper that says, look, five years ago, you made this prediction. 00:59:22.742 --> 00:59:26.122 And today I want to know whether you actually have falsified this. 00:59:26.222 --> 00:59:31.322 Being a Popperian, you would like to have it falsified. So what's the one prediction 00:59:31.322 --> 00:59:35.742 that you would like to commit to, to be tested within the coming five years? 00:59:37.621 --> 00:59:42.601 Well, we are dealing with something fundamental, too, and I haven't spoken about it. 00:59:44.341 --> 00:59:48.141 Most of our mental functions depend on attention. 00:59:49.781 --> 00:59:53.321 And I began doing experiments on this. 00:59:54.501 --> 01:00:02.321 And it's a big issue. So far, at this moment, nobody has been able to describe 01:00:02.321 --> 01:00:05.021 brain circuits associated to attention. 01:00:05.021 --> 01:00:11.441 And some colleagues of me think that attention is the key to understand consciousness. 01:00:12.781 --> 01:00:22.641 So I'm designing new experiments in which I think I will be able to hit on attentional circuits. 01:00:23.681 --> 01:00:28.981 In the way attention matters for work memory, attention matters for perception, 01:00:29.361 --> 01:00:35.401 for subjectivity or something like that. But if you like, I have done the first experiment. 01:00:35.481 --> 01:00:39.821 If I say my first experiment, I started three years ago. 01:00:39.921 --> 01:00:48.481 So we have gathered enough data, which is part of young people under training. 01:00:49.321 --> 01:00:55.821 Very young people that I would like to, they have enough time to continue with this tradition. 01:00:56.341 --> 01:01:01.241 So my next thing is to add attention to this. All right. Right. 01:01:01.241 --> 01:01:03.181 So, Tony, remember it. Attention. 01:01:04.081 --> 01:01:06.361 All right. Renulfo Romo, thank you so much for this conversation. 01:01:06.741 --> 01:01:08.761 It's a pleasure. Thank you. Thank you. 01:01:11.321 --> 01:01:16.981 The CSN podcast was produced by the Convergent Science Network of Biometrics 01:01:16.981 --> 01:01:23.321 and Biohybrid Systems, a project funded by the European Sevens Research Framework Program. 01:01:25.117 --> 01:01:30.177 For more interviews, recorded lectures, or upcoming conferences in the field 01:01:30.177 --> 01:01:36.417 of biomimetics and biohybrid systems, go to csnnetwork.eu. 01:01:36.757 --> 01:01:38.577 And thank you for listening. 01:01:44.177 --> 01:01:51.937 So, I made by purpose not to contaminate the sensory or the treating of this 01:01:51.937 --> 01:01:54.257 input, the transformation by the motor side. 01:01:54.257 --> 01:02:01.797 I do believe that there are motor signals coming back into there because the 01:02:01.797 --> 01:02:08.977 somatosensory, there is no other sensory system because it's more mixed with the motor out, 01:02:09.097 --> 01:02:12.257 on the motor side, you know, that somatosensory system. 01:02:12.437 --> 01:02:17.917 And we're dealing with the cutaneous modalities. You can deal with the deep modalities. 01:02:18.037 --> 01:02:23.557 It's a very complex system, this somatosensory. I think you're also simplifying 01:02:23.557 --> 01:02:27.437 it so that you move the spatial component in terms of where about on the skin 01:02:27.437 --> 01:02:30.997 that happened, whereas S2 maybe is very interesting. 01:02:30.997 --> 01:02:34.517 Something very important that you were not aware of this. 01:02:35.097 --> 01:02:40.337 The visual system treats the sensory input with the two eyes. 01:02:40.577 --> 01:02:45.437 There are two sensory inputs. In this case, it's a tiny patch of the skin. 01:02:45.437 --> 01:02:49.837 So it's allowed you to trace clean, 01:02:50.637 --> 01:02:58.917 the input signal at least at the entry and then it's very nice because and then 01:02:58.917 --> 01:03:02.617 Cajal developed I do not agree with. 01:03:04.257 --> 01:03:12.477 Gustavo says that the neuron doctrine made a lot of damage to I think you have 01:03:12.477 --> 01:03:18.917 to to take Cajal message after a certain point. 01:03:19.377 --> 01:03:22.717 And no more than that. And stop that, you know? 01:03:23.417 --> 01:03:31.897 So Cajal spoke about one of his concepts, which is called avalanche in conduction. 01:03:33.557 --> 01:03:39.877 And he thought about how it's possible that a tiny stimulus in the skin that 01:03:39.877 --> 01:03:42.817 engages few mechanoreceptors. 01:03:44.409 --> 01:03:47.729 Produces a very weak perceptual process. 01:03:48.129 --> 01:03:54.229 And he said that he traced one primary afferent that ends in the skin and then 01:03:54.229 --> 01:03:56.469 the other branch entering the spinal cord. 01:03:56.929 --> 01:04:01.449 And he said it's like an avalanche, a ball avalanche, a small one, 01:04:01.549 --> 01:04:05.509 a snowball that is moving, is recluding more and more and more. 01:04:05.649 --> 01:04:10.109 Something happened like that. The entry of that primary afferent, few primary, 01:04:10.309 --> 01:04:17.189 reclutes neurons in the spinal cord, then reclutes more neurons in the thalamus, 01:04:17.209 --> 01:04:21.749 but preserves somatotopy, and then enters into cerebral cortex. 01:04:21.929 --> 01:04:26.669 And columnar organization, you like, proposed by Bernoull-Mamcastle, 01:04:26.729 --> 01:04:33.109 have divergent some other cortical inputs, other hemisphere downstream structures. 01:04:33.529 --> 01:04:40.369 So there are many players from a column in S1 that puts in motion everything. 01:04:40.369 --> 01:04:44.429 There will be a symposium in Mountcastle on November. 01:04:44.769 --> 01:04:48.269 Ah, really? So I have to think about this. That's great. 01:04:48.449 --> 01:04:53.709 So I have to talk about models, columns, about distributed systems, 01:04:54.029 --> 01:04:58.029 some autosensory system, where he laid out some ideas. 01:04:58.949 --> 01:05:05.269 And what is left from this and what was not left? I have to be critical. 01:05:05.529 --> 01:05:08.669 Yes. Well, I think not much is left by now, right? 01:05:09.709 --> 01:05:14.749 Not much. People like these very compressed, simplified models. 01:05:14.969 --> 01:05:17.209 They really start to forget about the complexity. 01:05:17.509 --> 01:05:23.929 Yes, but if you read carefully his chapter in The Mindful Brain. 01:05:25.069 --> 01:05:36.169 He had an idea, but he was not beyond that, because he was scared that everything 01:05:36.169 --> 01:05:37.889 was wrong, Even with myself, 01:05:38.109 --> 01:05:43.969 because we design multiple electro recordings to hit the columns in S1. 01:05:44.109 --> 01:05:48.149 And very often we had a column and he didn't want to test it. 01:05:49.054 --> 01:05:53.974 He was scared about that. And of course, I said, why don't we, 01:05:54.014 --> 01:05:56.314 you know, the monkey's not working very well. 01:05:56.374 --> 01:06:00.834 I knew quite well that he was confronting something that. 01:06:01.814 --> 01:06:07.434 An idea. Yes. And once I asked him, listen, Vernon, why you never go to, 01:06:07.514 --> 01:06:10.474 didn't go to secondary somatosensory cortex? 01:06:10.694 --> 01:06:15.614 And reflexively told me, I didn't know how to go. and then and I said listen, 01:06:16.194 --> 01:06:22.614 why don't we go at least to the motor primary motor cortic now that's bullshit 01:06:22.614 --> 01:06:32.894 the motor system is the worst and I moved to Mexico in a week and he did some experiments in M1 and, 01:06:33.734 --> 01:06:42.154 he sent me a phone call to tell me listen I wasted time in the primary somatosensory, 01:06:42.814 --> 01:06:46.234 Now I see neurons associated to the session. 01:06:47.594 --> 01:06:52.414 Okay. So I went back to him to make some collision. We have to make some control, 01:06:52.494 --> 01:06:54.874 at least to do some recordings of the muscles. 01:06:55.274 --> 01:07:00.854 So I did some records of the muscles. And those were not decision signals. 01:07:01.014 --> 01:07:04.234 They were associated to motor responses. 01:07:04.894 --> 01:07:10.314 They were missing some controls. And in fact, we published those papers, 01:07:10.374 --> 01:07:16.614 that paper in 1992, that was the last paper in the cerebral cortex. 01:07:17.774 --> 01:07:21.154 But that paper can be criticized for many times. 01:07:22.594 --> 01:07:27.134 So, Ranulfo, I'm going to bring you to the... I can go. We want to talk to you 01:07:27.134 --> 01:07:28.914 about... Yes, I would like to. ...intention. Please.