PAWAN: I think all of us as parents, do wonder about what's going on inside that little head. What are the changes that are happening? How will this little creature eventually begin to make sense of the of the world?

MARY ELLEN: So today we're here with Pawan Sinha. He's a professor in the brain and cognitive sciences at MIT, and he's an expert in vision. And thank you for being here today.

PAWAN: Thank you, Mary Ellen.

MARY ELLEN: So let's start with a question related to the history of your field. And we'll, just start with the 1981 Nobel Prize given out in medicine in physiology for vision. And with that prize, they concluded that there is a critical period for vision in childhood. And could you explain at that point how they got to that conclusion and the rough ideas?

PAWAN: Yeah. The work you mention is really remarkable. Body of of research. This is work by David Hubel and Torsten Wiesel and, work from their post-doctoral advisor, Steven Kuffler. So what Koffler and Hubel and Wiesel, were interested in, in finding out, is the mechanism by which we do vision, the response properties of cells in the retina and the visual cortex. And what they found were a very interesting set of results, showing that we are not just detecting spots of light or regions of light, but we are doing some interesting computations on those regions of light, like detecting edges and other simple features.

But, the the specific results that you mentioned of the consequences of visual deprivation on, the response properties of the brain, that was work that Hubel and Wiesel conducted with kittens. And what they found was that if you have a normal, excited kitten who is constrained to view the world only through one eye for a few months. Right after birth. So you close one eyelid and now this kitten is going around experiencing the world with only one eye open. What you will and we found, quite surprisingly, is that even when you now open the temporarily shut eye and the eye looks perfectly fine. So now the kitten has two normal looking eyes, yet the kitten behaves as if it's functionally blind in the eye that was temporarily closed.

And no matter how long this kitten now experiences the world with both eyes open, it continues to behave as if its vision from the closed eye from the temporarily closed eye is essentially nonexistent. When Hubel and we looked at the correlates in the brain of this deprivation, of this monocular deprivation, they found that the brain, visual processing machinery, the cells that do visual processing, had been co-opted almost entirely by the open eye, and the closed eye had essentially lost it foothold, to the neural resources. And this seemingly could not be undone with extensive post, deprivation experiences.

And this led to the idea that maybe those early few months were a critical period, during which time the brain requires normal visual input from both eyes in order to develop normal processing mechanisms.

MARY ELLEN: And then in some ways, this, study and this work, really motivated you in your own work as you, became an expert in this field of vision. Before we get into the details of your own work, can we maybe give people a broad idea of how does vision work? Well, just if, you know, and especially focusing on as, babies born and thinking about that time period as well.

PAWAN: Yeah. So the question of how vision works, this is one of the largely still largely unsolved problems of science. It's a huge, big problem that's exciting for scientists and exciting for scientists to have a big problem to to devote once one's life to. There's a very interesting quote from a person considered the father of American psychology, William James. Who in describing a newborn's, sensory experience, said that the newborn is essentially experiencing a blooming, buzzing confusion. The problem that my lab and many other labs are animated by is in trying to understand how this blooming, buzzing confusion, this complex chaos of lights and sounds and tactile sensations, how that gets resolved into a meaningful world.

Yeah. And that essentially it connects to the question you posed. How do we get to do vision? So we are looking at that from the perspective of development. How do we learn to do vision not just how we do vision as adults have? So we want to to understand what are the very initial steps by which the brain begins to make sense of the environment that it's placed in. As I said, most of the big insights to this question are still to be to be discovered.

MARY ELLEN: And over the course of your career you've had even a funny moment where you had a son and your son played a role in your own studies. You just you mentioned that sidetrack of it.

PAWAN: It's a story very dear to my heart. So I, we had a son, about 19 years ago. He's now a sophomore, at MIT. But when he was born. Given my interest in visual development, I saw him. His name is Darius. So I saw Darius, baby Darius. A very interesting avenue by which I could explore questions of of development. And to my surprise, somewhat. Bam! My wife was completely opposed to the idea of the conducting any scientific studies with Darius. But I still felt that this is quite literally a once in a lifetime opportunity that our only child. So I wanted to derive some scientific, insights through through Darius. So what I did was to attach a small camera to his forehead, and I recorded Darius, his visual experience as a baby, as a baby.

So the world through a baby's eyes? Somewhat.

MARY ELLEN: So if you're a lab studying that, that's the risk of having a father who is a scientist studying vision. Especially in that period of being a baby.

PAWAN: It's very tempting. And I think all of us, as parents, do wonder about what's going on inside that little head. What are the changes that are happening? How will this little creature eventually begin to make sense of the of the world? I think that in the hands of a scientist translates into some specific studies.

MARY ELLEN: Through or through those recordings, you got to see the world through your son's eyes. And, not too many parents have that opportunity.

PAWAN: That's right. And I think it's a really interesting gift offered to a child who, say when he or she is a teenager.

MARY ELLEN: Yeah.

PAWAN: For them to see what were those initial weeks and months like?

MARY ELLEN: Right.

PAWAN: So I think both from the perspective of science and from the perspective of a given person.

MARY ELLEN: Yeah, it's a nice to have that. Yeah. Yeah. And then in your work you think about vision and studying the blindness as well. And so we want to understand, what causes blindness or how blindness works. And so could you give just a broad overview of blindness and the types of blindness?

PAWAN: Absolutely. Absolutely. And just to connect blindness with, with our work. So the backstory to how we got got interested in blindness is a story of serendipity. On a trip to India when I was visiting my my father.

MARY ELLEN: That's where you grew up.

PAWAN: That's where I grew up. And my father lived in, in New Delhi. So one evening, one winter evening, as I was going from my father's house to a friend's house in a cab, the cab stopped at the traffic light, and I noticed by the side of the road two little children and the mother, dressed barely in rags. And it was such a cold day. And, like anybody, I felt badly. And I called over the mother to give her some some money. She came over and holding on to her sari. Both children, who to my eyes were about 6 or 7 years old. They came over as well. And as I was giving, the mother, the money, I looked down at the children, and I noticed that both of them were blind.

And they were blind because of cataracts. And we'll talk about cataract in a in a moment. But in that moment, seeing two little children who already are having to deal with the deprivations of poverty, to also have to deal with the challenge of blindness that just seemed to, viscerally wrong. So I that image of, blind children stayed with me and I did some researching into is this just a rare instance that I have observed or is this the tip of the proverbial iceberg?

MARY ELLEN: And before that, you didn't study work with blindness?

PAWAN: No, no. Our lab was more a computational lab. And the experimental work we were doing was with normally sighted individuals.

MARY ELLEN: This was clearly a pivotal moment.

PAWAN: And it was, it was. And that's why I say serendipity played such a such an important role. The more I looked at the blogs or, or the registries of blindness, data from, the Government of India and from the World Health Organization, the more I realized just how big of a of an issue this was in the developing world. Certainly for India, but for many other countries in the global South.

MAARY ELLEN: How many children are impacted by blindness in India versus, interestingly, United States? Yeah.

PAWAN: Interestingly enough, there aren't any very good population based studies of the extent of blindness. But tragically, childhood blindness is so strongly correlated with childhood mortality that people have tried to estimate, the extent of blindness from the extent of mortality. Statistics and those estimates put the number of blind children somewhere in the range of a million or so. Well, that's the the sad part of the story. But the more optimistic part of the story is that a sizable proportion of these children actually have treatable conditions. Yeah. So when I mentioned cataract, I have or I used to think about cataracts

as an old age related condition, MARY ELLEN: most people probably have that experience of knowing a grandparent.

PAWAN: That's right. With cataracts, once you are, say, past 75 or 80, then you begin to develop some cloudiness of your lens and you can go in for a fairly straightforward surgery and get get that lens replaced. But it turns out that children can be born with cataracts. Certain kinds of maternal infections during pregnancy can lead to the development of cataracts while the the fetus is in the, in the womb.

MARY ELLEN: And you said you could see this when the children approach the taxi. So what does that look like when you see cataracts?

PAWAN: Yeah. So cataracts is the term means an opacity of the lens. So your lens and mine, they are beautifully transparent. We can't actually see our lenses for normally sighted individuals. Yeah. So the pupil looks black. And essentially we are seeing the inside of the eye through the pupil. It's just a hole. Even though that pupil is sitting in front of a lens. A child with the cataract has an opaque lens, and this opaque lens appears white. So for a child with the cataract, you would see instead of a black pupil, you would see a white pupil. So it even to an untrained eye, yeah, it's quite easy to detect. So that's why you knew in that moment. In that moment. Yes.

So it's a it's a condition that's easy to detect and is fairly easy to treat as well because the surgery is, in principle, the same as the surgery that we as adults would undergo a small incision in the cornea, removal of the opaque lens and insertion of a clear plastic lens.

MARY ELLEN: And really, this can be done in hours in the same day that are in and out of the medical. Yes.

PAWAN: Pediatric surgeries are a little more involved than adult surgeries. Adult surgeries can be done with local anesthesia. You don't need to go fully under. Yeah. With children, because of the concerns about movement during surgery, the child has to be completely, under general anesthesia. But even given that it's a fairly straightforward surgery, as surgeries go, you know, for that 30 minutes or an hour of surgery, you stand to completely transform a blind child's life. So seeing, that there were many children who had this condition. And also realizing that this is a fairly straightforward condition to to treat.

I felt that we ought to be doing something about it. But in thinking about doing something about it from the humanitarian perspective, I also realized that in bringing sight to children who have been born blind, we would have a very interesting way forward for the scientific question that we had been trying to grapple with. Yeah. Trying to understand what are the very initial stages of visual development. So a child who transitions from blindness to sight say at the age of ten years. Right after the bandages are opened, after the surgery from those very first minutes you have a ringside seat on to the process of visual development.

MARY ELLEN: And this ties back to the initial Nobel Prize work and thinking, you know someone may have told you at that time it's not worth studying that question because the child that has a surgery, even if you did remove the cataract, it was too late.

PAWAN: That's right. Yeah. Having grown up with that literature, I myself was not entirely convinced that the surgeries, would be worth even the minimal risk that, cataract surgery presents. So we weren't certain that the outcomes of these surgeries would provide adequate benefits to make them worth it. But we decided that it's worth taking a chance because most of the data until that point had come from animals from non-human subjects. And we would ideally want to have an understanding of how does the human brain respond to deprivation. Furthermore, because most of the data until that point had come from non-human subjects.

The scope of the studies that can be done and the kinds of aspects of vision that can be probed, see, with the kitten or even with the monkey, that's fairly limited. Yeah. And the kinds of aspects of vision that we would want to study, they would largely not understood. How would the human brain, respond to such treatment?

MARY ELLEN: You can't ask a cat. What do you see? That's right.

PAWAN: So for those reasons, we felt that if we were very careful about completely mitigating any surgical risks, it would be worth exploring what would be the outcomes of these treatments.

MARY ELLEN: So walk us through how you went from that moment in the cab. But then you decided, okay, there's a humanitarian need, but there's also the scientific questions that haven't been answered. How did you put it all together going forward in your career?

PAWAN: Yeah. So that that process, I think MIT deserves a lot of credit for facilitating that process. And NIH, the National Institutes of Health, the federal biomedical research funding body that deserves a lot of credit. And the reason I say that is in order for the germ of an idea such as this one. To get off the ground, you need an initial, bit of encouragement and an initial bit of resources to see whether there is any merit to this idea. And MIT provided that kind of initial encouragement and initial seed grant. For me to be able to explore this is what I'm thinking about. Is that even feasible? In principle. Right.

So with the seed grant from the MIT International Science and Technology Initiative, Misty, I was able to to convince myself by traveling around the country that this is indeed, a big problem. And we could potentially put together, a mechanism for identifying such children in, in the villages and then bringing them to New Delhi, to a surgical center to provide them care and then studying the post-operative, outcomes with that initial, proof of concept or the initial set of data that this might be feasible. I then applied to NIH, specifically to the National Institute, which is, a subcomponent of NIH. Yeah.

With some trepidation because essentially what I was asking any I for was support for a project that would be conducted largely in a different country. Right. And it would benefit children in that foreign country. But what I, what I tried to convince the reviewers was that the, the scientific insights that would flow out of this work would not be beholden to any political boundaries. Right. It would be science that belongs to all of humanity. And NIH, to the eternal credit. They responded very favorably, to this proposal they gave us, what's referred to as an R 21 grant, which is an exploratory grant. It's a two year grant that allows you to, to demonstrate, feasibility and get some initial results.

Yeah.

MARY ELLEN: Because at that time, you didn't know if what you were proposing to study really was worth it. That's right. That's right.

PAWAN: Yes. Would the outcomes be worth, the the surgical, logistics and, risks? So with that initial grant support, we were able to demonstrate that there's some merit in this work. And then NIH came in and supported us more extensively through a project grant called an R1 grant.

MARY ELLEN: Yeah. When you had signs of things turning out to work in the favor of, it's worth doing the cataract surgery. What were those early results like? How you would you test if for a child, they're able to gain sight back, even though they were out of that critical period that was described earlier? Yeah.

PAWAN: So that's a great question. And, so there are some observations that are just so self-evident that even without doing scientific studies, you see that the child is benefiting from from this. So anecdotes, like, you see a child come into the hospital, and they require other people's help even to cross the road from one side to the, to the other. Right. But then in a matter of a couple of weeks after the surgery, they are running around the hospital corridors on their own. And you see, a change in their demeanor. They look happy. They are able to navigate on their own. They are able to begin to recognize people.

Yeah. All of those anecdotal observations are already indicating

that the child has benefited, MARY ELLEN: and they don't have to be able to describe to you what they're able to see or do.

PAWAN: You can just observe their behavior. That's very powerful. But in order to convince ourselves that we're not just, wearing ruby glasses. Yeah. Seeing, hallucinating, benefits just because we want them, to have those benefits. We also needed to do rigorous scientific studies. So over the past several years, we've conducted studies that have examined a whole range of visual functions, low level visual functions, like, just the ability to resolve patterns in the environment. So the kinds of eye tests that all of us, I'm sure have done, like reading a letter chart, that's a very simple kind of visual function. But then also more complex ones, like, looking at an image and saying, how many objects do you see in there?

Yeah. What are the objects? Can you tell? Are these faces are these non faces? Can you catch a ball that's thrown to you? How accurate are those movements? Yeah. So across many of these dimensions, what we observe is that the children exhibit remarkable progress from the pre-operative to the post-operative stage.

MARY ELLEN: And in this case, you're you have human subjects now. So you're able to talk to them, you're able to do these experiments, record them and really go, at a research level to determine results. I know with, the identifying two objects, you realize there is a critical sort of factor that played into seeing two objects for these, post-surgery, children versus when it was just asked, looking at a screen.

PAWAN: Yeah. So that's, a very interesting, finding, to my mind. And it points to an important cue that we, as visual observers pick up from the from the environment. So the finding that you're referring to is the following. Let's say I, I show you two isolated objects, no overlap. Let's say one of them is a circle and the other is a square. I show them to you, and I ask you, how many objects do you see? Yeah. You would be able to say two objects. A square in a circle. Now imagine that I overlap these two objects. So there's a partial overlap. The square is partly, overlapping the circle. And these are line drawings. Yeah.

You would still be able to say, okay, still two objects, a circle and a square, but with some overlap. What we noticed with the, with the, Prakash children, we call this project Project Prakash Prakash. It's Sanskrit for light. What we noticed with the Prakash children is that while the objects were isolated, they could enumerate. Okay, we see two objects, a square in the circle. But if these two objects were overlapping, then it was really puzzling to see that that question of how many objects are there? You know, they would now begin to see three objects. So the little segment of the circle, little segment of the square and the overlap region all became distinct objects.

And they were unable to recognize what these objects were. Even if you give these the square in the circle different colors. So long as the overlapping the children are still confused about what they are. Yeah. But the crucial change that comes about in the perception happens with the introduction of dynamics. The time varying imagery. If you now put these objects in motion. Even though they don't lose their overlap. So they're never isolated. They are moving around while overlapping that movement seems to allow the the visual systems of the Prakash children to begin to see that these are two distinct objects.

MARY ELLEN: And that really probably plays back to thinking about development of a baby. The world is not static and not thinking about things and static. So, you know, by chance, in this lab study, you thought to add movement or, you know, your students you were working with student movement as, a factor in this.

PAWAN: So that, I think, is a crucial observation that the world that we inhabit is a dynamic one. And the brain, not just the human brain, but all animal brains seem to have figured out that the exploitation of these dynamics is a very efficient way for understanding which things go together and which things ought to be segregated from each other. Every animal visual system that has been studied has been found to have a sensitivity to dynamics. They might not have sensitivity to color information. They might not have sensitivity to stereo depth information. But motion sensitivity seems to be present in every animal model animal model including humans including humans.

And also to connect that to the to the point you mentioned. With babies. Babies. The studies that have been done with normally sighted infants indicate that sensitivity to motion is one of the very early onset, abilities. So it's as if the brain is making use of how things change over time. Yeah. In order to begin to make sense of that blooming, buzzing confusion we talked about. Yeah.

MARY ELLEN: So you refer to Project Prakash as, as you were answering the prior questions, and this is a nonprofit that you've established over the years, accomplishing this work. So do you want to, maybe give a summary of your accomplishments as part of, starting this nonprofit? What has the nonprofit been able to achieve with working with children in India up to this point? And also maybe give a sense of how many years you've been running Project Prakash to date?

PAWAN: Yeah. So project Prakash is, an affiliate that's very, very close to my heart, into the heart of all of us in in the lab, who have been fortunate to be associated with it. We started Project Prakash, I think about 21 years ago now. And over the course of this time, we have treated, close to, I think, 530, blind children. We have provided non-surgical care to over 3000 children. Well, and we've provided ophthalmic screening to, I think, over 63,000, children. So it's been a a very gratifying effort which has allowed us to connect with a real world problem while also, feeling that we are advancing the fundamentals of of science.

MARY ELLEN: Yeah. As scientists, you don't always get to see the impact of results because you're working in a lab setting. And, but you're really connecting those working in your lab to the outcome and results of and working with the, the children that this, you know, work in nonprofit work has been helping over the years.

PAWAN: Yeah. It's, and that's why I said, we're very fortunate to have this kind of, of opportunity, to not only, extend the frontiers of, of, neuroscience, but also to see in the moment the impact of the little intervention that we are we are making. We hope, like all scientists do, that the knowledge that we are discovering will have its own impact in the years to come. But to feel that even in the moment, we are bringing some relief and some betterment to human lives. That's a very, very nice feeling.

MARY ELLEN: Yeah. A very rewarding, part to see the whole picture with your work. I know that you've also had this work play into your education, work at MIT, that you teach classes, and you work with MIT undergrad students, as well as your graduate students and postdocs. And I recently you made a trip in January, this past January with MIT students. Could you maybe explain what that experience was like for the students and what you aim to do, but then really, what results you saw out of having students go visit India and visit with these Prakash children as well?

PAWAN: Yeah, that was also a very, very nice experience for for all of us, for all of the lab members, to see this group of undergraduates. The the trip that you mentioned that was sponsored by, Misti, the entity I mentioned earlier, the MIT International Science and Technology Initiative. Misti runs a program called the Global Classroom Program. With the intention of providing, a global perspective to research and technology to our to our students. So as part of this program, 12 students, out of, a large collection who had applied 12 students came with us to India for two and a half weeks. They wanted to see, firsthand the operations of Project Prakash.

All aspects of Prakash. Yeah, right. From outreach, identifying children to treatment to post-operative, studies and the the experience that they had, I think was quite impactful. And the reason I believe that it was quite impactful is on the last day. So when they stay in India was coming to an end and we asked them to reflect on on the experience of their some of the students actually had tears in their, in their eyes. And they they emphasized the fact that with Project Prakash, they were able to see how basic research does not need to be divorced from tackling, pressing problems in the moment. We don't, as scientists, always have to rely upon our work, eventually leading to some benefits to human lives.

But you can actually identify opportunities where you can be a basic scientist and also a do gooder at the at the same time. And that I think was, was very powerful.

MARY ELLEN: Yeah. These are undergraduate, so it may, you know, impact their future choices of the career path. They can go on now.

PAWAN: Indeed. And, some of the students who were upperclassmen, to juniors and seniors, they, mentioned that they would have wanted to have this experience very early in their in their undergraduate tenure. So that it could shape the kinds of coursework that they do. And I think that's an important lesson for us. Right. To expose our students to these kinds of opportunities. From early on in the educational journeys so they can begin to, to see how an MIT education can be further and can further, real problems in the, in the world.

MARY ELLEN: Yeah. And typically, they may not have that opportunity until their final year. And you're, you know, you have some science that's really worth trying to do this as early as possible for our students and bring that and, you know, showing the key critical aspects of learning outside of the classroom.

PAWAN: Yeah, I think, again, thinking of this from a very personal perspective. What kinds of experience would I want Darius. To have at MIT. I think this kind of an experience of knowing what are the big problems in the world. And how can an MIT education, put you in a position to begin to think about solutions to those problems. I think that's a very valuable thing that we can, we can do.

MARY ELLEN: And some of your work, you've also worked on autism and autism. Maybe just give a brief, explanation and description of what autism is, and then we can, explain how the vision works. Ties to autism? Absolutely.

PAWAN: Autism is a neuropsychiatric condition, that the CDC estimates affects about 1 in 37 children in, in the US. And the prevalence numbers across the world are also commensurate with this. With this statistic, it's often described as a social challenge. An individual on the autism spectrum. May find it difficult to look at people in the, in the eyes or to, have an extended conversation, with them or to understand what they have in mind. Something referred to as theory of mind. What's going on inside your your conversation partners mind. And how you should regulate your own conversation. Based on what you infer the state of mind to be.

These kinds of things prove to be challenging for, individuals on the autism spectrum. But besides the social correlates of autism, there are also other aspects to the to the condition. Things like sensory hypersensitivity. Many individuals on, the autism spectrum. Find it hard to tolerate repeating sequences, whether in sound or, in vision. In fact, some children, some autistic children find it hard to be in a room that has fluorescent lights. And it's a mystery why that is. When people have studied whether autism leads to a change in the basic sensory sensitivities of, say, the eye or the ear, they find that there aren't any, very strong data supporting that.

And yet it's undeniable that there they are reported sensory hypersensitivity. Similarly, on this on the spectrum, a person might find it hard to do things like play ball in a playground. So the simple act of catching a ball turns out to be puzzlingly hard. The simple act of crossing a road, and avoiding traffic that turns out to be, pretty hard. Autistic individuals find it hard to drive. So it's a it's a complex phenotype. Right. Many different behaviors seem to be impacted. What led us to think about, about autism is the fact that some of the, the results that we were getting from Project Prakash, in the visual domain seem to be quite reminiscent of what I had read about visual changes associated with with autism.

Specifically, there was this one result of over fragmentation. So, over fragmentation refers to if I were to show you an image and I want to ask you what are the, the objects in this image. And let's say it's an image of a natural scene. You would have no difficulty at all outlining the different objects. The Prakash children and to some extent autistic children who are believed to be normally sighted, they tend to over fragment the world through regions of different colors, different brightnesses. They get their own status as objects.

MARY ELLEN: More complex than a normal sighted child.

PAWAN: Right. So the images being broken up into too many pieces. Right. It's kind of like disassembling, a scene into many little jigsaw pieces and then not seeing how these pieces cohere into one, object percept. So that superficial similarity. In the visual behavior of the newly sighted children and what I'd read about autistic children, that led us to wonder whether there might be some, more substantial link to be made between these two conditions. What we were seeing with the Prakash children was that over time, over a matter of a few weeks or a few months, the Prakash children would eventually overcome this tendency to break up an image into too many pieces.

And the primary cue and this is something that we alluded to earlier. The primary cue that seemed to be allowing them to learn how to overcome over fragmentation was motion. Yeah. The appreciation of the temporal information in sequences. So the tentative hypothesis we've toyed with is that if there were to be some compromise. In processing dynamic information could that then lead to challenges in, in parsing an image into distinct spots. But could autism be associated with some kind of a difficulty in processing dynamic information. With that very tentative hypothesis, when we started working with autistic, children, looking at what aspects of dynamic information processing might be affected, if any.

And what we found, is that it's not the mere detection. Of dynamics. It's not seeing is something moving or not. Yeah. But rather the prediction of what's going to happen next. So based on the information that you have seen so far. Predict what's going to happen in the next second or next few seconds.

MARY ELLEN: And that ties to what you see with autistic children. You were saying is the challenge to receive a ball that's coming.

PAWAN: That's right. Yeah. The simple act of catching a ball actually draws upon prediction in a very big way. Based on what you've seen of the trajectory of the ball. You need to bring your hand in the right position at the right time in order to be prepared to catch the ball. You can't react to, to the ball if you are waiting to bring your hands together. When the ball is, almost at you, then you're too late. Similarly, to be able to cross a busy road, you need to be able to predict what's going to happen. Say 2 or 3 seconds from the speed of the car is coming. And how many are coming? Yeah. So, that basic idea that maybe, there might be a challenge to the dynamic prediction system of the brain that then led us to formulate a hypothesis, that we published some years ago, that autism might be associated with temporal prediction, challenges.

And that has led us and other labs to test this idea more rigorously with various studies. And we seem to find some significant, support for the idea

MARY ELLEN: and this as well as ongoing work. It's an interesting understanding more. That's right. And I think, we can sort of loop this whole conversation back to the starting point and another lesson of your career. That comes out from science. I think as scientists, we understand that one result is not the final answer, that it's worth pursuing. Answering more questions. And usually one result just leads us to more questions. And you started this entire work with vision. Based on something where people, you know, people would have told you at the time, it's not going to work. So can you give your perspective of how science changes over time?

And that is the normal pursuit of knowledge?

PAWAN: Absolutely. I think as scientists, we are obligated to challenge the status quo. And especially to be in a research focused university like MIT, I think the university and, all of the, the resources that support this university, require us not to be satisfied, not to be just make incremental changes to a state of knowledge, but to ask, questions that can change our thinking about, received wisdom. In that spirit, I think Project Prakash has been pursuing ideas that that one might have thought are completely settled. But, we, as researchers are all within the pursuit of of new knowledge. And in this case, that pursuit has yielded some changes in how we, how we think about, say, the notion of brain plasticity and how much plasticity there will be later on.

But I think, stepping back, that general idea motivates me. Of trying to go beyond what I might have learned in, in textbooks and trying to see whether there is either a simplification of the ideas that have been proposed or maybe a change. And, and I feel that, for me personally and for, for the students who I have the privilege of working with, that curiosity to always try to determine, whether there is, a better way to conceptualize the complexity of the world. I think that's, a very interesting pursuit and and keeps us excited and driving motivation. That's right. Yeah.

MARY ELLEN: So if you want to learn more from Pawan about his work, as well as what he's teaching, you can go to learn dot mit dot edu to find more there. And I want to congratulate you on the impact of your work. And, the success of the Prakash project to date and continued success in the future. And thank you so much for being here today and joining us. And we will, look forward to talking to you more because there's still so much more to learn from you.

PAWAN: Thank you very much, Marielle. And it's been such a pleasure to talk about a topic that's so dear to my heart.

Thank you. MARY ELLEN: Thank you for sharing. Thank you.