Neuro: 1:00 - 2:00 Scribe: Hillary Carney

Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 1 of 8

I. Introduction [S1]: a. My lab focus is on autism. So I’m sure all of you will have heard of Autism maybe through the media or through some papers. What we are going to talk about today is how behavior in autism can be explained by cognitive function, cognitive abnormalities and structural abnormalities of the brain.

II. Rain Man [S2] a. So most of you have probably seen the movie Rain Man. If you have seen it you’ve got a pretty good picture of a high functioning person with autism. Again I want to stress that point. The character played by Dustin Hoffman is a really high functioning autistic. So there are several good scenes in the movie, but one of the scenes captures what autism is. So there’s a scene where Dustin Hoffman is stuck in the elevator with Tom Cruse’s girlfriend and this girl likes him really well, and engages in a passionate kiss with him for 20 seconds or so. And then she asks him how do you feel? And he says “wet.” So he doesn’t understand what consequences this is going to have on this person and she is completely baffled that he responded this way. He just gave the sensory experience of it without thinking about what this person is going to think about it. The movie is based on this person named Kim Peek. He’s about 59 years old. (He didn’t mention this but Kim Peek actually died a few months ago). What he does basically is he travels to different parts of the country and different universities. He has an amazing memory. He knows all the zip codes in the United States. He can read several pages in a minute and has memorized about 7,000 books. So he goes to a gathering like this and someone will ask him what happened on Oct. 14, 1943 and he will narrate all the different things that happened on that date. So because of this amazing memory people call him kimputer. And the point is that he has this memory but at the same time if someone asks him about what his plans are for marriage or maybe social life and so on he may not have an answer for that.

III. Reported Cases Graph [S3] a. So here is a graph that shows the increasing incidence of autism. You can see up to 2003 here. From the year 1992 to 2003 there is a drastic increase in the rate of autism. You probably will have heard this in the media the statistics now are about 1/100 people are diagnosed with autism. Why is this? Is there a rise in incidence? As a researcher at this point it could be because of the refining of diagnostic criteria or categories, awareness of the disorder and so on. If you take a state like Alabama maybe 30 or 40 years ago nobody had a clue about autism. At this point, if you go to any part of the state at least they have heard about autism. So the awareness is tremendous. That leads people to take their kids if they suspect something to the clinic and that can lead to diagnosis.

IV. Autism: Triad of Impairments [S4] a. So how do we define autism? So this is the definition by the American psychiatric association. It classifies autism in terms of three impairments called the triad of impairments. The first one is problems in social interaction. So the difficulty is basically not understanding what the other person is thinking. Number two, is language and communication. If you meet with an Asbergers or high functioning person you will hardly notice any grammatical problems. But the problem is that any metaphorical or any figurative language they have difficulty understanding that. If I say “Jane hates eggplant. Her mother made eggplant for dinner. What a wonderful dinner it is.” So everyone knows that it’s an ironic statement but they have difficulty in understanding that that’s an ironic statement. b. The third category is repetitive behavior and restricted interests. In terms of repetitive behavior you will have seen severe cases of autism where some people do some hand flapping, writing in the air, and so on. So those can be considered as repetitive behavior. In terms of restrictive interests the focus of the interest is so specific that an aspersers syndrome patient might come and talk to you about BMW cars. He can talk about it for half an hour or one hour. I had an interaction with a 16-year-old boy who lived in London. If by chance London came up in the conversation he would talk about buses in London for the next hour without taking into consideration whether you are interested or not. So the interest is very focused and specific to a certain topic. So the symptoms are defined in terms of these three aspects: impairments in social interaction, impairments in language and communication, and repetitive behavior and restricted interests.

V. Overview [S5] a. In today’s lecture we are going to focus on the social interaction domain because I don’t think we will be able to cover all of it. So this is an overview. We’re going to look at social interaction in terms of how eyes are helping us play the game of social interaction: with is gaze and face processing. And then social interaction in terms of understanding other people’s mind: what other people are thinking, or simply we can call it mind reading. Finally Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 2 of 8 we will tie this thing together from some aspects of my own research and theories of connection abnormalities in people with autism and how their brain functions in a certain way which probably causes them to behave in that fashion.

VI. Eyes, Gaze and Face [S6] a. So we’ll start with the social interaction aspect. So here is where all social interaction starts. So as a baby you can see clearly they look at faces of people. They are interested in looking at the faces of people. They look at eyes of people. People with autism generally are not interested in eye contact, and their eye contact goes to different places. One of the gold standards for diagnosing people with autism is a diagnostic measure called diagnostic autism observation. It’s a 45 minute one-on-one interaction with a child or adult with a series of structured and semi-structured toys and other situations. So one of the things to record during that process is basically how many times and how long the child is making eye contact. So you can see a person like Kim Peek or this other very accomplished woman at Colorado State, named Temple Grandon and she’s published a lot of books, but when she’s engaging in conversation you can see her eyes wide open and she’s looking through you. So they don’t know how to balance. Nobody teaches us that you have to look at somebody in the eyes for a few seconds and withdraw and go back. We all learn these things automatically. They have difficulty doing that. What’s the big deal about it? That is probably the foundation of all social interaction. So if you’re having problems there it’s probably going to result in a cascade of problems later.

VII. Shift Away/Shift Toward [S7] a. So here is a study and this is a normal population. Participants were shown pictures like these and they were asked to rate how likable the target was by a scale of 1-5. You can see here that there are two different gazes: one shifted toward you and one shifted away. These are the results. People tend to spend more time focusing on the images with the gazes which are looking at them. So you want people to look at you. So you’re going to look at that photograph or that figure more than the shifting away picture.

VIII. Picture of Face [S8] a. So here’s an interesting experiment which is coming from that sort of insight. So what they did was, and this is a functioning neuroimaging experiment, they presented these avatar characters. You can see it’s a very simple experiment. You can see a checker board on the left side of the avatar. This is a simple animation that is happening here. So you can see a simple few seconds of video. You can see the eyes moving toward the checker board.

IX. Picture of Face 2 [S9] a. This is a different one. In this one the eyes are moving away from the target. In one case you are expecting the avatar to look at the checker board and she looks at it. In the other one you’re expecting the avatar to look at it, but she doesn’t look at it.

X. All Gaze vs. Incongruent [S10] a. This is what the brain activation looks like. So they did this in both controls as well as people with autism. So on top what you’re seeing is all gazes together for congruent and incongruent. Put together what kind of brain activation is coming out. What you can see here is all this activation seen here is in a region here called the superior temporal sulcus. Which is involved in detecting gaze as well as any biological characteristics like perception of biological motion. b. What’s more interesting is the second one. If you compare the congruent one (where the avatar looks in the direction expected) vs. the incongruent one (avatar looks in the unexpected direction) you can see the control group showing activation in the superior temporal sulcus but there is nothing in the autism group. So a simple task and again you can see one very focused region in the brain which is the posterior-superior temporal sulcus. The difference is that whenever you are perceiving the incongruent version you are showing more activation in the superior temporal sulcus than the participants with autism.

XI. Time course of activation in right STS [S11] a. Why is this happening? Here is another look at it. So this is the time course of that activation pattern. What this means basically is that you are watching for 10 seconds or so. So they pulled out brain activation and changes during that 10 seconds and that’s shown here. You can see in the control in the congruent and incongruent one a clear difference in the signal. Intensity is much more for the incongruent than for the congruent in the superior temporal sulcus. If you look at the autism group you cannot differentiate that. So there is no significant difference that’s why you don’t see the activation difference. So the point is that superior temporal sulcus activation in Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 3 of 8 autism spectrum disorders (ASD) does not seem to distinguish direct and averted gaze. Therefore, the deficit in ASD may reflect the difficulty they have in “reading intentions conveyed by shifts in eye gaze. b. So why we are activating this region is basically that you are expecting the avatar to look in a certain direction. It did not look in that direction so you are thinking why didn’t it look in that direction? You are reading into the intention of that character. That is exactly what happens if you walk down the hallway and one of your acquaintances is coming and you smile to this person and she just walks past. Immediately you start thinking about why did she do that. Does she hate me? Or did she not see me? So this is what we do as human beings. We read the mind of other people. Their actions, their gaze, their grimaces and so on. They are not detecting this in this simple eye movement experiment.

XII. What’s in a Face? [S12] a. So that leads to our next question. So we started with eye contact and then moved to gaze which is another level and that takes us to the next level: faces. Which is again where most of the time we spend in social interaction is looking at other people’s faces. What kind of expressions we can read from them. b. So this is another example of what kind of information we get from the face. If you’re looking at it you can get a sense of sex of this person (okay female), age (child), affect (she’s happy), race (white), gaze (she’s looking at you), direct emotion (are you happy about this person? Yeah she’s cute), biographical information (I have no idea who this person is), name (I don’t know). So you get a series of information polled immediately when you are looking at the face. That becomes all the more relevant when you see a recognizable face like this one where you get other information. Again are you happy about seeing Brad Pitt? Yes I am. The biographical information you get like he’s an actor and his name and so on. That is a lot of information that you get and you use that information for further interaction.

XIII. Altered face processing in Autism [S13] a. So here is an experiment. What they did was present pictures of faces and asked to focus on the face and identify the emotion portrayed in each face. What they did was when the participants were looking at these faces they tracked the eye movements of the participants. You can see here these are participants with autism. b. So let’s look at the control participants first. You can see this in the dotted lines that indicate where the eyes of the control participants are moving when they are watching this picture. In three of these cases you can see in the right hand column that it centers around the eye region and then coming down to the mouth in a kind of triangular fashion. c. But if you look at the autism participants there is no fixed route there. You can see here it’s starting from the mouth then goes to the clothes that she’s wearing and here it starts from the eyebrows and goes to the hair, etc. the point is that the controls are focusing on the core features of the face: eyes and mouth region. The people with autism are looking at the periphery. I can’t remember people based on their eyebrows. So you want to look at their eyes and mouth, some of the most salient features of the face and then figure out who that person is or memorize that person’s face. They are looking at a different place on the face.

XIV. Altered face processing cont. [S14] a. This is another study that comes from Yale. What they did was they showed the movie Who’s Afraid of Virginia Wolfe. They showed some clips of the movie. So the same thing—what they tracked was the eye movements of the participants. So what you can see here is the plus sign is the control or normal viewer. The eyes move from eyes of this character to the eyes of the other person. On the other hand you can see the opposite participants are going from the mouth to some other place.

XV. Picture: Autism vs. Normal [S15] a. Here is another slide that portrays another scene from that. You can see how the control, marked in yellow, go from the eyes of one person to the eyes of the other. The red are people with autism going from the jacket of this person to the mouth of the other person. Now the question is we always talk about people with autism being poor in social interaction. But you probably want to figure out what they are looking at when they are looking at other people. So if not looking at the face of the person you are not reading the emotions of that person probably. If you’re not reading the emotions of the person you don’t understand the mood or the temperament of the person. You have no sense of gauging what the person is thinking so you might as well continue talking about buses in London for half an hour.

XVI. Book quote [S16] a. So here is a novel called The Curious Incidence of the Dog in the Night-time written by a person who doesn’t have autism but it’s written from the perspective on someone who has autism. So Mark Hadden worked in a school with autistic people. So the protagonists in this novel says that this is how he recognizes someone in the Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 4 of 8 novel that he doesn’t know. “I see what they are wearing, or if they have a walking stick, or funny hair, or a certain type of glasses, or they have a particular way of moving their arms, and I do a Search through my memories to see if I have met them before.” b. So very strategic way of doing it, because it has nothing to do with the implicit or automatic way in which we all do but this is completely reliant on the peripheral features.

XVII. The Fusiform Face area [S17] a. So that leads us to the brain area which is responsible for looking at people’s faces. So fusiform gyrus is a small real estate sitting beneath the temporal lobe. If you have a lesion in the fusiform gyrus, that’s it, you’re probably not going to recognize faces. There are cases where the disorder is characterized by face blindness. So I might be giving the lecture and I take a break and you might ask me who are you? In autism the difficulty is not that severe because you don’t see an abnormality structurally in the fusiform gyrus. So the fusiform gyrus has been shown to be active in faces. If you’re recognizing houses vs. faces, faces are going to show activation in the fusiform gyrus. Matching faces will show more activation than matching locations.

XVIII. Same/ Different? [S18] a. This is a simple task. This is a paper published in 2001. There were not many papers on fusiform gyrus and autism at that time. Now you can see 50 or so papers on the topic. The task here is to judge whether these faces are the same or different or this object is the same or different. You can see the activation pattern in control participants. They have robust fusiform activation on right and left hemispheres. The participant with autism are not showing any response. In addition to the functional abnormalities which we see in terms of where they are looking and so forth, we are seeing they are not activating the fusiform region.

XIX. Activation of Fusiform gyrus [S19] a. Now I just mentioned that there are maybe 50 papers written talking about the fusiform gyrus. So this study came up in between. So they presented faces but they did something else. They put a small dot mark on the center of the forehead and told people to look at the mark. So again they did the same thing to the participants with autism and you can see every single subject with autism activated fusiform on both sides.

XX. Brain Images [S20] a. So you can ask the question is it because they don’t know where to look at? If they knew where to look at on faces they probably would activate their fusiform gyrus. Maybe they can learn the technique of face processing.

XXI. Thought questions [S21] a. So a couple of thought questions. Is it a social deficit or a perceptual deficit? So this is a huge argument in the literature. Some people say that they are not interested in looking at faces so why would they look at them? So they won’t activate fusiform gyrus. So that’s called the social motivation theory. The other point is that they are interested in looking at people’s faces but they just don’t know where to look then the deficit becomes more perceptual rather than social. b. Is the fusiform abnormality in autism structural, functional, or connectional? That’s another thing you can think about. So the face processing, when I say that it’s a perceptual problem you can see that they aren’t getting a global picture of the face. They are probably looking at local details of the face.

XXII. Clicker Question [S22] a. Answer is Featural. So that is exactly right. It’s not global. It’s not configural (not looking at everything together). But in the case of featural you’re focusing on little details.

XXIII. Social Cognition [S23] a. So we will move onto gaze, then to face processing, then all these things can be tied together into how children grow up. This is a process called “joint attention.” Kids when they are around 6-8 months they learn things like pointing to a certain object. So it’s not just simple pointing. They initiate a pointing by saying “look at that” and then they look back at the caregiver or the mother. So it’s kind of like they found something very interesting and they want someone else’s attention to it. It’s kind of a triadic interaction between the child, the object, and the mother or caregiver. They do that in the 2nd case where the caregiver or the experimenter is pointing at something and say “look at that” and they immediately look back them. These things are really important in terms of developing social interaction. It gives the child the feeling that there are other entities and I need to share information with them and that’s where to basis of social interaction start. It also predicts language development. So from joint attention we will take it to a bigger domain called social cognition. So as we grow up and interact with other people how do we become expert mind readers? Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 5 of 8

XXIV. Painting [S24] a. So here is a picture—a color page of a book called Autism: Explaining the Enigma. If I ask you what is happening in this picture you can give me an answer as to what is happening. Everyone has different theories about it, but one thing you would say is that people will focus on the gaze of the people in the picture. Basically, there is a card game going on here but there is large scale cheating going one. So we will have that idea that there is some deception or cheating going on here. I was reading on Amazon and one review was written by a man with high functioning autism. He said in the review that he had no idea this was the case. He was fascinated by three things: the color of the picture, the costumes, and their hairstyle. So until the end of the book he had no clue until he read about it. This is exactly the magic of social interaction in which we figure it out. One look at it and we immediately get this idea of what is happening. This is same thing which happens if someone comes into my office and I chat with this person talking about my research passionately and this person looks at her watch. Immediately a though passes through my mind saying that maybe this person is bored, or she has to get to another meeting. I have no clue exactly what is happening in this person’s mind, but what I do is I make theories about what is going on in this other persons mind. I make inferences about other people’s mind. This is what is called mind reading. That’s the basis of social interaction. This is what in cognitive science literature there is a term called theory of mind. That’s simply this kind of common sense judgment or inferences which we make about other people’s minds. People with autism have difficulty understand that. Where does this stem from? It stems from the idea of lack of transparency between two minds. So if the minds were transparent I wouldn’t be standing and talking to you right now. I could come and stand here for a few minutes and so “okay you all get it” but fortunately or unfortunately minds are opaque not transparent so we have to find a way to get around that to the other persons mind. That’s where people with autism have difficulty.

XXV. Drawing [S25] a. One of my earlier studies was how this can be assessed from a brain functioning point of view. So we designed this experiment where what you can see is a simple picture of two triangles: a larger one and a smaller one. We put together a series of animations of these triangles. You can watch a 30-40 sec animation of these triangles then we can talk about what is happening there. SHOWS VIDEO. So they show the video and then ask the participant what happened. So immediately if you watch this the first thing is that you are thinking that these two are not triangles they are people. So you might say that the bigger triangle is trying to persuade the other triangle to go out of the box and play or something like that. You can even go further and say that the mother is trying to coax the child to go out and play and so forth. But you might give me words like persuade, coax, convince. These are all mental state terms. So these are terms which involve two people interacting with each other. So when you’re watching these two lifeless triangles you see them interacting and you immediately put biological characteristics to it and read their minds. We compare this kind of animation of simple movements of triangles interacting to video of triangles not interacting but just bouncing around like tennis balls.

XXVI. Brain activation in STS and MPFC during attribution of mental states [S26] a. So this is the activation pattern you see here. On top is autism and on the bottom is the control. This is the right hemisphere. This region here where you see a lot of activation and this one is at the back, just behind the forehead. So this structure is called the medial prefrontal cortex and this is the superior temporal sulcus at the temporal parietal junction. This region is critical for thinking about the function of other people’s minds. So if you have a lesion in the temporal parietal junction usually they have difficulty reading other people’s minds. The other region involved is the medial prefrontal cortex. You can see that people with autism are not randomly responding with some regions. They do activate the same regions but to a much lesser extent. So if you do a direct subtraction between them you can see a series of regions in the frontal cortex that are statistically significant which includes the medial prefrontal. So many of the theories of mind reading regions don’t respond well in people with autism.

XXVII. Reduced functional connectivity in autism during mentalizing [S27] a. We did something else with it. So you say some of these regions are not responding well. So is there something else to it? So we measured something called functional connectivity. So this is a term I’m going to explain a few slides later but to give you an idea---so if there are two different regions active in your brain what we are checking is are these two regions talking to each other to get the task done. So we take the temporal correlation of these two regions, so the time coarse of activation you saw in region A and region B are they activating at the same time? If they are activating exactly in time that is taken as evidence for connectivity. So we calculated the functional connectivity measures, and what we did is by networks, and you can see the frontal-temporal connectivity, the parietal-frontal, and frontal-occipital. In every case you can see that people with autism Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 6 of 8 showing a significantly lower connection than the controls. Here is another fascinating aspect of it. If you look at these networks: frontal-parietal, frontal-occipital, frontal-temporal, in all the cases the frontal lobe in involved. The 2nd thing is that most of them are long distance connections. If you look at occipital-parietal, maybe occipital- temporal, you hardly see any problems in people with autism. So sometimes they have more connectivity than controls in those places. I’ll explain this further when I get to subject detail.

XXVIII. Simulation and Mindreading [S28] a. This leads to my next study. How do we read other people’s minds? You can make inferences or theories. One of things that we do is something which as kids we all learn to do which is imitation. So you always say that “I can understand your pain.” I can put myself in your shoes sort of thing. What we do basically there is a mental simulation of what’s happening. It’s simply imitation of simulation. XXIX. Faces [S29] a. So here is a researcher from Washington University. So in his important works earlier on he goes to hospitals with his lab and then he goes to the maternity wards. These are babies 12 days old, 16 days old, and he does all these tricks and the kids will respond. So for example lip protrusion, yawning, sticking out his tongue, and lip smacking, all these kinds of actions. They do them immediately when other people are doing it. The question here is babies haven’t seen their tongue. They don’t know that there is an organ like that but the moment you are putting your tongue out the baby is going to respond by imitating. Why do they do it?

XXX. Mirror Neurons [S30] a. That leads up to an amazing discovery in 1996. This whole thing happened in Italy. They were recording signals from monkeys’ brains in a particular region called F5, which is in the frontal cortex, when the monkey was performing certain actions. So the monkey was picking up food pellets or something like that and the neurons would fire. The same thing happened when somebody went to that room where the monkeys were and this guy went into the room and picked up something form the table. That led to the discovery that these set of neurons are not only active when monkey is performing an action but also when the monkey observed the action. So they named this set of neurons mirror neurons. And this idea of mirror neurons kind of fits in very well with our social interaction and how we interact with other people and it even predicts some aspects of language. So maybe mirror neurons are the mechanisms by which we understand other peoples’ minds and even empathize with other people. If not for mirror neurons we may not be able to put ourselves in other people’s shoes.

XXXI. Soccer Image [S31] a. So here is an example of that. So this is the 2006 world cup soccer match between France and Italy. As any soccer fan I was watching this one and something unexpected happened. SHOWS VIDEO. (Guy head buts another guy) So the match is between Italy and France. The guy in white is from France, one of the star players. So he headbutts this guy from Italy and gets thrown out of the game. Here’s the fascinating part, France loses the game to a single penalty kick which he would have probably scored and won it. So they lose the game. If I’m watching the video of this same game in 2020 I should be very concerned about that particular part where France loses the game to that penalty kick, but I’m not concerned about it at all actually. This scene from that game if I’m watching it I would wait for this over and over again. There is this same feeling which came over all of you probably when you were watching, it will come over and over again from me when I’m watching it. It won’t come when that guy is taking that final penalty kick because I know exactly where that ball is going to go and that’s an inanimate object that’s flying from the ground and hitting the bar and going out of the post. This is where mirror neurons come in. You easily identify. The point is when you are watching you are emotionally indentifying with that scene. So that makes me more attracted to that particular segment of the game. In the scheme of things what should be important to me is whether France lost the game or not.

XXXII. Intentional stance vs. physical stance [S32] a. So we wanted to check whether mirror neurons are directly involved in the theory of mind processing. This is one of our current experiments. What we did is presented a series of comic strips like this one. There are two different experimental conditions. The first one that we called physical causal attribution where you can see pictures like this one where a wine glass sitting at the corner of the table is falling and falling. We ask what’s going to follow this. We give three options. It’s pretty easy. We compared that with something like intentional causal attribution. Again three pictures in the comic, we ask what’s going to follow this one, and give three options. So the difference is that here things works according to the law of physics (on left). But here (on right) I can’t say that this guy is pulling out a quarter from his wallet to put in the parking meter if I read the other two things before that. So I know that the answer is this one because I’m getting into the mind of this person. This is exactly the case when we are reading other people’s mind. I can say “why did Sally kiss John?” Because she loves him. So that’s a sensible explanation. I can also say that she kissed John because suddenly neurons fired Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 7 of 8 and she had to kiss him. That’s a physical explanation where scientifically you can get it right but you can’t say that it’s because of gravitational force. b. We find that in the first case people with autism don’t have any difficulty but in the 2nd case they do have problems doing it. So here again that same region I showed you earlier comes up, Temporal-parietal junction. Very solid activation on both sides when you are looking at the intentional causal attribution contrasted with the physical attribution. They are engaging the same regions but it’s not coming up to the same level as the control in terms of activation. Now here is the interesting part, in addition to that they are activating, in autism a little but in the control a lot, the inferior-frontal gyrus. Which loosely corresponds to the same area where the monkey’s brain fired which is the mirror neuron system.

XXXIII. Reduced Functional Connectivity in Autism during Intentional Causal Attribution [S33] a. So we wanted to look at how the theory of mind regions are connecting with the mirror neuron centers. Our key region here was the inferior-frontal gyrus. We looked at how this is connected to the temporal-parietal junction of the right side and the left side. In each of those cases you can see people we autism are weakly connected compared to the other ones. So maybe they are assimilating, but it’s not going in conjunction with other people’s minds. The point is that we don’t know for sure whether they are assimilating other people’s minds or not but they do show some activation but it’s not well connected with the reasoning of other people’s minds.

XXXIV. Clicker Question [S34] a. The following brain area seems to be critical in reading other people’s mind: temporoparietal junction. Okay so that’s good.

XXXV. Functional connectivity [S35] a. So that leads to the term called functional connectivity that earlier I just browsed through. It’s basically refers to the correlation between timing of activation between two different brain regions. So if you have A and B it shows how these two regions are correlated in time. It’s computed as a correlation between two activated areas. The phrase was coined over a decade ago to indicate the synchronization that the synchronization implies to synchronized regions that are physically connected. So the relation if it’s high is taken as evidence that these two regions are probably talking to each other to solve this problem.

XXXVI. Underconnectivity: Theory of Autism [S36] a. Skipped

XXXVII. Football Image [S37] a. Let me conclude by saying a few more things. We’re not seeing this underconnectivity or weaker connectivity in just one study of theory of mind. We did several studies of higher cognitive function. In many of those cases we do find weaker connections in people with autism. So we came up with an idea of theory of cortical underconnectivity. So the point here is that as I said earlier if you look at the connections many of the connections between the frontal and posterior regions are impaired. Long distance connections seem to be weaker in people with autism. So what the theory states is that any facet of cognitive functioning which is computed more and more there is a chance that it’s going to fall apart. So if I wanted to pick up this pen I wouldn’t need a lot of help, but if I want to pick this whole thing up (the podium) I might need some help from a couple of strong guys. The brain works the same way. If the task is very easy it can easily get done by one or two regions. As the difficulty increases the need for collaboration increases. So that’s where people with autism fall apart with higher functions you know like executive function, theory of mind, working memory, and so on they have difficulty doing because of the lack of collaboration. b. So I usually compare this to a football game. You can say that the quarterback is throwing the ball, and someone in the front is catching it and running and he’s going to score a touchdown. The same way, people with autism information comes in from the back of the brain to the occipital region and that is thrown to the frontal cortex to make sense of the information, but what happens is that the frontal cortex keeps dropping the ball. And there’s hardly any touchdowns. So what happens is if this is repeated several times the quarterback will decide “Well I can’t rely on him.” So the brain in autism the occipital or the parietal regions kind of take over the function. You can call it paratial or occipital autonomy because they aren’t getting help from the frontal cortex and they decide to do things by themselves. The result of it is that becomes more and more spatially oriented. In behavior if you see people with autism you will see many of them are really good at spatial processing. It could be because of this finding. So this is just an explanation. Other theories are compelling in terms of the evidence of which we put together so definitely this may not explain autism completely. Neuro: 1:00 - 2:00 Scribe: Hillary Carney Monday, February 15, 2010 Proof: Dr. Kana Autism: cortex, cognition, and connectivity Page 8 of 8 c. So here’s an example if you give me a picture of two brains and ask me which one has autism I can’t do that. There are no gross structural abnormalities in the brain. The abnormality is how these different regions function together to produce cognitive function and social function. So one of the consistent findings in people with autism is larger brain size. So the consequence of larger head size that information has to travel a long distance. Another consistent finding is a smaller corpus collosum, which is the connecting link between the two hemispheres. So imagine a brain that is large, with a smaller corpus collosum, then you are talking about connectivity which is compromised because you have a long distance to cover, connection delay will be there. The cost to maintain the neuron probably increases too. So put together what is going to result is you will be compromised in long distance connectivity and you will probably be enhanced in local connectivity. That will probably be seen in some of our tasks and in some behavioral features.

XXXVIII. Clicker Question [S38] a. The synchronization of brain activation between two regions is called: Functional connectivity.

XXXIX. Anatomical abnormalities of the brain in autism [S39] a. Skipped XL. Brain Volume in 3-4 year olds [S40] a. Skipped XLI. Large Brains in Autism [S41] a. Skipped XLII. Brain areas implicated in the triad of impairments in autism [S42] a. Skipped XLIII. Conclusions [S43]

[end 48 min]