From BBRF's Brain & Behavior Magazine - July 2019 Issue

Dr. Klin, your research in the clinic suggests that there’s going to be a new way to diagnose autism, and a whole new way of imagining the world of the child who has autism spectrum disorder (ASD) that seems more hopeful than what we’re accustomed to. Tell us about how you’ve come to this view.

As a graduate student, I worked in a residential unit for adults with autism who had spent all of their lives in long-stay hospitals. They were profoundly disabled. My sense at the time was that autism was an unchangeable condition. We already knew that it was strongly genetic, and we wondered back then if a person’s state in life was wholly determined on the basis of genes.

In the years to come, I began to work with babies. Why? Because the only way we could trace the early development of individuals with autism was if we were to follow the younger siblings of children already diagnosed with autism. We weren’t sure of the recurrence rate in families, and in fact we greatly underestimated it. It became clear that about one in five of the younger siblings of children with autism also develop autism, and that an additional one in five developed something that either was a transient form of autism, or a sub-threshold form. We felt that we were looking at a broad spectrum, one that crossed thresholds of clinical diagnosis. We now know that this is true.

Once we began to follow babies from birth, it was possible to start tracing their developmental trajectories—those who developed normally as well as those who eventually developed autism. And what we and others in the field discovered is that there is much, much greater malleability in ASD than we once thought. We started looking into ways in which we could promote better outcomes by trying to intervene between birth and the age of 3 years. If we could increase their abilities by the age of 3, we would be changing their lifetime trajectory.

So the adults you observed early in your career had already been institutionalized for many years—and had passed that very early window of “plasticity.” In retrospect, can you say that they had not been treated early enough?

Yes, that, plus the fact that in the years when those individuals were growing up, there were few or no services in the community for their rehabilitation.

But here you touch on a second thread in my story. There is now incontrovertible science suggesting that early detection and early intervention does optimize outcomes in children. Yet we have a huge public health challenge on our hands, because the median age of diagnosis of autism in this country is stubbornly stuck at around 4 and a half to 5 years of age. Diagnosis is particularly problematic in children who have less access to services—minorities, low-income families, and rural populations, in whom the diagnosis is usually made later on in life.

There is this need for us as a society to focus on early identification and diagnosis, and provision of early treatment and early prevention services.

Parents will be very interested to know about the distinction you make between genetic and environmental factors contributing to the way a child with autism develops.

What is inherited in autism is the trait, and the trait is reduced sociability. But there are many different routes to autism, not all of them strictly genetic. The important fact is that autism might not relate back to a single gene, or to even a combination of genes. Rather, it may be the result of deviations from normative socialization. By this I mean that liabilities that a baby is born with, whether for genetic or environmental reasons, could impact normal development, a result of which can be autism. We wanted to discover where we could intervene in the process, to normalize the trajectory in more children so they could have better outcomes.

Tell us about a technology you were instrumental in helping to develop, which makes early diagnosis possible. I’m referring to “eyetracking” technology.

We began to develop eye-tracking technology around the year 2000. It is a quantitative way, using science and technology, to measure sociability— the way that children engage with the world around them. We learned how to quantify what happens when a child is looking at a caregiver, or a child is looking at some peers playing.

You’re trying to measure how children are seeing the world, and your technology gives you an ability to do that by tracking what their eyes are looking at, where they’re looking, how long their attention is sustained, and in general, the difference between children who are developing normally and are learning steadily to socialize, and children who diverge from that path. Your research reveals the significance of whether a child is looking at the eyes or the mouth of the caregiver, for instance.

When we study toddlers who have older siblings with autism, we have them look, for example, at a short film sequence of a couple of toddlers interacting. All of the children have this same stimulus in front of them, but brain connectivity—the neural tracts being formed as a result of those experiences—is radically different in the children who will go on to develop autism. They are looking at the same film, but what they are seeing is entirely different. What their brains are learning about is entirely different.

Eye-tracking data of very young typically developing children vs. children who go on to develop autism tell us amazing things that no parent could possibly detect. We found that children on the path to autism, beginning at a very early age, were missing about 500 moments of social learning in about 6 minutes of watching their peers playing. [This reflects where their eyes are focused while watching—the eyes and faces of those in the video, other objects in the room, etc.] If you do the math, if they are missing 500 momentary opportunities for social learning in 5 or 6 minutes, that translates into thousands of opportunities during one day, and into millions in the first 3 years of life.

Like all children, they are “creating” their own world, but they are diverging from the normative experience. As they are building their own brains, they are becoming autistic, as it were, every day of their young lives. If you’re a clinician, you have to realize that that wonderful human being right in front of you is seeing the world entirely differently than you expect. That’s why we needed a scientific and technological road into that child’s mind and brain and it’s why we developed the eye-tracking method.

When do the paths begin to diverge? One of your papers reveals that until a certain point, all newborns are processing the world in the same way.

Initially, in the first 2 months of life, all children are on the same track. All children are born with reflexes—social reflexes—signaling to caregivers that they are there. The caregivers accordingly will engage the babies, and it’s out of this mutually reinforcing choreography that the “social brain” emerges.

We found out that between 4 and 12 weeks of age, babies are transitioning from these “reflex” behaviors to what we call “volitional” behavior. The initial reflex behaviors are guided by subcortical structures in the brain. But this normally transitions to reward-driven visual behaviors that are guided by the cortex. We can see this transitioning happening. We see the emergence of the interactional smile. We see the emergence of, basically, a human being that is reacting to the surrounding world.

Because you were measuring a large group of children from birth—not knowing whether they would be typical or develop autism—were you able to see where the paths began to diverge?

Yes. In those babies who eventually, we found later, developed autism, those divergences began already by the age of 2 months. We learned this in 2013. They seem to be born with the typical visual and behavioral reflexes, but they don’t make that transition into volitional behavior. There is something that is not happening between 4 and 12 weeks of age that is not supporting that neurodevelopmental transition for children with autism.

Do you know what that is?

That’s the research focus of our Marcus Center here in Atlanta, which is a National Institutes of Health-designated Autism Center of Excellence, one of only five in the country. In our program we are looking at this from a social/visual engagement standpoint, because nothing shapes the brain of primates as much as sociality. The Marcus Center is the largest center of clinical care in the U.S. for children who have autism. Over 5,500 children are seen in the center every year, and another 5,000 are seen directly in the community. We are a diagnostic and a treatment center, with treatments ranging from skill acquisition early on in life, to severe behavior challenges, to feeding disorders, to maintenance in older children.

Having gained your insight about the diverging paths, what can you do to affect the outcome?

Our research suggested that if we could engineer the environment around these children in such a way that the environment would provide a kind of scaffold—one supporting the better engagement of affected children—we would be in a position of changing their developmental trajectory.

We are intervening in the child’s reduced level of engagement with others. The science that I described to you becomes the grounding for the kinds of treatments that we can offer children.

Tell us about the treatments.

Rather than having the child spend one hour a week with a developmental expert, we choose instead to treat the child through the engineering of social environments. The early divergence and our assumption that plasticity is greatest when these neural tracts are just being laid down, has led us to deploy a parentmediated treatment approach. We take this approach because every single second throughout the week, the child is going to be diverging.

So, in a sense, we “treat” the parents. We train parents to use everyday experiences, what they do with their babies every day, through all of the routines, in order to engineer the social engagement that is crucial. We use a particular form of treatment called early social interaction, and we send coaches to train parents in their homes, but we are also able to train parents who don’t have access to us, so we can treat from far away.

A parent is interacting with the child, has a “bud” in the ear, there is a camera, and our interventionist is sitting in our center monitoring that engagement in the home, and coaching parents on how to take advantage of those moment-bymoment experiences that are learning opportunities for socialization.

It’s literally one-on-one with the parents. It’s very one-on-one, on the basis that babies spend most of their time with their caregivers. And so, by engineering that environment, we are able to use one hour a week to reach the level of intensity in that child’s life in a way that can be scaled to work at the level of an entire community. That’s what we’re trying to do.

If I hear you right, you have to spend time with the parent and child together, but really aimed at getting the parent to be able to give the child that word-rich and supportrich environment, minute-to-minute, when you’re not there.

Absolutely. Now, needless to say, we do the same thing as children grow older. When the environment becomes the daycare center, we train the daycare providers. When it becomes preschool, we train the preschool teachers. Really, what we need to do is to become architects of our own community. It makes no sense at all for us to create treatment for which there is going to be very limited access.

What about the diagnostic part? You said it is critical to make the diagnosis early.

Right now, there aren’t enough resources to provide children with treatment. And yet, I go home every day with the thought that 66,000 children are born every year in the U.S. alone who are going to have autism. So, we are under tremendous pressure to take the NIMH motto seriously: We need to translate our science into solutions, and so that’s what we are doing.

We are now completing a national clinical trial that uses eye-tracking technology in a diagnostic device that we hope will substantially increase access to diagnosis. With the device, which is mobile, we hope that in a 12-minute procedure a trained technician will be able to do what expert clinicians can do in a multi-hour diagnostic assessment.

That is one approach. At the Marcus Center we also have over 1,000 children who have been through a procedure that we built for children aged 16 to 30 months. We focused on this age group to capitalize on “well-baby” checkups that all children have at ages 18 and 24 months. Any child with actionable delays under the age of 3 should be provided with federally mandated services. We wanted to create a procedure that would make this actionable.

All the children we see who are at high familial risk for autism receive treatment. We are beginning the treatment at 6 months, but from 6 to 12 months, our treatment is entirely informational and is about training parents. We are training them to become more sensitive to child development milestones, and to principles of engaging their own child. At 12 months, children who we feel are now showing risks for autism are randomized into two groups. One provides treatment on the existing model: treatment is given by an expert clinician. The other group gets parent-mediated treatment. Then, there is another assessment at 2 years.

And for those who do develop ASD symptoms?

We can substantially and meaningfully improve their lives. These children are uniquely human. It is within our power, and it’s both our responsibility and determination as a community to ensure that these children are afforded what they need in order to fulfill their potential and promise.

— Written By Peter Tarr

Click here to read the Brain & Behavior Magazine's July 2019 issue