Neuroscience of Autism
Have you ever noticed how many more cases of Autism there are in the world today?
In 2023, the World Health Organization predicts 1 in 100 people will be diagnosed with Autism (and USA Today predicts even more...)
But if you go back a few decades, there are dramatically fewer cases reported.
So what is causing the increase?
Are we just more aware of the symptoms, or have our brains begun to develop differently?
In this month's episode, Laine walks us through findings from Molden, Rubenstein, Hyman, Baron-Cohen, and many others to help us better understand the unique functions of the autistic brain, and how what we've learned has changed how we view or even diagnose autism. We'll look at things like:
Why there are more people with autism today than 30 years ago
Why autism does NOT mean a lack of empathy (even though their behaviors make it seem so)
And what preemptive actions we can take to better support the development and lives of those with autism
**Also enjoy a special "behind the scenes" tag at the end of this episode!
REFERENCES
Steven O. Moldin, John L. R. Rubenstein, and Steven E. Hyman - "Can Autism Speak to Neuroscience?"
S. Baron-Cohen - "The Cognitive Neuroscience of Autism"
Arianna Manzini, Emily J.H. Jones, Tony Charman, Mayada Elsabbagh, Mark H. Johnson, and Ilina Singh - "Ethical dimensions of translational developmental neuroscience research in autism"
Born For Love by Bruce Perry and Maria Szalavitz
General Outline of Episode
Starting to be looked at differently - Drax in GOTG, Sheldon in the BBT, and Even The Good Doctor.
Noticing a lot more individuals -
Increase in prevalence?
Awareness of diagnosis?
Both?
What is going on here?
This is the neuroscience of Autism.
LAINE
Prevalence “We know that, despite disagreements about prevalence, autism spectrum disorders may affect as many as 73 per 10,000 (Kadesjo et al., 1999; Fombonne, 2006).” According to 2023, WHO estimates 1 in 100. USA Today “2018 and 2020, the most recent year data is available, up from 1 in 44 children to 1 in 36. Many factors are likely to contribute to these rising rates, including that diagnoses among children of color have been catching up to – and are now passing – white children.”
Autism(colloquially) - need to talk about why we don’t have a colloquial version of this for most of our history - why we are getting one now
Neurodivergent
On the spectrum
Autism(clinically) - persistent deficits in 3 areas of social communication and interaction and two of four types of restricted repetitive behaviors
Must be across multiple situations
Social
Social-emotional reciprocity (back-and-forth conversation, sharing of interests, emotions, not initiating or response)
Nonverbal issues - eye contact or body language or not understanding this
Diffuucuility in maintaining and understanding relationships - difficulty with imaginative play, lack of interest
Restrictive repetitive behaviors, interests, or activity
Repetitive motor movements, speech, etc
Sameness - adherence to routine, ritualized patterns - high distress at changes, Transition
Rigid thinking patterns
Restricted fixated interests - abnormal in intensity
Hyper/Hyporeactivity to sensory input or unusual interest in sensory aspects - pain, temperature, sounds, textures, smelling, touching, light movement
Both are looking at the severity
Autism
Perry and Szalavitz dug deeper into this in regard to Empathy. We covered a lot of their book in the episodes of the neuroscience of empathy. Specifically looking at the fact that we think Autism is a deficit in empathy but the science is telling us otherwise, specifically that there are some areas with deficits and some that may be enhanced. This brings us to one of the tricky parts of Autism. To quote Perry and Svalvits “if you've seen one person on the spectrum you've seen one person on the spectrum the conditions are quite variable”. So why would they be so variable?
Let’s look at all the clusters within the syndrome - eye contact, making friends, differences in language up to the point of no speech at all. Sensory issues - over or under-response to pain.
All of this seems all over the place - until it all makes sense.
PART 1: Terms & Background Info (5-10 minutes)
Evans states Eugen Bleuler in 1908, specifically describing a patient of his who withdrew into his own world. “The Greek word ‘autos’ meant self and the word ‘autism’ was used by Bleuler to mean morbid self-admiration and withdrawal within the self. He was largely referencing Freud in this.
Moldin, Rubenstein, and Hyman state that it was first described in 1943 by Leo Kanner who identified that there were “significant impairments in social, communicative, cognitive, and behavioral functioning.” Was originally called Kanner syndrome. From there Victor Latter did an epidemiological study of children with this.
The 1960s is when the research took off to better understand this, specifically in regards to children.
Evans argues “That the change in the meaning of autism was part of a more general shift in Anglo-American psychiatric reasoning which sought to understand psychological problems through epidemiological studies rather than individual cases.”
Nowadays we are seeing more of a debate on what exactly Autism is, and how we may need to rethink how we have thought about it for the last hundred years.
PART 2: What About Neuroscience (5 minutes)
Why are we looking at THIS TOPIC through this lens?
What unique perspective will Neuroscience show us regarding this topic?
Manzini, Jones, Charman, Elsabbagh, Jonson, and Singh are stating that there has been increasing research for over 30 years looking at the biomarkers for autism to try to obtain a more objective diagnosis. This is a mental health diagnosis like ADHD, in that we specifically label it under ‘neurodevelopmental disorders. There has been a goal to get a clearer understanding of what it is, define it earlier if people have it, and increase options for what is next. To quote “Early studies focused on the identification of genetic variants associated with autism, but more recently, research has expanded to investigate neurodevelopmental markers. While ethicists have extensively discussed issues around advances in autism genomics, much less ethical scrutiny has focused on research on early neurodevelopment and the interventions being developed as a result. Biomarkers are measurable indicators of abiological state and they could be used to supplement an autism diagnosis based on behavioral criteria; indicate an individual’s increased likelihood of developing autism; identify individuals developing autism before they manifest clear observable traits; and provide indications for targeted treatment”
**BREAK**
PART 3: The Science (30-35 minutes)
We’ve been looking at the neuroscience of autism for over 30 years. What we have zeroed in on is not just what is firing, but also how the networking is different than in the brain of someone who doesn’t have autism.
Camilla and Henry Markram started us on a track where this all starts to make sense. The Markrams, who raised a son with autism, worked with Tanya Rinaldie to study rats exposed as fetuses to Depakote - a medication that has been known to cause autism when there is exposure in utero. What they found were rats that avoided other rats, seemed to be more fearful, showed repetitive behaviors, and were oversensitive to noise and light. What they found on a neurological level was that these rats had a group of cells, a cluster, in their cortex - this is the youngest child - it is the most recently evolved area - and it specializes in interpreting complex information. Not only are there more cells, but they are also focused in their connection to one another.
Moldin, Rubenstein, and Hyman also found this - specifically looking at understanding the parts of the cerebral cortex that regulate patterning and plasticity – they were looking at connections with other brain regions and how we develop processing networks and adapt to change, this is based on research from Hensch, Sur, and Rubenstein.
Baron-Cohen specifically looked at the “abnormalities in the density of packing of neurons” and what they believe to be a failure of synaptic pruning or a lot of synaptogenesis, which is a formation of synapses - that is the phone call/text/dms that happens between one neuron and another.
Rinaldi and the Mackrams found this in their rats as well. The rats had a higher amount of connection between the synapses within the cluster, but the long-range connections to other parts of the brain - not so much.
What does this mean - clustering of cells is very likely to create an intensity around where those clusters of cells are. Think of the episode of phantom limbs - when your brain has the ability to increase the resources to your groin if you have lost your foot in a car accident, the sensation around your groin becomes more intense, right? So let’s think of this within your cortex. Where you are processing complex information. This clustering very much explains why people with autism both have significant issues with sensations (sight, sound, smell, taste) and why we can notice savant-like behavior. Think of this like being right-handed. Your brain chose to specialize, or cluster around one hand over the other - we are the only mammals that do this. It did this so you could do complex, difficult intense tasks…with one hand. This would mean that in the brains of people with autism - there is a sensory dominant experience. And certain other things, things neurotypical people take for granted - are like operating them with your left hand. Its harder.
Areas specifically impacted
Rinaldi and Markram noticed not just intensity within the cortex - they also saw rats with quicker and higher responses to fear and a lower response to safety (hard time realizing that a situation was now safe) Why- no surprise increased connectivity in the amygdala! There is more of that intensity but less of the dendrite branches to the other part of the brain to help someone understand it's okay, my amygdala is being dumb and over-sensitive, so I’ll be ok. Can you imagine why the brain would go into overload? Imagine when you’ve had that intense fear response and nothing would calm you down? For someone with autism, it can be like this all the time.
Baron-Cohen specifically looked at the “abnormalities in the density of packing of neurons” in the hippocampus, amygdala, and other parts of the limbic system” They also found an abnormally low degree of dendritic branching, specifically in the hippocampus, though they would like to confirm this with a larger sample. - same results - it does echo Rinaldi and Markram’s data.
Baron-Cohen also looked at what is called the ‘‘social brain’’. This is “a neural basis of empathy has built on a model first proposed by Brothers”. Leslie Brothers looked at animal lesion studies, single-cell recording studies, and neurological studies and found that social intelligence is done through three regions of the brain- the amygdala, the orbitofrontal and medial frontal cortex, and the superior temporal sulcus and gyrus STG. We have found abnormalities in the amygdala with autism, as mentioned, which has been shown in multiple studies. In addition, we have found reduced activity in the left medial frontal cortex and the orbitofrontal cortex, specifically when we look at theory of mind tasks.
It is often believed that people with autism are without empathy. Research is showing this is not the case, but instead what is missing is theory of mind - as shown in Brother’s study. Remember from Neuroscience of Empathy - Theory of mind is being able to understand that people’s perceptions, emotions, thoughts, and knowledge are different from yours. It’s called perspective-taking. To quote Perry “One way that you know a child has obtained theory of mind is that he or she begins to lie”
Simon Baron-Cohen, Alan Lesiel, and Uta Frith did a study almost 40 years ago on this.
Sally and Ann Puppet
Sally - basket
Anne Box
Sally - marble to basket - leaves stage
Anne - moves it
Where does it go?
Normal 4-year-olds will agree with you
Children with severe intellectual disability will agree with you
80% of children with autism will not
Where is the marble
There is a deficit in the ability to do perspective-taking
This can be hard for most of us to do perspective-taking on having no perspective-taking! But think of what this explains
Less talking - why?
Not lying- why?
Social lies - why?
Sarcasm - why?
Talking forever about a topic you know nothing about or don’t care about - why wouldn’t you?
This is not uncaring - this is misreading
Also, Perry brings up that perspective-taking is much easier when most people's brains work like yours!
In addition -
We have seen some studies showing increased activity in areas focused on stimulus and decreased in higher cognitive processing.
One study “also failed to show normal activity in the fusiform ‘‘face area’’”
We want to learn WHY we do what we do as humans, and we’ve looked to the brain for explanations…
**BREAK**
PART 4: TAKEAWAYS (10-15 minutes)
Moldin, Rubenstein, and Hyman “genes play a greater role in the risk of autism than in any other common neuropsychiatric disorder, with a reported monozygotic-twin concordance/dizygotic-twin concordance ratio of 25 and heritability 90% (Bailey et al., 1996; Risch et al., 1999). Although genes exert a strong influence in aggregate, it is clear that autism is genetically complex, meaning that multiple genes of relatively small effect must interact to produce risk in combination with nongenetic factors.”
To quote Perry and Szalavitz “If one identical twin is autistic then the other one will have an autistic spectrum condition about 60% of the time period and fraternal twins who unlike identical twins do not share 100% of their genes the odds of the second having an autistic condition are only one in 10%”. Genes impact this, but it’s not just genes and environmental influences that have not been, on the whole, scientifically proven.
We do see a correlation between interest and likelihood of autism.
According to a study by Barron-Cohen, Bolton, Weelwrite, Scahill, Short, Mead and Smith “College students studying engineering math and physics are six times more likely to have a close autistic relative compared to those majoring in literature and by a survey of the British National Autistic Society found that its members were twice as likely to have fathers or grandfathers who worked in those kind of professions than the general population”.In addition - we are more likely to see savant skills in people with autism and 1 in 10,000 neurotypical people have absolute pitch, however in Autism that number rises to 1 in 13.
To quote Perry and Svalavits “There are researchers who suspect the same gene expression that carries this evolutionary edge could also carry risk for autism”. - they have used this to express the importance that reducing or removing autism could have very harmful impacts on society
What does this mean for society?
To quote Manzini, Jones, Charman, Elsabbagh, Johnson, and Singh “Autism can be viewed as a neurodevelopmental condition characterized by difficulties in social communication, patterns of restricted and repetitive behavior, and sensory anomalies and/or as a fundamental part of someone’s identity that comes with strengths and weaknesses and is part of the spectrum of human neurodiversity”
And it’s both right? Wrong is the viewpoint that all people with autism are Rainman - neither a person who has to live in a group home nor someone who can help you cheat casinos. If you have seen one person with autism, you have seen one person with autism.
What’s important to know is that the brain is wired differently - instead of one-hand dominance, it’s one thing dominance - and the rest of the world is your left hand. With that comes pros and cons. There are multiple times it would be great to be ambidextrous - but for a person who is left-hand dominant, there’s nothing wrong with left-hand dominance - except for the fact that they have to live in a right-handed world.
So we need to think about how to make the world easier for left-handers and people with autism.
They are specifically arguing for the need to understand autism early - infancy - so that we can see some of the trajectories in brain development- not because they are wrong - but so we can reduce the clinically significant distress of the side effects of brain clustering. So we can reduce the likelihood of a person with autism dealing with the cons of living in a right-handed world - which often looks like anxiety, depression, bullying, and isolation
They specifically argue for a better understanding the subtypes of Autism, citing Wolferset et al. Specifically, the DSM could also reframe this - moving more towards the RDoC or ESSENCE - so we can understand the specific needs of individuals better and make the world easier to operate.
Early identification was requested repeatedly -because it’s very possible if we can see it early, we can expand on the neuroplasticity. This is from Webb, Jones, Kelly, and Dawson. To quote “This involves a shift from viewing autism as a categorical state that is determined from birth by genetic factors, to a polygenic and multifactorial condition with a spectrum of possible presentations whose symptoms result from an atypical developmental path that could be targeted with early intervention”
As such, some have proposed that early interventions could prevent or ameliorate the emergence of the disabilities associated with autistic traits if successful (Klin et al., 2020). Important to state - that this is not to prevent, but instead a preemptive approach.
To cite Jhonson, Johnson, Jones, and Gligia View” traits associated with autism not as maladaptive, but as the result of an alternative developmental pathway, or as an adaptive response to a brain that processes information in a different way” - Kapp, Gillespie-Lynch, Sherman and Huntmsat state “the proposition that flourishing with autism is both reasonable and desirable is an important motivation for the neurodiversity movement and its allies”
If you know someone with severe autism this might feel difficult to believe - so let me extrapolate -
There was a study of scientists who were autopsied and found that their brains matched those of someone with autism - that clustering occurs, however, they never were diagnosed and did not, according to the study, happier to have any social problems. What’s the difference?
The question is what are the side effects of clustering and what can we do to get around it
As we’ve mentioned, this clustering is more likely to make th world more intense - imagine if you stepped outside and the lights were always so bright it hurt to have your eyes open. Imagine if every time anyone talked it felt too intense to feel comfortable. That you felt like you were walking around wearing sandpaper. That you could taste if someone had cross-contaminated a dish with a spoon of a dish way spicier than it was supposed to be. Imagine being a toddler and trying to go to preschool. Would you want to play with other children if their voices hurt? If your skin felt overwhelmed all the time, oh and there wasn’t the part of your brain that helped you soothe to ‘get over’ this experience- you might also want to go into a corner and rock. Play alone by yourself. Do anything you can to not feel that way.
However, an important part of our brain that we discussed in the neuroscience of empathy is the brain needs specific information at a specific time - neuroplasticity exists - not saying it doesn’t - but we have a higher amount of neuroplasticity early on in life - and that is the time we are teaching ourself how to talk (we do this by making noise and listening to others make noise and mimicking their noise - harder to do when the noise hurts!). We do this in early childhood. But if people talking hurts, and engaging with the world is too intense and we don’t have a way to do it and we self soothe - we miss out. But this is bigger than missing out on that trip you wanted to take. This is the brain missing out on crucial information at a crucial time
For the same reason, a child can learn a foreign language more easily and without an accent if taught soon enough is the same reason some children will grow up not being able to say a full sentence
Once before when we didn’t understand hearing loss, deaf children would often go undiagnosed or misunderstood - they wouldn’t get access to language early enough - with language - nothing was different, without language in the early part of life - it was very hard if not impossible to catch up
Bruce Perry has treated children in orphanages where kids were left in cribs for days at a time with little to no human contact or kids who were raised in dog cages or the wild. If we catch this too late - we don’t get the brain what it needs when it needs it and this means lifelong consequences
To quote Perry “Cats with perfectly normal eyes can go blind if they cannot open their eyes during a specific period of time when they are kittens. If this happens earlier or later there's no damage but if their brains don't get visual information during this sensitive time, they will be blind for life”
As Perry states for a child with autism trying to learn language “It's like he's at a front row of a rock concert near a blaring speaker trying to figure out what someone next to him is whispering and then in total silence with no sound coming through at all. It's impossible to filter out the unnecessary information or home in on the important stuff. Not surprisingly he retreats into repetitive behaviors and craves routine at least predictability can minimize the fear that results from this chaos. But this retreat has serious consequences.”
Children who are overwhelmed and can’t not engage because they are overwhelmed do not get the same exposure to verbal language or body language or facial expressions. These aren’t just things we know, they are things we learn. We learn through lots of repetition
But without that how do we learn
As Perry states “Deaf children whose disability is discovered late can appear to be mentally disabled again not because their brains don't have the ability to learn but because they didn't receive necessary early stimulation. Since infants are now routinely screened for deafness late diagnosis have become rare and most are exposed to sign language right away. As a result, many cases of mental disability that were once thought as to be inherent to some type of deafness have been eliminated. Things that look fixed like mental retardation linked with deafness or social withdrawal in autism may really be caused by environmental deficiencies not a lack of genetic capacity”.
The Early Start Denver Model by Dawson et all is working on just that - focusing on 18 to 30-month-old toddlers with interventions early found that “seven of the 24 children given the intervention known as early start Denver model did not receive an autism diagnosis when evaluated by a psychologist who did not know whether they had been treated or not compared to just one child out of 21 in the control group”.
As Perry states “Autistic children may be failing to receive necessary social inputs during the critical period because of sensory issues, not because of the problems inherent in their social brains”
