Autism Best Treated

The glare of overhead lights. The smell of a forgotten half-sandwich in the trash can in the corner. The breeze from a window.

For most people, this sensory information fades into the background, ignored in favor of more relevant information such as a friend talking, a program on television, or work on a computer screen.

However, for many people with autism, these background sensations are just as powerful as the intended focus, if not more so. The sensations can become so overwhelming that the person tries to withdraw from the world simply to control the incoming onslaught.


So holds the Intense World Theory of autism, proposed by Kamila and Henry Markram in 2007. It contends that people with autism don’t have an underdeveloped brain but rather an overdeveloped one.

New research released today in Frontiers in Neuroscience lends considerable weight to this theory. It also concludes that predictability can significantly help those with autism explore their intense world.

Read More: Why Autistic Kids Get Lost in the Details »

A Model for Autism

To simulate autism in rats, researchers at the Swiss Federal Institute of Technology in Lausanne (EPFL) exposed developing male rat fetuses to valproate. This is an anti-epileptic and mood stabilizing drug that is known to cause birth abnormalities in humans, including a 9 to 60 percent increase in autistic symptoms.

Among the grown rats, the symptoms were similar. The valproate-exposed rats spent less time playing and socializing with other rats, they showed more repetitive behaviors and anxiety, and they formed fear memories more easily.

However, no two rats were identical. Each had its own array of specific autism-like symptoms, which is consistent with the knowledge that autism symptoms can vary greatly in humans. Each rat likely had a different genetic profile, with a different level of vulnerability to valproate.

Previous research had tested whether an enriched, stimulating environment would help such rats develop properly, as compared to the barren and lonely cages that typically house lab rats. However, while combing through the research, the scientists noticed these studies hadn’t controlled for whether the environmental enrichment was predictable.

Just by introducing predictability and a lot of structure, and eliminating any type of surprise in this type of enriched environment, you can eliminate some of the crucial autistic symptoms.
Kamila Markram, Ph.D., Laboratory of Neural Microcircuits

To test the effects of environmental predictability, the researchers set up three test groups.

Non-enriched rats lived three to a cage, with only a single cardboard tube as a hiding spot and basic rat chow for food.

Enriched rats received larger cages with five other cagemates to socialize with, as well as a running wheel, ramps to climb on, multiple tubes to hide in, toys to play with, tissue paper with interesting odors to smell, and dried fruit or cereal to eat in addition to their chow.

However, for half the rats in the enriched condition, the environment changed every few days with new toys, different odors, and climbing platforms in new places.

For rats that had not been exposed to valproate, this unpredictability was no problem. The enriched environment still gave them plenty to do.

But the autistic rats noticed the difference. For them, the unpredictable enriched environment was just as bad as the non-enriched environment. They showed the same antisocial and repetitive behaviors and the same fears and anxieties.

The autistic rats in the predictable and enriched environment, however, fared far better. Although they still showed repetitive behaviors, they were more sociable, and they didn’t show the same anxiety or fear learning. By knowing what to expect, they were able to learn to trust the world around them. Of the valproate-treated rats in the predictable and enriched environment, more than half didn’t show major symptoms of autism at all.

“Just by introducing predictability and a lot of structure, and eliminating any type of surprise in this type of enriched environment, you can eliminate some of the crucial autistic symptoms, such as increased anxiety and fear memory formation,” said Kamila Markram, Ph.D., director of autism research at the Laboratory of Neural Microcircuits at EPFL and supervisor of the study, in an interview with Healthline.

Read More: Intervention at 6 Months Old Erases Autism Symptoms by Age 3 »

The Hyper-Functional Brain

Previous theories of autism had held that the autistic brain was undeveloped and underperforming, confirmed by functional MRI studies that found weaker connections between different brain regions. However, delving into the rats’ brains on a much smaller level, the scientists made a surprising discovery.

The individual cells in the autistic rats’ brains were actually hyperactive, firing signals more frequently and at lower thresholds of stimulation. They were also connected far more closely with their neighboring cells than in non-autistic brains. When given chances to learn, new connections formed far more quickly and more strongly. On a micro level, the autistic brain was actually hyperfunctional.

“The brain is supercharged because the elementary functional units of the brain are supercharged,” explained Markram. “These units are called neural microcircuits. These microcircuits react and process information much stronger, [and] they can learn much more and remember longer. The Intense World Theory proposes that having such powerful units makes orchestration difficult — like trying to play a piano with a million run-a-way keys.”


This mean that while it’s harder for people with autism to grasp the “big picture,” individual sensations or behaviors can become greatly amplified depending on which microcircuits have been activated.

“Each autistic child will therefore be unique because different microcircuits dominate the pattern that emerges,” Markram said.

The hyperfunctionality was particularly pronounced in the rats’ amygdala, the region of the brain that governs anxiety and fear learning. Not only is the autistic world too intense, it’s also scary — fear associations form at a much lower threshold, creating avoidant and aversive behaviors.

For example, an autistic person might avoid eye contact not because their brain is unable to process the face, but because looking directly at the eyes conveys an overwhelming flood of information and activates the amygdala’s anxieties. Looking away helps control the barrage.

In turn, this avoidance lowers the number of opportunities that each autistic person has to learn valuable life skills.

“The world is not just intense, it actually turns aversive as well, and the consequence of that is that the individual will then retract,” said Markram. “They will react less, they will interact less with other people, and as a consequence they will have less occasion and opportunities to make certain learning experiences with the world and acquire certain knowledge — for example, communication.”

The findings also explain why repetitive behaviors are so common among people with autism. When a microcircuit becomes prominent, reactivating it over and over offers a sense of comfort and familiarity.

“We think that the repetitive behaviors are self-medication attempts where the autistic person uses a certain activity as a release,” Markram said. “It’s a way to shutdown the rest of the world. It’s a mechanism of withdrawal and focusing on a soothing activity that calms them down. The autistic child is retreating into a controllable and predictable bubble to protect themselves from the intensity and pain.”

Learn More: Are Environmental Toxins to Blame for Rising Rates of Autism? »

No More Surprises

For anyone, some degree of predictability is a good thing, as is some degree of novelty. Too much predictability results in boredom and too much novelty makes the world chaotic.

“In animals and in humans, we know that a little bit of change in the environment and novelty are rewarding and they stimulate well-being and cognitive functions,” explained Markram. “However, a highly unpredictable environment is also detrimental. When one cannot predict danger and every event or person is seen as threatening, then a maladaptive stress response is in place, and psychopathology is much more likely to develop.”

For people with autism, it appears from the study, the tolerance to novelty is much lower and the need for predictability much higher.

But with the predictability, at least in rats, comes great results.

“The striking result was that just this one manipulation of predictability completely prevented autistic-like behaviors in animals exposed to an autism risk factor,” Markram said.

The individual variation between rats in the study mirrored what we see in humans. It took a combination of vulnerable genetics, exposure to a toxin (valproate), and then unpredictable or unenriched environments to activate autism in the rats.

“Certain individuals are more sensitive to predictability in the environment than others,” explained Monica Favre, first author of the study, to Healthline.

Learn More: Genes Reveal That Not Even Siblings with Autism Share the Same Genetic Risk Factors »

Helping Autistic Children Early On

While parents can’t control their child’s genetics and often have limited control over what chemicals they’re exposed to in daily life, there’s still a great deal they can do to help their children.

“While it will be difficult to reverse and correct these developmental changes completely, the theory points to many exciting new possibilities for diagnosing, treating, and helping autistic children benefit from their unique brain,” said Markram. “For example, if the environment can be carefully controlled after birth, then the autistic child could potentially keep the supercharged microcircuits as well as their ability to orchestrate these microcircuits to fully express their genius without the suffering that can come with a supercharged brain.”

She added, “The curious thing is that any therapist or family member, or affected person, will confirm the importance of an organized schedule and a structured environment, with specific places and times for things and events, speaking to the need of the autistic person for sameness. Intriguingly, this is not at the core of how we approach an autistic child.”

The theory points to many exciting new possibilities for diagnosing, treating, and helping autistic children benefit from their unique brain.
Kamila Markram, Ph.D., Laboratory of Neural Microcircuits

Because of the great variance in autistic symptoms, different children will respond to different therapies, with intensive behavioral therapies usually being the most effective.

“However, each therapy is not successful in all children, and each patient and family goes through an exhausting list of attempts until they identify specific treatment features and approaches that are most useful for their child,” said Markram. “This causes a heavy financial and psychological burden on autistic people and caretakers and a loss of that time window early in development when therapy could be most effective.”

Since there is currently no foolproof way to diagnose autism at birth, and early development appears to be the most crucial window for intervention, Markram recommends some measure of predictability and structure for all young children.

“It seems reasonable that exposing any child to an enriched, yet also highly predictable environment, ideally from early on, would in the worst case cause no harm, and in the most sensitive cases, foster exceptional outcomes,” she said. “If autistic children are indeed more neurobiologically sensitive, such tamed and tailored early environmental stimulation could foster a dramatically improved quality of life.”

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