By Emily Leclerc | Waisman Science Writer
*Note: The Travers lab has chosen to use identity first language in response to the growing preference for this type of language in the autism community. The language in this story reflects that choice.*
Autism is often associated with complex tasks like social processing and language and the later-developing brain regions that control them. But what if autism is more rooted in the earliest developing and most reflex-like part of the brain – the brainstem? This brainstem focused hypothesis about autism was put forth nearly 60 years ago by scientists but was left virtually untested due to the challenges of imaging the area in living individuals.
This new research by Brittany Travers, PhD, Waisman investigator and associate professor of kinesiology, is the first to officially test this hypothesis in children thanks to the advancements in brain imaging techniques. Her work reveals that the brainstem may indeed be central to core autism features. “It is a pivotal brain structure and deserves some attention, particularly in autism,” Travers says.
A stalk-like structure located at the base of the brain, the brainstem controls the body’s involuntary and automatic processes such as heart rate, blood pressure, breathing, digestion, and swallowing, among other functions. Even though we may not be aware of it, this autonomic nervous system – the name given to the specific bundle of nerves in the brainstem that regulate those processes – is in a constant state of responding to external and internal information.
The brainstem has reactions and sets of reactions to a variety of stimuli to try to keep our body in a state of balance, or homeostasis. Increase heart rate when this happens. Lower blood pressure when that happens. Disrupt digestion to reallocate energy when this happens. In turn, our behavior may be subtly or not so subtly affected by the underlying autonomic nervous system processing, even if we are not aware of it. So, what happens when this system is acting differently in a person?
“The brainstem is one of the earliest developing parts of the brain. So, it makes sense, in a neurodevelopmental condition like autism, that there would be differences that are happening in the brainstem that help explain the individual differences in autism,” Travers says.
Travers’ recent paper, “Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features” published in the journal Autism Research, shows that several core autism features, such as social communication differences and restrictive or repetitive behavior, may be directly related to the areas of the brainstem involved in autonomic functions, which may lead autistic individuals to experience or interpret the world’s stimuli in different ways.
Travers and her team utilized diffusion tensor imaging (DTI), a type of magnetic resonance imaging (MRI) that specifically measures how water diffuses through different tissue types, to look at the brainstem’s structure in autistic individuals and non-autistic individuals. Traditionally, the brainstem is a hard structure to image due to its location and the similarities in its tissue composition. DTI makes it possible to visualize the brainstem’s unique structure and tissue composition. Travers found differences in the autonomic nervous system’s structure between the two groups of participants that correlated with social communication differences and more restrictive or repetitive behavior.
DTI allowed Travers to focus specifically on the nuclei in the brainstem that are involved in our autonomic functions, pain systems, and the limbic system – which handles memory, emotion, and stress responses. “The autonomic nervous system is very much tied to the pain network and also to emotional structures. The original theories were also in line with these parts of the brainstem,” Travers says. “So, we chose to look at this particular grouping of brainstem structures.”
In particular, Travers found two nuclei in the brainstem that showed microstructural differences in autistic individuals and significant association with core autism features. The first nucleus, LPB, is involved in the pain processing system for internal organs and showed a significant relationship with an increase in repetitive behaviors. The second nucleus, PCRtA, is involved in digestion, swallowing, eating, and cardio-respiration and showed a meaningful relationship with more pronounced social communication challenges. Travers hypothesizes that structural changes in PCRtA could contribute to why it is fairly common for autistic individuals to have gastrointestinal discomfort and struggles eating or swallowing.
“This study was the first to be able to test this 60-year-old hypothesis in living children, and found that specific areas within the brainstem are linked to autism features,” Travers says. “This study directly tests and confirms this prior theory while also extending the literature to show that it is not all of the brainstem but some very specific nuclei that are involved in autonomic processing.”
Even the oldest and most rudimentary part of the brain still presents with great complexity. This work indicates that the brainstem likely plays an important role in the core features of autism but the mechanisms behind it are still a mystery. The study’s results did not reveal to Travers what exact changes to the brainstem are contributing to the core features. “We don’t know from our DTI if it is the myelination or the number of neurons or something else because we’re only looking at how water interacted with the tissues. This study helps us locate differences within the brainstem, but It brings up more questions than it solves,” Travers says. She hopes to answer those questions in future research.
“The brainstem is so important because it is this intersection between the brain and the rest of the body. So much information is transmitted through the brainstem and yet we’ve omitted it from most of our studies,” Travers says. “I’ve learned that the brainstem seems to be important in autism and it’s time that we really dug into this.”
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