Simon and Ezra are Autistic, and they stim. Stimming can help regulate what they are experiencing.

Autism has yet to be linked to a single cause due to the wide range of its symptoms and severity. However, a study by University of Virginia researchers suggests a promising new approach to finding answers that could advance the study of other neurological conditions.

Current approaches to autism research involve observing and understanding the condition through studying its behavioural consequences, using techniques like functional magnetic resonance imaging that map the brain’s responses to input and activity. However, little work has been done to understand what causes those responses.

However, researchers with UVA’s College and Graduate School of Arts & Sciences have been able to better understand the physiological differences between the brain structures of autistic and non-autistic individuals by using Diffusion MRI, a technique that measures molecular diffusion in biological tissue, to observe how water moves throughout the brain and interacts with cellular membranes. The approach has helped the UVA team develop mathematical models of brain microstructures that have helped identify structural differences in the brains of those with autism and those without.

“It hasn’t been well understood what those differences might be,” said Benjamin Newman, a postdoctoral researcher with UVA’s Department of Psychology, a recent graduate of UVA School of Medicine’s neuroscience graduate program and lead author of a paper published this month in PLOS: One. “This new approach looks at the neuronal differences contributing to the aetiology of autism.”

Building on the work of Alan Hodgkin and Andrew Huxley, who won the 1963 Nobel Prize in Medicine for describing the electrochemical conductivity characteristics of neurons, Newman and his co-authors applied those concepts to understand how that conductivity differs in those with autism and those without, using the latest neuroimaging data and computational methodologies.  The result is a first-of-its-kind approach to calculating neural axons’ conductivity and capacity to carry information through the brain. The study also offers evidence that those microstructural differences are directly related to participants’ scores on the Social Communication Questionnaire, a common clinical tool for diagnosing autism.

“What we’re seeing is that there’s a difference in the diameter of the microstructural components in the brains of autistic people that can cause them to conduct electricity slower,” Newman said.  “It’s the structure that constrains how the function of the brain works.”

One of Newman’s co-authors, John Darrell Van Horn, a professor of psychology and data science at UVA, said that we often try to understand autism through a collection of behavioural patterns that might be unusual or seem different.

“But understanding those behaviours can be a bit subjective, depending on who’s observing,” Van Horn said. “We need greater fidelity in terms of the physiological metrics that we have so that we can better understand where those behaviours coming from. This is the first time this kind of metric has been applied in a clinical population, and it sheds some interesting light on the origins of autism .”

Van Horn said there’s been a lot of work done with functional magnetic resonance imaging, looking at blood oxygen-related signal changes in autistic individuals, but this research ” goes a little bit deeper.” 

“It’s asking not if there’s a particular cognitive functional activation difference; it’s asking how the brain conducts information around itself through these dynamic networks,” Van Horn said. “And I think that we’ve been successful showing that there’s something uniquely different about autistic diagnosed individuals relative to otherwise typically developing control subjects.”

Newman and Van Horn, along with co-authors Jason Druzgal and Kevin Pelphrey from the UVA School of Medicine, are affiliated with the National Institute of Health’s Autism Center of Excellence (ACE). This initiative supports large-scale multidisciplinary and multi-institutional studies on autism to determine the disorder’s causes and potential treatments. 

According to Pelphrey, a neuroscientist and expert on brain development and the study’s principal investigator, the overarching aim of the ACE project is to lead the way in developing a precision medicine approach to autism. 

“This study provides the foundation for a biological target to measure treatment response and allows us to identify avenues for future treatments to be developed,” he said.

Van Horn added that the study may also have implications for the examination, diagnosis, and treatment of other neurological disorders like Parkinson’s and Alzheimer’s.

“This is a new tool for measuring the properties of neurons, which we are particularly excited about. We are still exploring what we can detect with it,” Van Horn said.