The National Institutes of Health is funding University of Illinois Urbana-Champaign researchers to study risk factors for autism spectrum disorders using magnetic resonance imaging.

Howard Gritton, professor of comparative bioscience and bioengineering; Jozien Goense, professor of psychology and bioengineering; and Paul Bonthuis, professor of comparative biosciences and neuroscience; are working to better understand the relationship between phthalate exposure on the developing brain and consequences for social behavior in connection with autism spectrum disorders.

Howard Gritton (left) and Paul Bonthuis at the Beckman Institute. Jozien Goense not pictured. Credit: Elizabeth Bello, Beckman Communications Office.

The team recently received a $2.7 million grant from the U.S. National Institutes of Health. They originally received a Beckman seed grant in 2024 and the current funding developed from the work that was done on the original project.

In 2024, Gritton and Goense, along with Beckman collaborators Benjamin Auerbach and Brad Sutton, received seed funding from the Beckman Institute research seed grant program to investigate the genetic basis of altered behavior and brain function related to autism spectrum disorder.

A key component of the seeded project was using functional MRI in mice to image neural circuits and whole brain function in response to gene alterations that eventually cause downstream behavioral changes. 

The Bruker 9.4 Tesla preclinical functional MRI scanner located at the Biomedical Imaging Center, Beckman Institute. Credit: Scott Paceley.

Data collected from the seed funded project proved to be instrumental in demonstrating feasibility for the NIH application and funded award.

“The seed grant was involved in establishing functional imaging in mice and collaborations between Jozien, the Biomedical Imaging Center and myself,” Gritton said.

Using the methods and knowledge established during the seed project, Gritton, Goense and Bonthuis along with other Illinois collaborators, will now focus on the relationship between exposure to endocrine disrupting compounds, or EDCs, and nervous system alterations during fetal development. These alterations may ultimately contribute to abnormal changes in social behavior and communication which are often markers of autism spectrum disorder.

“The NIH grant is about using our prior imaging framework to look at an autism model associated with environmental toxins,” Gritton said. “In this case the toxicants are phthalates, a type of plasticizer that makes plastic flexible and are widely present in our environment and in our bodies.”

Phthalates can be found in vinyl flooring, shower curtains, food and beverage containers, children’s toys and various other plastic products and fragrances. They are pervasive in the environment and because they mimic hormones and can bind to hormone receptors, they are classified as EDCs that may have potentially profound impacts on neurodevelopment.

Prior studies have shown that pregnant women are exposed to phthalates throughout pregnancy and that phthalate concentrations are highest in children 6-11 years old. Other studies have shown that individuals exposed to phthalates during fetal development also show higher incidences of autistic traits including impaired social behavior and communication.

“During pregnancy, everything is timed, the right hormones must signal at the right time and in the right amount. If something disrupts that timeline, we want to know if it causes changes in the brain that lead to eventual changes in behavior which are linked with autism,” Goense said.

The team will use functional MRI to track changes in the brain when exposed to different levels of phthalates. Looking at both changes to anatomical connections that exist within the brain, and changes to functional networks or the way those connections communicate with one another, the team will be able to relate that information to downstream behavioral changes like social behavior, avoidant behavior and different anxiety measures.

“There is a correlational relationship between plastic exposure during development and autism, and we want to look into that in more detail,” Gritton said. “We’re looking at dopamine and glutamate signals in different regions of the brain that we know are important for the expression of social behavior in another aim of this grant that is informed by the MRI work.”

To visualize changes in the brain, Goense and Illinois graduate students will operate the Bruker 9.4 Tesla MRI scanner in Beckman’s Biomedical Imaging Center. The scanner gives researchers the ability to closely look at circuit function in various brain structures. 

"In addition to running the scanner, we also work on image analysis and developing data analysis pipelines for image post-processing,” Goense said.

One advantage to using MRI is that the images will provide the team with a brain-wide measure of alterations after exposure to phthalates.

This allows the researchers to dial in their focus from an observed behavior to whole brain activity, to a specific brain region down to the neural circuits that are involved and ultimately to the genomic level by looking at gene expression as another part of the awarded grant.

This image shows that phthalate exposure developmentally reduces network measures of connectivity in the brain. (A) Pearson’s correlation matrix showing reduced anatomical connectivity across multiple brain regions of a phthalate-exposed subject (lower-left image) compared to normal connectivity in the same regions of a control subject (upper left image). (B) MRI tractography images showing reduced axon connectivity (colored regions, lower-right image) from a region of the brain known as the retrosplenial cortex in a phthalate-exposed brain compared to the control group (upper right image). Credit: Howard Gritton.

Bonthuis, having expertise in genome function and genetics, will focus on gene expression patterns in the brain in response to phthalate exposure and its effects on social behaviors. The goal is to identify neural circuits affected by phthalates that regulate specific aspects of sociality.

“Research shows that exposure to endocrine-disrupting toxicants can alter neural development and produce long‑lasting changes in gene expression in the brain. Through our multidisciplinary and complementary approaches, this collaboration will enable us to identify the affected neural circuits, uncover cell type–specific gene expression changes, and map these alterations onto the relevant brain circuits,” Bonthius said.

 Autism spectrum disorder is inherently complex and there is no singular identifiable cause or solution. By taking a closer look at the mechanisms at play and at various levels – gene expression, neural circuits and brain connectivity – the team will begin to unravel its complexity.

“It is simply a pressing issue that is prevalent in our society, and we are doing our best to understand its mechanisms,” Gritton said.

Editor’s notes:

Research reported in this press release was supported by the National Institutes of Health under award number 1R01ES036997-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.