Study reveals greater excitability in social brain regions of autistic men compared to women

August 04, 2020

New insight on differences in the brains of men and women with autism has been published today in the open-access journal eLife.

The study suggests that autistic men, but not women, have enhanced neural excitability in specific brain regions that are important for social cognition and self-reflection, and this may differentially impact their ability to navigate social situations.

These findings support the idea that imbalances between excitation and inhibition in the brain affect some individuals with autism more than others. They also pave the way for further research to measure the imbalance of excitation and inhibition with non-invasive neuroimaging techniques. This could help scientists evaluate how different treatments may affect this aspect of the brain's biology.

The brain possesses its own natural balance between excitation and inhibition, but this balance differs among individuals. Higher levels of excitation are linked to the function of some autism-relevant genes that are found on the sex chromosomes, and can also be affected by hormones produced in higher quantities in men, such as testosterone. Differences in these sex-related mechanisms are important as autism affects males more than females.

"With this study, we wanted to gain a better understanding of how excitation-inhibition imbalance may affect autistic men differently to women," says one of the study's lead authors, Stavros Trakoshis, a graduate student at the Laboratory for Autism and Neurodevelopmental Disorders at the Istituto Italiano di Tecnologia (IIT) in Rovereto, Italy, and also based at the University of Cyprus.

To do this, Trakoshis and his colleagues started by using a computer model that simulates excitatory and inhibitory neurons as they interact and influence each other within the brain. The model allowed them to control the ratio of mixture between excitation and inhibition, simulated these interactions, and then reported neuronal population responses over time. The outputs are similar to data commonly measured with neuroimaging techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI).

Trakoshis and the team observed that specific statistical attributes of the simulated data changed systematically with changes to the underlying excitation-inhibition ratios. These statistical changes were also validated using data from fMRI scans of brains in living mice that were given drugs to induce enhanced excitation.

After validating that non-invasive fMRI can reveal changes to the underlying cellular excitation-inhibition ratio, the team next applied their technique to fMRI data from adult men and women with autism. This revealed that autistic men, but not women, have atypically enhanced excitation in a brain region called the medial prefrontal cortex. The function of this brain region is typically associated with social cognition and self-reflection. The analysis also showed that, in women with autism, a more intact medial prefrontal cortex response (with less enhanced excitation, for example) was associated with better camouflaging of social difficulties in real-world social situations.

"Our work suggests that sex-related biological mechanisms could be integral for how excitation-inhibition balance develops in autistic men versus women," says senior author Michael Lombardo, Director of the Laboratory for Autism and Neurodevelopmental Disorders at the IIT. "This could help explain why we see phenomena such as camouflaging manifesting differently in autistic males versus females."

"Our approach could also be useful for understanding other neurodevelopmental conditions that affect males more than females, such as attention deficit-hyperactivity disorder," Lombardo concludes.
-end-
Reference

The paper 'Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women' can be freely accessed online at https://doi.org/10.7554/eLife.55684. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We work across three major areas: publishing, technology and research culture. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Human Biology and Medicine and Neuroscience, while exploring creative new ways to improve how research is assessed and published. We also invest in open-source technology innovation to modernise the infrastructure for science publishing and improve online tools for sharing, using and interacting with new results. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Human Biology and Medicine research published in eLife, visit https://elifesciences.org/subjects/human-biology-medicine.

And for the latest in Neuroscience, see https://elifesciences.org/subjects/neuroscience.

eLife

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.