Published by the Students of Johns Hopkins since 1896
July 5, 2020

Noninvasive biomarker could identify autism

By ISAAC CHEN | November 8, 2018

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted interests and impaired social interaction and communication. Currently the diagnosis of ASD primarily relies on behavioral assessments, including the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) and the Autism Diagnostic Observation Schedule (ADOS). 

While these diagnoses are conducted by trained psychiatrists and clinical speech therapists, there is a need for an objective and quantifiable method for the diagnosis of autism. 

Kyung-min An, a researcher at the Research Center for Child Mental Development in Kanazawa University and the first author of a new autism study, shared his belief in the importance of giving an early ASD diagnosis.

“Early diagnosis of ASD is highly important so that we can actively manage the disorder as soon as possible,” An said in a press release.

One of the hypotheses regarding the neurophysiology aspect of ASD claims that the cortical excitatory and inhibitory (E/I) balance is altered in individuals with ASD, specifically a lack of inhibition. Previous studies have demonstrated that this decreased cortical inhibition is associated with decreased levels of inhibitory gamma-aminobutyric acid (GABA) neurotransmitters, which further reflects a lower frequency of gamma waves in the brain. 

Besides socio-communicative deficits in ASD, abnormalities in motor control have also been widely prevalent in people with ASD. 

In fact, Leo Kanner, a physician at the Hopkins School of Medicine and the founder of the first child psychiatry clinic in the country, reported such atypicalities in his first description of autism back in 1943. 

The high prevalence of motor impairments in individuals with ASD is something not to be ignored due to its significant impacts on one’s quality of life. Some researchers have even suggested to constitute this abnormality as a core symptom of ASD.

In the experiment conducted by An’s research team, the researchers recruited 14 children with ASD and age and IQ-matched typically developing children for a video game task while recording their motor-induced brain waves using magnetoencephalography (MEG). MEG provides both high temporal and good spatial resolution. 

Based on the reduced inhibition hypothesis and known motor impairments, the researchers hypothesized that the children with ASD would demonstrate motor-induced gamma waves with lower frequency and reduced power. Power refers to the percent contribution of a specific brain wave to the overall recorded MEG signal. 

The experiment provided a video game-like motor task with the goal of collecting fruits. In the game, a puppy is running and then a fruit appears on the screen. Participants then have to press a button as soon as possible for the puppy to collect the fruit. Afterward, a visual target appears randomly 3.5 to 4.5 seconds after the button press. If the participant presses the button when the visual target is absent, the puppy falls down, and the trial is counted as a failure. 

Only considering the successful trials, the researchers measured three distinct parameters. Mitsuru Kikuchi is a doctor at the Research Center for Child Mental Development in Kanazawa University. His research is aimed at establishing new physiological indices for evaluating child cerebrum development using technologies such as MEG and Near-infrared spectroscopy (NIRS). 

“We measured the button response time, motor-evoked magnetic fields, and motor-related gamma oscillations,” Kikuchi said in a press release. 

Part of the collected data confirmed results from previous related studies. 

“As found in other studies, the ASD children’s response time was slightly slower and the amplitude in their magnetic fields was a bit decreased. The gamma oscillations were where we saw significant and interesting differences,” Kikuchi said.

Matching up with their earlier hypothesis, the frequency of the motor-induced gamma waves was lower in the ASD group compared to the typically developing (TD) group. This result suggests a lower GABA concentration in the primary motor area. In addition, children with more severe autism symptoms were associated with lower gamma wave frequencies. The ASD group also demonstrated reduced gamma wave power. 

Overall this study improved understandings of the underlying mechanisms in motor control in children with ASD.

“These findings may prove to be extremely useful in helping us understand the neurophysiological mechanism behind social and motor control development in children with ASD. Using magnetoencephalography in this way gives us a noninvasive and quantifiable biomarker, which is something we are in great need of,” An said.

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