EEG signals accurately predict autism as early as 3 months of age

Early diagnosis by 'digital biomarkers' may allow early intervention, better outcomes

May 1, 2018

Science Daily/Boston Children's Hospital

Autism is challenging to diagnose, especially early in life. A new study shows that inexpensive EEGs, which measure brain electrical activity, accurately predict or rule out autism spectrum disorder in infants, even in some as young as three months.

"EEGs are low-cost, non-invasive and relatively easy to incorporate into well-baby checkups," says Charles Nelson, PhD, director of the Laboratories of Cognitive Neuroscience at Boston Children's Hospital and co-author of the study. "Their reliability in predicting whether a child will develop autism raises the possibility of intervening very early, well before clear behavioral symptoms emerge. This could lead to better outcomes and perhaps even prevent some of the behaviors associated with ASD."

The study analyzed data from the Infant Sibling Project (now called the Infant Screening Project), a collaboration between Boston Children's Hospital and Boston University that seeks to map early development and identify infants at risk for developing ASD and/or language and communication difficulties.

William Bosl, PhD, associate professor of Health Informatics and Clinical Psychology at the University of San Francisco, also affiliated with the Computational Health Informatics Program (CHIP) at Boston Children's Hospital, has been working for close to a decade on algorithms to interpret EEG signals, the familiar squiggly lines generated by electrical activity in the brain. Bosl's research suggests that even an EEG that appears normal contains "deep" data that reflect brain function, connectivity patterns and structure that can be found only with computer algorithms.

The Infant Screening Project provided Bosl with EEG data from 99 infants considered at high risk for ASD (having an older sibling with the diagnosis) and 89 low-risk controls (without an affected sibling). The EEGs were taken at 3, 6, 9, 12, 18, 24 and 36 months of age by fitting a net over the babies' scalps with 128 sensors as the babies sat in their mothers' laps. (An experimenter blew bubbles to distract them.) All babies also underwent extensive behavioral evaluations with the Autism Diagnostic Observation Schedule (ADOS), an established clinical diagnostic tool.

Bosl's computational algorithms analyzed six different components (frequencies) of the EEG (high gamma, gamma, beta, alpha, theta, delta), using a variety of measures of signal complexity. These measures can reflect differences in how the brain is wired and how it processes and integrates information, says Bosl.

The algorithms predicted a clinical diagnosis of ASD with high specificity, sensitivity and positive predictive value, exceeding 95 percent at some ages.

"The results were stunning," Bosl says. "Our predictive accuracy by 9 months of age was nearly 100 percent. We were also able to predict ASD severity, as indicated by the ADOS Calibrated Severity Score, with quite high reliability, also by 9 months of age."

Bosl believes that the early differences in signal complexity, drawing upon multiple aspects of brain activity, fit with the view that autism is a disorder that begins during the brain's early development but can take different trajectories. In other words, an early predisposition to autism may be influenced by other factors along the way.

"We believe that infants who have an older sibling with autism may carry a genetic liability for developing autism," says Nelson. "This increased risk, perhaps interacting with another genetic or environmental factor, leads some infants to develop autism -- although clearly not all, since we know that four of five "infant sibs" do not develop autism."

https://www.sciencedaily.com/releases/2018/05/180501085140.htm

Stress exposure during pregnancy observed in mothers of children with autism

More research needed to understand gene-stress interaction

June 7, 2016

Science Daily/University of Missouri-Columbia

Stress during pregnancy has been linked to several conditions, including some instances of autism spectrum disorder. Now, researchers have observed a variant of a stress-sensitive gene and exposure to stress during pregnancy among two groups of mothers of children with autism. The finding could be a step toward helping identify women who have greater risks for having children with autism when exposed to stressors during pregnancy.

"Autism was thought to be largely a genetic disorder, but previous research has shown that environmental influences such as stress can play an important role in the development of the condition," said David Beversdorf, M.D., associate professor in the departments of radiology, neurology and psychological sciences at the University of Missouri and the MU Thompson Center for Autism and Neurodevelopmental Disorders, and senior author of the study. "We know that some mothers who experience significant levels of stress don't have children with autism, but others do. To help understand why, we studied a gene that is known to affect stress and found a link between it and the development of autism with exposure to stress."

Led by Beversdorf's graduate student, Patrick Hecht, Ph.D., in collaboration with Xudong Liu, Ph.D., with Queen's University in Ontario, Canada, the researchers studied two separate groups of mothers of children with autism spectrum disorder -- a group of families at MU and a group of families at Queen's University. The mothers were surveyed about stress during their pregnancy, such as loss of a job, moving or divorce. The mothers' blood was tested for a variation of the stress-sensitive gene known as 5-HTTLPR, which regulates the neurotransmitter serotonin in the nervous system. When a variation of the gene is present, the availability of serotonin is altered, causing an increased reaction to stress.

In both groups, mothers of children with autism who have the variation of the stress-sensitive gene reported experiencing more stress during the end of the second and the beginning of the third trimester of pregnancy, compared to mothers who did not carry the altered gene.

"Though this was an observational study and future confirmation of this finding is needed, it's possible we could, one day, identify women who may be at a greater risk of having a child with autism when exposed to stress," said Beversdorf, who also serves as the William and Nancy Thompson Endowed Chair in Radiology. "More research is needed to understand the mechanisms of how this gene-stress interaction works, but hopefully this could someday help prevent some cases of autism."

https://www.sciencedaily.com/releases/2016/06/160607220116.htm

Fine particulate air pollution linked with increased autism risk

December 18, 2014

Science Daily/Harvard School of Public Health

Women exposed to high levels of fine particulate matter specifically during pregnancy -- particularly during the third trimester -- may face up to twice the risk of having a child with autism than mothers living in areas with low particulate matter, according to a study. The greater the exposure, the greater the risk, researchers found. It was the first US-wide study exploring the link between airborne particulate matter and autism.

"Our data add additional important support to the hypothesis that maternal exposure to air pollution contributes to the risk of autism spectrum disorders," said Marc Weisskopf, associate professor of environmental and occupational epidemiology and senior author of the study. "The specificity of our findings for the pregnancy period, and third trimester in particular, rules out many other possible explanations for these findings."

The researchers explored the association between autism and exposure to PM2.5 before, during, and after pregnancy. They also calculated exposure to PM2.5 during each pregnancy trimester.

Exposure to PM2.5 was significantly associated with autism during pregnancy, but not before or after, the study found. And during the pregnancy, the third trimester specifically was significantly associated with an increased risk. Little association was found between air pollution from larger-sized particles (PM10-2.5) and autism.

"The evidence base for a role for maternal exposure to air pollution increasing the risk of autism spectrum disorders is becoming quite strong," said Weisskopf. "This not only gives us important insight as we continue to pursue the origins of autism spectrum disorders, but as a modifiable exposure, opens the door to thinking about possible preventative measures."

http://www.sciencedaily.com/releases/2014/12/141218081334.htm