Patches of cortical layers disrupted during early brain development in autism

March 26, 2014
Postmortem analysis of autistic brain tissue revealed patch-like areas of disorganized neurons. Arrows show a patch of decreased or absent expression of genetic markers across multiple layers of the dorsolateral prefrontal cortex. Credit: Rich Stoner, Ph.D., University of California, San Diego

Researchers at the University of California, San Diego School of Medicine and the Allen Institute for Brain Science have published a study that gives clear and direct new evidence that autism begins during pregnancy.

The study will be published in the March 27 online edition of the New England Journal of Medicine.

The researchers – Eric Courchesne, PhD, professor of neurosciences and director of the Autism Center of Excellence at UC San Diego, Ed S. Lein, PhD, of the Allen Institute for Brain Science in Seattle, and first author Rich Stoner, PhD, of the UC San Diego Autism Center of Excellence – analyzed 25 genes in post-mortem brain tissue of children with and without . These included genes that serve as biomarkers for brain cell types in different layers of the cortex, genes implicated in autism and several control genes.

"Building a baby's brain during pregnancy involves creating a cortex that contains six layers," Courchesne said. "We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism." Stoner created the first three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern.

"The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder," explained Lein.

During early brain development, each cortical layer develops its own specific types of , each with specific patterns of brain connectivity that perform unique and important roles in processing information. As a brain cell develops into a specific type in a specific layer with specific connections, it acquires a distinct genetic signature or "marker" that can be observed.

The study found that in the brains of children with autism, key genetic markers were absent in brain cells in multiple layers. "This defect," Courchesne said, "indicates that the crucial early developmental step of creating six distinct layers with specific types of brain cells – something that begins in prenatal life – had been disrupted."

Equally important, said the scientists, these early developmental defects were present in focal patches of cortex, suggesting the defect is not uniform throughout the cortex. The brain regions most affected by focal patches of absent gene markers were the frontal and the , possibly illuminating why different functional systems are impacted across individuals with the disorder.

The is associated with higher-order brain function, such as complex communication and comprehension of social cues. The temporal cortex is associated with language. The disruptions of frontal and temporal cortical layers seen in the study may underlie symptoms most often displayed in autistic spectrum disorders. The visual cortex – an area of the brain associated with perception that tends to be spared in autism – displayed no abnormalities.

"The fact that we were able to find these patches is remarkable, given that the cortex is roughly the size of the surface of a basketball, and we only examined pieces of tissue the size of a pencil eraser," said Lein. "This suggests that these abnormalities are quite pervasive across the surface of the cortex."

Data collected for the Allen Brain Atlas, as well as the BrainSpan Atlas of the Developing Human Brain was developed by a consortium of partners and funded by the National Institute of Mental Health. It allowed scientists to identify specific genes in the developing human brain that could be used as biomarkers for the different layer cell types.

Researching the origins of autism is challenging because it typically relies upon studying adult brains and attempting to extrapolate backwards. "In this case," Lein noted, "we were able to study autistic and control cases at a young age, giving us a unique insight into how autism presents in the developing brain."

"The finding that these defects occur in patches rather than across the entirety of gives hope as well as insight about the nature of autism," added Courchesne.

According to the scientists, such patchy defects, as opposed to uniform cortical pathology, may help explain why many toddlers with autism show clinical improvement with early treatment and over time. The findings support the idea that in children with autism the can sometimes rewire connections to circumvent early focal defects, raising hope that understanding these patches may eventually open new avenues to explore how that improvement occurs.

Explore further: Study identifies gene expression abnormalities in autism

More information: Patches of disorganization in the neocortex of children with autism. Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, Wynshaw-Boris A, Colamarino SA, Lein ES, Courchesne E. NEJM, March 27, 2014.

Related Stories

Study identifies gene expression abnormalities in autism

March 22, 2012
A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms ...

Autism linked with excess of neurons in prefrontal cortex

November 8, 2011
A study by researchers at the University of California, San Diego Autism Center of Excellence shows that brain overgrowth in boys with autism involves an abnormal, excess number of neurons in areas of the brain associated ...

Gene family mutation, autism linked

January 28, 2014
(Medical Xpress)—Harvard Medical School researchers at McLean Hospital have found that a gene family linked to autism, EphB, is essential for proper brain wiring during development. The findings suggest that the abnormal ...

Autism in children affects not only social abilities, but also broad range of sensory and motor skills

June 25, 2013
A group of investigators from San Diego State University's Brain Development Imaging Laboratory are shedding a new light on the effects of autism on the brain.

Team first to map autism-risk genes by function

November 21, 2013
Pity the poor autism researcher. Recent studies have linked hundreds of gene mutations scattered throughout the brain to increased autism risk. Where do you start?

Social symptoms in autistic children may be caused by hyper-connected neurons

November 7, 2013
The brains of children with autism show more connections than the brains of typically developing children do. What's more, the brains of individuals with the most severe social symptoms are also the most hyper-connected. ...

Recommended for you

'Residual echo' of ancient humans in scans may hold clues to mental disorders

July 26, 2017
Researchers at the National Institute of Mental Health (NIMH) have produced the first direct evidence that parts of our brains implicated in mental disorders may be shaped by a "residual echo" from our ancient past. The more ...

Laser used to reawaken lost memories in mice with Alzheimer's disease

July 26, 2017
(Medical Xpress)—A team of researchers at Columbia University has found that applying a laser to the part of a mouse brain used for memory storage caused the mice to recall memories lost due to a mouse version of Alzheimer's ...

Cognitive cross-training enhances learning, study finds

July 25, 2017
Just as athletes cross-train to improve physical skills, those wanting to enhance cognitive skills can benefit from multiple ways of exercising the brain, according to a comprehensive new study from University of Illinois ...

Brain disease seen in most football players in large report

July 25, 2017
Research on 202 former football players found evidence of a brain disease linked to repeated head blows in nearly all of them, from athletes in the National Football League, college and even high school.

Zebrafish study reveals clues to healing spinal cord injuries

July 25, 2017
Fresh insights into how zebrafish repair their nerve connections could hold clues to new therapies for people with spinal cord injuries.

Lutein may counter cognitive aging, study finds

July 25, 2017
Spinach and kale are favorites of those looking to stay physically fit, but they also could keep consumers cognitively fit, according to a new study from University of Illinois researchers.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.