Genetic MEG Study Links Language Delay to Chromosome Deletion

Feb 25 2015

Genetic MEG Study Links Language Delay to Chromosome Deletion

chromosome As each child heard a series of tones, the MEG machine analyzed changing magnetic fields in the child’s brain, just as electroencephalography (EEG) detects electrical fields.

 

According to new research, children born with a DNA abnormality on chromosome 16 already linked to neurodevelopmental problems show measurable delays in processing sound and language. By strengthening the case that the deleted gene disrupts a key biological pathway, the study may lay the foundation for future medical treatments for specific subtypes of autism, along with cognitive and language disabilities.

“This study shows an important connection between gene differences and differences in neurophysiology,” said Timothy P.L. Roberts, PhD, vice chair of Radiology Research at The Children’s Hospital of Philadelphia and a researcher at CHOP’s Center for Autism Research. “It may also help to bridge a largely unexplored gap between genetics and behavior.”

Dr. Roberts led the study published recently in Cerebral Cortex, collaborating with a group from the University of California, San Francisco. The researchers examined children with copy number variants — either deletions or duplications of DNA — at the genetic site 16p11.2. Previous researchers had found that this location on chromosome 16 was associated with a subset of autism spectrum disorders (ASDs) and with developmental and language delays.

The researchers used magnetoencephalography (MEG), which detects magnetic fields in the brain, just as electroencephalography (EEG) detects electrical fields. As each child heard a series of tones, the MEG machine analyzed changing magnetic fields in the child’s brain, measuring an auditory processing delay called the M100 response latency. The researchers analyzed 115 children: 43 with the 16p11.2 deletion, 23 with the 16p11.2 duplication, and 49 healthy controls. Only a fraction of the children had ASD diagnoses: 11 of the 43 with the deletion, and 2 of the 23 with the duplication.

In children with the deletion, the researchers found a significant delay: 23 milliseconds (ms), a figure that Dr. Roberts called “stunningly high” compared to the healthy children. There was no such delay among children with the duplication, who actually had a non-significant tendency to process sounds faster than the control subjects.

The 23-ms delay, about one-fortieth of a second, was twice as high as the 11-ms M100 delay that Dr. Roberts found in a 2010 magnetoencephalography study of children with ASDs.

While the 2010 study focused on children diagnosed with autism spectrum disorders, the Cerebral Cortex study took a “genetics first” approach, analyzing children known to have genetic variants with or without ASD diagnoses. “We have approached the problem from both ends,” Dr. Roberts said. The previous study found a link between the brain and behavior, while this new study found a link between genetics and the brain.”

Although not all of the children with CNVs had autism, all of them had some neurological or learning disabilities, he noted. Because the severity of neurodevelopmental symptoms did not correlate with the length of the auditory processing delay, the M100 delay may not become a clear-cut diagnostic biomarker in neurological disorders, but it may be a clue to an important common pathway in neurobiology.

“We don’t yet know the significance of the 23-millisecond delay, but we have established its origin in genetics,” Dr. Roberts said. “It seems to be a proxy for something of biological significance.”

Further studies will investigate other genes previously implicated in autism spectrum disorders  and other psychiatric disorders, to determine whether they also involve M100 response delays. “Our goal is to unify diverse genes along a few common pathways, some of which may be treatable with specific therapies,” said Dr. Roberts.

To read more about the Cerebral Cortex magnetoencephalography study, see a press release about the project.