The children who speak least — or not at all — are rarely represented in cutting-edge brain imaging research on autism spectrum disorder (ASD). Researchers at The Children’s Hospital of Philadelphia aim to change that with a new study enrolling children with ASD who are minimally verbal or nonverbal.
“This is really an underserved community who have not been given the opportunity to participate in research,” said Timothy Roberts, PhD, vice chair of research in the Department of Radiology at CHOP and a professor of Radiology at the Perelman School of Medicine at the University of Pennsylvania. “More importantly, the results of the research are not directly applicable to them, so even if we developed a drug for ASD impairments led by our biomarkers, we wouldn’t know if this treatment really was good for individuals with ASD with more limited verbal and cognitive ability.”
Dr. Roberts and colleagues from CHOP’s Center for Autism Research want to know whether certain aspects of neural rhythms and timing of neural firing that they found to be characteristic of ASD in previous studies, using noninvasive brain imaging called magnetoencephalography (MEG), are indeed common across the spectrum.
“When neural activity is happening, it produces electrical and magnetic fields,” said J. Christopher Edgar, PhD, a co-leader of the study and a clinical neuropsychologist and brain imaging researcher in the Department of Radiology at CHOP. “We use this machine to measure the magnetic field. We do that to look at brain function.”
The neural biomarkers that Dr. Edgar and Dr. Roberts have found correlate with the level of clinical impairment in the children they have studied to date, particularly in the realm of language ability.
“There is a scientific question: Does this correlation extend into this nonverbal and minimally verbal population in a continuous way, or is it a separate disorder?” Dr. Roberts said. “I suppose a fundamental question is: Is the autism spectrum continuous or discrete in terms of these brain markers?”
To better define how specific these brain markers are for ASD, or to identify possible neural brain measures shared across neurodevelopmental disorders, the study will also include children with intellectual disability without ASD.
Innovative Study Creates Unique Behavioral Plan for Each Child
A significant innovation in the CHOP team’s new study is how they designed it for inclusion of minimally verbal and nonverbal children. The team calls the approach MEG-PLAN (MEG Protocol for Low-Language/Cognitive Ability Neuroimaging). It tailors the study participation experience to each child by engaging with parents as partners early and throughout the process. Study Co-leader Emily Kuschner, PhD, spearheads this behavioral aspect of the study design and its emphasis on taking the standard effort at autism-friendliness in research to a new, more personalized level.
In MEG-PLAN, Dr. Kuschner and the study team will work with parents to conduct a “mini” functional behavior assessment to identify difficulties or behaviors that might arise when children come in for the MEG visit. The research team will become familiar with the child’s particular sources of motivation and anxiety before the child visits the hospital. This helps the researchers to customize each child’s experience to minimize negative stimuli and to offer personally meaningful forms of positive reinforcement, such as favorite songs, toys, or foods, to reward participation. In essence, they create a unique behavior plan for each child participating in the study.
Parents and caregivers will receive videos and CDs to help prepare their child for participation. The video will help them know what to expect, and audio recordings will familiarize (and desensitize) them to the sounds of the MEG machine.
The research team will also rely on parents and caregivers to facilitate effective communication with their nonverbal and minimally verbal children. For example, parents are likely to know their child’s nonverbal cues well enough to recognize whether he or she has understood a request, or to recognize when they need to take a break. Parents and caregivers will work hand in hand with the study team throughout the visit; the process will be extremely collaborative.
Study Technology Tailored to Population’s Unique Needs
The CHOP team also designed technical aspects of the study to ensure success by measuring neural processes that happen automatically when the brain is stimulated, such as auditory nerve signaling when the child hears a sound. This way, the children do not need to consciously follow any instructions or complete any tasks for the scan in order for the researchers to receive useful information about their brain signaling patterns.
Under MEG-PLAN, participating children are also not required to hold extremely still while undergoing brain scans — a requirement in other studies that often makes minimally verbal and nonverbal children ineligible. Magnetic Resonance Imaging (MRI), which requires children to remain motionless for an extended period, was eliminated from the MEG-PLAN study protocol. The researchers will use age-matched template MRIs instead of the individual participants’ own MRIs to enable mathematical interpretations of MEG scans. In addition, they have developed motion-tracking methods and algorithms to compensate for minor or moderate movements a child may make during MEG scanning, which is sensitive to motion but less so than MRI.
Dr. Roberts noted that, if successful, the behavioral aspects of their study design could translate well to other studies, and even other study populations who are less able to participate, hold still, or follow instructions during brain scans, such as younger children and infants. The technical aspects of MEG-PLAN are fairly specific to conducting MEG studies, which are only conducted at a few centers including CHOP — but could still prove useful for future MEG research as well.
A Signature Project of CHOP and Penn Research Strengths
Research using MEG to detect novel brain measures (biomarkers) with which to diagnose and evaluate minimally verbal individuals on the autism spectrum is the signature research project of the Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP and Penn. This IDDRC center recently received renewed funding for the next five years from the Eunice Kennedy Shriver National Institute of Child Health and Development, its sixth successful and consecutive IDDRC grant application since its establishment in 1990. It is one of 15 centers in the national IDDRC network, which represent the nation’s first and foremost sustained effort to prevent and treat disabilities through biomedical and behavioral research.
On CHOP and Penn campuses, the IDDRC promotes intellectual and developmental disability related research through advocacy, education, and research support for investigators. It offers core laboratory services in areas including analytical neurochemistry, biostatistics and bioinformatics, clinical translational research, neuroimaging and neurocircuitry, and preclinical models. For more information about the IDDRC, contact Kristen Hearty at firstname.lastname@example.org.
The MEG-PLAN study is recruiting participants now, including school-age children (age 8 to 12 years) with ASD who are minimally verbal or nonverbal, and children with cognitive disabilities but not ASD (including those with 22q deletion syndrome, spina bifida, trisomy 21, Turner Syndrome, and intellectual disability with no known etiology). For more information, contact 267-426-6373 or MurrayR1@email.chop.edu.
Produced by The Children’s Hospital of Philadelphia Research Institute.
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