Studying the Brain’s Fundamental Drum Beat to Understand Autism

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A drum beat coordinating brain activity and thus organizing the music of life emerges from deep inside the human brain. This electromagnetic neural pulse —eight to 12 beats per second — is known as the resting-state alpha rhythm.

“Alpha rhythms may be the most fundamental brain rhythm, involved in coordinating brain processes from those as simple as hearing tones and those as complex as consciousness,” said  J. Christopher Edgar, PhD, a clinical neuropsychologist and brain imaging researcher in the Department of Radiology at The Children’s Hospital of Philadelphia.

Researchers have known for some time that electromagnetic (neural) brain activity is different in individuals on the autism spectrum. In a series of recent studies, Dr. Edgar and colleagues have shown that the resting-state alpha rhythm is stronger among individuals on the autism spectrum, and that stronger alpha rhythms are associated with more severe clinical symptoms.

With a new grant from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), Dr. Edgar will use state-of-the-art noninvasive brain imaging called magnetoencephalography (MEG) scanning to measure brain activities, including alpha rhythms, and magnetic resonance imaging to obtain structural brain measures in adolescents with and without autism spectrum disorder (ASD). He aims to find out why that metaphorical drum beat, setting the pace for the activities of other players or different parts of the brain, sounds different in children on the autism spectrum.

“The main goal of our study is to obtain measures of activity throughout the entire brain, rather than just on the surface of the head,” Dr. Edgar said. “We want to examine the association between the structure of the thalamus, pathways from the thalamus to the brain surface, and brain activity.”

Dr. Edgar suspects that timing abnormalities in the thalamus, a deep brain structure, may be the cause of surface-level brain alpha abnormalities in individuals with ASD. The thalamus acts as a central relay station, controlling the flow of information from the outside world into the brain. The thalamus is likely also the drummer that sets the pace of the alpha rhythm.

If Dr. Edgar’s findings bear out the hypothesis that the thalamus is associated with alpha-rhythm abnormalities in ASD (and perhaps also related to clinical symptoms), these findings would suggest new approaches to treating autism-related impairments via therapies that target the alpha-related activities. For instance, identifying possible abnormalities in the pathways between the thalamus and cortex, whose typical functioning is already known, could help to identify clear targets for treatments with medication or behavioral therapies.

“There are not yet any pharmaceutical treatments for the core symptoms of autism, and there are few promising treatments in the pipeline,” Dr. Edgar said. “A lack of effective treatment indicates the need to identify abnormal brain structure and function in ASD.”

Connecting the identification of brain abnormalities to treatment strategies will require many years of further work and may follow a long and winding path. Still, many researchers are committed to using brain imaging to guide the development of treatments for ASD and other neurodevelopmental disorders, as they consider this one of the most promising ways to make progress.

The example of the drug STX209 (arbaclofen) illustrates how brain-imaging research in ASD informs drug development, along the journey to potential future drug approval. This investigational drug targets a neurotransmitter involved in generating the brain’s gamma rhythm (30 to 50 beats per second), which is abnormal in several conditions including ASD and Fragile X syndrome.

A new MEG study at CHOP is being conducted to identify potential acute effects of STX209 on brain activity in adolescent boys with ASD. This study follows on past testing of STX209 in clinical trials, which did not achieve these trials’ intended clinical outcomes — a failure potentially attributable to variability between participants, as not all individuals with ASD have abnormal gamma rhythms.

The new, small study at CHOP addresses the hypothesis that the drug will have a brief “normalizing” effect on brain activity, potentially only in the subset of individuals with ASD who have abnormal gamma rhythms. Any positive finding could inform future clinical trials that may use brain imaging to identify individuals with the most potential to benefit based on their gamma rhythm abnormalities.

In the case of alpha rhythms, there is no drug yet known to directly target alpha rhythm abnormalities. As such, any discovery Dr. Edgar makes would be more foundational, proving an understanding of exactly how individuals on the autism spectrum march to a different beat.

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