Functional Connectivity on Magnetoencephalography May Be a Biomarker of Autism Spectrum Disorder
Key findings
- In this study, magnetoencephalography was used to measure evoked responses and functional connectivity in response to inverted faces in children with autism spectrum disorder (ASD) and typically developing (TD) children, ages seven to 18
- There were no differences between the two groups in evoked responses to inverted faces
- In response to inverted faces, local functional connectivity and long-range functional connectivity between the fusiform face area (FFA) and the inferior frontal gyrus (IFG) were reduced in the ASD group compared with the TD group
- Reduced functional connectivity between the FFA and the IFG was correlated with more severe ASD symptomatology, and alterations in both local and long-range functional connectivity distinguished ASD from TD participants with 81% accuracy
- Together with earlier findings by researchers at Massachusetts General Hospital, this work indicates the potential value of magnetoencephalography for understanding the neural mechanisms of ASD and aiding development of ASD therapies
Recent research has pointed to abnormalities in functional connectivity—the integration of brain activity across brain regions—as a possible biomarker of autism spectrum disorder (ASD). Some of these studies have documented abnormalities in how people with ASD process information conveyed by faces, a critical component of social communication.
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Researchers at Massachusetts General Hospital previously showed in PNAS that in adolescents and young adults with ASD, local functional connectivity in the fusiform face area (FFA, part of a specializing face processing system in the brain) can be abnormal even in the presence of normal evoked responses (measures of electrical activity). The same was true for long-range functional connectivity between the FFA and cortical areas involved in top-down processing.
However, as reported in Human Brain Mapping, children with ASD showed no differences in functional connectivity compared with typically developing (TD) children.
Like most research about face processing in ASD, these studies involved having subjects view upright pictures of faces. In Autism Research, Fahimeh Mamashli, PhD, and Tal Kenet, PhD, researchers in the Martinos Center for Biomedical Imaging at Mass General, and colleagues now report that to their surprise, they detected neurophysiological abnormalities in children with ASD when faces were inverted.
Study Methods
Study participants were 21 children with ASD and 27 TD children ages seven to 18. The two groups were matched for age and verbal and nonverbal IQ.
Like the previous research at Mass General, the study made use of magnetoencephalography, which measures brain waves indirectly by measuring magnetic fields produced by electrical activity. With much higher temporal resolution than functional MRI, it can detect changes that happen over tens of milliseconds.
During magnetoencephalography, participants viewed pictures of upright neutral, angry or fearful adult faces; pictures of inverted neutral faces; and pictures of houses, in randomized order. This analysis considered only the houses, upright neutral faces and inverted neutral faces.
Magnetoencephalography Results
- As expected from the prior research, there were no between-group differences in evoked responses elicited by any set of pictures
- Unexpectedly, in response to inverted faces, local functional connectivity in the FFA was reduced in the ASD group compared with the TD group
- Similarly, long-range functional connectivity between the FFA and the inferior frontal gyrus (IFG) was reduced in the ASD group in response to inverted faces
Correlations
- Reduced functional connectivity between the FFA and the IFG was correlated with more severe ASD symptomatology
- Functional connectivity between the FFA and the IFG increased with age in the TD group but not the ASD group
- Alterations in both local and long-range functional connectivity, considered together, distinguished ASD from TD participants with 81% accuracy
Implications
This work indicates the potential value of magnetoencephalography for understanding the neural mechanisms of ASD and aiding in the development of ASD therapies. Together with the previous studies at Mass General, it also suggests caveats for researchers investigating the neurophysiology of ASD: abnormalities are often more subtle than can be detected using common measures such as evoked responses, a range of methodologies are needed and abnormalities are age-dependent.
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