Summary: Researchers identify network inefficiencies in the auditory cortex by the age of 6 months in infants who go on to be diagnosed with autism.
Source: McGill University.
Abnormalities shown to first appear in brain networks involved in sensory processing.
The origins of autism remain mysterious. What areas of the brain are involved, and when do the first signs appear? New findings published in Biological Psychiatry brings us closer to understanding the pathology of autism, and the point at which it begins to take shape in the human brain. Such knowledge will allow earlier interventions in the future and better outcomes for autistic children.
Scientists used a type of magnetic resonance imaging (MRI), known as diffusion weighted imaging, to measure the brain connectivity in 260 infants at the ages of 6 and 12 months, who had either high or low risks of autism. The lengths and strengths of the connections between brain regions was used to estimate the network efficiency, a measure of how well each region is connected to other regions. A previous study with 24-month-old children found that network efficiency in autistic children was lower in regions of the brain involved in language and other behaviours related to autism. The goal of this new study was to establish how early these abnormalities occur.
Lead author John Lewis, a researcher at the Montreal Neurological Institute and Hospital of McGill University and the Ludmer Centre for Bioinformatics and Mental Health, found network inefficiencies had already been established in six-month-old infants who went on to be diagnosed with autism. Inefficiencies in the six-month-olds appeared in the auditory cortex. He also found the extent of the inefficiency at six months of age was positively related to the severity of autistic symptoms at 24 months. As the children aged, areas involved in processing of vision and touch, as well as a larger set of areas involved in sound and language, also showed such a relation between inefficiency and symptom severity.
Identifying the earliest signs of autism is important because it may allow for diagnosis before behavioural changes appear, leading to earlier intervention and better prospects for a positive outcome. By pinpointing the brain regions involved in processing sensory inputs as the earliest known locations of neural dysfunction related to autism, researchers narrow down the genetic factors and mechanisms that could be responsible for its development. The fact that neurological signs are already present at six months also eliminates some environmental factors as potential causes of the disorder.
“Our goal was to discover when and where in the brain the network inefficiencies first appeared,” says Lewis. “The results indicate that there are differences in the brains of infants who go on to develop autism spectrum disorder even at six months of age, and that those early differences are found in areas involved in processing sensory inputs, not areas involved in higher cognitive functions. We hope that these findings will prove useful in understanding the causal mechanisms in autism spectrum disorder, and in developing effective interventions.”
The research comes from the Infant Brain Imaging Study (IBIS), a collaborative effort by investigators at the Montreal Neurological Institute, and four clinical sites in the United States, coordinated to conduct a longitudinal brain imaging and behavioural study of infants at high risk for autism.
Funding: The work was supported by a National Institutes of Health grant, by the Azrieli Neurodevelopmental Research Program in partnership with the Brain Canada Multi-Investigator Research Initiative, and by funding from Autism Speaks, the Simons Foundation, the Canada Foundation for Innovation, the Government of Québec, the National Science and Engineering Research Council, the Fonds Québécois de Recherche sur la Nature et les Technologies, and La Fondation Marcelle et Jean Coutu.
Source: Shawn Hayward – McGill University
Image Source: NeuroscienceNews.com image is credited to Ludmer Centre.
Original Research: Full open access research for “The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder” by John D. Lewis, Alan C. Evans, John R. Pruett Jr., Kelly N. Botteron, Robert C. McKinstry, Lonnie Zwaigenbaum, Annette M. Estes, D. Louis Collins, Penelope Kostopoulos, Guido Gerig, Stephen R. Dager, Sarah Paterson, Robert T. Schultz, Martin A. Styner, Heather C. Hazlett, and Joseph Piven in Biological Psychiatry. Published online August 1 2017 doi:10.1016/j.biopsych.2017.03.006
The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life.
This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion.
Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity.
These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.
“The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder” by John D. Lewis, Alan C. Evans, John R. Pruett Jr., Kelly N. Botteron, Robert C. McKinstry, Lonnie Zwaigenbaum, Annette M. Estes, D. Louis Collins, Penelope Kostopoulos, Guido Gerig, Stephen R. Dager, Sarah Paterson, Robert T. Schultz, Martin A. Styner, Heather C. Hazlett, and Joseph Piven in Biological Psychiatry. Published online August 1 2017 doi:10.1016/j.biopsych.2017.03.006