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How Autism-Risk Gene Rewires the Brain

UCLA SCIENTISTS HAVE ILLUSTRATED how a gene variant tied to autism rewires the brain. Their discovery, which was published in the online edition of Science and Translational Medicine, pinpoints the crucial Autism-Risk Genemissing mechanism that links altered genes to modified brain function and disrupted learning.

“This is a key piece of the puzzle we’ve been searching for,” says Professor of Neurology and Psychiatry Daniel Geschwind, M.D., Ph.D., the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics. “Now we can begin to unravel the mystery of how genes rearrange the brain’s circuitry, not only in autism but also in many related neurological disorders.”

The UCLA team scrutinized the differences in brain connectivity and function that result from two forms of the CNTNAP2 gene, one of which boosts the risk of autism. Suspecting that CNTNAP2 might influence brain activity, the researchers used functional magnetic resonance imaging (fMRI) to scan the brains of 32 children as they performed learning-related tasks. Half of the children had autism and half did not.

Depending on which CNTNAP2 version the child carried, the researchers observed a difference in connectivity between the left and right sides of the brain. In children with the non-risk gene, communication pathways in the frontal lobe linked more strongly to the left side of the brain, which processes functions tied to language. In children with the risk variant, communications pathways in the front lobe connected more broadly to both sides of the brain, suggesting that the gene variant rewires connections in the brain.

The finding could lead to earlier detection for autism and new interventions to strengthen connections between the frontal lobe and the left side of the brain.


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