Abnormal auditory and language pathways in children with 16p11.2 deletion

Area of Science:

• Neuroscience
• Genetics
• Developmental Disorders

Background:

• Copy number variations at chromosome 16p11.2 are associated with neurodevelopmental disorders like autism spectrum disorder (ASD).
• Children with the 16p11.2 BP4-BP5 deletion often exhibit significant disruptions in spoken language abilities.

Purpose of the Study:

• To investigate the biological underpinnings of behavioral phenotypes in ASD, specifically focusing on language deficits in 16p11.2 deletion carriers.
• To examine the structure of auditory and language white matter pathways in pediatric 16p11.2 deletion carriers using diffusion MRI.

Main Methods:

• A cohort of 36 pediatric 16p11.2 deletion carriers and 45 age-matched controls underwent diffusion MRI.
• Diffusion MR tractography was used to analyze the auditory radiations and arcuate fasciculus, measuring white matter microstructure.
• Tract-specific diffusion parameters were correlated with clinical language and non-verbal cognitive abilities.

Main Results:

• Deletion carriers showed significantly higher diffusivity in both the auditory radiations and arcuate fasciculus compared to controls.
• White matter microstructure in these tracts matured with age similarly in both groups.
• In deletion carriers, left-hemisphere arcuate fasciculus diffusivity negatively correlated with language ability, but not non-verbal cognition.

Conclusions:

• The 16p11.2 deletion is associated with altered white matter structure in auditory and language pathways.
• These microstructural differences in the arcuate fasciculus may contribute to the spoken language deficits observed in ASD.
• Findings provide insights into the neurobiological mechanisms linking genetic variations to behavioral phenotypes in neurodevelopmental disorders.