Abnormal Association Between Neural Activity and Genetic Expressions of Impulsivity in...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Impulsivity in Attention Deficit Hyperactivity Disorder (ADHD) is highly heritable.
• Previous research focused on neural activity (fMRI) or genetics separately.
• Multivariate methods linking both neural activity and gene expression in ADHD were underexplored.

Purpose of the Study:

• To investigate coupled neural activity and gene expression signatures in ADHD.
• To utilize parallel independent component analysis (pICA) for analyzing neuroimaging and genetic data.
• To link these multimodal signatures to behavioral and cognitive measures of impulsivity.

Main Methods:

• Used data from the Adolescent Brain Cognitive Development (ABCD) study.
• Included children with ADHD (n=394) and healthy controls (n=1,000).
• Applied pICA to discovery datasets and validated findings in replication datasets, analyzing fMRI and gene expression data.

Main Results:

• Identified three paired independent components (pICs) linking gene expression (cortex, cerebellum, nucleus accumbens) with neural activity.
• Found significant associations between these pICs and ADHD-related genes, including immunoglobulin and immunity terms.
• Demonstrated that multimodal regression using paired pICs significantly predicted behavioral inhibition and reaction times in the stop signal task (SST).

Conclusions:

• Reported biologically plausible pairs of neural activity and gene sets in ADHD.
• These multimodal signatures are significantly associated with impulsivity-related behavioral and cognitive data.
• Highlights the potential of integrating neuroimaging and genetic data for understanding ADHD.