For the first time, a USC-led research team has mapped the genetic architecture of a crucial part of the human brain known as the corpus callosum—the thick band of nerve fibers that connects the brain’s left and right hemispheres. The findings open new pathways for discoveries about mental illness, neurological disorders and other diseases related to defects in this part of the brain. In the new study, published in Nature Communications, the team analyzed brain scans and genetic data from over 50,000 people, ranging from childhood to late adulthood, with the help of a new tool the team created that leverages artificial intelligence. The AI tool finds the corpus callosum in different types of brain MRI scans and automatically takes its measurements. Using this tool, the researchers identified dozens of genetic regions that influence the size and thickness of the corpus callosum and its subregions. The study revealed that different sets of genes govern the area versus the thickness of the corpus callosum—two features that change across the lifespan and play distinct roles in brain function. Several of the implicated genes are active during prenatal brain development, particularly in processes like cell growth, programmed cell death, and the wiring of nerve fibers across hemispheres. These findings provide a genetic blueprint for one of the brain’s most essential communication pathways. By uncovering how specific genes shape the corpus callosum and its subregions, researchers can start to understand why differences in this structure are linked to various mental health and neurological conditions at a molecular level.