Mapping human functional white matter using intracranial stereoelectroencephalography electrode stimulation and high-resolution tractography

For decades, brain function was thought to follow a simple rule: each brain region performs a single function. It is now understood that the brain operates as a complex network, where different regions work together. The cortex (gray matter) forms the outer layer of the brain and is responsible for processing information, while the white matter lies beneath the cortex and contains bundles of connections, called tracts, that act as wires to link different cortical areas. These tracts are the communication highways, allowing the cortex to share information across the brain. However, despite their essential contribution in brain interaction, the functions of most human white matter tracts remain unknown, especially in relation to complex cognitive processes such as attention, memory, and planning.

This project uses a clinical procedure called stereoelectroencephalography (SEEG) in people with drugresistant epilepsy, performed to locate seizure sources. During this minimally invasive diagnostic procedure, thin electrodes are temporarily implanted in the brain for about two weeks. While patients are awake and carefully monitored, specific white matter tracts can be safely stimulated, and both basic and complex cognitive functions can be repeatedly assessed. By combining SEEG stimulation with advanced brain imaging, major white matter tracts will be visualized and linked to the responses they produce. This will allow the creation of the first detailed functional atlas (map) of human white matter.

This atlas offers a unique opportunity to reveal the functions of brain connections that were previously unknown, filling a major gap in our understanding of how the human brain works. It will show how different pathways support movement, language, attention, memory, and other behaviors. Clinically, this knowledge will help neurosurgeons protect critical pathways during surgery—reducing the risk of neurological complications—and highlight vulnerable networks that could be targeted in treatments for neurological disorders, ultimately improving patients’ recovery.