Revell, Andrew Y.; Alexander B. Silver; Dhanya Mahesh; Lena Armstrong; T. Campbell Arnold; John M. Bernanei; Joel M. Stein; Sandhitsu R. Das; Russell T. Shinohara; Dani S. Bassett; Brian Litt and Kathryn A. Davis

White matter supports critical brain functions such as learning and memory, modulates the distribution of action potentials, and acts as a relay of neural communication between different brain regions. Interestingly, neuronal cell bodies exist in deeper white matter tissue, neurotransmitter vesicles are released directly in white matter, and white matter blood-oxygenation level dependent (BOLD) signals are detectable across a range of different tasks—all appearing to reflect intrinsic electrical signals in white matter. Yet, such signals within white matter have largely been ignored. Here, we elucidate the properties of white matter signals using intracranial EEG. We show that such signals capture the communication between brain regions and differentiate pathophysiologies of epilepsy. In direct contradiction to past assumptions about white matter in-activity, we show that white matter recordings can elucidate brain function and pathophysiology not apparent in gray matter. Broadly, white matter functional recordings acquired through implantable devices may provide a wealth of currently untapped knowledge about the neurobiology of disease.