TY - JOUR T1 - White Matter Network Architecture Guides Direct Electrical Stimulation Through Optimal State Transitions JF - bioRxiv DO - 10.1101/313304 SP - 313304 AU - Jennifer Stiso AU - Ankit N. Khambhati AU - Tommaso Menara AU - Ari E. Kahn AU - Joel M. Stein AU - Sandihitsu R. Das AU - Richard Gorniak AU - Joseph Tracy AU - Brian Litt AU - Kathryn A. Davis AU - Fabio Pasqualetti AU - Timothy Lucas AU - Danielle S. Bassett Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/02/313304.abstract N2 - Electrical brain stimulation is currently being investigated as a potential therapy for neurological disease. However, opportunities to optimize and personalize such therapies are challenged by the fact that the beneficial impact (and potential side effects) of focal stimulation on both neighboring and distant regions is not well understood. Here, we use network control theory to build a formal model of brain network function that makes explicit predictions about how stimulation spreads through the brain’s white matter network and influences large-scale dynamics. We test these predictions using combined electrocorticography (ECoG) and diffusion weighted imaging (DWI) data from patients with medically refractory epilepsy undergoing evaluation for resective surgery, and who volunteered to participate in an extensive stimulation regimen. We posit a specific model-based manner in which white matter tracts constrain stimulation, defining its capacity to drive the brain to new states, including states associated with successful memory encoding. In a first validation of our model, we find that the true pattern of white matter tracts can be used to more accurately predict the state transitions induced by direct electrical stimulation than the artificial patterns of a topological or spatial network null model. We then use a targeted optimal control framework to solve for the optimal energy required to drive the brain to a given state. We show that, intuitively, our model predicts larger energy requirements when starting from states that are farther away from a target memory state. We then suggest testable hypotheses about which structural properties will lead to efficient stimulation for improving memory based on energy requirements. We show that the strength and homogeneity of edges between controlled and uncontrolled nodes, as well as the persistent modal controllability of the stimulated region, predict energy requirements. Our work demonstrates that individual white matter architecture plays a vital role in guiding the dynamics of direct electrical stimulation, more generally offering empirical support for the utility of network control theoretic models of brain response to stimulation. ER -