Functional control of electrophysiological network architecture using direct neurostimulation in humans

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multimodal intracranial recordings and diffusion-weighted imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition. Brain stimulation devices capable of perturbing the physiological state of neural systems are rapidly gaining popularity for their potential to treat neurological and psychiatric disease. A root problem is that underlying dysfunction spans a large-scale network of brain regions, requiring the ability to control the complex interactions between multiple brain areas. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. We demonstrate the ability to predictably reconfigure patterns of interactions between functional brain areas by modulating the strength and location of stimulation. Our findings have high significance for designing stimulation protocols capable of modulating distributed neural circuits in the human brain.