Rational design of transcranial current stimulation (TCS) through mechanistic insights into cortical network dynamics

Transcranial current stimulation (TCS) is a promising method of non-invasive brain stimulation to modulate cortical network dynamics. Preliminary studies have demonstrated the ability of TCS to enhance cognition and reduce symptoms in both neurological and psychiatric illnesses. Despite the encouraging results of these studies, the mechanisms by which TCS and endogenous network dynamics interact remain poorly understood. Here, we propose that the development of the next generation of TCS paradigms with increased efficacy requires such mechanistic understanding of how weak electric fields (EFs) imposed by TCS interact with the nonlinear dynamics of large-scale cortical networks. We highlight key recent advances in the study of the interaction dynamics between TCS and cortical network activity. In particular, we illustrate an interdisciplinary approach that bridges neurobiology and electrical engineering. We discuss the use of (1) hybrid biological-electronic experimental approaches to disentangle feedback interactions; (2) large-scale computer simulations for the study of weak global perturbations imposed by TCS; and (3) optogenetic manipulations informed by dynamic systems theory to probe network dynamics. Together, we here provide the foundation for the use of rational design for the development of the next generation of TCS neurotherapeutics.