Cortical excitability, defined as the cortex's responsiveness to incoming stimuli, is a fundamental concept in neuroscience and a targetable mechanism for controlling brain dysfunctions such as epilepsy, as well as other neurological and psychiatric disorders. In this review, we delineate the boundaries between physiological and pathological excitability, highlighting recent theoretical, experimental, and translational advances relevant to human brain disorders. Specifically, we describe the dynamic regulation of cortical excitability and propose practical means to monitor its known fluctuations as to guide therapeutic interventions.
From a conceptual standpoint, the last decade of research on cortical excitability has benefited from dynamical systems theory, which studies the behavior of nonlinear systems (here, the cortex) and their resilience to perturbations in different conditions (here, variable excitability). We review how fundamental relationships between excitability and resilience were verified in the brain in a series of recent studies. We also review natural fluctuations in cortical excitability, and how these may open windows of vulnerability for the expression of cortical dysfunctions. We then turn to the practicalities of measuring and monitoring cortical excitability, a latent variable that must be actively probed.
Practical means for gauging cortical excitability likely have broad applicability. To enable new developments in clinical practice, a principled design of pharmacological and neurostimulation therapies must leverage current understanding of cortical dynamics.