Fig. 1: Multidimensional E/I homeostasis is more than hypo- and hyper-excitation.

A theoretical example of two similar individuals with altered dyshomeostasis, that can separately be interpreted as a “hyperexcitation phenotype,” but through two distinct combinations of microscale, mesoscale, and macroscale observations (blue and red). Thus, a multidimensional E/I framework is more optimal to describe these two distinct phenotypes that don’t fit neatly into a binary hyper- vs hypo-phenotype and considers population and network dynamics. Four axes to describe E/I homeostasis through this multidimensional E/I framework are represented as sliding toggles including population synchrony (asynchrony versus synchronous), intrinsic cell state (hypoexcitable versus hyperexcitable), spatial scale (local vs global), and behavioral context (rest versus task). Hp = Hippocampus.