E/I ratio and net E+I strength are differentially affected across brain disorders

Neuronal oscillations wax and wane near criticality, switching between high- and low-power states. However, the link between this bistability and excitation–inhibition balance is not well understood. Using a computational model, we demonstrate that bistability is influenced by two key factors: the excitatory-inhibitory (E/I) ratio and the combined strength of excitatory and inhibitory activity (E+I). We developed algorithms to infer both metrics from electrophysiological data and validated them in vivo. In intracranial recordings from epilepsy patients, both E/I and E+I increased during seizures, while interictally, E+I remained elevated in seizure zones as E/I decreased—consistent with compensatory inhibition. Extending the framework to scalp EEG from eight disorders, we found that Alzheimer’s disease is better classified by E/I changes, whereas autism spectrum disorder and ADHD are distinguished by E+I alterations. Our findings highlight the importance of bistability in understanding EI regulation and offer handles for diagnostic and treatment decision support.