Abstract / Summary
Quantifying neural health with a single measure remains a major unmet challenge. Here, we report a physiological marker based on the spatial distribution of signal-derived energy correlates in the resting brain. We hypothesize that energy organization in the healthy brain approaches an entropy-maximizing, homeostatically regulated state characterized by five properties: lognormal energy distributions, balanced spatial allocation, statistical independence between regions, low energy variance, and temporal stability. Together, these properties define an energetic profile that the Neural Health Index (NHI) summarizes as a single score, computable from (scalp/intracranial) electroencephalography, magnetoencephalography, or functional magnetic resonance imaging. Across 808 participants spanning neurological, psychiatric, neurodevelopmental, and neurodegenerative disorders, NHI distinguished healthy from clinical populations with sensitivity and specificity exceeding 95% in internal and external validation, scaled with disease severity, tracked pharmacological treatment exposure, and generalized to unseen diagnoses. These findings support NHI as a disease-agnostic, modality-invariant candidate biomarker for disease stratification and treatment monitoring.