The vP300 Framework: Trial-to-Trial Variability in the P300 Event-Related Potential as a Signal of Locus Coeruleus-Norepinephrine Dynamics

The P300 event-related potential is one of the most studied electrophysiological markers of cognition, yet trial-to-trial variability within conditions has traditionally been treated as measurement error.The vP300 framework proposes that P300 variability, quantified by the coefficient of variation (CV), may reflect locus coeruleus-norepinephrine (LC-NE) mode dynamics. A computational simulation (N = 80) tested three hypotheses. Empirical P3 oddball data from the ERP CORE dataset (N = 39) provided partial validation. Mean amplitude and CV were orthogonal in simulation (r = −0.14, n.s.) and moderately correlated in empirical data (r = −0.418, p = .008), with 82.5% of CV variance independent of mean amplitude. CV significantly predicted cognitive flexibility (r = −0.319, p = .004) while mean amplitude did not (r = .010, p = .928). Trial- to-trial P300 variability carries information orthogonal to traditional mean amplitude, supporting a potential revision of how variability is treated in ERP research.