Measuring Phase-Amplitude Coupling Between Neuronal Oscillations of Different Frequencies

TLDR

Neuronal oscillations of different frequencies can interact, and recent evidence suggests that the amplitude of high‑frequency activity is modulated by the phase of low‑frequency rhythms, a cross‑frequency coupling phenomenon observed at both local and macroscopic brain scales. The study introduces a novel metric for quantifying phase‑amplitude coupling. The metric adapts the Kullback‑Leibler distance to measure how the empirical amplitude distribution across phase bins deviates from uniformity, and is benchmarked against seven existing CFC measures while addressing epoch length and surrogate control considerations. The new measure proves effective, outperforming alternatives in benchmark tests, and reveals distinct CFC patterns between CA3 and CA1 in freely moving rats.

Abstract

Neuronal oscillations of different frequencies can interact in several ways. There has been particular interest in the modulation of the amplitude of high-frequency oscillations by the phase of low-frequency oscillations, since recent evidence suggests a functional role for this type of cross-frequency coupling (CFC). Phase-amplitude coupling has been reported in continuous electrophysiological signals obtained from the brain at both local and macroscopic levels. In the present work, we present a new measure for assessing phase-amplitude CFC. This measure is defined as an adaptation of the Kullback-Leibler distance-a function that is used to infer the distance between two distributions-and calculates how much an empirical amplitude distribution-like function over phase bins deviates from the uniform distribution. We show that a CFC measure defined this way is well suited for assessing the intensity of phase-amplitude coupling. We also review seven other CFC measures; we show that, by some performance benchmarks, our measure is especially attractive for this task. We also discuss some technical aspects related to the measure, such as the length of the epochs used for these analyses and the utility of surrogate control analyses. Finally, we apply the measure and a related CFC tool to actual hippocampal recordings obtained from freely moving rats and show, for the first time, that the CA3 and CA1 regions present different CFC characteristics.