Time-resolved phase-amplitude coupling in neural oscillations.

Cross-frequency coupling between neural oscillations is a phenomenon observed across spatial scales in a wide range of preparations, including human non-invasive electrophysiology. Although the functional role and mechanisms involved are not entirely understood, the concept of interdependent neural oscillations drives an active field of research to comprehend the ubiquitous polyrhythmic activity of the brain, beyond empirical observations. Phase-amplitude coupling, a particular form of cross-frequency coupling between bursts of high-frequency oscillations and the phase of lower frequency rhythms, has recently received considerable attention. However, the measurement methods have relatively poor sensitivity and require long segments of experimental data. This obliterates the resolution of fast changes in coupling related to behavior, and more generally, to the non-stationary dynamics of brain electrophysiology. We propose a new measure of phase-amplitude coupling that can resolve up to one, optimally two, cycles of the underlying slow frequency component. The method also provides a measure of the coupling strength, for augmented insight into the mechanisms involved. We demonstrate the technique with synthesized data and compare its performances with existing methods. We also show that the method reveals rapid changes in coupling parameters in data from the entorhinal cortex of a free-behaving rat. The time-resolved changes revealed are compatible with behavior and complement observed modulations of oscillatory power. We anticipate that this new measure of dynamic phase-amplitude coupling will contribute to accelerate research into the dynamics of inter-dependent oscillatory components related to brain functions and dysfunctions.