AUTHOR=Perley Andrew S. , Coleman Todd P. 

TITLE=A mutual information measure of phase-amplitude coupling using gamma generalized linear models

JOURNAL=Frontiers in Computational Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2024.1392655

DOI=10.3389/fncom.2024.1392655

ISSN=1662-5188

ABSTRACT=Cross frequency coupling (CFC) between electrophysiological signals in the brain is a longstudied phenomenon and its abnormalities have been observed in conditions such as Parkinson's disease and epilepsy. More recently, CFC has been observed in stomach-brain electrophysiologic studies and thus becomes an enticing possible target for diseases involving aberrations of the gutbrain axis. However, current methods of detecting coupling, specifically phase-amplitude coupling (PAC), do not attempt to capture the phase and amplitude statistical relationships. In this paper, we first demonstrate a method of modeling these joint statistics with a flexible parametric approach, where we model the conditional distribution of amplitude given phase using a gamma distributed generalized linear model (GLM) with a Fourier basis of regressors. We perform model selection with minimum description length (MDL) principle, demonstrate a method for assessing goodnessof-fit (GOF), and showcase the efficacy of this approach in multiple electroencephalography (EEG) datasets. Secondly, we showcase how we can utilize the mutual information, which operates on the joint distribution, as a canonical measure of coupling, as it is non-zero and non-negative if and only if the phase and amplitude are not statistically independent. Using synthetically generated gut-brain coupled signals, we demonstrate that our method outperforms the existing gold-standard methods for detectable low-levels of phase-amplitude coupling through receiver operating characteristic (ROC) curve analysis. To validate our method, we test on invasive EEG recordings by generating comodulograms, and compare our method to the gold standard PAC measure, Modulation Index, demonstrating comparable performance in exploratory analysis.Furthermore, to showcase its use in joint gut-brain electrophysiology data, we generate topoplots of simultaneous high-density EEG and electrgastrography recordings and reproduce seminal work by Richter et al. that demonstrated the existence of gut-brain PAC. In addition, we build off of previous work by Martinez-Cancino et al., and Voytek et al., and  show that the information density, evaluated using our method along the given sample path, is a promising measure of time-resolved PAC. Using simulated data, we validate our method for different types of time-varying coupling and then demonstrate it's performance in sleep spindle EEG and mismatch negativity (MMN) datasets.