Development of a Phase-amplitude Coupling Toolbox for Assessing Changes in Cross-frequency Coupling Due to Deep Brain Stimulation Therapies for Treatment Resistant Depression

Abstract

Phase-amplitude coupling (PAC) is theorized to play a fundamental physiological role in neuronal oscillations of the brain. This work contends that changes in PAC due to deep brain stimulation (DBS) in treatment-resistant depression (TRD) can account for the palliative effects observed in TRD patients. Part of this work compares the efficacy of six metrics for PAC based on their application to synthetic signals: the Kullback-Leibler based modulation index (KL-MI), the heights ratio (HR), the general linear model (GLM), the phase locking value (PLV), the mean vector length normalized by principal component analysis (PCA), and the coherence value (CV). GLM gives the smallest region of detected coupling in the comodulograms, evades bimodality artifacts arising from the continuous wavelet transform (CWT) in this region of interest, and provides the greatest visual contrast. After an initial stage of validation and characterization of each metric, these metrics would then be applied to recorded local field potentials (LFP) before and after DBS to assess PAC. The goal of this work is to present a toolbox of metrics that are characterized on synthetic signals which would serve as a benchmark to clinicians for application to patient data.