PT  - JOURNAL ARTICLE
AU  - Jessica Nadalin
AU  - Louis-Emmanuel Martinet
AU  - Ethan Blackwood
AU  - Meng-Chen Lo
AU  - Alik S. Widge
AU  - Sydney S. Cash
AU  - Uri T. Eden
AU  - Mark A. Kramer
TI  - A statistical framework to assess cross-frequency coupling while accounting for modeled confounding effects
AID  - 10.1101/519470
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 519470
4099  - http://biorxiv.org/content/early/2019/06/11/519470.short
4100  - http://biorxiv.org/content/early/2019/06/11/519470.full
AB  - Cross frequency coupling (CFC) is emerging as a fundamental feature of brain activity, correlated with brain function and dysfunction. Many different types of CFC have been identified through application of numerous data analysis methods, each developed to characterize a specific CFC type. Choosing an inappropriate method weakens statistical power and introduces opportunities for confounding effects. To address this, we propose a statistical modeling framework to estimate high frequency amplitude as a function of both the low frequency amplitude and low frequency phase; the result is a measure of phase-amplitude coupling that accounts for changes in the low frequency amplitude. We show in simulations that the proposed method successfully detects CFC between the low frequency phase or amplitude and the high frequency amplitude, and outperforms an existing method in biologically-motivated examples. Applying the method to in vivo data, we illustrate how CFC evolves during a seizure and is affected by electrical stimuli.