On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus

Abstract
Data availability
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Abstract

Phase-amplitude coupling between theta and multiple gamma sub-bands is a hallmark of hippocampal activity and believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit phase-phase coupling, or n:m phase-locking, suggesting an important mechanism of neuronal coding that has long received theoretical support. However, by analyzing simulated and actual LFPs, here we question the existence of theta-gamma phase-phase coupling in the rat hippocampus. We show that the quasi-linear phase shifts introduced by filtering lead to spurious coupling levels in both white noise and hippocampal LFPs, which highly depend on epoch length, and that significant coupling may be falsely detected when employing improper surrogate methods. We also show that waveform asymmetry and frequency harmonics may generate artifactual n:m phase-locking. Studies investigating phase-phase coupling should rely on appropriate statistical controls and be aware of confounding factors; otherwise, they could easily fall into analysis pitfalls.

Data availability

The following data sets were generated

1. Scheffer-Teixeira R
2. Tort A.
(2016) Multisite LFP recordings from the rat hippocampus during REM sleep
Available at Dryad Digital Repository under a CC0 Public Domain Dedication.

http://dx.doi.org/10.5061/dryad.12t21

The following previously published data sets were used

(2013) Multiple single unit recordings from different rat hippocampal and entorhinal regions while the animals were performing multiple behavioral tasks
Publicly available at CRCNS.

http://dx.doi.org/10.6080/K09G5JRZ

Article and author information

Author details

Robson Scheffer-Teixeira

Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil

Competing interests
The authors declare that no competing interests exist.
Adriano BL Tort

Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil

For correspondence
tort@neuro.ufrn.br

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9877-7816

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Robson Scheffer-Teixeira
Adriano BL Tort

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Robson Scheffer-Teixeira
Adriano BL Tort

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were approved by our local institutional ethics committee (Comissão de Ética no Uso de Animais - CEUA/UFRN, protocol number 060/2011) and were in accordance with the National Institutes of Health guidelines.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.