PT - JOURNAL ARTICLE AU - Edden M. Gerber AU - Boaz Sadeh AU - Andrew Ward AU - Robert T. Knight AU - Leon Y. Deouell TI - Periodic Non-Sinusoidal Activity Can Produce Cross-Frequency Coupling in Cortical Signals in the Absence of Functional Interaction Between Neural Sources AID - 10.1101/062190 DP - 2016 Jan 01 TA - bioRxiv PG - 062190 4099 - http://biorxiv.org/content/early/2016/07/05/062190.short 4100 - http://biorxiv.org/content/early/2016/07/05/062190.full AB - The analysis of cross-frequency coupling (CFC) has become popular in studies involving intracranial and scalp EEG recordings in humans. It has been argued that some cases where CFC is mathematically present may not reflect an interaction of two distinct yet functionally coupled neural sources with different frequencies. Here we provide two empirical examples from intracranial recordings where CFC can be shown to be driven by the shape of a periodic waveform rather than by a functional interaction between distinct sources. Using simulations, we also present a generalized and realistic scenario where such coupling may arise. This scenario, which we term waveform-dependent CFC, arises when sharp waveforms (e.g., cortical potentials) occur in a periodic manner throughout parts of the data. Since the waveforms are repeated periodically, they constitute a slow wave that is inherently phase-aligned with the high-frequency component carried by the same waveforms. We submit that such behavior of the data, which seems to be present in various cortical signals, cannot be interpreted as reflecting functional modulation between distinct neural sources without additional evidence. In addition, we show that even low amplitude periodic potentials that cannot be readily observed or controlled for, are sufficient for significant CFC to occur.