Quantifying phase-amplitude coupling in neuronal network oscillations

Neuroscience time series data from a range of techniques and species reveal complex, non-linear interactions between different frequencies of neuronal network oscillations within and across brain regions. Here, we briefly review the evidence that these nested, cross-frequency interactions act in concert with linearly covariant (within-frequency) activity to dynamically coordinate functionally related neuronal ensembles during behaviour. Such studies depend upon reliable quantification of cross-frequency coordination, and we compare the properties of three techniques used to measure phase-amplitude coupling (PAC)--Envelope-to-Signal Correlation (ESC), the Modulation Index (MI) and Cross-Frequency Coherence (CFC)--by standardizing their filtering algorithms and systematically assessing their robustness to noise and signal amplitude using artificial signals. Importantly, we also introduce a freely-downloadable method for estimating statistical significance of PAC, a step overlooked in the majority of published studies. We find that varying data length and noise levels leads to the three measures differentially detecting false positives or correctly identifying frequency bands of interaction; these conditions should therefore be taken into careful consideration when selecting PAC analyses. Finally, we demonstrate the utility of the three measures in quantifying PAC in local field potential data simultaneously recorded from rat hippocampus and prefrontal cortex, revealing a novel finding of prefrontal cortical theta phase modulating hippocampal gamma power. Future adaptations that allow detection of time-variant PAC should prove essential in deciphering the roles of cross-frequency coupling in mediating or reflecting nervous system function

A canonical circuit for generating phase-amplitude coupling

‘Phase amplitude coupling’ (PAC) in oscillatory neural activity describes a phenomenon whereby the amplitude of higher frequency activity is modulated by the phase of lower frequency activity. Such coupled oscillatory activity – also referred to as ‘cross-frequency coupling’ or ‘nested rhythms’ – has been shown to occur in a number of brain regions and at behaviorally relevant time points during cognitive tasks; this suggests functional relevance, but the circuit mechanisms of PAC generation remain unclear. In this paper we present a model of a canonical circuit for generating PAC activity, showing how interconnected excitatory and inhibitory neural populations can be periodically shifted in to and out of oscillatory firing patterns by afferent drive, hence generating higher frequency oscillations phase-locked to a lower frequency, oscillating input signal. Since many brain regions contain mutually connected excitatory-inhibitory populations receiving oscillatory input, the simplicity of the mechanism generating PAC in such networks may explain the ubiquity of PAC across diverse neural systems and behaviors. Analytic treatment of this circuit as a nonlinear dynamical system demonstrates how connection strengths and inputs to the populations can be varied in order to change the extent and nature of PAC activity, importantly which phase of the lower frequency rhythm the higher frequency activity is locked to. Consequently, this model can inform attempts to associate distinct types of PAC with different network topologies and physiologies in real data