Detection of Multiway Gamma Coordination Reveals How Frequency Mixing Shapes Neural Dynamics

A principle of communication technology, frequency mixing, describes how novel oscillations are generated when rhythmic inputs converge on a nonlinearly activating target. As expected given that neurons are nonlinear integrators, it was demonstrated that neuronal networks exhibit mixing in response to imposed oscillations of known frequencies. However, determining when mixing occurs in spontaneous conditions, where weaker or more variable rhythms prevail, has remained impractical. Here, we show that, by exploiting the predicted phase (rather than frequency) relationships between oscillations, the contributions of mixing can be readily identified, even in small samples of noisy data. Assessment of extracellular data using this approach revealed that frequency mixing is widely expressed in a state- and region-dependent manner and that oscillations emerging from mixing entrain unit activity. Frequency mixing is thus intrinsic to the structure of neural activity and contributes importantly to neural dynamics.