Nonsinusoidal neuronal oscillations: bug or feature?

Abstract

There is compiling evidence suggesting that independent neuronal ensembles are coordinated in time and space through cross-frequency coupling (CFC). However, recent studies have convincingly demonstrated that nonsinusoidal oscillations produce serious biases in state of the art CFC metrics. Although most of studies treat nonsinusoidal waves as a nuisance or just ignore them, fortunately some scientists are starting to exploit their neurophysiological relevance opening new research vistas with critical implications. There is a wide consensus regarding the key role of neuronal oscillations during perceptive and cognitive operations. Neuronal oscillations are cyclical voltage fluctuations generated by pools of neurons that fire in synchrony. They can be characterized by three features: frequency (how fast they cycle), amplitude (strength of the rhythm), and phase (where in the cycle the signal is sitting). Recently, studies have focused on how different oscillations interact with each other and synchronize independent sets of neuronal ensembles, forming the so-called cross-frequency coupling (CFC) (Jensen and Colgin 2007). One attractive idea behind CFC is that the phase of slower rhythms could support long-range synchronization while faster frequencies could modulate their amplitude at specific phases of the slower oscillations. This notion has received strong empirical support (Lisman and Jensen 2013) and it has provided important theoretical insights about how different neuronal architectures can favor communication between brain regions during cognitive processing (Hyafil et al. 2015). The CFC framework is not exempt of caveats nonetheless. Using simulations, Kramer et al. (2008) succinctly showed how “spurious” gamma oscillations arose from sharp edges inserted periodically in a signal. They convincingly demonstrated that state of the art CFC metrics failed to differentiate “real” CFC (two independent brain sources on where the faster modulates its amplitude at specific phase bins of the slower rhythm) from the spurious cases. The latter is of theoretical importance given that oscillations whose waveform deviate from sine functions yield multiple peaks in the power spectrum (harmonics). In sum, they concluded that oscillations with nonsinusoidal properties can produce spurious CFC.