Resolving equivocal gain modulation of corticospinal excitability.

The ratio between the input and output of neuronal populations, usually referred to as gain modulation, is rhythmically modulated along the oscillatory cycle. Previous research on spinal neurons, however, revealed contradictory findings: both uni- and bimodal patterns of increased responsiveness for synaptic input have been proposed for the oscillatory beta rhythm. In this study, we compared previous approaches of phase estimation directly on simulated data and empirically tested the corresponding predictions in healthy males and females. We applied single-pulse transcranial magnetic stimulation over the primary motor cortex at rest, and assessed the spinal output generated by this input. Specifically, the peak-to-peak amplitude of the motor evoked potential in the contralateral forearm was estimated as a function of the EMG phase at which the stimulus was applied. The findings indicated that human spinal neurons adhere to a unimodal pattern of increased responsiveness, and suggest that the rising phase of the upper beta band maximizes gain modulation. Importantly, a bimodal pattern of increased responsiveness was shown to result in an artifact during data analysis and filtering. This observation of invalid preprocessing could be generalized to other frequency bands (i.e., delta, theta, alpha, and gamma), different task conditions (i.e., voluntary muscle contraction), and EEG-based phase estimations. Appropriate analysis algorithms, such as broad-band filtering, enable us to accurately determine gain modulation of neuronal populations and to avoid erroneous phase estimations. This may facilitate novel phase-specific interventions for targeted neuromodulation.