Dithering suppresses half-harmonic neural synchronisation to photic stimulation in humans

BACKGROUND: While entraining neural rhythms using brain stimulation has been suggested as a therapeutic mechanism to normalise brain activity in conditions such as depression, chronic pain, or Alzheimer's disease, periodic stimulation can also inadvertently entrain brain rhythms at sub- and superharmonics of the stimulation frequency, which could lead to deleterious effects. Slightly jittering stimulation pulses (called "dithering") was previously proposed on the basis of mathematical modelling to selectively entrain a target neural rhythm while avoiding harmonic entrainment. In this study, we investigated the potential of dithering in humans. METHODS: We recorded EEG in healthy adults during photic stimulation (light flicker) under periodic, dithered, reduced-strength, and control conditions. Synchronisation was quantified using spectral power and the phase-locking value. RESULTS: We showed that dithering suppresses half-harmonic synchronisation relative to perfectly periodic flicker, and that dithering affects synchronisation at the stimulation frequency less than at the half-harmonic. This was also the case for a periodic condition with reduced stimulation strength, as predicted by theory. Furthermore, we demonstrated using synthetic data and modelling that the half-harmonic responses observed in participants cannot be explained by the superposition of evoked responses (even when modulated at the half-harmonic frequency), and are better matched by a minimal oscillator model. CONCLUSION: Our findings are consistent with half-harmonic EEG synchronisation in response to photic stimulation predominantly reflecting half-harmonic entrainment rather than the summation of evoked responses, and with dithering being an effective strategy to suppress subharmonic entrainment without reducing the energy delivered.