40 Hz steady-state visually evoked potentials recovered during oscillating transcranial electrical stimulation

Background . Combining Transcranial Electrical Stimulation and Visual Stimulation at the gamma frequency of 40 Hz holds scientific and clinical potential, but requires concurrent electrophysiological measurement to quantify neuronal effects. This poses substantial methodological challenges: electrical stimulation artifacts largely overshadow EEG signals; gamma signals’ amplitude is particularly low; and oculo-muscular confounds overlap in frequency. With appropriate artifact removal, we aimed to record 40 Hz Steady-State Visually Evoked Potentials (SSVEPs) with EEG during frequency-matched electrical stimulation and explore possible interactions. Methods . In three experiments (N = 25 healthy volunteers each), we tested if electrical and visual stimulation might interact depending on which brain areas are electrically stimulated or whether the respective frequencies match—and, importantly, how effectively the data processing pipeline can separate artifacts from genuine neuronal activity. Analysing SSVEPs in the time domain, as opposed to the traditional frequency domain, enabled us to mitigate electrical artifacts flexibly through an adaptive template subtraction approach with millisecond precision. It also allowed us to extract SSVEP waveform information, in addition to amplitude. Compared to previous approaches for low frequencies, our algorithm has improved artifact template fitting, a new interpolation feature, and refined segment rejection criteria. Main Results . We successfully recovered 40 Hz SSVEPs during frequency-matched electrical stimulation applied to central and occipital regions. They closely matched baseline SSVEPs without electrical stimulation in waveform shape. A control condition (no visual stimulation, only electrical) produced uncorrelated low-amplitude signals, further demonstrating robust artifact removal. No interactions between electrical and visual stimulation were found. Significance . We demonstrated how 40 Hz SSVEPs can be reliably measured with EEG during frequency-matched electrical brain stimulation, distinguishing neuronal activity from electrical or physiological confounds. This method now enables fundamental and clinical researchers to combine rhythmic sensory and electrical stimulation in the gamma band and concurrently quantify neuronal electrophysiological effects.