A Real-Time Optimization-Based Approach to Phase-Specific Triggering during Transcranial Current Stimulation

Transcranial alternating current stimulation (tACS) and transcranial temporal interference stimulation (tTIS) are non-invasive brain stimulation techniques used to probe causal relationships between brain oscillations and behavior. The ability of tACS to entrain brain oscillations has been previously tested by phase-locking transcranial magnetic stimulation (TMS) to the tACS signal in order to observe tACS-phase dependency of the motor evoked response. Prior investigations using this technique have been limited by suboptimal accuracy in triggering of TMS to a specific phase of the tACS signal. Furthermore, these approaches cannot be applied to more complex waveforms such as those utilized in tTIS. This paper introduces a real-time, optimization-based method for phase-specific triggering compatible with tACS and tTIS. Our approach uses waveform fitting to estimate phase in real-time on the deterministic Real-Time eXperimental Interface (RTXI) platform. Across multiple frequencies of tACS and tTIS (5-80 Hz), results show high accuracy and low variability in phase targeting (1 degree) in all tested conditions. Limitations of the approach and generalizability of the platform to other closed-loop neurostimulation techniques are given in the discussion.