Temporal interference stimulation disrupts spike timing in the primate brain

Abstract

Electrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only where they overlap. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we show that TI reliably alters the timing of spiking activity. However, we find that the strategies which improve the focality of TI -- high frequencies, multiple electrodes, and amplitude-modulated waveforms -- also limit its effectiveness. Combined, they make TI 80% weaker than other forms of non-invasive brain stimulation. Although this is too weak to cause widespread neuronal entrainment, it may be ideally suited for disrupting pathological synchronization, a hallmark of many neurological disorders.