Speaker
Description
Targeted non-invasive deep brain electrostimulation, aimed at activating deep neural structures without stimulation at the surface, relies on the interference of electric fields from two or more sources. Temporal interference (TI) stimulation employs frequency-shifted sine waves which overlap into an amplitude-modulated sine wave at the deep target. It is assumed that “pure” (unmodulated) high-frequency sine waves will not excite neurons but the modulated ones will, despite a (much) weaker electric field distantly from the electrodes. However, we found that unmodulated high-frequency sine waves are no less potent at exciting neurons than amplitude-modulated ones. Dissociated hippocampal neurons stimulated by unmodulated 2- and 20-kHz sine waves fired action potentials (APs) at a rate proportional to the electric field strength. After reaching the physiological rate limit of 60-90 Hz, APs coalesced into a sustained depolarization that blocked excitation. Adding 20-Hz modulation to emulate TI did not reduce excitation thresholds, but aligned APs with sine wave “beats” and prevented the excitation block. We used strobe photography to analyze membrane charging and relaxation kinetics with nanoscale resolution and proposed an excitation mechanism independent of sine wave rectification. Our results suggest that off-target effects of TI stimulation are unavoidable, although the excitation patterns near electrodes may differ from those at the deep target.
