Orientation-dependent effects of transcranial alternating current stimulation (tACS) on spike timing in awake non-human primates

Transcranial alternating current stimulation (tACS) is a non-invasive method to modulate ongoing neural activity in the brain. Previous work shows that external oscillations entrain neural firing activity in a phase- and dose- dependent manner. Thus, tACS holds promise as a new treatment for people suffering from brain disorders. However, neural responses to oscillating electric fields exhibit variability and we hypothesize that they largely depend on the neocortical column orientations relative to the induced electric fields. We first perform a computational study to investigate the relationship between tACS and neural entrainment in a set of 25 morphologically realistic neocortical neurons exhibiting ongoing spiking activity. The electric field was aligned with the somato-dendritic axis of the pyramidal cells and intensities were between 0.1 mV/mm and 3 mV/mm. We then computed the phase-locking value (PLV) of spikes times across neurons and field strengths. We found that 1) pyramidal neurons are more entrained than interneurons resulting in a higher phase-locked spiking to the applied oscillation (pyramidal cells n=15, 0.0788 +/-0.0821 and interneurons n=10, 0.0495 +/-0.0414 at 1mV/mm) and 2) pyramidal cells are more preferentially entrained when parallel to the electric field direction. Second, we perform in-vivo recordings of single-unit activity in awake non-human primates while applying tACS in 3 orientations (Anterior-Posterior, Left-Right and diagonal orientations) and 2 intensities for each of them (0.4mA and 0.8mA). We record neuronal activities using a 128-channel amplifier at 30 kHz sampling rate. Preliminary findings in one macaque (8 y.o., male) show that neurons (N=159) exhibit significant entrainment to tACS with strong orientation preference (Rayleigh test p ≤ 0.01). Overall, these findings advance our mechanistic understanding of tACS effects and highlight the importance of neuronal architecture on the susceptibility to the external electric fields. Highlighting neural directional sensitivity represents a milestone for understanding brain networks interactions. Keywords: tACS, single unit activity, Orientation-dependency, neural entrainment