Repeated tDCS at clinically-relevant field intensity can boost concurrent motor learning in rats.

Abstract

Electric fields used in clinical trials with transcranial direct current stimulation (tDCS) are small, with magnitudes that have yet to demonstrate measurable effects in preclinical animal models. We hypothesized that weak stimulation will nevertheless produce sizable effects, provided that it is applied concurrently with behavioral training, and repeated over multiple sessions. We tested this here in a rodent model of dexterous motor-skill learning. We developed a preparation that allows concurrent stimulation during the performance of a pellet-reaching task in freely behaving rats. The task was automated to minimize experimenter bias. We measured field magnitudes intracranially to calibrate the stimulation current. In this study, only male rats were used. Animals were trained for 20 min with concurrent epicranial tDCS over 10 daily sessions. Behavior was recorded with high-speed video to quantify reaching dynamics. We also measured motor-evoked potentials (MEPs) bilaterally with epidural microstimulation. The new electrode montage enabled stable stimulation over 10 sessions with a field intensity of 2V/m at the motor cortex. The number of successful reaches improved across days of training, and the rate of learning was higher in the anodal group as compared to sham-control animals (F(1)=7.12, p=0.008, N=24). MEPs were not systematically affected by tDCS. Posthoc analysis suggests that tDCS modulated motor learning only for right-pawed animals, improving success of reaching, but limiting stereotypy in these animals. Repeated and concurrent anodal tDCS can boost motor-skill learning at clinically-relevant field intensities. In this animal model the effect interacted with paw preference and was not associated with corticospinal excitability. Significance StatementThe effects of tDCS have been explored in numerous human clinical trials, but the mechanisms of action of weak electric fields remain unclear. In vitro studies show that constant electric fields at 2.5 V/m can enhance the efficacy of synapses undergoing plasticity. This study demonstrates in a rodent model that tDCS of only 2 Vm when applied concurrently to behavioral training can improve motor skill learning, and reduce stereotypy of reaching behavior. These effects accumulated over 10 days of training. Motor evoked potentials (MEP), which are often used to demonstrate plastic effects in humans on a time scale of hours, were not measurably affected by tDCS on this longer time scale.