Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning

Abstract

SUMMARY Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity-specific, NMDA-receptor dependent and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB-activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF-secretion and TrkB-activation within M1.

Effects of transcranial direct-current stimulation on laparoscopic surgical skill acquisition

“…Increased spontaneous neuronal firing and synaptic efficacy induced by direct‐current stimulation may strengthen neuronal connectivity through long‐term potentiation‐like mechanisms41, 42, 43. These mechanisms may potentiate motor learning, which is also thought to depend on long‐term potentiation‐like plasticity occurring in the motor cortex44.…”

“…Modulation of the motor network, including the primary motor cortex, premotor cortex, supplementary motor areas and basal ganglia, has been implemented in motor learning45 46. Modulated synaptic efficacy43 and cortical connectivity47 between these regions may facilitate tDCS‐enhanced motor learning. It is also important to consider that the tDCS montage applied here involved passing current through a large anode to a large cathode.…”

Effects of tDCS on motor learning and memory formation: A consensus and critical position paper

“…Thus, variants of the same basic task may assess very different learning processes. This may be particularly important for a technique like tDCS (which may exert its effect through the alteration of thresholds for neuronal discharge (Fritsch et al, 2010)) as observed effects may be highly dependent on the specific context in which it is applied. Currently, the most frequently used tasks to investigate motor skill learning in experimental settings are: (1) sequential finger tapping tasks (SFTT; which can include either implicit or explicit sequence structure) (Ghilardi, Moisello, Silvestri, Ghez, & Krakauer, 2009;Nitsche et al, 2010;Reis et al, 2015;Song & Cohen, 2014); and (2) the sequential visual isometric pinch force task (SVIPT) (Reis et al, 2009).…”

“…Using the same task, Bastani & Jaberzadeh (2014) investigated the effect of repeated offline application (up to 3) of relatively low intensity (0.2 mA) and duration (10 min) anodal tDCS to the dominant (left) M1 on corticospinal excitability and behavior (Bastani & Jaberzadeh, 2014). Not surprisingly, given our understanding of the need for synchronous application of tDCS with training (Fritsch et al, 2010), no behavioral effects were observed. Of note however, corticospinal excitability was significantly facilitated up to 24 hours depending on the interval between subsequent stimulation applications, which had been reported previously .…”

“…Several recommendations from that paper have been advanced in the literature. For example, many studies have utilized multi-session rather than single-session tDCS application (Hashemirad et al, 2016), greater emphasis has been placed on monitoring long-term effects of tDCS on motor learning (Hashemirad et al, 2016), evidence of dissociation of tDCS effects applied to distinct brain regions on different stages of motor learning (Galea et al, 2011;Reis et al, 2015;Wymbs, Bastian, & Celnik, 2016) has begun to emerge, and mechanisms underlying tDCS effects are starting to be elucidated (Fritsch et al, 2010; H. I. Kuo et al, 2013; M. F. Kuo et al, 2008;Lang, Nitsche, Sommer, Tergau, & Paulus, 2003;Stagg, Bachtiar, & Johansen-Berg, 2011).…”