Timing is everything event-related TDCS (er-TDCS) improves motor adaptation
Coincident, time-dependent mechanisms of synaptic plasticity are the canonical basis of theories of motor learning. These ‘Hebbian’ mechanisms are ubiquitous throughout the mammalian brain, having been described in the hippocampus, cerebellum, and sensory-motor cortices, and are believed to underpin all forms of learning and memory. Yet, protocols for non-invasive brain stimulation intended to promote motor learning and rehabilitation - particularly transcranial direct current stimulation (TDCS) - largely ignore timing-dependent mechanisms. Changes in neuronal excitation have been shown to be almost instantaneous in terms of increases in firing rates and motor evoked potentials following the application of TDCS and other forms of polarising currents. Despite this, most conventional studies apply TDCS for 15-20 minutes in a continuous stimulation period, prior to and/or during a motor task. If TDCS can instantaneously modulate neural activity, applying short duration epochs of TDCS temporally aligned with movement has the potential to specifically and selectively enhance learning, by driving coincident mechanisms of plasticity in the circuits of the brain that are active during the movement. Thus, we designed a context-dependent force-field adaptation task, in which we applied short epochs of TDCS coincidentally with one of two reaching movements performed during the task - a stimulation protocol we termed event-related TDCS (er-TDCS). Healthy young participants (n = 60) learned to reach through two opposing velocity-dependent force-fields, applied on interleaved trials in a pseudorandomised order. The two force-fields were contextually distinguished by a leftward or rightward shift in the visual display, although the movement was always performed in the midline. During adaptation a leftward shift in visual task display was associated with a clockwise (CW) curl-field and a rightward shift in display was associated with a counter-clockwise (CCW) curl-field. During baseline and washout, trials were still distinguished by workspace shifts but were performed without any forces applied (null-field). er-TDCS was selectively applied over the cerebellum or M1 in brief (< 3 second bouts) during movements through the CCW force-field, and associated rightward shift in visual task display. Consequently, only one of the two learning contexts was performed with simultaneous stimulation, while the unstimulated context provided a within-subject control. We demonstrate that brief epochs of stimulation, applied in synchrony with movement, selectively enhanced motor adaptation whilst, importantly, leaving adaptation of the non-stimulated (yet interleaved) movements unaffected.