Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms

The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-tsDCS (c-tsDCS), but reduced during anodal-tsDCS (a-tsDCS). After-effects were dependent on the frequency of the test stimulation. c-tsDCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-tsDCS had opposite effects. During and after c-tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a-tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS-based interventions.