Polarity-independent effects of tDCS on paired associative stimulation-induced plasticity

Background Transcranial direct current stimulation (tDCS) can polarize the cortex of the human brain. Objective/Hypothesis We sought to verify the hypothesis that posterior-anterior (PA) but not anterior-posterior (AP) tDCS of primary motor cortex (M1) produces cooperative effects with corticospinal plasticity induced by paired associative stimulation of the supplementary motor area (SMA) to M1 projection (PAS_SMA→M1) in a highly controlled experimental design. Methods Three experimental conditions were tested in a double-blinded, randomized crossover design in 15 healthy adults: Navigated PAS_SMA→M1 during PA-tDCS (35 cm² electrodes, anode 3 cm posterior to M1 hand area, cathode over contralateral frontopolar cortex, 1 mA, 2 × 5 min) or AP-tDCS (reversed polarity), or sham-tDCS. Effects were analyzed over 120 min post-intervention by changes of motor evoked potential (MEP) amplitude in a hand muscle. Results There was no significant effect of tDCS on PAS_SMA→M1 induced plasticity in the repeated-measures ANOVA. However, post-hoc within-subject contrasts revealed a significant tDCS with PAS_SMA→M1 interaction. This was explained by PA-tDCS and AP-tDCS modifying the PAS_SMA→M1 effect into the same direction in 13/15 subjects (87%, p = 0.004 for deviation from equality). Sizes of the PA-tDCS and AP-tDCS effects were correlated (r_s = 0.53, p = 0.044). A control experiment demonstrated that PA-tDCS and AP-tDCS alone (without PAS_SMA→M1) had no effect on MEP amplitude. Conclusions Data point to unidirectional tDCS effects on PAS_SMA→M1 induced plasticity irrespective of tDCS polarity, in contrast to our hypothesis. We propose that radial symmetry of cortical columns, gyral geometry of motor cortex, and cooperativity of plasticity induction can explain the findings.