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Background: Anodal transcranial Direct Current Stimulation (tDCS) has been shown to be effective in improving human motor learning when applied over the contralateral primary motor cortex (M1). However, the stimulation of other cortical areas, such as the posterior parietal (PPC) and premotor (PMC) cortices, may be also beneficial.Methods: The present study (crossover design) investigated the effects of tDCS applied over PPC, PMC, and M1 on the acquisition and retention of a new motor skill, and on the generalization of such learned skill in healthy individuals. During a sequential finger-tapping task (FTT), performed with the non-dominant (left) hand, participants received real or sham anodal tDCS (1.5 mA, 20 min) over PPC, PMC, and the M1 of the right hemisphere. Explicit motor sequence learning was measured online (during the training with tDCS; primary outcome) and 24 hours after tDCS (retention, secondary outcome). A new, untrained, sequence was used to assess generalization effects (secondary outcome).Results: Anodal tDCS of M1 improved both online learning and retention. PMC tDCS facilitated the generalization of the learning effect to the untrained motor sequence. In contrast, neuromodulation of the PPC does not influence motor sequence learning.Conclusions: These findings show that, in addition to M1, higher-order associative cortical regions (PMC and PPC) are involved in explicit online motor sequence learning, retention and generalization playing different roles, as indicated by the differential modulatory effects of anodal tDCS.

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Neuromodulation of premotor and posterior parietal cortices for enhancing explicit motor sequence learning in healthy individuals: a randomized, sham-controlled crossover trial