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Description: Data linked to BioXriv article https://doi.org/10.1101/2020.04.13.039214 Prefrontal Transcranial Direct Current Stimulation globally improves learning, but does not selectively potentiate the benefits of Targeted Memory Reactivation on awake memory consolidation. Médhi Gilson, Michael A. Nitsche and Philippe Peigneux Abstract: Targeted Memory Reactivation (TMR) and transcranial Direct Current Stimulation (tDCS) can enhance memory consolidation. It is currently unknown whether TMR reinforced by simultaneous tDCS has superior efficacy. In this study, we investigated the complementary effect of TMR and bilateral tDCS on the consolidation of emotionally neutral and negative declarative memories. Participants learned neutral and negative word pairs. Each word pair was presented with an emotionally compatible sound. Following learning, participants spent a 20-minutes retention interval awake under 4 possible conditions: (1) TMR alone (i.e. replay of 50% of the associated sounds), (2) TMR combined with anodal stimulation of the left DLPFC, (3) TMR combined with anodal stimulation of the right DLPFC and (4) TMR with sham tDCS. Results evidenced selective memory enhancement for the replayed stimuli in the TMR-only and TMR-sham conditions, which confirms a specific effect of TMR on memory. However, memory was enhanced at higher levels for all learned items (irrespective of TMR) in the TMR-anodal right and TMR-anodal left tDCS conditions, suggesting that the beneficial effects of tDCS overshadow the specific effects of TMR. Emotionally negative memories were not modulated by tDCS hemispheric polarity. We conclude that electrical stimulation of the DLPFC during post-learning period globally benefits memory consolidation, but does not potentiate the specific benefits of TMR.