Functionally Relevant and Reliable Brain Stimulation Targets for Enhancement of Novel Word-Learning

Linking word-forms and their meanings is central to language learning. Transcranial direct current stimulation (tDCS), has shown potential to enhance this process, but with variable effects. This study aimed to (1) identify reliable and functionally relevant tDCS target brain regions to enhance novel-word learning, using a functional magnetic resonance imaging (fMRI) compatible associative picture-pseudoword learning task, and (2) assess test–retest reliability (TRR) of behavioral and imaging outcomes. Twenty healthy individuals completed two fMRI sessions using parallel task versions. Participants learned picture-pseudoword associations across four learning blocks. A lexical decision task served as control condition. Behavioral learning was analyzed using linear-mixed models. Whole-brain and region-of-interest analyses examined learning-related activity changes and their behavioral relevance. TRR was assessed using intraclass correlation coefficients. Participants successfully acquired the novel-word forms, indexed by increased accuracy and faster latency across stages. Behavioral outcomes showed good-to-excellent TRR. The task elicited robust language-learning related activity and activity changes across stages were correlated with learning success. The control task showed no consistent activity changes. Task-related brain activity showed substantial variability, but a subset of voxels (∼30%) within significant clusters showed good consistency. In sum, we identified accessible, reliable and functionally relevant cortical targets for enhancing novel-word learning by tDCS. TRR results support the APPL task’s usefulness for future concurrent tDCS–fMRI research. Our study also outlines a general path towards optimization of brain stimulation studies by implementing an empirically informed approach for selecting reliable and relevant target regions and implementation of reliable experimental and imaging paradigms.