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 identify reliable and functionally relevant tDCS target brain regions to enhance novel-word learning and assess test-retest reliability (TRR) of behavioral and imaging outcomes. Twenty healthy individuals completed two functional magnetic resonance imaging (fMRI) sessions using parallel task versions. Participants learned picture-pseudoword associations across six blocks. Learning was analyzed using linear-mixed-models. Whole-brain and region-of-interest (ROI) analyses examined learning-related activity changes and their behavioral relevance. TRR was assessed using intraclass correlation coefficients (ICCs). 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. Task-related activity was variable, but voxels within significant clusters (∼81%) and most ROIs showed moderate-to-excellent consistency. Power analyses confirmed a sufficient sample size for detecting the reported ICCs. Current modeling suggested that focal-tDCS can induce neurophysiologically relevant current intensity in potential target regions (V/m: Left Inferior Frontal Gyrus=0.19, Temporoparietal Junction=0.28, Supplementary Motor Area=0.11). Hence, we identified accessible, reliable and functionally relevant cortical targets for enhancing novel-word learning. TRR results support the paradigms' usefulness for concurrent tDCS-fMRI research. Our study also outlines a 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.