Transcranial direct current stimulation over the temporal-parietal junction yields no lexical-semantic effects in logopenic primary progressive aphasia: a double-blind sham-controlled study.

Transcranial direct current stimulation (tDCS) has generated some promising outcomes in primary progressive aphasia (PPA). The logopenic variant (lv-PPA), one of the most frequent PPA phenotypes, erodes the temporal-parietal junction (TPJ) generating impaired lexical processing, rapidly extending to semantic deficits. Positive tDCS effects have been reported in several small-cohort studies but there is need for rigorous sham-controlled double-blind investigations to substantiate, or not, beneficial effects. We used a sham-controlled double-blind counter-balanced crossover design with 12 clinically and imaging-characterized lv-PPA patients applying, according to the principle of interhemispheric rivalry, anodal and cathodal tDCS over the left and right TPJ, respectively, as compared to sham. A letter fluency (lexical access), a picture-naming (lexical/semantic access), and a semantic-matching task (semantic access) were applied before and after tDCS. Computational modeling was used to characterize predicted cortical tDCS current distribution. Comparisons of post/pre-tDCS results did not show language improvement in any task. Finite element models showed impact for both tDCS modalities on the TPJ, but with lower radial field-strength when atrophy was implemented in the model. Correlation analyses on individual data, uncorrected for multiples comparisons, suggested that lesser aphasia severity and shorter disease duration are associated with more efficient tDCS effects. Our results showing the absence of significant tDCS outcomes in lv-PPA mitigate previous reports of positive tDCS effects with similar or smaller patient sample sizes, and they demonstrate the need for exploring factors influencing stimulation effects. Findings from computational modelling combined with our uncorrected correlation results suggest that tDCS use might be most appropriate in PPA patients having slight atrophy and aphasia severity. Future studies on larger patient populations are required for robust proof-of-concept regarding therapy use of tDCS in PPA.