Teichmann Marc, Sanches Clara, Bourbon Angelina, Truong Dennis Q, Bikson Marom, Valero-Cabré Antoni
Pitié Salpêtrière University Hospital, Department of Neurology, National Reference Center for 'Rare or Early Onset Dementias', AP-HP Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM-UMR INSERM-CNRS-SU 1127, Frontlab team, Paris, France.
Institut du Cerveau et de la Moelle Epinière, ICM-UMR INSERM-CNRS-SU 1127, Frontlab team, Paris, France; Institut du Cerveau et de la Moelle Epinière, UMR INSERM-CNRS-SU 1127, Groupe de Dynamiques Cérébrales, Plasticité et Rééducation, ICM, CNRS UMR 7225, Paris, France.
Neuroimage Clin. 2025;46:103798. doi: 10.1016/j.nicl.2025.103798. Epub 2025 May 5.
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.
经颅直流电刺激（tDCS）在原发性进行性失语（PPA）中已产生了一些有前景的结果。语言迟缓变异型（lv-PPA）是最常见的PPA表型之一，它会侵蚀颞顶联合区（TPJ），导致词汇加工受损，并迅速扩展至语义缺陷。在几项小样本队列研究中已报道了tDCS的积极效果，但需要进行严格的假对照双盲研究来证实其有益效果与否。我们采用了假对照双盲平衡交叉设计，对12名经临床和影像学特征化的lv-PPA患者，根据半球间竞争原则，分别在左、右TPJ上施加阳极和阴极tDCS，并与假刺激进行比较。在tDCS前后分别进行了字母流畅性（词汇提取）、图片命名（词汇/语义提取）和语义匹配任务（语义提取）。使用计算模型来表征预测的皮质tDCS电流分布。tDCS前后结果的比较未显示在任何任务中语言有改善。有限元模型显示两种tDCS模式对TPJ均有影响，但在模型中纳入萎缩情况时，径向场强较低。对未进行多重比较校正的个体数据进行的相关分析表明，失语严重程度较低和病程较短与更有效的tDCS效果相关。我们的结果显示lv-PPA中tDCS无显著效果，这削弱了之前在类似或更小患者样本量下报道的tDCS积极效果，并且表明需要探索影响刺激效果的因素。计算建模的结果与我们未校正的相关结果表明，tDCS可能最适合于轻度萎缩和失语严重程度较轻的PPA患者。未来需要对更大患者群体进行研究，以获得关于tDCS在PPA中治疗应用的有力概念验证。
