Granadillo Elias D, Fellmeth Mason, Youssofzadeh Vahab, Heffernan Joseph, Shah-Basak Priyanka P, Pillay Sara B, Ustine Candida, Kraegel Peter, Schold Shelby, Mueller Kimberly D, Ikonomidou Chrysanthy, Okonkwo Ozioma, Raghavan Manoj, Binder Jeffrey R
Institute for Clinical and Translational Research, University of Wisconsin-Madison, Madison, WI, United States.
Neurology, Medical College of Wisconsin, Milwaukee, WI, United States.
Front Psychol. 2025 Feb 25;16:1492447. doi: 10.3389/fpsyg.2025.1492447. eCollection 2025.
High-definition-tDCS (HD-tDCS) is a recent technology that allows for localized cortical stimulation, but has not yet been investigated as an augmentative therapy while targeting the left temporoparietal cortex in logopenic variant PPA (lvPPA). The changes in neuronal oscillatory patterns and resting-state functional connectivity in response to HD-tDCS also remains poorly understood.
We sought to investigate the effects of HD-tDCS with phonologic-based language training on language, cognition, and resting-state functional connectivity in lvPPA.
We used a double-blind, within-subject, sham-controlled crossover design with a 4-month between-treatment period in four participants with lvPPA. Participants completed language, cognitive assessments, and imaging with magnetoencephalography (MEG) and resting-state functional MRI (fMRI) prior to treatment with either anodal HD-tDCS or sham targeting the left supramarginal gyrus over 10 sessions. Language and cognitive assessments, MEG, and fMRI were repeated after the final session and at 2 months follow-up. Preliminary data on efficacy was evaluated based on relative changes from baseline in language and cognitive scores. Language measures included metrics derived from spontaneous speech from picture description. Changes in resting-state functional connectivity within the phonological network were analyzed using fMRI. Magnitudes of source-level evoked responses and hemispheric laterality indices from language task-based MEG were used to assess changes in cortical engagement induced by HD-tDCS.
All four participants were retained across the 4-month between-treatment period, with satisfactory blinding of participants and investigators throughout the study. Anodal HD-tDCS was well tolerated with a side effect profile that did not extend past the immediate treatment period. No benefit of HD-tDCS over sham on language and cognitive measures was observed in this small sample. Functional imaging results using MEG and fMRI indicated an excitatory effect of anodal HD-tDCS compared to sham and suggested that greater temporoparietal activation and connectivity was positively associated with language outcomes.
Anodal HD-tDCS to the inferior parietal cortex combined with language training appears feasible and well tolerated in participants with lvPPA. Language outcomes may be explained by regression to the mean, and to a lesser degree, by ceiling effects and differences in baseline disease severity. The intervention has apparent temporoparietal correlates, and its clinical efficacy should be further studied in larger trials.
ClinicalTrials.gov, Number NCT03805659.
高清经颅直流电刺激（HD-tDCS）是一种新近的技术，可实现局部皮质刺激，但尚未作为一种辅助治疗方法用于针对语法缺失型原发性进行性失语（lvPPA）患者的左侧颞顶叶皮质。对于HD-tDCS引起的神经元振荡模式和静息态功能连接性的变化，目前仍知之甚少。
我们旨在研究HD-tDCS联合基于语音的语言训练对lvPPA患者语言、认知和静息态功能连接性的影响。
我们采用双盲、受试者内、假刺激对照的交叉设计，对4名lvPPA患者进行为期4个月的治疗间隔期研究。在对左侧缘上回进行10次阳极HD-tDCS或假刺激治疗前，参与者完成语言、认知评估以及脑磁图（MEG）和静息态功能磁共振成像（fMRI）检查。在最后一次治疗后以及随访2个月时，重复进行语言和认知评估、MEG和fMRI检查。基于语言和认知评分相对于基线的相对变化评估疗效的初步数据。语言测量包括从图片描述的自发言语中得出的指标。使用fMRI分析语音网络内静息态功能连接性的变化。基于语言任务的MEG的源水平诱发反应幅度和半球偏侧性指数用于评估HD-tDCS引起的皮质参与度变化。
在4个月的治疗间隔期内，所有4名参与者均完成研究，在整个研究过程中参与者和研究者的盲法效果良好。阳极HD-tDCS耐受性良好，副作用未超出即时治疗期。在这个小样本中，未观察到HD-tDCS在语言和认知测量方面优于假刺激。使用MEG和fMRI的功能成像结果表明，与假刺激相比，阳极HD-tDCS具有兴奋作用，并表明更大的颞顶叶激活和连接性与语言结果呈正相关。
对顶下皮质进行阳极HD-tDCS联合语言训练，在lvPPA患者中似乎可行且耐受性良好。语言结果可能由均值回归来解释，在较小程度上，也可由天花板效应和基线疾病严重程度差异来解释。该干预措施与颞顶叶明显相关，其临床疗效应在更大规模试验中进一步研究。
ClinicalTrials.gov，编号NCT03805659。
