Behavioral and Neural Effects of Temporoparietal High-Definition Transcranial Direct Current Stimulation in Logopenic Variant Primary Progressive Aphasia: A Preliminary Study

Elias Granadillo ^1,2* Mason Fellmeth ¹ Vahab Youssof-Zadeh ¹ Joseph Heffernan ^1* Priyanka Shah-Basak ¹ Sara Pillay ¹ Candida Ustine ^1* Peter Kraegel ^1* Shelby Schold ^1* Kimberly Diggle Mueller ² Hrissanthi Ikonomindou ^2* Manoj Raghavan ¹ Jeffrey R Binder ¹

• ¹ Medical College of Wisconsin, Milwaukee, Wisconsin, United States
• ² University of Wisconsin-Madison, Madison, Wisconsin, United States

Background: High-definition-tDCS (HD-tDCS) is a recent technology that allows for localized stimulation, but has not yet been investigated as an augmentative therapy while targeting the temporoparietal cortex in logopenic variant PPA (lvPPA). Changes in neuronal oscillatory patterns and resting-state functional connectivity in response to HD-tDCS also remain poorly understood. Objective: To investigate the effects of HD-tDCS with phonologic-based language training on language, cognition, and resting-state functional connectivity in lvPPA.Methods: Double-blind, within-subject, sham-controlled crossover design with a 4-month between-treatment period in four participants with lvPPA. Participants completed language, and cognitive assessments, and imaging with magnetoencephalography (MEG) and resting-state functional MRI (fMRI) before 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. Preliminary data was evaluated based on relative changes from baseline in language and cognitive scores. Language measures included metrics derived from spontaneous speech from picture descriptions. 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. Results: 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 were positively associated with language outcomes. Conclusion: 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