ABSTRACT Background Primary progressive aphasia (PPA) is associated with progressive loss of language functions in the context of irreversible neurodegeneration, for which there is no cure. Speech-language therapy can help preserve language abilities, and most promisingly, interventions like transcranial direct current stimulation (tDCS) have been shown to augment the effectiveness of therapy. However, the underlying mechanism for this enhancement is unknown. Objectives We evaluated the behavioural and physiological (using resting-state magnetoencephalography [rsMEG]) effects of contemporary naming treatment provided with tDCS in a patient with an advanced case of nonfluent variant PPA (P01; 67 year old male). P01 was mute but had preserved written abilities, which we aimed to enhance with written naming therapy and excitatory or anodal-tDCS. We hypothesized greater improvement in written performance, particularly immediate gains, maintenance, and generalization, after anodal- than sham-tDCS. Additionally, reductions in oscillatory abnormal activity, as indicated by rsMEG, were expected after repeated sessions of anodal-tDCS with the naming treatment. Methods A written picture naming therapy was paired with five sessions of anodal and five sessions of sham high-definition tDCS over two weeks. Anatomical and neurophysiological abnormalities were mapped with structural-MRI and rsMEG, respectively. TDCS was targeted towards an anatomically intact left supramarginal gyrus. The therapy-induced changes in written performance were evaluated on both trained and untrained pictures using Levenshtein Distances (LD). The neurophysiological changes were evaluated by comparing spectral relative power estimates in frequency bands ranging from delta to low-gamma (1–50 Hz), before and after therapy. All evaluations were completed immediately after therapy with sham- and anodal-tDCS, and at a 3-month follow-up. Results Compared to sham-tDCS, anodal-tDCS augmented the immediate therapy-induced gains on trained items, as indicated by reductions in LD scores, reflecting improvement in written performance, particularly for more difficult target words. Neural activity at the stimulation spot and in surrounding and remote regions exhibited reduced oscillatory slowing, both immediately after one session (short-term) and after completion of five sessions (long-term) of anodal-tDCS compared to sham-tDCS. This is manifested as decreased theta (1–4 Hz) and increased beta and low-gamma (15–50 Hz) power. No additional gains with anodal-tDCS were found on untrained items (generalization) or at 3-month follow-up (maintenance). Conclusions Our findings suggest that five sessions of anodal-tDCS can improve written performance by partially reversing abnormal neural activity and thus boosting the functional capacity of the structurally intact cortex. Longer duration of treatment may be needed for additional gains in maintenance and generalization with anodal-tDCS.
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