Effects of Cerebellar Transcranial Direct Current Stimulation in Bilingual Logopenic Primary Progressive Aphasia.

Background: Primary progressive aphasia (PPA) is a language-based dementia, causing progressive decline of language functions. Transcranial direct current stimulation (tDCS) can augment effects of speech-and language therapy (SLT). However, this has not been investigated in bilingual patients with PPA. Objective: We evaluated the case of Mr. G., a French (native language, L1)/Dutch (second language, L2)-speaking 59-year-old male, with logopenic PPA, associated with Alzheimer's disease pathology. We aimed to characterize his patterns of language decline and evaluate the effects of tDCS applied to the right posterolateral cerebellum on his language abilities and executive control circuits. Methods: In a within-subject controlled design, Mr. G received 9 sessions of sham and anodal tDCS combined with semantic and phonological SLT in L2. Changes were evaluated with an oral naming task in L2, the Boston Naming Task and subtests of the Bilingual Aphasia Test in in L2 and L1, the Stroop Test and Attention Network Test, before and after each phase of stimulation (sham/tDCS) and at 2-month follow-up. Results: After anodal tDCS, but not after sham, results improved significantly on oral naming in L2, with generalization to untrained tasks and cross-language transfer (CLT) to L1: picture naming in both languages, syntactic comprehension and repetition in L2, and response times in the incongruent condition of the Attention Network Test, indicating increased inhibitory control. Conclusions: Our preliminary results are the first to indicate that tDCS applied to the cerebellum may be a valuable tool to enhance the effects of SLT in bilingual patients with logopenic PPA.

Case report: the effects of cerebellar tDCS in bilingual post-stroke aphasia.

Transcranial Direct Current Stimulation may be a useful neuromodulation tool for enhancing the effects of speech and language therapy in people with aphasia, but research so far has focused on monolinguals. We present the effects of 9 sessions of anodal cerebellar tDCS (ctDCS) coupled with language therapy in a bilingual patient with chronic post-stroke aphasia caused by left frontal ischemia, in a double-blind, sham-controlled within-subject design. Language therapy was provided in his second language (L2). Both sham and anodal treatment improved trained picture naming in the treated language (L2), while anodal ctDCS in addition improved picture naming of untrained items in L2 and his first language, L1. Picture description improved in L2 and L1 after anodal ctDCS, but not after sham.

Executive functions in primary progressive aphasia: A meta-analysis.

Executive functions (EFs) refer to a set of cognitive processes, specifically shifting, inhibition, updating of working memory, and are involved in the cognitive control of behavior. Conflicting results have been reported regarding impairments of EFs in Primary Progressive Aphasia (PPA). We performed a multi-level meta-analysis to confirm whether deficits of EFs exist in this population, focusing on a common EFs composite, and the components shifting, inhibition and updating separately. We included 141 studies that report on 294 EFs tasks. The overall mean weighted effect size was large (d = -1,28), indicating poorer EFs in PPA as compared to age-matched cognitively healthy controls. Differences between effect sizes of the EFs components were not significant, indicating all components are affected similarly. Overall, moderator analysis revealed that PPA variant and disease duration were significant moderators of performance, while task modality and years of education were not. The non-fluent/agrammatic PPA and the logopenic PPA variants were similarly affected, but the semantic variant was affected to a lesser extent. We discuss implications for clinical and research settings, and future research.

A Systematic Review of Transcranial Direct Current Stimulation in Primary Progressive Aphasia: Methodological Considerations.

A variety of tDCS approaches has been used to investigate the potential of tDCS to improve language outcomes, or slow down the decay of language competences caused by Primary Progressive Aphasia (PPA). The employed stimulation protocols and study designs in PPA are generally speaking similar to those deployed in post-stroke aphasic populations. These two etiologies of aphasia however differ substantially in their pathophysiology, and for both conditions the optimal stimulation paradigm still needs to be established. A systematic review was done and after applying inclusion and exclusion criteria, 15 articles were analyzed focusing on differences and similarities across studies especially focusing on PPA patient characteristics (age, PPA variant, language background), tDCS stimulation protocols (intensity, frequency, combined therapy, electrode configuration) and study design as recent reviews and group outcomes for individual studies suggest tDCS is an effective tool to improve language outcomes, while methodological approach and patient characteristics are mentioned as moderators that may influence treatment effects. We found that studies of tDCS in PPA have clinical and methodological and heterogeneity regarding patient populations, stimulation protocols and study design. While positive group results are usually found irrespective of these differences, the magnitude, duration and generalization of these outcomes differ when comparing stimulation locations, and when results are stratified according to the clinical variant of PPA. We interpret the results of included studies in light of patient characteristics and methodological decisions. Further, we highlight the role neuroimaging can play in study protocols and interpreting results and make recommendations for future work.

Septal cholinergic input to CA2 hippocampal region controls social novelty discrimination via nicotinic receptor-mediated disinhibition.

Acetylcholine (ACh), released in the hippocampus from fibers originating in the medial septum/diagonal band of Broca (MSDB) complex, is crucial for learning and memory. The CA2 region of the hippocampus has received increasing attention in the context of social memory. However, the contribution of ACh to this process remains unclear. Here, we show that in mice, ACh controls social memory. Specifically, MSDB cholinergic neurons inhibition impairs social novelty discrimination, meaning the propensity of a mouse to interact with a novel rather than a familiar conspecific. This effect is mimicked by a selective antagonist of nicotinic AChRs delivered in CA2. Ex vivo recordings from hippocampal slices provide insight into the underlying mechanism, as activation of nAChRs by nicotine increases the excitatory drive to CA2 principal cells via disinhibition. In line with this observation, optogenetic activation of cholinergic neurons in MSDB increases the firing of CA2 principal cells in vivo. These results point to nAChRs as essential players in social novelty discrimination by controlling inhibition in the CA2 region.