Long-term, home-based transcranial direct current stimulation coupled with computerized cognitive training in frontotemporal dementia: A case report.

We present the case of a 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) with cognitive/language deficits who demonstrated improved performance on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS (anode on the left prefrontal cortex and cathode on the right homologue) for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by 3 points on the Mini-Mental State Exam (MMSE) (23 to 26). She also showed improvement on several cognitive/language tasks, such as immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members reported subjective improvements in expressiveness, communication, and interaction with others as well as increased attention to grooming and style which contrasted with her pre-treatment condition. This report suggests that home-based tDCS combined with CCT for an extended period may slow decline, and improve cognitive/language performance and everyday function in FTD.

Long-term, Home-based Transcranial Direct Current Stimulation Coupled with Computerized Cognitive Training in Frontotemporal Dementia: A Case Report: A 62-year-old woman with probable behavioral variant of frontotemporal dementia (bvFTD) improved on cognitive/language testing and in functional tasks following long-term, home-based transcranial direct current stimulation (tDCS) coupled with computerized cognitive training (CCT). The patient underwent home-based tDCS for 46 sessions over 10 weeks along with CCT. On post-treatment testing, the patient improved by three points on the Mini-Mental State Exam (MMSE) (23 to 26). She also improved immediate recall of single words and word pairs, total accurate words in sentence repetition, delayed recall, semantic processing, and sentence level comprehension. There was no decline in several other cognitive and language tasks. Family members described improvements in expressiveness, communication, and interaction with others and increased attention to grooming and style which was different from her pre-treatment condition. This case report suggests that home-based tDCS combined with CCT for an extended period may slow decline and improve cognitive/language performance and everyday function in FTD.

Baseline functional connectivity predicts who will benefit from neuromodulation: evidence from primary progressive aphasia.

Background: Identifying the characteristics of individuals who demonstrate response to an intervention allows us to predict who is most likely to benefit from certain interventions. Prediction is challenging in rare and heterogeneous diseases, such as primary progressive aphasia (PPA), that have varying clinical manifestations. We aimed to determine the characteristics of those who will benefit most from transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus (IFG) using a novel heterogeneity and group identification analysis. Methods: We compared the predictive ability of demographic and clinical patient characteristics (e.g., PPA variant and disease progression, baseline language performance) vs. functional connectivity alone (from resting-state fMRI) in the same cohort. Results: Functional connectivity alone had the highest predictive value for outcomes, explaining 62% and 75% of tDCS effect of variance in generalization (semantic fluency) and in the trained outcome of the clinical trial (written naming), contrasted with <15% predicted by clinical characteristics, including baseline language performance. Patients with higher baseline functional connectivity between the left IFG (opercularis and triangularis), and between the middle temporal pole and posterior superior temporal gyrus, were most likely to benefit from tDCS. Conclusions: We show the importance of a baseline 7-minute functional connectivity scan in predicting tDCS outcomes, and point towards a precision medicine approach in neuromodulation studies. The study has important implications for clinical trials and practice, providing a statistical method that addresses heterogeneity in patient populations and allowing accurate prediction and enrollment of those who will most likely benefit from specific interventions.

Home-Based Transcranial Direct Current Stimulation in Primary Progressive Aphasia: A Pilot Study.

BACKGROUND: This study aims to determine (a) if home-based anodal transcranial direct current stimulation (a-tDCS) delivered to the left supramarginal gyrus (SMG) coupled with verbal short-term memory/working memory (vSTM/WM) treatment ("RAM", short for "Repeat After Me") is more effective than sham-tDCS in improving vSTM/WM in patients with primary progressive aphasia (PPA), and (b) whether tDCS effects generalize to other language and cognitive abilities. METHODS: Seven PPA participants received home-based a-tDCS and sham-tDCS coupled with RAM treatment in separate conditions in a double-blind design. The treatment task required participants to repeat word spans comprising semantically and phonologically unrelated words in the same and reverse order. The evaluation of treatment effects was carried out using the same tasks as in the treatment but with different items (near-transfer effects) and tasks that were not directly related to the treatment (far-transfer effects). RESULTS: A-tDCS showed (a) a significant effect in improving vSTM abilities, measured by word span backward, and (b) a generalization of this effect to other language abilities, namely, spelling (both real words and pseudowords) and learning (retention and delayed recall). CONCLUSIONS: These preliminary results indicate that vSTM/WM intervention can improve performance in trained vSTM/WM tasks in patients with PPA, especially when augmented with home-based tDCS over the left SMG.

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.

The right hemisphere's capacity for language: evidence from primary progressive aphasia.

The role of the right hemisphere (RH) in core language processes is still a matter of intense debate. Most of the relevant evidence has come from studies of gray matter, with relatively little research on RH white matter (WM) connectivity. Using Diffusion Tensor Imaging-based tractography, the current work examined the role of the two hemispheres in language processing in 33 individuals with Primary Progressive Aphasia (PPA), aiming to better characterize the contribution of the RH to language processing in the context of left hemisphere (LH) damage. The findings confirm the impact of PPA on the integrity of the WM language tracts in the LH. Additionally, an examination of the relationship between tract integrity and language behaviors provides robust evidence of the involvement of the WM language tracts of both hemispheres in language processing in PPA. Importantly, this study provides novel evidence of a unique contribution of the RH to language processing (i.e. a contribution independent from that of the language-dominant LH). Finally, we provide evidence that the RH contribution is specific to language processing rather than being domain general. These findings allow us to better characterize the role of RH in language processing, particularly in the context of LH damage.

Specificity in Generalization Effects of Transcranial Direct Current Stimulation Over the Left Inferior Frontal Gyrus in Primary Progressive Aphasia.

OBJECTIVES: Generalization (or near-transfer) effects of an intervention to tasks not explicitly trained are the most desirable intervention outcomes. However, they are rarely reported and even more rarely explained. One hypothesis for generalization effects is that the tasks improved share the same brain function/computation with the intervention task. We tested this hypothesis in this study of transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) that is claimed to be involved in selective semantic retrieval of information from the temporal lobes. MATERIALS AND METHODS: In this study, we examined whether tDCS over the left IFG in a group of patients with primary progressive aphasia (PPA), paired with a lexical/semantic retrieval intervention (oral and written naming), may specifically improve semantic fluency, a nontrained near-transfer task that relies on selective semantic retrieval, in patients with PPA. RESULTS: Semantic fluency improved significantly more in the active tDCS than in the sham tDCS condition immediately after and two weeks after treatment. This improvement was marginally significant two months after treatment. We also found that the active tDCS effect was specific to tasks that require this IFG computation (selective semantic retrieval) but not to other tasks that may require different computations of the frontal lobes. CONCLUSIONS: We provided interventional evidence that the left IFG is critical for selective semantic retrieval, and tDCS over the left IFG may have a near-transfer effect on tasks that depend on the same computation, even if they are not specifically trained. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02606422.

Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia.

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner.

Brain total creatine differs between primary progressive aphasia (PPA) subtypes and correlates with disease severity.

Primary progressive aphasia (PPA) is comprised of three subtypes: logopenic (lvPPA), non-fluent (nfvPPA), and semantic (svPPA). We used magnetic resonance spectroscopy (MRS) to measure tissue-corrected metabolite levels in the left inferior frontal gyrus (IFG) and right sensorimotor cortex (SMC) from 61 PPA patients. We aimed to: (1) characterize subtype differences in metabolites; and (2) test for metabolite associations with symptom severity. tCr differed by subtype across the left IFG and right SMC. tCr levels were lowest in lvPPA and highest in svPPA. tCr levels predicted lvPPA versus svPPA diagnosis. Higher IFG tCr and lower Glx correlated with greater disease severity. As tCr is involved in brain energy metabolism, svPPA pathology might involve changes in specific cellular energy processes. Perturbations to cellular energy homeostasis in language areas may contribute to symptoms. Reduced cortical excitatory capacity (i.e. lower Glx) in language regions may also contribute to symptoms. Thus, tCr may be useful for differentiating between PPA subtypes, and both tCr and Glx might have utility in understanding PPA mechanisms and tracking progression.

Differences in functional connectivity distribution after transcranial direct-current stimulation: A connectivity density point of view.

In this manuscript, we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting-state functional magnetic resonance imaging association with an intervention. The method uses the estimated density of connectivity between nodes of interest as a functional covariate. Moreover, we demonstrate the utility of the procedure in an instance where connectivity is naturally considered an outcome by reversing the predictor/response relationship using case/control methodology. The method utilizes the density quantile, the density evaluated at empirical quantiles, instead of the empirical density directly. This improved the performance of the method by highlighting tail behavior, though we emphasize that by being flexible and non-parametric, the technique can detect effects related to the central portion of the density. To demonstrate the method in an application, we consider 47 primary progressive aphasia patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, transcranial direct-current stimulation and language therapy versus sham (language therapy only), in a clinical trial. We use the method to analyze the effect of direct stimulation on functional connectivity. As such, we estimate the density of correlations among the regions of interest and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. The new approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared with edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.

Association of Regional Atrophy With Naming Decline in Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: Primary progressive aphasia (PPA) is a neurodegenerative condition that predominantly impairs language. Most investigations of how focal atrophy affects language consider 1 time point compared with healthy controls. However, true atrophy quantification requires comparing individual brains over time. In this observational cohort study, we identified areas where focal atrophy was associated with contemporaneous decline in naming in the same individuals. METHODS: Cross-sectional analyses-related Boston Naming Test (BNT) performance and volume in 22 regions of interests (ROIs) at each time point using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Longitudinal analysis evaluated changes in BNT performance and change in volume in the same ROIs. RESULTS: Participants (N = 62; 50% female; mean age = 66.8 ± 7.4 years) with PPA completed the BNT and MRI twice (mean = 343.9 ± 209.0 days apart). In cross-sectional left inferior frontal gyrus pars opercularis, superior temporal pole, middle temporal gyrus, and inferior temporal gyrus were identified as critical for naming at all time points. Longitudinal analysis revealed that increasing atrophy in the left supramarginal gyrus and middle temporal pole predicted greater naming decline, as did female sex and longer intervals between time points. DISCUSSION: Although cross-sectional analyses identified classic language areas that were consistently related to poor performance at multiple time points, it was not increasing atrophy in these areas that lead to further decline: longitudinal analysis of each person's atrophy over time instead identified nearby but distinct regions where increased atrophy was related to decreasing performance. The results demonstrate that directly examining atrophy (in each individual) over time furthers understanding of decline in PPA and reveal the importance of left supramarginal gyrus and middle temporal pole in maintaining naming when areas normally critical for language degenerate. The novel results provide insight into how the underlying disease progresses to result in the clinical decline in naming, the deficit most common among all 3 PPA variants.

Inter-hemispheric synchronicity and symmetry: The functional connectivity consequences of stroke and neurodegenerative disease.

Stroke and neurodegenerative diseases differ along several dimensions, including their temporal trajectories -abrupt onset versus slow disease progression. Despite these differences, they can give rise to very similar cognitive impairments, such as specific forms of aphasia. What has been scarcely investigated, however, is the extent to which the underlying functional neuroplastic consequences are similar or different for these diseases. Here, for the first time, we directly compare changes in the brain's functional network connectivity, measured with resting-state fMRI, in stroke and progressive neurological disease. Specifically, we examined two groups of individuals with chronic post-stroke aphasia or non-fluent primary progressive aphasia, matched for their behavioral profiles and distribution of left-hemisphere damage. Using previous proposals regarding the neural functional connectivity (FC) phenotype of stroke as a starting point, we compared the two diseases in terms of homotopic FC, intra-hemispheric FC changes and also the symmetry of the FC patterns between the two hemispheres. We found, first, that progressive disease showed significantly higher levels of homotopic connectivity than neurotypical controls and, further, that stroke showed the reverse pattern. For both groups these effects were found to be behaviorally relevant. In addition, within the directly impacted left hemisphere, FC changes for the two diseases were significantly correlated. In contrast, in the right hemisphere, the FC changes differed markedly between the two groups, with the progressive disease group exhibiting rather symmetrical FC changes across the hemispheres whereas the post-stroke group showed asymmetrical FC changes across the hemispheres. These findings constitute novel evidence that the functional connectivity consequences of stroke and neurodegenerative disease can be very different despite similar behavioral outcomes and damage foci. Specifically, stroke may lead to greater independence of hemispheric responses, while neurodegenerative disease may produce more symmetrical changes across the hemispheres and more synchronized activity between the two hemispheres.

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.

The Contribution of Working Memory Areas to Verbal Learning and Recall in Primary Progressive Aphasia.

Recent evidence of domain-specific working memory (WM) systems has identified the areas and networks which are involved in phonological, orthographic, and semantic WM, as well as in higher level domain-general WM functions. The contribution of these areas throughout the process of verbal learning and recall is still unclear. In the present study, we asked, what is the contribution of domain-specific specialized WM systems in the course of verbal learning and recall? To answer this question, we regressed the perfusion data from pseudo-continuous arterial spin labeling (pCASL) MRI with all the immediate, consecutive, and delayed recall stages of the Rey Auditory Verbal Learning Test (RAVLT) from a group of patients with Primary Progressive Aphasia (PPA), a neurodegenerative syndrome in which language is the primary deficit. We found that the early stages of verbal learning involve the areas with subserving phonological processing (left superior temporal gyrus), as well as semantic WM memory (left angular gyrus, AG_L). As learning unfolds, areas with subserving semantic WM (AG_L), as well as lexical/semantic (inferior temporal and fusiform gyri, temporal pole), and episodic memory (hippocampal complex) become more involved. Finally, a delayed recall depends entirely on semantic and episodic memory areas (hippocampal complex, temporal pole, and gyri). Our results suggest that AG_L subserving domain-specific (semantic) WM is involved only during verbal learning, but a delayed recall depends only on medial and cortical temporal areas.

Sleep as a predictor of tDCS and language therapy outcomes.

STUDY OBJECTIVES: To determine whether sleep at baseline (before therapy) predicted improvements in language following either language therapy alone or coupled with transcranial direct current stimulation (tDCS) in individuals with primary progressive aphasia (PPA). METHODS: Twenty-three participants with PPA (mean age 68.13 ± 6.21) received written naming/spelling therapy coupled with either anodal tDCS over the left inferior frontal gyrus (IFG) or sham condition in a crossover, sham-controlled, double-blind design (ClinicalTrials.gov identifier: NCT02606422). The outcome measure was percent of letters spelled correctly for trained and untrained words retrieved in a naming/spelling task. Given its particular importance as a sleep parameter in older adults, we calculated sleep efficiency (total sleep time/time in bed x100) based on subjective responses on the Pittsburgh Sleep Quality Index (PSQI). We grouped individuals based on a median split: high versus low sleep efficiency. RESULTS: Participants with high sleep efficiency benefited more from written naming/spelling therapy than participants with low sleep efficiency in learning therapy materials (trained words). There was no effect of sleep efficiency in generalization of therapy materials to untrained words. Among participants with high sleep efficiency, those who received tDCS benefitted more from therapy than those who received sham condition. There was no additional benefit from tDCS in participants with low sleep efficiency. CONCLUSION: Sleep efficiency modified the effects of language therapy and tDCS on language in participants with PPA. These results suggest sleep is a determinant of neuromodulation effects.Clinical Trial: tDCS Intervention in Primary Progressive Aphasia https://clinicaltrials.gov/ct2/show/NCT02606422.

Treating lexical retrieval using letter fluency and tDCS in primary progressive aphasia: a single-case study.

Background: In early stages, individuals with Primary Progressive Aphasia (PPA) report language symptoms while scoring within norm in formal language tests. Early intervention is important due to the progressive nature of the disease. Method: We report a single case study of an individual with logopenic variant PPA (lvPPA). We tested whether letter fluency, used as a therapy task, can improve lexical retrieval when combined with tDCS to either the left inferior-frontal gyrus (IFG) or the left inferior parietal lobe (IPL), administered in two separate therapy phases separated by a wash-out period of three months. Outcomes and results: We observed increases in number of words retrieved during a letter fluency task in trained and untrained letters, when letter fluency therapy (LeFT) was administered with anodal tDCS. When LeFT was combined with left IFG stimulation, words produced in a letter fluency task were lower frequency and higher age of acquisition after treatment, compared to before treatment and there was also an increase in accuracy and response times in an untrained picture-naming task. Conclusions: The results indicate that letter fluency therapy combined anodal tDCS is effective in improving lexical retrieval, particularly when left IFG stimulation was used. Effects generalize beyond the trained task, albeit slowing down of responses in picture naming. This task may provide a useful clinical intervention strategy for patients with mild anomia, who are not challenged enough by traditional naming therapies.

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.

Selective Functional Network Changes Following tDCS-Augmented Language Treatment in Primary Progressive Aphasia.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has shown promising results when used as an adjunct to behavioral training in neurodegenerative diseases. However, the underlying neural mechanisms are not understood and neuroimaging evidence from pre/post treatment has been sparse. In this study, we examined tDCS-induced neural changes in a language intervention study for primary progressive aphasia (PPA), a neurodegenerative syndrome with language impairment as the primary clinical presentation. Anodal tDCS was applied to the left inferior frontal gyrus (LIFG). To evaluate the hypothesis that tDCS promotes system segregation, analysis focused on understanding tDCS-induced changes in the brain-wide functional network connectivity of the targeted LIFG. METHODS: Resting-state fMRI data were obtained from 32 participants with PPA before and after receiving a written naming therapy, accompanied either by tDCS or sham stimulation. We focused on evaluating changes in the global connectivity of the stimulated LIFG-triangularis (LIFG-tri) region given its important role in lexical processing. Global connectivity was indexed by the graph-theoretic measure participation coefficient (PC) which quantifies a region's level of system segregation. The values before and after treatment were compared for each condition (tDCS or Sham) as well as with age-matched healthy controls (n = 19). RESULTS: Higher global connectivity of the LIFG-tri before treatment was associated with greater dementia severity. After treatment, the tDCS group showed a significant decrease in global connectivity whereas the Sham group's did not change, suggesting specific neural effects induced by tDCS. Further examination revealed that the decrease was driven by reduced connectivity between the LIFG-tri and regions outside the perisylvian language area, consistent with the hypothesis that tDCS enhances the segregation of the language system and improves processing efficiency. Additionally, we found that these effects were specific to the LIFG-tri and not observed in other control regions. CONCLUSION: TDCS-augmented language therapy in PPA increased the functional segregation of the language system, a normalization of the hyper-connectivity observed before treatment. These findings add to our understanding of the nature of tDCS-induced neural changes in disease treatment and have applications for validating treatment efficacy and designing future tDCS and other non-invasive brain stimulation (NIBS) treatments.

Effects of tDCS on Sound Duration in Patients with Apraxia of Speech in Primary Progressive Aphasia.

Transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus (IFG) was found to improve oral and written naming in post-stroke and primary progressive aphasia (PPA), speech fluency in stuttering, a developmental speech-motor disorder, and apraxia of speech (AOS) symptoms in post-stroke aphasia. This paper addressed the question of whether tDCS over the left IFG coupled with speech therapy may improve sound duration in patients with apraxia of speech (AOS) symptoms in non-fluent PPA (nfvPPA/AOS) more than sham. Eight patients with non-fluent PPA/AOS received either active or sham tDCS, along with speech therapy for 15 sessions. Speech therapy involved repeating words of increasing syllable-length. Evaluations took place before, immediately after, and two months post-intervention. Words were segmented into vowels and consonants and the duration of each vowel and consonant was measured. Segmental duration was significantly shorter after tDCS compared to sham and tDCS gains generalized to untrained words. The effects of tDCS sustained over two months post-treatment in trained and untrained sounds. Taken together, these results demonstrate that tDCS over the left IFG may facilitate speech production by reducing segmental duration. The results provide preliminary evidence that tDCS may maximize efficacy of speech therapy in patients with nfvPPA/AOS.