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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.

ObjectiveTranscranial 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.MethodsResting-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).ResultsHigher 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.ConclusionTDCS-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.

The current study aims to determine the brain areas critical for response to anodal transcranial direct current stimulation (tDCS) in PPA. Anodal tDCS and sham were administered over the left inferior frontal gyrus (IFG), combined with written naming/spelling therapy. Thirty people with PPA were included in this study, and assessed immediately, 2 weeks, and 2 months post-therapy. We identified anatomical areas whose volumes significantly predicted the additional tDCS effects. For trained words, the volumes of the left Angular Gyrus and left Posterior Cingulate Cortex predicted the additional tDCS gain. For untrained words, the volumes of the left Middle Frontal Gyrus, left Supramarginal Gyrus, and right Posterior Cingulate Cortex predicted the additional tDCS gain. These findings show that areas involved in language, attention and working memory contribute to the maintenance and generalization of stimulation effects. The findings highlight that tDCS possibly affects areas anatomically or functionally connected to stimulation targets.

Purpose: The evaluation of spelling performance in aphasia reveals deficits in written language and can facilitate the design of targeted writing treatments. Nevertheless, manual scoring of spelling performance is time-consuming, laborious, and error prone. We propose a novel method based on the use of distance metrics to automatically score spelling. This study compares six automatic distance metrics to identify the metric that best corresponds to the gold standard--manual scoring--using data from manually obtained spelling scores from individuals with primary progressive aphasia. Method: Three thousand five hundred forty word and nonword spelling productions from 42 individuals with primary progressive aphasia were scored manually. The gold standard--the manual scores--were compared to scores from six automated distance metrics: sequence matcher ratio, Damerau-Levenshtein distance, normalized Damerau-Levenshtein distance, Jaccard distance, Masi distance, and Jaro-Winkler similarity distance. We evaluated each distance metric based on its correlation with the manual spelling score. Results: All automatic distance scores had high correlation with the manual method for both words and nonwords. The normalized Damerau-Levenshtein distance provided the highest correlation with the manual scoring for both words (r[subscript s] = 0.99) and nonwords (r[subscript s] = 0.95). Conclusions: The high correlation between the automated and manual methods suggests that automatic spelling scoring constitutes a quick and objective approach that can reliably substitute the existing manual and time-consuming spelling scoring process, an important asset for both researchers and clinicians.

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network. We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming). Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy. These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.

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. Plain Language Summary: 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. [ABSTRACT FROM AUTHOR]

We investigated the on-line processing of unaccusative and unergative sentences in a group of eight Greek-speaking individuals diagnosed with Broca aphasia and a group of language-unimpaired subjects used as the baseline. The processing of unaccusativity refers to the reactivation of the postverbal trace by retrieving the mnemonic representation of the verb's syntactically defined antecedent provided in the early part of the sentence. Our results demonstrate that the Broca group showed selective reactivation of the antecedent for the unaccusatives. We consider several interpretations for our data, including explanations focusing on the transitivization properties of nonactive and active voice-alternating unaccusatives, the costly procedure claimed to underlie the parsing of active nonvoice-alternating unaccusatives, and the animacy of the antecedent modulating the syntactic choices of the patients.

The aim of this study is to test the validity and reliability of the Bilingual Aphasia Test as a measure of language impairment in a Greek-speaking Broca's aphasic population and to investigate relationships with the same aphasic group's performance on the Greek version of the short form of the Boston Diagnostic Aphasia Examination battery, mainly focusing on a series of subtests which are shared by the two batteries, yet occasionally differ in content. Correlation analyses showed that the two instruments yielded highly comparable results with respect to the measurement of reading and listening comprehension, as well as in the performance-based measurement of the automated sequence capacity of the patients. Nevertheless, the Bilingual Aphasia Test, as a more extensive battery, proved to be more sensitive and objective in characterizing the patients' language abilities in a number of individual language functions, including commands, sentence repetition, naming, verbal fluency and syntactic comprehension. (Contains 5 tables and 4 notes.)

Previous research has suggested that a failure in processing contextual information may account for the heterogeneous clinical manifestations and cognitive impairments observed in schizophrenia. In the domain of language, context processing in schizophrenia has been investigated mostly with single-word semantic priming paradigms; however, natural language comprehension depends on more than semantic relations between words. The present study aimed to systematically assess sentence context effects in homonym meaning activation in patients with schizophrenia. Fourteen patients with schizophrenia and 14 normal controls matched to the patients on sex, age, education and parental education, were examined using a cross-modal priming paradigm. Primes were sentences biasing the first, second, or neither meaning of a sentence-final equibiased homonym; targets were related to either the first or the second meaning of the homonym and appeared after an interstimulus interval (ISI) of 0 ms or 750 ms. Patients with schizophrenia exhibited a trend towards facilitation of both target types following unbiased sentences at ISI = 0 ms, similar to controls. However, in contrast to the pattern of selective target facilitation exhibited by control subjects following first- or second meaning-biased sentences, no significant target facilitation was observed in patients in the same condition. At ISI = 750 ms, patients did no longer exhibit significant target facilitation in any sentence context condition. This pattern of results is compatible with the assumption of a combined impairment in lexical (automatic spreading of activation within the semantic network) and extralexical (working memory) processes in patients with schizophrenia. (Contains 3 tables.)

In 1906, Pierre Marie triggered a heated controversy and an exchange of articles with Jules Dejerine over the localization of language functions in the human brain. The debate spread internationally. One of the timeliest responses, that appeared in print 1 month after Marie's paper, came from Christofredo Jakob, a Bavarian-born neuropathologist working in Buenos Aires. The present study comprises an English translation of Jakob's 1906 paper and a discussion of Jakob's ideas on the localizationist-holistic approach regarding the role of Broca's area. This issue is still at the core of scientific debate in the light of current neuropsychological and neuroimaging findings. (Contains 1 table and 2 figures.)

The issue of regular-irregular past tense formation was examined in a cross-modal lexical decision task in Modern Greek, a language where the orthographic and phonological overlap between present and past tense stems is the same for both regular and irregular verbs. The experiment described here is a follow-up study of previous visual lexical decision experiments (Tsapkini, Kehayia, & Jarema, 2002) that also addressed the regular-irregular distinction in Greek. In the present experiment, we investigated the effect of input modality in lexical processing and compared different types of regular and irregular verbs. In contrast to our previous intra-modal (visual-visual) priming experiments, in this cross-modal (auditory-visual) priming study, we found that regular verbs with an orthographically salient morphemic aspectual marker elicited the same facilitation as those without an orthographically salient marker. However, irregular verbs did not exhibit a different priming pattern with respect to modality. We interpret these results in the framework of a two-level lexical processing approach with modality-specific access representations at a surface level and modality-independent morphemic representations at a deeper level.

In this paper we investigated the effects of configurational asymmetry in prefixed verbs in French. We used a simple lexical decision paradigm to compare prefixed verbs with external and internal prefixes as specified in linguistic theory (Di Sciullo, 1997) where external prefixes do not change the aktionsart and the verb argument structure of the verb, but internal prefixes do change the aktionsart and may change the verb argument structure of the verb. In Experiment 1 we tested the bi-valent prefix "de-" where the configurational difference between external and internal properties of a prefix did not elicit differential response latencies. However, in Experiment 2, where unambiguous prefixes (internal "en-" and external "re-") were tested, the external prefix elicited longer latencies. These results are discussed with respect to the linguistic constraints the configurational properties of prefixes place upon psycholinguistic models of lexical access, as well as with respect to the effects of prefix bi-valence in the recognition of prefixed verbs.

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. [ABSTRACT FROM AUTHOR]