Agrammatic Aphasia Research Articles

Narrative production and executive functions in post-stroke agrammatic aphasia

ABSTRACT Background Narrative production has been widely characterized as providing an ecologically valid way to assess language skills in post-stroke aphasia. Although narrative tasks have been instrumental in delineating patterns of lexical and syntactic production in individuals with agrammatic aphasia, our knowledge of how narrative skills are affected in agrammatic aphasia is still limited. Aims The study’s aims were to (a) compare narrative performance between individuals with agrammatic aphasia and a language-unimpaired group, (b) investigate the contribution of lexical and syntactic skills in each group’s narrative organizational skills, and (c) explore the effects of executive functions on each group’s narrative performance. Methods & Procedures The study included 14 individuals with agrammatic aphasia and 14 age- and education-matched language unimpaired individuals as the control group. Both groups told the Cinderella story, and their narrative production was analyzed in terms of microstructure (lexical diversity, syntactic complexity, clause length) and macrostructure (story grammar, story structure complexity). Each group’s executive functions were evaluated through the One-Touch Stockings of Cambridge test that assesses working memory, and the Intra-Extra Dimensional Set Shift test that assesses cognitive flexibility. Outcomes & Results Regarding narrative microstructure, the individuals with agrammatism scored significantly lower than controls in syntactic complexity and clause length, but not in lexical diversity, but they performed lower than controls in both narrative macrostructural measurements. Also, the agrammatic group scored lower than controls in both executive function tasks. A series of linear regression models showed that microstructural skills significantly affected narrative macrostructural abilities in the cohort with agrammatic aphasia, while controls’ macrostructure was affected by both narrative microstructure and executive function skills. Conclusions The individuals with agrammatic aphasia exhibited impairment in both low-level language features of narrative production, such as syntactic complexity and narrative length, and global measures of narrative organization. Their macrostructural performance critically relied on their language resources, while controls’ narrative macrostructure seemed to also draw on domain-general cognitive skills. These findings suggest that both low-level language and high-level discourse organizational skills are vulnerable in narrative production in agrammatic aphasia, and that macrostructural skills are mainly related to the individuals’ microstructural skills.

Cerebrospinal Fluid Total and Phosphorylated Tau Protein in Behavioral Variant Frontotemporal Dementia, Progressive Supranuclear Palsy, Corticobasal Syndrome and Non-Fluent Agrammatic Primary Progressive Aphasia: A Systematic Review and Meta-Analysis.

(1) Background: Frontotemporal lobar degeneration (FTLD) is a generic term which refers to multiple pathologies, including FTLD-tau. The most common FTLD-tau diseases are Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). These diseases share four major syndromes: behavioral variant frontotemporal dementia (bvFD), Richardson syndrome (RS), corticobasal syndrome (CBS) and non-fluent agrammatic primary progressive aphasia (nfa-PPA). The primary aim of this meta-analysis was to examine the diagnostic performance of CSF total (t-tau) and phosphorylated (p-tau) protein in bvFTD, RS, CBS, nfa-PPA and pathologically or genetically defined tauopathy. (2) Methods: A systematic review and meta-analysis was performed on all studies with >10 subjects in a bvFTD/RS/CBS/nfa-PPA group and control group and available data on CSF t-tau or p-tau (mean, SD). Cohen's d was used to quantify the effect size of each study (3) Results: The PSP/tauopathy patients exhibited decreased levels of CSF p-tau compared to the control subjects. The CBS/bvFTD/nfa-PPA cohorts exhibited an increase in t-tau compared to the control groups. (4) Conclusions: Tauopathies may exhibit an inherent decrease in CSF p-tau. The admixture of AD patients in FTD cohorts and high heterogeneity among studies on rare diseases are significant confounding factors in FTLD studies.

Are Personal and Reflexive Pronouns Dissociated in Agrammatic Comprehension? An Individual Participant Meta-Analysis With Clinical Implications.

This study had three objectives: (a) to verify if Grodzinsky et al.'s (1993) findings of worse comprehension of personal than reflexive pronouns can be replicated in a larger meta-analysis of individual participant data, (b) to examine if the heterogeneity found in the patterns of pronoun comprehension in agrammatism can be attributed to task effects, and (c) to evaluate the risk of bias in the reviewed studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search was performed to identify studies examining the personal-reflexive pronoun dissociation in agrammatic comprehension. Seven studies met the search criteria and were included in the meta-analysis. For each participant, individual accuracy scores for the comprehension of personal and reflexive pronouns were extracted in addition to information on the study methods. Individual accuracy data were analyzed using the Fisher's exact test and the binomial test. The risk of bias in the studies was assessed using an adapted version of the Newcastle-Ottawa Quality Assessment Scale. The meta-analysis had three main findings: (a) The majority of the persons with agrammatic aphasia (89%) had no dissociation between the comprehension of personal and reflexive pronouns; (b) 8% revealed a pattern consistent with a neuropsychological dissociation, faring worse on the comprehension of personal than reflexive pronouns; and (c) 2% performed worse on reflexive than personal pronouns. The type of the task used affected pronoun comprehension accuracy and accounted for the heterogeneity in the patterns of pronoun comprehension attested across the different participants. Taken together, the meta-analysis did not support a dissociation between personal and reflexive pronoun comprehension in agrammatic comprehension. When confirmed, the dissociation was driven by task effects. The clinical implications of these findings were discussed together with implications to minimize the risk of bias in future examinations of the topic.

Characterization of agrammatism in Tagalog: Evidence from narrative spontaneous speech

ABSTRACT Background Agrammatism in agglutinative languages exhibits preservation of verb morphology due to their rich morphological paradigms. Tagalog, an agglutinative language mainly spoken in the Philippines, remains uncharacterized in agrammatism yet holds potential for future research that can challenge existing theories and help advance novel ones. Aims The purpose of this study is to quantify and describe the characteristics of agrammatism in Tagalog in narrative spontaneous speech, to examine whether these patterns resemble those reported in other agglutinative languages, and to compare the results obtained to those emerging in literature for non-agglutinative languages. Methods & Procedures Narrative spontaneous speech was elicited from 10 individuals with non-fluent Broca’s aphasia and 12 matched controls. A series of parameters, both conventional and language-specific measures, were selected for analyses. Outcomes & Results Tagalog-speaking individuals with agrammatism exhibited slow and fragmented speech, with a strong preference for minor and simple constructions resulting to decrease in overall grammaticality and sentence complexity. Verb deficits were also found specifically in verbal predication, lexical diversity, and finiteness. There is a prevalent use of bare verb forms, consequently resulting to the decline of verb finiteness and inflections. Code-mixing is found to be extremely variable and statistically non-prominent between groups but patterns may be attributed to personal and sociolinguistic factors. Conclusion Patterns of agrammatism in Tagalog majorly mirror the trends reported in other agglutinative and non-agglutinative languages. Where Tagalog agrammatism departs from other agglutinative languages is the increased use of bare verbs as opposed to the obligatory inflected forms. Although still many questions are unresolved, Tagalog offers an interesting testing ground for variety of topics and issues in agrammatic aphasia.

QUESTION PRODUCTION IN ITALIAN-SPEAKING PWAGR

This paper presents the results of an elicitation task run with Italian-speaking people with agrammatic aphasia (PWAgr). Linguistic theories of aphasia have analysed the production of PWAgr as stemming either from a deterioration of grammatical knowledge or a limitation of extra-linguistic capacities which affect language. Among the former, the Tree Pruning Hypothesis (Friedmann and Grodzinsky, 1997) relates the height of the projections involved in the production of a structure with the chances of it being produced: the stronger the impairment in the speaker, the less likely they are to produce a structure involving higher nodes. Alternatively, syntactic knowledge may be preserved but its use is compromised by Working Memory (WM) limitations (e.g., Miyake et al., 1994; Jakubowicz, 2005). The two approaches make different predictions with respect to question production in Italian: according to the TPH, the production rates of yes/no-questions and who-questions should be comparable in moderate and mild aphasia. Why-questions involve a higher node and should thus not be available. Under a WM-limitation approach, the production rates of why-questions and yes/no-questions should be comparable and higher than those of who-questions. To determine which, if any, of the two approaches makes the correct predictions, three adult Italian speakers diagnosed with Broca’s aphasia and one with anomia performed an elicitation task targeting these three types of structures. Overall, yes/no-questions were the most frequent structures to be produced. The lack of who-questions, as opposed to the production of yes/no-questions, can be accounted for only if derivational complexity is taken into account, but the scarcity of why-questions suggests that the height of the nodes involved may play a role as well.

Primary Progressive Apraxia of Speech Caused by TDP-43: A Case Report.

To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau. This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech, language, cognitive, and neurologic assessments were administered. Neuroimaging was also acquired. Apraxia of speech was diagnosed at his initial visit with a comprehensive neurologic examination further revealing subtle motor findings in the right hand. At subsequent visits, agrammatic aphasia and motor symptoms consistent with corticobasal syndrome were evident. Cognition and behavior remained relatively intact until advanced stages. FDG-PET revealed hypometabolism in the right temporoparietal cortex and left premotor and motor cortices. There was also low-level signal in the right temporoparietal cortex on tau-PET. A sequence variation in the progranulin gene was identified (GRN c.1A>C, p.Met1). Pathologic diagnosis was TDP-43 Type A with an atypical distribution of inclusions in premotor and motor cortices. This case report demonstrates that TDP-43 Type A inclusions in an atypical distribution can present clinically as PPAOS. The sequence variation in the progranulin gene and asymmetric temporoparietal cortex involvement were the strongest indications of the unusual neuropathophysiology prior to autopsy.

The left posterior sMMN: a marker of syntactic processing compensation in agrammatic aphasia

ABSTRACT Background Agrammatic aphasia poses challenges in assessing grammatical abilities due to language comprehension difficulties. The suitability of sMMN as an indicator of syntactic processing abilities in these individuals remains uncertain. Aims Two ERP experiments were conducted to investigate whether early syntactic mismatch negativity (sMMN) could assess the syntactic processing ability of Chinese-speaking individuals with agrammatic aphasia. Methods & Procedures Prior to the ERP experiments, the Western Aphasia Battery (WAB) and the Northwestern Assessment of Verbs and Sentences-Chinese (NAVS-C) were used to screen people with agrammatism. ERP data were collected for both the agrammatic group (AG) (n = 12) and the control group (CG) (n = 12). The first experiment (Experiment 1) involved a passive tone oddball task to control for the influence of primary sound perception. The second experiment (Experiment 2: experiment 2a and experiment 2b) investigated syntactic processing through a passive speech oddball task. Experiment 2a examined the processing of correct sentences and syntactic violation sentences in context. In contrast, Experiment 2b assessed well-formed sequences and ill-formed sequences out of context. Outcomes & Results The results revealed that frontocentral distributed acoustic MMNs were recorded for the CG between 176 - 196ms in Experiment 1, but not for the AG. In Experiment 2, during the 143 - 173ms window, the left anterior sMMN was exclusively observed for the CG, while the left posterior sMMN was specific to the AG. Furthermore, the amplitudes of the left posterior sMMN (143-173ms) were found to have a negative correlation with scores on sentence comprehension tests: the more negative the sMMN, the lower the scores of people with agrammatic aphasia. Notably, this left posterior MMN was absent in Experiment 1. Conclusions The early posterior sMMN, discovered for the first time in our study, appears to be more sensitive in detecting syntactic processing impairments in agrammatics compared to the early anterior sMMN. This finding has the potential to enhance the precision of aphasia assessment.

Treatment of verb tense inflection and sentence production in Persian individuals with agrammatism

Production of verb morphology, especially tense inflection, is usually impaired in individuals with agrammatism. There have been relatively few studies on treatment of verb tense inflection in agrammatic aphasia. In this study we adapted ACTION (a linguistically motivated treatment) to Persian language, to treat the production of regular and irregular verbs separately in sentence context. A single-subject multiple-baseline across behaviors design was used to establish the treatment effect. Using a non-probable convenience sampling, four Persian agrammatic patients with Broca’s aphasia resulting from cerebrovascular accident (CVA) were recruited for this study. Two participants received treatment first for regular verbs (Phase 1, 4 weeks), and then for irregular verbs (Phase 2, 4 weeks). The other two participants received treatment in reverse order. In the final phase of treatment (Phase 3, 4 weeks), all 4 participants underwent a sentence construction treatment. All participants showed improvement in the production of trained tenses. Treatment also generalized to production of untrained regular verbs while generalization to irregular verbs was modest. Furthermore, improvement was found on narrative scores (e.g. MLU) after treatment. These findings suggest that Persian individuals with agrammatism could be trained to correctly apply temporal information to verb inflection in elicited speech.

Amyloid and Tau PET Positivity in Progressive Apraxia of Speech and Agrammatic Aphasia

AbstractBackgroundThe spectrum of what is referred to as nonfluent/agrammatic primary progressive aphasia includes patients with isolated apraxia of speech (PPAOS), progressive agrammatic aphasia (PAA), or a combination thereof (AOS‐PAA). When AOS is present, there is typically an underlying 4R tauopathy (corticobasal degeneration; progressive supranuclear palsy); isolated PAA is more often associated with a 3R tauopathy (Pick’s disease). While pathological studies confirm the clinical syndrome is the sequela of these proteinopathies, beta‐amyloid (Aβ) deposition has also been observed. Given the growing number of treatment options, it is important to better understand the incidence of Alzheimer’s disease (AD) in PPAOS‐PAA spectrum disorders.Methods65 patients recruited by the Neurodegenerative Research Group at Mayo Clinic underwent Aβ‐PET imaging using Pittsburgh Compound B (PiB) and tau‐PET imaging with [18F]flortaucipir at the same visit (PPAOS = 23; PAA = 6; AOS‐PAA = 36). A global PiB SUVR (standardized uptake value ratio)≥1.48 and temporal lobe tau meta‐ROI SUVR≥1.25 were deemed Aβ and tau positive, respectively. The incidence of Aβ and tau positivity and clinical‐demographic profiles were compared among groups.ResultsThere was no difference in age, sex, APOE status, tau/Aβ positivity or PET SUVRs across clinical groups (Table 1). Patients differed on indices of aphasia and AOS severity, in concordance with group membership; there was no difference on a memory measure. Eight patients (12%) were both Aβ and tau positive (indicative of the presence of AD), with an additional 20 patients (31%) positive on only one biomarker (Table 1). Of the eight Aβ and tau positive patients, seven had AOS (six prosodic predominant AOS). Aβ more than tau SUVRs increased with age and were related to each other (Figure 1).ConclusionsAβ and tau positivity is not uncommon in AOS and/or PAA patients, particularly in older patients. Enrollment criteria for Aβ or tau targeted pharmacological trials should consider concordance of biological variables and clinical presentations, rather than simply biological biomarkers. Alternatively, if such patients are enrolled, the outcome measures should reflect the clinical impairments, as it is not yet known if or how concomitant AD influences the clinical presentation.

Clinical Manifestations.

It is unclear whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) represent the two ends of a clinical continuum or exist as distinct syndromic entities with specific pathologic/prognostic correlates. We aimed to characterize the main clinical features along the spectrum of progressive non-fluent speech-language disorders (nf-SLD) and explore the existence of data-driven symptom clusters with etiological/prognostic value. We included 98 participants presenting with progressive motor speech impairment and/or agrammatism, of which 43 had an autopsy-confirmed neuropathological diagnosis. Speech pathologists rated motor speech features indicative of dysarthria and AOS. Quantitative measures of expressive/receptive agrammatism were obtained and compared with healthy controls. Baseline and longitudinal disease severity was assessed with the Clinical Dementia Rating sum-of-boxes (CDR-SB). We explored the clustering tendency of the data to form robust symptom clusters and used principal component analysis to extract data-driven clinical components. The longitudinal CDR-SB change was estimated with linear mixed-effects models. Ninety-one participants fitted previously reported clinical profiles (69 AOS+agrammatism, 18 PPAOS and 4 PAA), while 7 remained unclassifiable and were characterized by nonfluent speech and dysarthria in the absence of apraxia of speech or agrammatism. None of the baseline clinical features discriminated between FTLD subgroups. The Hopkins statistic ruled out the existence of syndromic clusters in the whole sample. Three data-driven components explained 71% of the variance ([i]severity-agrammatism, [ii]AOS, and [iii]dysarthria). The component characterized by prominent dysarthria was more specific to patients with Progressive Supranuclear Palsy while the component characterized by severity-agrammatism predicted a faster CDR-SB increase. Our results suggest that nf-SLD represents a clinical continuum. Splitting this continuum into different clinical phenotypes based on its major clinical features does not improve clinical-pathological correlations, stressing the need for new clinical and biological markers. The term nf-SLD could be used to group together these speech-language phenotypes strongly associated with FTLD.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

Amyloid and Tau PET Positivity in Progressive Agrammatic Aphasia and Apraxia of Speech.

The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer's disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers.

The production of adjectives in narratives by individuals with primary progressive aphasia

Adjectives (e.g., hungry) are an important part of language, but have been little studied in individuals with impaired language. Adjectives are used in two different ways in English: attributively, to modify a noun (the hungry dog); or predicatively, after a verb (the dog is hungry). Attributive adjectives have a more complex grammatical structure than predicative adjectives, and may therefore be particularly prone to disruption in individuals with grammatical impairments. We investigated adjective production in three subtypes of primary progressive aphasia (PPA: agrammatic, semantic, logopenic), as well as in agrammatic stroke aphasia and a group of healthy control participants. Participants produced narratives based on picture books, and we coded every adjective they produced for its syntactic structure. Compared to healthy controls, the two agrammatic groups, but not the other two patient groups, produced significantly fewer attributive adjectives per sentence. All four patient groups were similar to controls for their rate of predicative adjective production. In addition, we found a significant correlation in the agrammatic PPA participants between their rate of producing attributive adjectives and impaired production of sentences with complex syntactic structure (subject cleft sentences like It was the boy that chased the girl); no such correlation was found for predicative adjectives. Irrespective of structure, we examined the lexical characteristics of the adjectives that were produced, including length, frequency, semantic diversity and neighborhood density. Overall, the lexical characteristics of the produced adjectives were largely consistent with the language profile of each group. In sum, the results suggest that attributive adjectives present a particular challenge for individuals with agrammatic language production, and add a new dimension to the description of agrammatism. Our results further suggest that attributive adjectives may be a fruitful target for improved treatment and recovery of agrammatic language.

‘To be’ or not ‘to be’: an analysis of copula production and omission in people with non-fluent aphasia

ABSTRACT Background Agrammatic aphasia has been widely associated with impairments with functional words and complex sentences. Speech errors of people with aphasia (PWA) have been reported to be selective, with patterns of omissions in functional words, most notably in the domain of tense inflection on verbs compared to agreement in morphologically rich languages. Aims In languages like English, where tense and agreement are hard to disentangle in their inflectional paradigms, investigations of the inflectional domain in PWA are rare. In this study, we introduce a novel approach that allows the disentangling of inflectional errors in English through the patterns of copula omission of the verb to be. The inflectional system of the functional verb to be is richer, and its distribution in the sentence is based on the semantics of its predicate (stage-level vs. individual-level). Methods and procedures Spontaneous productions of 16 PWA collated from AphasiaBank transcripts were analysed for violations of tense alongside other patterns of error that could suggest an impairment in the inflectional domain. Outcomes and results Copula deletion was found to be modulated by the semantics of the predicate, showing a selective pattern of omission in stage-level predicates. Incorrect case assignment (accusative in place of nominative) was also observed as an indicator of impaired tense. Conclusions The results confirm the effectiveness of copula to be to investigate the English inflectional system and substantiate previous studies on selective errors in the verbal domain in PWA in English.

Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.

A reconceptualization of sentence production in post-stroke agrammatic aphasia: the synergistic processing bottleneck model.

The language production deficit in post-stroke agrammatic aphasia (PSA-G) tends to result from lesions to the left inferior frontal gyrus (LIFG) and is characterized by a triad of symptoms: fragmented sentences, errors in functional morphology, and a dearth of verbs. Despite decades of research, the mechanisms underlying production patterns in PSA-G have been difficult to characterize. Two major impediments to progress may have been the view that it is a purely morphosyntactic disorder and the (sometimes overzealous) application of linguistic theory without interceding psycholinguistic evidence. In this paper, empirical evidence is examined to present an integrated portrait of language production in PSA-G and to evaluate the assumption of a syntax-specific syndrome. In light of extant evidence, it is proposed that agrammatic language production results from a combination of morphosyntactic, phonomotor, and processing capacity limitations that cause a cumulative processing bottleneck at the point of articulatory planning. This proposed Synergistic Processing Bottleneck model of PSA-G presents a testable framework for future research. The paper ends with recommendations for future research on PSA-G.

Predicting change in semantic fluency performance over time in patients with progressive speech and language disorders

AbstractBackgroundThe semantic fluency task involves naming as many items as possible in a given category (e.g., animals) in one minute. It is often interpreted as a measure of word retrieval, but also draws on executive function abilities to organize responses and develop task‐specific strategies. Indeed, both language skills and dementia severity ratings have recently been found to correlate with semantic fluency performance in patients with primary progressive aphasia (Riello et al., 2022; Scheffel et al., 2021). Here, we focused instead on how performance on language and executive function measures predicts longitudinal change in semantic fluency performance in patients with progressive agrammatic aphasia and/or apraxia of speech (AOS).MethodPatients with isolated agrammatic aphasia (n = 10), isolated AOS (n = 42), or a combination of the two (n = 59) with 1‐7 visits (mean = 2.19) were included. We used Bayesian hierarchical linear models to investigate whether baseline measures of executive function or language were associated with the rate at which semantic fluency performance changes over time while accounting for baseline diagnosis group, sex, education, age at baseline, and baseline disease duration.ResultSemantic fluency performance declined over time, at a similar rate irrespective of diagnostic group (isolated or combined aphasia or AOS; Figure 1). Across all patients, higher executive function abilities at baseline, as indicated by faster Trails Making Test B completion times, predicted higher baseline semantic fluency performance and also a steeper annual rate of decline (Figure 2). Similarly, higher fluency ratings during the Western Aphasia Battery‐Revised picture description at baseline were associated with higher baseline semantic fluency performance and faster decline. Baseline performance on the Boston Naming Test and Token Test were also associated with baseline semantic fluency, but not with longitudinal change.ConclusionThese results better delineate how language and executive function abilities support performance in the semantic fluency task. Higher abilities in those areas at baseline do not appear to be protective over time. Rather, the differences in semantic fluency that are present at baseline disappear as the disease progresses.

The role of category ambiguity in normal and impaired lexical processing: can you paint without the paint?

Many words are categorially ambiguous and can be used as a verb (to paint) or as a noun (the paint) due to the presence of unpronounced morphology or "zero morphology". On this account, the verb "paint" is derived from the noun "paint" through the addition of a silent category-changing morpheme. Past studies have uncovered the syntactic and semantic properties of these categorially ambiguous words, but no research has been conducted on how people process them during normal or impaired lexical processing. Are these two different uses of "paint" processed in the same way? Does this morphosyntactic structure have an effect on online sentence processing? This study presents two experiments that investigate the effect of morphosyntactic complexity in categorially ambiguous words presented in isolation (experiment 1) and in a sentential context (experiment 2). The first experiment tested the ability to process categorially unambiguous and ambiguous nouns and verbs in 30 healthy older adults and 12 individuals with aphasia, using a forced choice phrasal-completion task, in which individuals choose whether the or to is most compatible with target words. Healthy controls and individuals with fluent aphasia all showed: (1) a bias toward the base category in selection rates for the and to, where the was selected more frequently for words identified to be base nouns, and to was selected more frequently for base verbs, and (2) longer reaction times for ambiguous (over unambiguous) words. However, individuals with non-fluent agrammatic aphasia showed a base-category effect only for nouns, with chance performance for verbs. The second experiment, using an eye-tracking while reading paradigm with 56 young healthy adults, showed a reading time slowdown for derived forms (to paint) compared to their base-category counterparts (the paint) in sentence contexts. These findings suggest that categorially ambiguous words likely share a common root, and are related by zero-derivation, and that impaired access to the base-category (i.e., verbs like to visit) precludes associated morphological processes and therefore the retrieval of the derived-category (i.e., nouns like the visit) in non-fluent agrammatic aphasia. This study provides insights into the theory of zero morphology, and the principles that need to be accounted for in models of the lexicon.

Neurolinguistics: A scientometric review

This scientometric study aimed to map the knowledge domains of neurolinguistics, an interdisciplinary field of linguistics, to provide a comprehensive understanding of the development process and structural relationships of scientific knowledge in neuroscience. A total of 5,104 neurolinguistics documents published between 1913 and 2022 were analysed and visualized from three databases, Scopus, WOS, and Lens, using CiteSpace 5.8.R3 and VOSviewer 1.6.18. Knowledge production was mapped by country, university, journal, publisher, research field, and author, and examined using scientometric indicators, including co-citation networks, citation networks, sigma metrics, and clusters of topics. The identified clusters include discourse processing of flexible word order language language-ready brain, and language talent in cultural neurolinguistics; object knowledge of agrammatic aphasia; early experience of cerebral localization; language in autism spectrum disorder; and language evolution in relation to cognitive adequacy in language-ready brain. This study provides valuable insights into the field of neurolinguistics and offers a visual representation of the development process of scientific knowledge in neuroscience.

CSF Alzheimer’s biomarkers in clinical practice

AbstractBackgroundCSF biomarkers are well validated and a useful tool for the diagnosis of Alzheimer’s disease (AD). However, in some cases results are not consistent. In this study we examine to which extent CSF biomarkers support diagnosis in clinical practice.MethodAnalysis of 141 consecutive CSF samples of patients referred to our memory clinic with suspected cognitive decline, using the Lumipulse G600II chemiluminescent immunoassay (Fujirebio, Spain) to determine Ab‐42/Ab‐40 ratio (A+ if <0.068), total Tau (N+ if >410 pg/ml), and phospho‐Tau (T+ if >59 pg/ml).Clinical diagnosis was classified into three categories: AD, degenerative non‐AD, and non degenerative, considering current clinical criteria at last visit.Based on biomarkers, we separated the groups as follows: negative for AD (A‐T‐N‐ and A‐T‐N+), positive for AD (A+T+N+ and A+T+N‐), cases with amyloidosis A+ but T‐ (A+T‐N+; A+T‐N‐), and cases without amyloidosis A‐ but T+ (A‐T+N+).Result50,5% of the patients had a positive AD result that correlated in a majority of cases with a clinical amnestic AD phenotype or other highly related phenotypes (logopenic aphasia and posterior cortical atrophy). The exceptions were 5 cases meeting diagnostic criteria for non‐fluent/agrammatic aphasia or corticobasal syndrome.37% had a negative AD result which correlated with a clinical diagnosis of non‐AD neurodegeneration (25 cases) or non degenerative (27 cases).Therefore, in 87% of the cases CSF biomarkers supported a clinical diagnosis.On the other hand, 18 cases (13%) had some inconsistencies within biomarkers: 7 with A‐ and 11 with A+ results. As regards clinical diagnosis, all A‐T+N+ and many of the patients with A+ biomarkers (8/11) had been considered AD phenotypes. In two of the cases with A+T‐N‐, an AD diagnosis was later confirmed, respectively, by a positive PET‐amyloid study and full positive CSF biomarkers analyzed two years later.No differences were found in family history, age of onset, or age at lumbar puncture between the groups of AD positive biomarkers and just amyloidosis A+.ConclusionCSF biomarkers were clearly supportive of the clinical diagnosis in a majority of the cases of our cohort. However, in 13% of the cases, most of them with an AD type phenotype, biomarkers were unclear.