Formulaic Language in People with Probable Alzheimer's Disease: A Frequency-Based Approach

BACKGROUND: Language change can be a valuable biological marker of overall cognitive change in Alzheimer's disease (AD) and other forms of dementia. Previous reports have described increased use of language formulas in AD, i.e., combinations likely processed in a holistic manner. Words that commonly occur together are more likely to become a formula. OBJECTIVE: To determine if frequency of co-occurrence as one indicator for formulaic language can distinguish people with probable AD from controls and if variables are sensitive to time post-symptom onset. METHODS: We developed the Frequency in Language Analysis Tool (FLAT), which indicates degrees of formulaicity in an individual language sample. The FLAT accomplishes this by comparing individual language samples to co-occurrence data from the British National Corpus (BNC). Our analysis also contained more conventional language variables in order to assess novel contributions of the FLAT. We analyzed data from the Pitt Corpus, which is part of DementiaBank. RESULTS: Both conventional and co-occurrence variables were able to distinguish AD and control groups. According to co-occurrence data, people with probable AD produced more formulaic language than controls. Only co-occurrence variables correlated with disease progression. DISCUSSION: Frequency of word co-occurrences is one indicator for formulaicity and a valuable contribution to characterizing language change in AD

The Language Profile of Behavioral Variant Frontotemporal Dementia

BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker

A case of "order insensitivity"? Natural and artificial language processing in a man with primary progressive aphasia.

Processing of linear word order (linear configuration) is important for virtually all languages and essential to languages such as English which have little functional morphology. Damage to systems underpinning configurational processing may specifically affect word-order reliant sentence structures. We explore order processing in WR, a man with primary progressive aphasia (PPA). In a previous report, we showed how WR showed impaired processing of actives, which rely strongly on word order, but not passives where functional morphology signals thematic roles. Using the artificial grammar learning (AGL) paradigm, we examined WR's ability to process order in non-verbal, visual sequences and compared his profile to that of healthy controls, and aphasic participants with and without severe syntactic disorder. Results suggested that WR, like some other patients with severe syntactic impairment, was unable to detect linear configurational structure. The data are consistent with the notion that disruption of possibly domain-general linearization systems differentially affects processing of active and passive sentence structures. Further research is needed to test this account, and we suggest hypotheses for future studies

Automated Analysis of Language Production in Aphasia and Right Hemisphere Damage: Frequency and Collocation Strength

BACKGROUND: Reliance on formulaic language, i.e., holistically processed multiword chunks, is claimed to distinguish speakers with aphasia, speakers with right-hemisphere damage (RHD), and neurotypical controls (NC). Frequency and collocation strength of word combinations are indicators of formulaic language. AIMS: We aimed to determine frequency and collocation properties of spoken production, as indicators of formulaic language, in people with aphasia, speakers with RHD and NC. METHODS AND PROCEDURES: We used computerized methods to investigate spontaneous language in 40 speakers: 10 with fluent aphasia (fA), 10 with non-fluent aphasia (nfA), 10 with RHD, and 10 NC. Our analysis not only focused on frequency and collocation strength of grammatical combinations as markers of formulaic language (using the British National Corpus as reference), but also looked at word frequency, language fluency, proportion of content words, and measures of lexical and combinatorial diversity. OUTCOME AND RESULTS: Both groups with aphasia differed from neurotypical speakers with regard to lexical features and word combinations. Their language was less fluent, less diverse at the word level, and, in the non-fluent group, contained a higher proportion of content words. Each aphasic group also differed significantly from controls with increased values on at least one marker of formulaic language. Speakers with RHD produced less-frequent combinations, which were more weakly collocated; however, these effects did not reach statistical significance. Conclusions: Our results show that formulaic language use distinguishes aphasic from other speakers and that differences can be tracked with an automated, corpus-based script that uses frequency and collocation variables. We present our study in the context of usage-based frameworks of language

"I don't know": a usage-based approach to familiar collocations in non-fluent aphasia

Background: Familiar collocations (e.g., “it’s alright”) are an important part of everyday conversation. Such word combinations are often retained in speakers with Broca’s aphasia. However, only few investigations have studied the forms and functions of familiar collocations available to speakers with Broca’s aphasia. // Aims: We first apply a frequency-based perspective to word combinations produced by speakers with Broca’s aphasia and their conversation partners (CPs), and compare the frequency characteristics of word combinations in dyadic and non-dyadic speech. Second, we investigate the conversational functions of one prominent familiar collocation, “I don’t know” (IDK). // Methods & Procedures: In the first analysis, speech samples from interactions of nine dyads (each a speaker with Broca’s aphasia and their CP) were examined. Non-dyadic samples were selected from 39 speakers with Broca’s aphasia from AphasiaBank (MacWhinney et al., 2011). The Frequency in Language Analysis Tool (FLAT; Zimmerer & Wibrow, 2015) was used to estimate collocation strength (the degree of association between words in a combination) of well-formed bigrams (two-word combinations) and trigrams (three-word combinations). The second analysis presents a qualitative investigation of uses of IDK in dyadic exchanges. // Outcomes & Results: Analysis 1 revealed that residual trigrams in Broca’s aphasia were more strongly collocated in comparison to language produced by CPs. There was no difference in frequency-based profiles between dyadic and non-dyadic aphasic speech. Analysis 2 indicated that speakers with Broca’s aphasia and CPs used IDK to achieve a variety of communicative functions. However, patterns specific to each participant group were found. // Conclusions: These findings highlight that frequency-based analysis is useful in explaining residual, grammatically well-formed word combinations in Broca’s aphasia. This study provides evidence that IDK can aid turn construction in aphasia

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Leucine-rich glioma-inactivated 1 versus contactin-associated protein-like 2 antibody neuropathic pain: clinical and biological comparisons

Pain is a under-recognized association of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. Of 147 patients with these autoantibodies, pain was experienced by 17 of 33 (52%) with CASPR2- versus 20 of 108 (19%) with LGI1 antibodies (p = 0.0005), and identified as neuropathic in 89% versus 58% of these, respectively. Typically, in both cohorts, normal nerve conduction studies and reduced intraepidermal nerve fiber densities were observed in the sampled patient subsets. In LGI1 antibody patients, pain responded to immunotherapy (p = 0.008), often rapidly, with greater residual patient-rated impairment observed in CASPR2 antibody patients (p = 0.019). Serum CASPR2 antibodies, but not LGI1 antibodies, bound in vitro to unmyelinated human sensory neurons and rodent dorsal root ganglia, suggesting pathophysiological differences that may underlie our clinical observations