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.

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.

Behavioral Treatment for Speech and Language in Primary Progressive Aphasia and Primary Progressive Apraxia of Speech: A Systematic Review.

Primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS) are neurodegenerative syndromes characterized by progressive decline in language or speech. There is a growing number of studies investigating speech-language interventions for PPA/PPAOS. An updated systematic evaluation of the treatment evidence is warranted to inform best clinical practice and guide future treatment research. We systematically reviewed the evidence for behavioral treatment for speech and language in this population. Reviewed articles were published in peer-reviewed journals through 31 May 2021. We evaluated level of evidence, reporting quality, and risk of bias using a modified version of the American Speech-Language Hearing Association (ASHA) Levels of Evidence, an appraisal point system, additional reporting quality and internal/external validity items, and, as appropriate, the Single Case Experimental Design Scale or the Physiotherapy Evidence Database - PsycBITE Rating Scale for Randomized and Non-Randomized Controlled Trials. Results were synthesized using quantitative summaries and narrative review. A total of 103 studies reported treatment outcomes for 626 individuals with PPA; no studies used the diagnostic label PPAOS. Most studies evaluated interventions for word retrieval. The highest-quality evidence was provided by 45 experimental and quasi-experimental studies (16 controlled group studies, 29 single-subject designs). All (k = 45/45) reported improvement on a primary outcome measure; most reported generalization (k = 34/43), maintenance (k = 34/39), or social validity (k = 17/19) of treatment for at least one participant. The available evidence supports speech-language intervention for persons with PPA; however, treatment for PPAOS awaits systematic investigation. Implications and limitations of the evidence and the review are discussed.

Modified script training for nonfluent/agrammatic primary progressive aphasia with significant hearing loss: A single-case experimental design.

Speech-language pathology caseloads often include individuals with hearing loss and a coexisting neurogenic communication disorder. However, specific treatment techniques and modifications designed to accommodate this population are understudied. Using a single-case experimental design, the current study investigated the utility of modified Video Implemented Script Training for Aphasia (VISTA) for an individual with nonfluent/agrammatic variant primary progressive aphasia and severe-to-profound, bilateral hearing loss. We analyzed the impact of this intervention, which incorporates orthographic input and rehearsal, on script production accuracy, speech intelligibility, grammatical complexity, mean length of utterance, and speech rate. Treatment resulted in comparable positive outcomes relative to a previous study evaluating script training in nonfluent/agrammatic primary progressive aphasia patients with functional hearing. Follow-up data obtained at three months, six months, and one year post-treatment confirmed maintenance of treatment effects for trained scripts. To our knowledge, this is the first study to investigate a modified speech-language intervention tailored to the needs of an individual with PPA and hearing loss, with findings confirming that simple treatment modifications may serve to broaden the range of treatment options available to those with concomitant sensory and communication impairments.

Disorders of Emotional Communication in Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to a wide array of behavioral and cognitive deficits. Individuals with TBI often demonstrate difficulties with the recognition and expression of emotion communicated through multiple modalities including facial expression, vocal prosody, and linguistic content. Deficits in emotional communication contribute to a pattern of social pragmatic communication problems, leading to decreased psychosocial function. Growing evidence supports intervention targeting affective processing. This article summarizes the current evidence for evaluation and treatment of affective processing disorders in TBI.

MEDUSA: Marine benthic Ecological Data from Underwater imagery Surveys of sub-Antarctic Crozet environments.

Inscribed on the UNESCO World Heritage list, the sub-Antarctic Crozet archipelago is located in a region facing significant environmental changes impacting a poorly known marine biodiversity. Underwater imagery constitutes a valuable non-invasive approach for gathering ecological data and improving our knowledge of ecosystems' vulnerability. We here compiled two datasets, encompassing 17 video-imagery surveys of Crozet nearshore environments conducted in 2021 and 2022 at two sites of Ile de la Possession: Baie du Marin and Crique du Sphinx. Faunal abundance and algal cover data related to each survey are also provided. A total of 755 images were analysed, comprising 52 faunal and 14 algal taxa identified in 2021, as well as 45 faunal and 14 algal taxa identified in 2022. Video-transects were performed in shallow waters by scuba divers using a GoPro®HERO7 multiple camera set-up, and in deeper waters using a remotely operated vehicle. These data provide a first baseline for biodiversity and ecosystem studies, and for monitoring the long-term dynamics of Crozet benthic habitats facing natural and anthropogenic disturbances.

Digital language markers distinguish frontal from right anterior temporal lobe atrophy in frontotemporal dementia.

Background and Objectives: Within frontotemporal dementia (FTD), the behavioral variant (bvFTD) characterized by frontal atrophy, and semantic behavioral variant (sbvFTD) characterized by right anterior temporal lobe (rATL) atrophy, present diagnostic challenges due to overlapping symptoms and neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related rATL and frontal atrophy, potentially offering a non-invasive diagnostic tool. Methods: In a cross-sectional design, we included 40 participants with FTD-related predominant frontal atrophy (n=16) or predominant rATL atrophy (n=24) and 22 healthy controls from the UCSF Memory and Aging Center. Using stepwise logistic regression and receiver operating characteristic (ROC) curve analysis, we analyzed 16 linguistic and acoustic features that were extracted automatically from audio-recorded picture description tasks. Neuroimaging data were analyzed using voxel-based morphometry to examine brain-behavior relationships of regional atrophy with the features selected in the regression models. Results: Logistic regression identified three features (content units, lexical frequency, familiarity) differentiating the overall FTD group from controls (AUC=.973), adjusted for age. Within the FTD group, five features (adpositions/total words ratio, arousal, syllable pause duration, restarts, words containing 'thing') differentiated frontal from rATL atrophy (AUC=.943). Neuroimaging analyses showed that semantic features (lexical frequency, content units, 'thing' words) were linked to bilateral inferior temporal lobe structures, speech and lexical features (syllable pause duration, adpositions/total words ratio) to bilateral inferior frontal gyri, and socio-emotional features (arousal) to areas known to mediate social cognition including the right insula and bilateral anterior temporal structures. As a composite score, this set of five features was uniquely associated with rATL atrophy. Discussion: Automated speech analysis effectively distinguished the overall FTD group from controls and differentiated between frontal and rATL atrophy. The neuroimaging findings for individual features highlight the neural basis of language impairments in these FTD variants, and when considered together, underscore the importance of utilizing features' combined power to identify impaired language patterns. Automated speech analysis could enhance early diagnosis and monitoring of FTD, offering a scalable, non-invasive alternative to traditional methods, particularly in resource-limited settings. Further research should aim to integrate automated speech analysis into multi-modal diagnostic frameworks.

Baseline structural imaging correlates of treatment outcomes in semantic variant primary progressive aphasia.

Semantic variant primary progressive aphasia (svPPA) is a neurodegenerative disorder characterized by a loss of semantic knowledge in the context of anterior temporal lobe atrophy (left > right). Core features of svPPA include anomia and single-word comprehension impairment. Despite growing evidence supporting treatment for anomia in svPPA, there is a paucity of research investigating neural mechanisms supporting treatment-induced gains and generalization to untrained items. In the current study, we examined the relation between the structural integrity of brain parenchyma (tissue inclusive of gray and white matter) at pre-treatment and treatment outcomes for trained and untrained items in a group of 19 individuals with svPPA who completed lexical retrieval treatment. Two structural neuroimaging approaches were used: an exploratory, whole-brain, voxel-wise approach and an a priori region of interest (ROI) approach. Based on previous research, bilateral temporal (inferior, middle, and superior temporal gyri), parietal (supramarginal and angular gyri), frontal (inferior and middle frontal gyri) and medial temporal (hippocampus and parahippocampal gyri) ROIs were selected from the Automated Anatomical Labeling (AAL) atlas. Analyses revealed improved naming of trained items and generalization to untrained items following treatment, providing converging evidence that individuals with svPPA can benefit from treatment for anomia. Better post-treatment naming accuracy was associated with the structural integrity of inferior parietal cortex and the hippocampus. Specifically, improved naming of trained items was related to the left supramarginal (phonological processing) and angular gyri (phonological and semantic processing), and improved naming of trained and untrained items was related to the left hippocampus (episodic, context-based memory). Future research should examine treatment outcomes in relation to pre-treatment functional and structural connectivity as well as changes in network dynamics following speech-language intervention to further elucidate the neural mechanisms underlying treatment response in svPPA and related disorders.

Verbal fluency in three Spanish-English bilingual speakers with TBI.

This study investigated differences between healthy bilingual participants and bilingual participants with traumatic brain injury (TBI) on verbal fluency tasks. The performance of three Spanish-English bilingual speakers with traumatic brain injury was compared to the performance of 30 neurotypical bilingual speakers on tasks of category and letter verbal fluency in English and Spanish. Responses were analyzed for total number of correct productions, differences in correct productions between languages, average cluster size, total number of switches, and rates of language choice errors. The data were analyzed using predicted scores from regression equations based on neurotypical data and modified t-tests. Analyses revealed significantly lower total output than predicted by the regression equations for both task types and in both languages for one TBI participant. The same participant demonstrated significantly lower total number of switches than the neurotypical group. Two participants demonstrated higher rates of language choice errors than the neurotypical group. There were no significant differences between TBI participants and the neurotypical group for average cluster size. There were no significant differences between predicted and obtained values for differences between English and Spanish total number correct in each task type. Results are discussed in the context of individual cognitive and linguistic profiles of the TBI participants.

Category, Letter, and Emotional Verbal Fluency in Spanish-English Bilingual Speakers: A Preliminary Report.

OBJECTIVE: The purpose of this study was to compare the performance of bilingual speakers on an emotional verbal fluency task to category and letter verbal fluency tasks. A second purpose was to compare performances on these tasks to language proficiency ratings. METHOD: Twelve verbal fluency tasks were administered to 21 Spanish-English bilingual speakers. Results were analyzed for differences between fluency types (category, letter, and emotional) and languages (English and Spanish). RESULTS: Participants generated the most items in category fluency tasks and the least items in emotional fluency tasks. The number of items generated for letter and emotional fluency tasks were not significantly different, but both were significantly lower than the number of items generated in category fluency. More items were generated for positive emotions than for negative emotions. Differences between languages for category and letter fluency tasks were significantly correlated with differences in language proficiency ratings, but this finding was not found for emotional fluency tasks. CONCLUSIONS: Self-ratings of proficiency and language dominance correlated significantly with performance on category and letter fluency tasks and may be useful predictors of differences between languages on these tasks. Emotional fluency was not significantly correlated with language proficiency ratings, suggesting that performance on emotional fluency may be more significantly affected by emotional processing ability. The emotional verbal fluency task has potential as a component of neuropsychological evaluations to screen easily and quickly for emotional processing deficits, including those associated with traumatic brain injury and depression. Additionally, results support a positivity bias in language and cognition processes.