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Language impairments caused by stroke (post-stroke aphasia, PSA) and neurodegeneration (primary progressive aphasia, PPA) have overlapping symptomatology, nomenclature and are classically divided into categorical subtypes. Surprisingly, PPA and PSA have rarely been directly compared in detail. Rather, previous studies have compared certain subtypes (e.g. semantic variants) or have focused on a specific cognitive/linguistic task (e.g. reading). This study assessed a large range of linguistic and cognitive tasks across the full spectra of PSA and PPA. We applied varimax-rotated principal component analysis to explore the underlying structure of the variance in the assessment scores. Similar phonological, semantic and fluency-related components were found for PSA and PPA. A combined principal component analysis across the two aetiologies revealed graded intra- and intergroup variations on all four extracted components. Classification analysis was used to test, formally, whether there were any categorical boundaries for any subtypes of PPA or PSA. Semantic dementia formed a true diagnostic category (i.e. within group homogeneity and distinct between-group differences), whereas there was considerable overlap and graded variations within and between other subtypes of PPA and PSA. These results suggest that (i) a multidimensional rather than categorical classification system may be a better conceptualization of aphasia from both causes; and (ii) despite the very different types of pathology, these broad classes of aphasia have considerable features in common.

Background: The loss of semantic memory is a key feature of frontotemporal dementia (FTD), and is associated with atrophy of the anterior temporal lobes (ATLs). The role of the left and right ATLs in supporting social‐semantic knowledge is unclear. To address this, we developed a social‐semantic battery comprising exemplars of social concepts such as person‐specific knowledge, abstract social concepts, and understanding of social norms. Performance on this battery was directly compared with non‐social semantic knowledge, measured using the Cambridge Semantic Test Battery. Method: 48 people with FTD (behavioural‐variant FTD = 26, semantic dementia = 22), and 19 age‐matched healthy controls were recruited. Participants completed both semantic batteries, alongside tests of general cognition and executive function. Participants also underwent a 3T T1‐weighted structural MRI scan. All neuropsychological tasks were entered into a principal component analysis (with varimax rotation) to explore graded variations in cognitive performance in FTD. Voxel‐based morphometry was conducted to explore grey matter correlates of social and non‐social semantic knowledge. The relative contributions of the left and right ATL to social‐semantic knowledge were tested by including ATL volume and asymmetry indices as predictors in a multiple regression analysis. Result: People with SD and bvFTD were impaired in both social‐and non‐social knowledge tasks. The principal component analysis indicated separate components for semantic memory and executive function. Both social and non‐social semantic tasks loaded onto the semantic memory component (Figure 1). People with SD scored significantly worse than bvFTD on the semantic memory component (t = 5.18, p<0.0001), while people with bvFTD scored worse than SD on the executive function component (t = 3.97, p<0.001) (Figure 2). Semantic memory factor scores were correlated with grey matter in the bilateral ATLs (Figure 3). There were no significant clusters associated with scores on the executive function component. Multiple regression revealed that performance on the semantic memory component was predicted by the magnitude but not the asymmetry of ATL atrophy. Conclusion: Both social and non‐social forms of semantic knowledge are impaired by FTD, and this degradation is associated with bilateral ATL atrophy. These results suggest a shared representation for all types of semantic memory across the ATLs. [ABSTRACT FROM AUTHOR]

Tractography is widely used in human studies of connectivity with respect to every brain region, function, and is explored developmentally, in adulthood, ageing, and in disease. However, the core issue of how to systematically threshold, taking into account the inherent differences in connectivity values for different track lengths, and to do this in a comparable way across studies has not been solved. By utilising 54 healthy individuals' diffusion‐weighted image data taken from HCP, this study adopted Monte Carlo derived distance‐dependent distributions (DDDs) to generate distance‐dependent thresholds with various levels of alpha for connections of varying lengths. As a test case, we applied the DDD approach to generate a language connectome. The resulting connectome showed both short‐ and long‐distance structural connectivity in the close and distant regions as expected for the dorsal and ventral language pathways, consistent with the literature. The finding demonstrates that the DDD approach is feasible to generate data‐driven DDDs for common thresholding and can be used for both individual and group thresholding. Critically, it offers a standard method that can be applied to various probabilistic tracking datasets. [ABSTRACT FROM AUTHOR]

Background: Clinical variants of primary progressive aphasia (PPA) are diagnosed on unique patterns of language dysfunction and corresponding brain changes. Mounting evidence indicates (i) within‐/between‐category clinical heterogeneity; (ii) overlapping language profiles between variants; and (iii) the presence of co‐occurring non‐linguistic cognitive deficits in some patients that may be independent of aphasia magnitude and disease severity. The neurobiological bases of such cognitive‐linguistic heterogeneity further remain unclear. An understanding of the relationship between these variables is important for improved PPA characterisation. Here, we bridge these knowledge gaps using a data‐driven transdiagnostic approach to capture language, cognitive changes and their associations with grey and white matter degeneration across PPA variants, irrespective of diagnostic labels. Method: Forty‐seven PPA patients (13 semantic, 15 non‐fluent and 19 logopenic variant) underwent assessments of general cognition (Addenbrooke's Cognitive Examination – III), errors on language performance (Mini Linguistic Status Examination), and structural and diffusion magnetic resonance imaging to capture whole‐brain grey and white matter changes, respectively. Behavioural data for all patients were entered into varimax‐rotated principal component analyses to derive statistically independent dimensions explaining the majority of performance variation. To uncover neural correlates of cognitive heterogeneity in PPA, emergent components were used as covariates in neuroimaging analyses of grey matter (voxel‐based morphometry) and white matter (network‐based statistics of structural connectomes). Result: Four behavioural principal components emerged: general cognition, semantics, working memory, and motor‐speech/phonology (Figure 1). Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile (Figure 2). General cognitive changes were most marked in logopenic PPA. Regardless of clinical diagnosis, general cognitive performance was associated with inferior/posterior parietal grey and white matter involvement, semantic dysfunction with bilateral temporal grey and white matter, working memory deficits with temporoparietal and frontostriatal involvement, and motor‐speech/phonology impairment with inferior/middle frontal regions (Figure 3). Conclusion: Pervasive cognitive and linguistic heterogeneity in PPA closely relates to individual‐level variations on multiple dimensions of behavioural changes and grey and white matter degeneration of regions within and beyond the language network. The employment of such transdiagnostic approaches may help expand clinical boundaries by showing symptom clusters shared across distinct variants. [ABSTRACT FROM AUTHOR]

Focal brain damage caused by stroke can result in aphasia and advances in cognitive neuroscience suggest that impairment may be associated with network-level disorder rather than just circumscribed cortical damage. A number of studies have shown meaningful relationships between brain-behaviour using lesions; however only a handful of studies have incorporated in-vivo structural and functional connectivity. Patients with chronic post-stroke aphasia were assessed with structural (N = 68) and functional (N = 39) MRI to assess whether predicting performance can be improved with multiple modalities and if additional variance can be explained compared to lesion models alone. These neural measurements were used to construct models to predict four key language-cognitive factors: 1) phonology, 2) semantics, 3) executive function, and 4) fluency. Our results showed that each factor (except executive ability) could be significantly related to each neural measurement alone; however, structural and functional connectivity models did not explain additional variance above the lesion models. We did find evidence that the structural and functional predictors may be linked to the core lesion sites. First, the predictive functional connectivity features were found to be located within functional resting state networks identified in healthy controls, suggesting that the result might reflect functionally-specific reorganisation (damage to a node within a network can result in disruption to the entire network). Second, predictive structural connectivity features were located within core lesion sites, suggesting that multi-modal information may be redundant in prediction modelling. In addition, we observed that the optimum sparsity within the regularised regression models differed for each behavioural component and across different imaging features, suggesting that future studies should consider optimising hyperparameters related to sparsity per target. Together, the results indicate that the observed network-level disruption was predicted by the lesion alone and does not significantly improve model performance in predicting the profile of language impairment. [ABSTRACT FROM AUTHOR]

These features could result in a more global recovery pattern reflecting the impact of generalized recovery mechanisms acting systemically across multiple neurocognitive components. Given the urgent and pressing need to understand language recovery mechanisms in post-stroke aphasia, we were delighted in the interest taken by Walker and Hickok[1] in our recent exploration. [Extracted from the article]

Background: Despite the clinical importance of assessing the efficiency and accuracy of fluency in terms of content words production during connected speech, assessments based on discourse tasks are very time-consuming and thus not clinically feasible. Aims: (1) Examine the relationship between single-word naming and word retrieval during discourse production. (2) Investigate the relationship between word retrieval and content word fluency derived from a simple versus naturalistic discourse tasks. (3) Develop and validate an efficient and accurate index of content word fluency that is clinically viable. Methods: Two discourse tasks (simple picture description and naturalistic storytelling narrative) were collected from 46 participants with post-stroke aphasia, and 20 age/education matched neuro-typical controls. Each discourse sample was fully transcribed and quantitative analysis was applied to each sample to measure word retrieval and content word fluency. Three single-word naming tasks were also administered to each participant with aphasia. Results: Correlational analyses between single-word naming and word retrieval in connected speech revealed weak/moderate relationships. Conversely, strong correlations were found between measures derived from simple picture description against naturalistic storytelling discourse tasks. Moreover, we derived a novel, transcription-less index of content word fluency from the discourse samples of an independent group (neuro-typical controls), and then we validated this index across two discourse tasks in the tested group (persons with aphasia). Correlation and regression analyses revealed extremely strong relationships between participants' (neuro-typical controls and persons with aphasia) scores on the novel index and measures of content word fluency derived from the formal transcription and quantitative analyses of discourse samples, indicating high accuracy and validity of the new index. Conclusions: Simple picture description rather than picture naming provides a better estimate of word retrieval in naturalistic connected speech. The novel developed index is transcription-less and can be implemented online to provide an accurate and efficient measure of content word fluency. Thus, it is viable during clinical practice for assessment purposes, and possibly as an outcome measure to monitor therapy effectiveness, which can also be used in randomised clinical trials. [ABSTRACT FROM AUTHOR]

Although limited and reduced connected speech production is one, if not the most, prominent feature of aphasia, few studies have examined the properties of content words produced during discourse in aphasia, in comparison to the many investigations of single-word production. In this study, we used a distributional analysis approach to investigate the properties of content word production during discourse by 46 participants spanning a wide range of chronic poststroke aphasia and 20 neurotypical adults, using different stimuli that elicited three discourse genres (descriptive, narrative, and procedural). Initially, we inspected the discourse data with respect to the quantity of production, lexical–semantic diversity, and psycholinguistic features (frequency and imageability) of content words. Subsequently, we created a "lexical–semantic landscape," which is sensitive to subtle changes and allowed us to evaluate the pattern of changes in discourse production across groups. Relative to neurotypical adults, all persons with aphasia (both fluent and nonfluent) showed significant reduction in the quantity and diversity of production, but the lexical–semantic complexity of word production directly mirrored neurotypical performance. Specifically, persons with aphasia produced the same rate of nouns/verbs, and their discourse samples covered the full range of word frequency and imageability, albeit with reduced word quantity. These findings provide novel evidence that, unlike in other disorders (e.g., semantic dementia), discourse production in poststroke aphasia has relatively preserved lexical–semantic complexity but demonstrates significantly compromised quantity of content word production. Voxel-wise lesion-symptom mapping using both univariate and multivariate approaches revealed left frontal regions particularly the pars opercularis, insular cortex, and central and frontal opercular cortices supporting word retrieval during connected speech, irrespective of their word class or lexical–semantic complexity. [ABSTRACT FROM AUTHOR]

The clinical profiles of individuals with post-stroke aphasia demonstrate considerable variation in the presentation of symptoms. Recent aphasiological studies have attempted to account for this individual variability using a multivariate data-driven approach (principal component analysis) on an extensive neuropsychological and aphasiological battery, to identify fundamental domains of post-stroke aphasia. These domains mainly reflect phonology, semantics and fluency; however, these studies did not account for variability in response to different forms of connected speech, i.e. discourse genres. In the current study, we initially examined differences in the quantity, diversity and informativeness between three different discourse genres, including a simple descriptive genre and two naturalistic forms of connected speech (storytelling narrative, and procedural discourse). Subsequently, we provided the first quantitative investigation on the multidimensionality of connected speech production at both behavioural and neural levels. Connected speech samples across descriptive, narrative, and procedural discourse genres were collected from 46 patients with chronic post-stroke aphasia and 20 neurotypical adults. Content analyses conducted on all connected speech samples indicated that performance differed across discourse genres and between groups. Specifically, storytelling narratives provided higher quantities of content words and lexical diversity compared to composite picture description and procedural discourse. The analyses further revealed that, relative to neurotypical adults, patients with aphasia, both fluent and non-fluent, showed reduction in the quantity of verbal production, lexical diversity, and informativeness across all discourses. Given the differences across the discourses, we submitted the connected speech metrics to principal component analysis alongside an extensive neuropsychological/aphasiological battery that assesses a wide range of language and cognitive skills. In contrast to previous research, three unique orthogonal connected speech components were extracted in a unified model, reflecting verbal quantity, verbal quality, and motor speech, alongside four core language and cognitive components: phonological production, semantic processing, phonological recognition, and executive functions. Voxel-wise lesion-symptom mapping using these components provided evidence on the involvement of widespread cortical regions and their white matter connections. Specifically, left frontal regions and their underlying white matter tracts corresponding to the frontal aslant tract and the anterior segment of the arcuate fasciculus were particularly engaged with the quantity and quality of fluent connected speech production while controlling for other co-factors. The neural correlates associated with the other language domains align with existing models on the ventral and dorsal pathways for language processing. [ABSTRACT FROM AUTHOR]

There is growing awareness that aphasia following a stroke can include deficits in other cognitive functions and that these are predictive of certain aspects of language function, recovery and rehabilitation. However, data on attentional and executive (dys)functions in individuals with stroke aphasia are still scarce and the relationship to underlying lesions is rarely explored. Accordingly in this investigation, an extensive selection of standardized non-verbal neuropsychological tests was administered to 38 individuals with chronic post-stroke aphasia, in addition to detailed language testing and MRI. To establish the core components underlying the variable patients' performance, behavioural data were explored with rotated principal component analyses, first separately for the non-verbal and language tests, then in a combined analysis including all tests. Three orthogonal components for the non-verbal tests were extracted, which were interpreted as shift-update, inhibit-generate and speed. Three components were also extracted for the language tests, representing phonology, semantics and speech quanta. Individual continuous scores on each component were then included in a voxel-based correlational methodology analysis, yielding significant clusters for all components. The shift-update component was associated with a posterior left temporo-occipital and bilateral medial parietal cluster, the inhibit-generate component was mainly associated with left frontal and bilateral medial frontal regions, and the speed component with several small right-sided fronto-parieto-occipital clusters. Two complementary multivariate brain-behaviour mapping methods were also used, which showed converging results. Together the results suggest that a range of brain regions are involved in attention and executive functioning, and that these non-language domains play a role in the abilities of patients with chronic aphasia. In conclusion, our findings confirm and extend our understanding of the multidimensionality of stroke aphasia, emphasize the importance of assessing non-verbal cognition in this patient group and provide directions for future research and clinical practice. We also briefly compare and discuss univariate and multivariate methods for brain-behaviour mapping. [ABSTRACT FROM AUTHOR]

One-third of stroke survivors experience deficits in word retrieval as a core characteristic of their aphasia, which is frustrating, socially limiting and disabling for their professional and everyday lives. The, as yet, undiscovered 'holy grail' of clinical practice is to establish a treatment that not only improves item naming, but also generalizes to patients' connected speech. Speech production in healthy participants is a remarkable feat of cognitive processing being both rapid (at least 120 words per minute) and accurate (∼one error per 1000 words). Accordingly, we tested the hypothesis that word-finding treatment will only be successful and generalize to connected speech if word retrieval is both accurate and quick. This study compared a novel combined speed- and accuracy-focused intervention-'repeated, increasingly-speeded production'-to standard accuracy-focused treatment. Both treatments were evaluated for naming, connected speech outcomes, and related to participants' neuropsychological and lesion profiles. Twenty participants with post-stroke chronic aphasia of varying severity and subtype took part in 12 computer-based treatment sessions over 6 weeks. Four carefully matched word sets were randomly allocated either to the speed- and accuracy-focused treatment, standard accuracy-only treatment, or untreated (two control sets). In the standard treatment, sound-based naming cues facilitated naming accuracy. The speed- and accuracy-focused treatment encouraged naming to become gradually quicker, aiming towards the naming time of age-matched controls. The novel treatment was significantly more effective in improving and maintaining picture naming accuracy and speed (reduced latencies). Generalization of treated vocabulary to connected speech was significantly increased for all items relative to the baseline. The speed- and accuracy-focused treatment generated substantial and significantly greater deployment of targeted items in connected speech. These gains were maintained at 1-month post-intervention. There was a significant negative correlation for the speed- and accuracy-focused treatment between the patients' phonological scores and the magnitude of the therapy effect, which may have reflected the fact that the substantial beneficial effect of the novel treatment generated a ceiling effect in the milder patients. Maintenance of the speed- and accuracy-treatment effect correlated positively with executive skills. The neural correlate analyses revealed that participants with the greatest damage to the posterior superior temporal gyrus extending into the white matter of the inferior longitudinal fasciculus, showed the greatest speed- and accuracy treatment benefit. The novel treatment was well tolerated by participants across the range of severity and aphasia subtype, indicating that this type of intervention has considerable clinical utility and broad applicability. [ABSTRACT FROM AUTHOR]

Focal brain damage caused by stroke can result in aphasia and advances in cognitive neuroscience suggest that impairment may be associated with network-level disorder rather than just circumscribed cortical damage. Several studies have shown meaningful relationships between brain-behaviour using lesions; however, only a handful of studies have incorporated in vivo structural and functional connectivity. Patients with chronic post-stroke aphasia were assessed with structural (n = 68) and functional (n = 39) MRI to assess whether predicting performance can be improved with multiple modalities and if additional variance can be explained compared to lesion models alone. These neural measurements were used to construct models to predict four key language-cognitive factors: (i) phonology; (ii) semantics; (iii) executive function; and (iv) fluency. Our results showed that each factor (except executive ability) could be significantly related to each neural measurement alone; however, structural and functional connectivity models did not explain additional variance above the lesion models. We did find evidence that the structural and functional predictors may be linked to the core lesion sites. First, the predictive functional connectivity features were found to be located within functional resting-state networks identified in healthy controls, suggesting that the result might reflect functionally specific reorganization (damage to a node within a network can result in disruption to the entire network). Second, predictive structural connectivity features were located within core lesion sites, suggesting that multimodal information may be redundant in prediction modelling. In addition, we observed that the optimum sparsity within the regularized regression models differed for each behavioural component and across different imaging features, suggesting that future studies should consider optimizing hyperparameters related to sparsity per target. Together, the results indicate that the observed network-level disruption was predicted by the lesion alone and does not significantly improve model performance in predicting the profile of language impairment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The ability to communicate, functionally, after stroke or other types of acquired brain injury is crucial for the person involved and the people around them. Accordingly, assessment of functional communication is increasingly used in large-scale randomized controlled trials as the primary outcome measure. Despite the importance of functional communication abilities to everyday life and their centrality to the measured efficacy of aphasia interventions, there is little knowledge about how commonly used measures of functional communication relate to each other, whether they capture and grade the full range of patients' remaining communication skills and how these abilities relate to the patients' verbal and non-verbal impairments as well as the underpinning lesions. Going beyond language-only factors is essential given that non-verbal abilities can play a crucial role in an individual's ability to communicate effectively. This study, based on a large sample of patients covering the full range and types of post-stroke aphasia, addressed these important, open questions. The investigation combined data from three established measures of functional communication with a thorough assessment of verbal and non-verbal cognition as well as structural neuroimaging. The key findings included: (i) due to floor or ceiling effects, the full range of patients' functional communication abilities was not captured by a single assessment alone, limiting the utility of adopting individual tests as outcome measures in randomized controlled trials; (ii) phonological abilities were most strongly related to all measures of functional communication and (iii) non-verbal cognition was particularly crucial when language production was relatively impaired and other modes of communication were allowed, when patients rated their own communication abilities, and when carers rated patients' basic communication abilities. Finally, in addition to lesion load being significantly related to all measures of functional communication, lesion analyses showed partially overlapping clusters in language regions for the functional communication tests. Moreover, mirroring the findings from the regression analyses, additional regions previously associated with non-verbal cognition emerged for the Scenario Test and for the Patient Communication Outcome after Stroke rating scale. In conclusion, our findings elucidated the cognitive and neural bases of functional communication abilities, which may inform future clinical practice regarding assessments and therapy. In particular, it is necessary to use more than one measure to capture the full range and multifaceted nature of patients' functional communication abilities and a therapeutic focus on non-verbal cognition might have positive effects on this important aspect of activity and participation., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

The pursuit of relating the location of neural damage to the pattern of acquired language and general cognitive deficits post-stroke stems back to the 19th century behavioural neurology. While spatial specificity has improved dramatically over time, from the large areas of damage specified by post-mortem investigation to the millimetre precision of modern MRI, there is an underlying issue that is rarely addressed, which relates to the fact that damage to a given area of the brain is not random but constrained by the brain's vasculature. Accordingly, the aim of this study was to uncover the statistical structure underlying the lesion profile in chronic aphasia post-stroke. By applying varimax-rotated principal component analysis to the lesions of 70 patients with chronic post-stroke aphasia, we identified 17 interpretable clusters, largely reflecting the vascular supply of middle cerebral artery sub-branches and other sources of individual variation in vascular supply as shown in classical angiography studies. This vascular parcellation produced smaller displacement error in simulated lesion-symptom analysis compared with individual voxels and Brodmann regions. A second principal component analysis of the patients' detailed neuropsychological data revealed a four-factor solution reflecting phonological, semantic, executive-demand and speech fluency abilities. As a preliminary exploration, stepwise regression was used to relate behavioural factor scores to the lesion principal components. Phonological ability was related to two components, which covered the posterior temporal region including the posterior segment of the arcuate fasciculus, and the inferior frontal gyrus. Three components were linked to semantic ability and were located in the white matter underlying the anterior temporal lobe, the supramarginal gyrus and angular gyrus. Executive-demand related to two components covering the dorsal edge of the middle cerebral artery territory, while speech fluency was linked to two components that were located in the middle frontal gyrus, precentral gyrus and subcortical regions (putamen and thalamus). Future studies can explore in formal terms the utility of these principal component analysis-derived lesion components for relating post-stroke lesions and symptoms., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Linking both structural lesions and the functional integrity of remaining brain tissue to patients' behavioural profile may be critical in discovering the limits of behavioural recovery post stroke. In the present study, we explored the relationship between temporal hemodynamic changes and language performance in chronic post-stroke aphasia. We collected detailed language and neuropsychological data for 66 patients with chronic (>1 year) post-stroke aphasia. We used principal component analysis to extract their core language-neuropsychological features. From resting-state fMRI scans in 35 patients, we calculated the lag in the time-course of the intact brain voxels in each patient. Finally, variation across the language-cognitive factors was related to both the patients' structural damage and the time-course changes in each patient's intact tissue. Phonological abilities were correlated with the structural integrity of the left superior temporal, angular gyrus, supramarginal gyrus and arcuate fasciculus regions and hemodynamic advance in the left intra-parietal sulcus. Speech fluency related to integrity of premotor regions, plus hemodynamic advance in the left middle/superior temporal gyrus, left middle occipital gyrus, and right angular gyrus. Semantic performance reflected a combination of medial ventral temporal lobe status and hemodynamic delay in the left posterior middle temporal gyrus. Finally, executive abilities correlated with hemodynamic delay in the left middle/inferior frontal gyrus, right rolandic operculum, bilateral supplementary motor areas/middle cingulum areas, and bilateral thalamus/caudate. Following stroke, patients' patterns of chronic language abilities reflects a combination of structural and functional integrity across a distributed network of brain regions. The correlation between hemodynamic changes and behaviours may have clinical importance.

One-third of stroke survivors experience deficits in word retrieval as a core characteristic of their aphasia, which is frustrating, socially limiting and disabling for their professional and everyday lives. The, as yet, undiscovered 'holy grail' of clinical practice is to establish a treatment that not only improves item naming, but also generalizes to patients' connected speech. Speech production in healthy participants is a remarkable feat of cognitive processing being both rapid (at least 120 words per minute) and accurate (∼one error per 1000 words). Accordingly, we tested the hypothesis that word-finding treatment will only be successful and generalize to connected speech if word retrieval is both accurate and quick. This study compared a novel combined speed- and accuracy-focused intervention-'repeated, increasingly-speeded production'-to standard accuracy-focused treatment. Both treatments were evaluated for naming, connected speech outcomes, and related to participants' neuropsychological and lesion profiles. Twenty participants with post-stroke chronic aphasia of varying severity and subtype took part in 12 computer-based treatment sessions over 6 weeks. Four carefully matched word sets were randomly allocated either to the speed- and accuracy-focused treatment, standard accuracy-only treatment, or untreated (two control sets). In the standard treatment, sound-based naming cues facilitated naming accuracy. The speed- and accuracy-focused treatment encouraged naming to become gradually quicker, aiming towards the naming time of age-matched controls. The novel treatment was significantly more effective in improving and maintaining picture naming accuracy and speed (reduced latencies). Generalization of treated vocabulary to connected speech was significantly increased for all items relative to the baseline. The speed- and accuracy-focused treatment generated substantial and significantly greater deployment of targeted items in connected speech. These gains were maintained at 1-month post-intervention. There was a significant negative correlation for the speed- and accuracy-focused treatment between the patients' phonological scores and the magnitude of the therapy effect, which may have reflected the fact that the substantial beneficial effect of the novel treatment generated a ceiling effect in the milder patients. Maintenance of the speed- and accuracy-treatment effect correlated positively with executive skills. The neural correlate analyses revealed that participants with the greatest damage to the posterior superior temporal gyrus extending into the white matter of the inferior longitudinal fasciculus, showed the greatest speed- and accuracy treatment benefit. The novel treatment was well tolerated by participants across the range of severity and aphasia subtype, indicating that this type of intervention has considerable clinical utility and broad applicability.

Neuropsychological assessment, brain imaging and computational modelling have augmented our understanding of the multifaceted functional deficits in people with language disorders after stroke. Despite the volume of research using each technique, no studies have attempted to assimilate all three approaches in order to generate a unified behavioural-computational-neural model of post-stroke aphasia. The present study included data from 53 participants with chronic post-stroke aphasia and merged: aphasiological profiles based on a detailed neuropsychological assessment battery which was analysed with principal component and correlational analyses; measures of the impairment taken from Dell's computational model of word production; and the neural correlates of both behavioural and computational accounts analysed by voxel-based correlational methodology. As a result, all three strands coincide with the separation of semantic and phonological stages of aphasic naming, revealing the prominence of these dimensions for the explanation of aphasic performance. Over and above three previously described principal components (phonological ability, semantic ability, executive-demand), we observed auditory working memory as a novel factor. While the phonological Dell parameter was uniquely related to phonological errors/factor, the semantic parameter was less clear-cut, being related to both semantic errors and omissions, and loading heavily with semantic ability and auditory working memory factors. The close relationship between the semantic Dell parameter and omission errors recurred in their high lesion-correlate overlap in the anterior middle temporal gyrus. In addition, the simultaneous overlap of the lesion correlate of omission errors with more dorsal temporal regions, associated with the phonological parameter, highlights the multiple drivers that underpin this error type. The novel auditory working memory factor was located along left superior/middle temporal gyrus and ventral inferior parietal lobe. The present study fused computational, behavioural and neural data to gain comprehensive insights into the nature of the multifaceted presentations in aphasia. Our unified account contributes enhanced knowledge on dimensions explaining chronic post-stroke aphasia, the variety of factors affecting inter-individual variability, the neural basis of performance, and potential clinical implications.

There is an ever-increasing wealth of knowledge arising from basic cognitive and clinical neuroscience on how speech and language capabilities are organised in the brain. It is, therefore, timely to use this accumulated knowledge and expertise to address critical research challenges, including the ability to predict the pattern and level of language deficits found in aphasic patients (a third of all stroke cases). Previous studies have mainly focused on discriminating between broad aphasia dichotomies from purely anatomically-defined lesion information. In the current study, we developed and assessed a novel approach in which core language areas were mapped using principal component analysis in combination with correlational lesion mapping and the resultant ' functionally - partitioned ' lesion maps were used to predict a battery of 21 individual test scores as well as aphasia subtype for 70 patients with chronic post-stroke aphasia. Specifically, we used lesion information to predict behavioural scores in regression models (cross-validated using 5-folds). The winning model was identified through the adjusted R 2 (model fit to data) and performance in predicting holdout folds (generalisation to new cases). We also used logistic regression to predict fluent/non-fluent status and aphasia subtype. Functionally-partitioned models generally outperformed other models at predicting individual tests, fluency status and aphasia subtype.

The behavioural and neural processes underpinning different word classes, particularly nouns and verbs, have been a long-standing area of interest in psycholinguistic, neuropsychology and aphasiology research. This topic has theoretical implications concerning the organisation of the language system, as well as clinical consequences related to the management of patients with language deficits. Research findings, however, have diverged widely, which might, in part, reflect methodological differences, particularly related to controlling the psycholinguistic variations between nouns and verbs. The first aim of this study, therefore, was to develop a set of neuropsychological tests that assessed single-word production and comprehension with a matched set of nouns and verbs. Secondly, the behavioural profiles and neural correlates of noun and verb processing were explored, based on these novel tests, in a relatively large cohort of 48 patients with chronic post-stroke aphasia. A data-driven approach, principal component analysis (PCA), was also used to determine how noun and verb production and comprehension were related to the patients' underlying fundamental language domains. The results revealed no performance differences between noun and verb production and comprehension once matched on multiple psycholinguistic features including, most critically, imageability. Interestingly, the noun-verb differences found in previous studies were replicated in this study once un-matched materials were used. Lesion-symptom mapping revealed overlapping neural correlates of noun and verb processing along left temporal and parietal regions. These findings support the view that the neural representation of noun and verb processing at single-word level are jointly-supported by distributed cortical regions. The PCA generated five fundamental language and cognitive components of aphasia: phonological production, phonological recognition, semantics, fluency, and executive function. Consistent with the behavioural analyses and lesion-symptom mapping results, both noun and verb processing loaded on common underlying language domains: phonological production and semantics. The neural correlates of these five principal components aligned with existing models of language and the regions implicated by other techniques such as functional neuroimaging and neuro-stimulation.

Typically, processing is more accurate and efficient for concrete than abstract concepts in both healthy adults and individuals with aphasia. While, concreteness effects have been thoroughly documented with respect to noun processing, other words classes have received little attention despite tending to be less concrete than nouns. The aim of the current study was to explore concrete-abstract differences in verbs and identify their neural correlates in post-stroke aphasia. Given the dearth of comprehension tests for verbs, a battery of neuropsychological tests was developed in this study to assess the comprehension of concrete and abstract verbs. Specifically, a sensitive verb synonym judgment test was generated that varied both the items' imageability and frequency, and a picture-to-word matching test with numerous concrete verbs. Normative data were then collected and the tests were administered to a cohort of 48 individuals with chronic post-stroke aphasia to explore the behavioural patterns and neural correlates of verb processing. The results revealed significantly better comprehension of concrete than abstract verbs, aligning with the existing aphasiological literature on noun processing. In addition, the patients performed better during verb comprehension than verb production. Lesion-symptom correlational analyses revealed common areas that support processing of concrete and abstract verbs, including the left anterior temporal lobe, posterior supramarginal gyrus and superior lateral occipital cortex. A direct contrast between them revealed additional regions with graded differences. Specifically, the left frontal regions were associated with processing abstract verbs; whereas, the left posterior temporal and occipital regions were associated with processing concrete verbs. Moreover, overlapping and distinct neural correlates were identified in association with the comprehension and production of concrete verbs. These patient findings align with data from functional neuroimaging and neuro-stimulation, and existing models of language organisation.

In order to gain a better understanding of aphasia one must consider the complex combinations of language impairments along with the pattern of paraphasias. Despite the fact that both deficits and paraphasias feature in diagnostic criteria, most research has focused only on the lesion correlates of language deficits, with minimal attention on the pattern of patients' paraphasias. In this study, we used a data-driven approach (principal component analysis - PCA) to fuse patient impairments and their pattern of errors into one unified model of chronic post-stroke aphasia. This model was subsequently mapped onto the patients' lesion profiles to generate the triangulation of language-cognitive impairments, naming errors and their neural correlates. Specifically, we established the pattern of co-occurrence between fifteen error types, which avoids focussing on a subset of errors or the use of experimenter-derived methods to combine across error types. We obtained five principal components underlying the patients' errors: omission errors; semantically-related responses; phonologically-related responses; dysfluent responses; and a combination of circumlocutions with mixed errors. In the second step, we aligned these paraphasia-related principal components with the patients' performance on a detailed language and cognitive assessment battery, utilising an additional PCA. This omnibus PCA revealed seven unique fused impairment-paraphasia factors: output phonology; semantics; phonological working memory; speech quanta; executive-cognitive skill; phonological (input) discrimination; and the production of circumlocution errors. In doing so we were able to resolve the complex relationships between error types and impairments. Some are relatively straightforward: circumlocution errors formed their own independent factor; there was a one-to-one mapping for phonological errors with expressive phonological abilities and for dysfluent errors with speech fluency. In contrast, omission-type errors loaded across both semantic and phonological working memory factors, whilst semantically-related errors had the most complex relationship by loading across four factors (phonological ability, speech quanta, executive-cognitive skills and circumlocution-type errors). Three components had unique lesion correlates: phonological working memory with the primary auditory region; semantics with the anterior temporal region; and fluency with the pre-central gyrus, converging with existing literature. In conclusion, the data-driven approach allowed derivation of the triangulation of deficits, error types and lesion correlates in post-stroke aphasia.