Evaluating the granularity and statistical structure of lesions and behaviour in post-stroke aphasia

The pursuit of relating the location of neural damage to the pattern of acquired language and general cognitive deficits post-stroke stems back to 19th century behavioural neurology. Whilst 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 PCA-derived lesion components for relating post-stroke lesions and symptoms

The verbal, nonverbal and structural bases of functional communication abilities in aphasia

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 nonverbal impairments as well as the underpinning lesions. Going beyond language-only factors is essential given that nonverbal abilities can play a crucial role in an individual’s ability to communicate effectively. The current study, based on a large sample of patients covering the full range and types of poststroke aphasia, addressed these important, open questions. The investigation combined data from three established measures of functional communication (ANELT, Scenario Test, COAST) with a thorough assessment of verbal and nonverbal cognition as well as structural neuroimaging. The key findings included: (a) 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; (b) phonological abilities were most strongly related to all measures of functional communication; and (c) nonverbal 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 nonverbal cognition emerged for the Scenario Test and for the Patient COAST. 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 nonverbal cognition might have positive effects on this important aspect of activity and participation

A unified model of post-stroke language deficits including discourse production and their neural correlates.

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

Efficient and effective assessment of deficits and their neural bases in stroke aphasia

ObjectiveMulti-assessment batteries are necessary for diagnosing and quantifying the multifaceted deficits observed post-stroke. Extensive batteries are thorough but impractically long for clinical settings or large-scale research studies. Clinically-targeted “shallow” batteries superficially cover a wide range of language skills relatively quickly but can struggle to identify mild deficits or quantify the impairment level. Our aim was to compare these batteries across a large group of chronic stroke aphasia and to test a novel data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure.MethodsWe tested 75 chronic left-sided stroke participants, spanning global to mild aphasia. The underlying structure of these three batteries was analysed using cross-validation and principal component analysis, in addition to univariate and multivariate lesion-symptom mapping.ResultsThis revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (language severity and cognitive severity). Lesion symptom mapping using participants’ factor scores identified convergent neural structures for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex). The two shallow battery components converged with the phonology and executive function clusters. In addition, we show that multivariate models could predict the component scores using neural data, however not for every component.ConclusionsOverall, the data-driven battery appears to be an effective way to save time yet retain maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure observed in post-stroke aphasia

Comparing short and long batteries to assess deficits and their neural bases in stroke aphasia

Multiple language assessments are necessary for diagnosing, characterising and quantifying the multifaceted deficits observed in many patients’ post-stroke. Current language batteries, however, tend to be an imperfect trade-off between time and sensitivity of assessment. There have hitherto been two main types of battery. Extensive batteries provide thorough information but are impractically long for application in clinical settings or large-scale research studies. Clinically-targeted batteries tend to provide superficial information about a large number of language skills in a relatively short period of time by reducing the depth of each test but, consequently, can struggle to identify mild deficits, qualify the level of each impairment or reveal the underlying component structure. In the current study, we compared these batteries across a large group of individuals with chronic stroke aphasia to determine their utility. In addition, we developed a data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the component structure. The underlying structure of these three language batteries (extensive, shallow and data-reduced) was analysed using cross-validation analysis and principal component analysis. This revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (phonological/language severity and cognitive severity). Lesion symptom mapping using participants’ factor scores identified convergent neural structures based on existing language models for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex) based on the extensive and data-reduced batteries. The two components in the shallow battery converged with the phonology and executive function clusters. In addition, we show that multivariate prediction models could be utilised to predict the component scores using neural data, however not for every component score within every test battery. Overall, the data-reduced battery appears to be an effective way to save assessment time yet retain the underlying structure of language and cognitive deficits observed in post stroke aphasia

Time for a quick word? The striking benefits of training speed and accuracy of word retrieval in post-stroke aphasia

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

Assessing and mapping language, attention and executive multidimensional deficits in stroke aphasia.

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

Dual-echo fMRI can detect activations in inferior temporal lobe during intelligible speech comprehension

AbstractThe neural basis of speech comprehension has been investigated intensively during the past few decades. Incoming auditory signals are analysed for speech-like patterns and meaningful information can be extracted by mapping these sounds onto stored semantic representations. Investigation into the neural basis of speech comprehension has largely focused on the temporal lobe, in particular the superior and posterior regions. The ventral anterior temporal lobe (vATL), which includes the inferior temporal gyrus (ITG) and temporal fusiform gyrus (TFG) is consistently omitted in fMRI studies. In contrast, PET studies have shown the involvement of these ventral temporal regions. One crucial factor is the signal loss experienced using conventional echo planar imaging (EPI) for fMRI, at tissue interfaces such as the vATL. One method to overcome this signal loss is to employ a dual-echo EPI technique. The aim of this study was to use intelligible and unintelligible (spectrally rotated) sentences to determine if the vATL could be detected during a passive speech comprehension task using a dual-echo acquisition. A whole brain analysis for an intelligibility contrast showed bilateral superior temporal lobe activations and a cluster of activation within the left vATL. Converging evidence implicates the same ventral temporal regions during semantic processing tasks, which include language processing. The specific role of the ventral temporal region during intelligible speech processing cannot be determined from this data alone, but the converging evidence from PET, MEG, TMS and neuropsychology strongly suggest that it contains the stored semantic representations, which are activated by the speech decoding process