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Semantic knowledge includes understanding of objects and their features and also understanding of the characteristics of events. The hub-and-spoke theory holds that these conceptual representations rely on multiple information sources that are integrated in a central hub in the ventral anterior temporal lobes. The dual-hub theory expands this framework with the claim that the ventral anterior temporal lobe hub is specialized for object representation, while a second hub in angular gyrus is specialized for event representation. To test these ideas, we used representational similarity analysis, univariate and psychophysiological interaction analyses of fMRI data collected while participants processed object and event concepts (e.g. "an apple," "a wedding") presented as images and written words. Representational similarity analysis showed that angular gyrus encoded event concept similarity more than object similarity, although the left angular gyrus also encoded object similarity. Bilateral ventral anterior temporal lobes encoded both object and event concept structure, and left ventral anterior temporal lobe exhibited stronger coding for events. Psychophysiological interaction analysis revealed greater connectivity between left ventral anterior temporal lobe and right pMTG, and between right angular gyrus and bilateral ITG and middle occipital gyrus, for event concepts compared to object concepts. These findings support the specialization of angular gyrus for event semantics, though with some involvement in object coding, but do not support ventral anterior temporal lobe specialization for object concepts.
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Mapeamento Encefálico , Lobo Temporal , Humanos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Lobo Parietal/fisiologia , Semântica , Imageamento por Ressonância Magnética/métodosRESUMO
Making sense of natural language and narratives requires building and manipulating a situation model by adding incoming information to the model and using the context stored in the model to comprehend subsequent details and events. Situation model maintenance is supported by the default mode network (DMN), but comprehension of the individual moments in the narratives relies on access to the conceptual store within the semantic system. The present study examined how these systems are engaged by different narrative content to investigate whether highly informative, or semantic, content is a particularly strong driver of semantic system activation compared with contextually driven content that requires using the situation model, which might instead engage DMN regions. The study further investigated which subregions of the graded semantic hub in the left anterior temporal lobe (ATL) were engaged by the type of narrative content. To do this, we quantified the semantic, pragmatic, social, ambiguous, and emotional content for each sentence in a complete narrative, the English translation of The Little Prince. Increased activation in the transmodal hub in the ventral ATL was only observed for high semantic (i.e., informative) relative to low semantic sentences. Activation in the dorsolateral and ventrolateral ATL subregions was observed for both high relative to low semantic and social content sentences, but the ventrolateral ATL effects were more extensive in the social condition. There was high correspondence between the social and pragmatic content results, particularly in the ventrolateral ATL. We argue that the ventrolateral ATL may be particularly engaged by internal, or endogenous, processing demands, aided by functional connections between the anterior middle temporal gyrus and the DMN. Pragmatic and social content may have driven endogenous processing given the pervasive and plot-progressing nature of this content in the narrative. We put forward a revised account of how the semantic system is engaged in naturalistic contexts, a critical step toward better understanding real-world semantic and social processing.
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The ease with which narratives are understood belies the complexity of the information being conveyed and the cognitive processes that support comprehension. The meanings of the words must be rapidly accessed and integrated with the reader's mental representation of the overarching, unfolding scenario. A broad, bilateral brain network is engaged by this process, but it is not clear how words that vary on specific semantic dimensions, such as ambiguity, emotion, or socialness, engage the semantic, semantic control, or social cognition systems. In the present study, data from 48 participants who listened to The Little Prince audiobook during MRI scanning were selected from the Le Petit Prince dataset. The lexical and semantic content within the narrative was quantified from the transcript words with factor scores capturing Word Length, Semantic Flexibility, Emotional Strength, and Social Impact. These scores, along with word quantity variables, were used to investigate where these predictors co-vary with activation across the brain. In contrast to studies of isolated word processing, large networks were found to co-vary with the lexical and semantic content within the narrative. An increase in semantic content engaged the ventral portion of ventrolateral ATL, consistent with its role as a semantic hub. Decreased semantic content engaged temporal pole and inferior parietal lobule, which may reflect semantic integration. The semantic control network was engaged by words with low Semantic Flexibility, perhaps due to the demand required to process infrequent, less semantically diverse language. Activation in ATL co-varied with an increase in Social Impact, which is consistent with the claim that social knowledge is housed within the neural architecture of the semantic system. These results suggest that current models of language processing may present an impoverished estimate of the neural systems that coordinate to support narrative comprehension, and, by extension, real-world language processing.
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Compreensão , Semântica , Humanos , Compreensão/fisiologia , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Idioma , Imageamento por Ressonância Magnética/métodosRESUMO
Aphasia is an acquired impairment in the production or comprehension of language, typically caused by left hemisphere stroke. The subtyping framework used in clinical aphasiology today is based on the Wernicke-Lichtheim model of aphasia formulated in the late 19th century, which emphasizes the distinction between language production and comprehension. The current study used a data-driven approach that combined modern statistical, machine learning, and neuroimaging tools to examine behavioural deficit profiles and their lesion correlates and predictors in a large cohort of individuals with post-stroke aphasia. First, individuals with aphasia were clustered based on their behavioural deficit profiles using community detection analysis (CDA) and these clusters were compared with the traditional aphasia subtypes. Random forest classifiers were built to evaluate how well individual lesion profiles predict cluster membership. The results of the CDA analyses did not align with the traditional model of aphasia in either behavioural or neuroanatomical patterns. Instead, the results suggested that the primary distinction in aphasia (after severity) is between phonological and semantic processing rather than between production and comprehension. Further, lesion-based classification reached 75% accuracy for the CDA-based categories and only 60% for categories based on the traditional fluent/non-fluent aphasia distinction. The results of this study provide a data-driven basis for a new approach to classification of post-stroke aphasia subtypes in both research and clinical settings.
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Afasia/classificação , Afasia/etiologia , Aprendizado de Máquina , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Afasia/patologia , Análise por Conglomerados , HumanosRESUMO
BACKGROUND: Previous research has suggested that there is substantial heterogeneity in the developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms. Sometimes, qualitative distinctions between trajectories with different ages of onset and/or patterns of remission are made; however, little is known about the predictors and broader clinical meaningfulness of these candidate 'developmental subtypes' of ADHD symptoms. METHODS: We applied latent class growth analysis to data from the UK Millennium Cohort Study (MCS; N = 11 316; ages 3, 5, 7, 11 and 14) to evaluate whether developmental trajectories of ADHD symptoms differing in early life predictors could be identified. Our optimal model included six trajectory groups, labelled unaffected (34.9% of the sample), mildly affected (24.1%), subclinical remitting (12.8%), pre-school onset partially remitting (14.1%), developmentally increasing (7.6%) and pre-school onset persistent (6.4%). RESULTS: Factors such as gender, conduct problems, cognitive ability, maternal education, premature birth, peer problems and school readiness scores differentiated between specific ADHD symptom trajectories. CONCLUSIONS: Taken together, our findings provide preliminary evidence that distinguishing different trajectories of ADHD symptoms could be clinically informative.
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The health benefits of resistance exercises are well established; however, the effects of resistance training on cognition are not as well understood. The purpose of this meta-analysis was to evaluate the evidence of resistance exercise's effects on cognition. A systematic search identified 24 studies that were included in the analyses. These articles ranged in the protocols utilized and in how they studied the effects of resistance training on cognition. Four primary analyses were carried out to assess the effects of resistance exercise on cognitive outcomes: (1) composite cognitive scores, (2) screening measures of cognitive impairment, (3) measures of executive functions, and (4) measures of working memory. Results revealed positive effects of resistance training on composite cognitive scores (SMD 0.71, 95% CI 0.30-1.12), screening measures of cognitive impairment (SMD 1.28, 95% CI 0.39-2.18), and executive functions (SMD 0.39, 95% CI 0.04-0.74), but no effect on measures of working memory (SMD 0.151, 95% CI - 0.21 to 0.51). High heterogeneity was observed in all analyses. Resistance training appears to have positive effects on cognition; however, future research will need to determine why the effects are so variable.
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Cognição/fisiologia , Função Executiva/fisiologia , Exercício Físico/fisiologia , Memória de Curto Prazo/fisiologia , Treinamento Resistido , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Eye-tracking is widely used throughout the scientific community, from vision science and psycholinguistics to marketing and human-computer interaction. Surprisingly, there is little consistency and transparency in preprocessing steps, making replicability and reproducibility difficult. To increase replicability, reproducibility, and transparency, a package in R (a free and widely used statistical programming environment) called gazeR was created to read and preprocess two types of data: gaze position and pupil size. For gaze position data, gazeR has functions for reading in raw eye-tracking data, formatting it for analysis, converting from gaze coordinates to areas of interest, and binning and aggregating data. For data from pupillometry studies, the gazeR package has functions for reading in and merging multiple raw pupil data files, removing observations with too much missing data, eliminating artifacts, blink identification and interpolation, subtractive baseline correction, and binning and aggregating data. The package is open-source and freely available for download and installation: https://github.com/dmirman/gazer . We provide step-by-step analyses of data from two tasks exemplifying the package's capabilities.
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Piscadela , Pupila , Software , Humanos , Leitura , Reprodutibilidade dos TestesRESUMO
Despite the critical importance of close replications in strengthening and advancing scientific knowledge, there are inherent challenges to conducting replications of lesion-based studies. In the present study, we conducted a close conceptual replication of a study (i.e., Hope et al., 2016) that found that fluency and naming scores in post-stoke aphasia were more strongly associated with a binary measure of structural white matter integrity (tract disconnection) than a graded measure (lesion load). Using a different sample of stroke patients (Nâ¯=â¯128) and four language deficit measures (aphasia severity, picture naming, and composite scores for speech production and semantic cognition), we examined tract disconnection and lesion load in three white matter tracts that have been implicated in language processing: arcuate fasciculus, uncinate fasciculus, and inferior fronto-occipital fasciculus. We did not find any consistent evidence that binary tract disconnection was more strongly associated with language impairment over and above lesion load, though individual deficit measures differed with respect to whether lesion load or tract disconnection was the stronger predictor. Given the mixed findings, we suggest caution when using such indirect estimates of structural white matter integrity, and direct individual measurements (for example, using diffusion weighted imaging) should be preferred when they are available. We end by highlighting the complex nature of replication in lesion-based studies and offer some potential solutions.
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Afasia/patologia , Afasia/fisiopatologia , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , Adulto , Idoso , Afasia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Fluent speech production is a critical aspect of language processing and is central to aphasia diagnosis and treatment. Multiple cognitive processes and neural subsystems must be coordinated to produce fluent narrative speech. To refine the understanding of these systems, measures that minimize the influence of other cognitive processes were defined for articulatory deficits and grammatical deficits. Articulatory deficits were measured by the proportion of phonetic errors (articulatory and prosodic) in a word repetition task in 115 participants with aphasia following left hemisphere stroke. Grammatical deficits were assessed in 46 participants based on two measures-proportion of closed class words and proportion of words in sentences-generated during semistructured narrative speech production (telling the Cinderella story). These measures were used to identify brain regions critical for articulatory and grammatical aspects of speech production using a multivariate lesion-symptom mapping approach based on support vector regression. Phonetic error proportion was associated with damage to the postcentral gyrus and the inferior parietal lobule (particularly the supramarginal gyrus). Proportion of closed class words in narrative speech did not have consistent lesion correlates. Proportion of words in sentences was strongly associated with frontal lobe damage, particularly the inferior and middle frontal gyri. Grammatical sentence structuring relies on frontal regions, particularly the inferior and middle frontal gyri, whereas phonetic-articulatory planning and execution relies on parietal regions, particularly the postcentral and supramarginal gyri. These results clarify and extend current understanding of the functional components of the frontoparietal speech production system.
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Afasia/patologia , Encéfalo/patologia , Fala/fisiologia , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Afasia/etiologia , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , FonéticaRESUMO
Drivers' population-level crash rates incrementally decrease following licensure, which has led to the implicit assumption that an individual driver's crash risk also decreases incrementally after licensure as they accrue experience. However, in the aggregate data an incremental decrease in crash rate can reflect both incremental reductions in crash risk within individuals and an incremental increase in the proportion of drivers who have experienced an abrupt decrease in crash risk. Therefore, while it is true to say that the population of drivers' crash risk reduces in the months following licensure, it is not necessarily true to say that a driver's crash risk reduces in the months following licensure; that is, it cannot be assumed that individual-level changes in crash risk mirror the population-level changes in crash rates. In statistics, this is known as an ecological fallacy and in formal logic it is known as the fallacy of division, a type of category error. Using computational cognitive modeling methods we demonstrate that aggregating individual-level abrupt decreases in crash risk (i.e., non-incremental change trajectories) accurately fits population-level crash rate data from over 1 million adolescents and uniquely accounts for effects of two interventions found to reduce police-reported MVCs. Thus, we demonstrate that (1) a power-law artifact is readily observable in newly licensed drivers' aggregate crash data, which is not necessarily indicative of individual-level change processes, (2) interventions can alter crash risk trajectories by inducing immediate phase changes in crash risk into a lower risk stratum, or increasing the probability of such a change, (3) a phase transition model provides a stronger and more parsimonious account of the existing data than an incremental-accrual model.
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Current models and theories of semantic knowledge primarily capture taxonomic relationships (DOG and WOLF) and largely do not address the role of thematic relationships in semantic knowledge (DOG and LEASH). Recent evidence suggests that processing or representation of thematic relationships may be distinct from taxonomic relationships. If taxonomic and thematic relations are distinct, then there should be a cost associated with switching between them even when the task remains constant. This hypothesis was tested using two different semantic-relatedness judgment tasks: Experiment 1 used a triads task and Experiment 2 used an oddball task. In both experiments, participants were faster to respond when the same relationship appeared on consecutive trials than when the relationship types were different, even though the task remained the same and the specific relations were different on each trial. These results are consistent with the theory that taxonomic and thematic relations rely on distinct processes or representations.
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Associação , Memória/fisiologia , Desempenho Psicomotor/fisiologia , Semântica , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
It is thought that semantic memory represents taxonomic information differently from thematic information. This study investigated the neural basis for the taxonomic-thematic distinction in a unique way. We gathered picture-naming errors from 86 individuals with poststroke language impairment (aphasia). Error rates were determined separately for taxonomic errors ("pear" in response to apple) and thematic errors ("worm" in response to apple), and their shared variance was regressed out of each measure. With the segmented lesions normalized to a common template, we carried out voxel-based lesion-symptom mapping on each error type separately. We found that taxonomic errors localized to the left anterior temporal lobe and thematic errors localized to the left temporoparietal junction. This is an indication that the contribution of these regions to semantic memory cleaves along taxonomic-thematic lines. Our findings show that a distinction long recognized in the psychological sciences is grounded in the structure and function of the human brain.
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Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Classificação , Memória , Semântica , Mapeamento Encefálico , Humanos , Neuroanatomia , Lobo Temporal/fisiologiaRESUMO
Decoding social environments and engaging meaningfully with other people are critical aspects of human cognition. Multiple cognitive systems, including social and semantic cognition, work alongside each other to support these processes. This study investigated shared processing between social and semantic systems using neuroimaging data collected during movie-viewing, which captures the multimodal environment in which social knowledge is exchanged. Semantic and social content from movie events (event-level) and movie transcripts (word-level) were used in parametric modulation analyses to test (1) the degree to which semantic and social information is processed within each respective network and (2) engagement of the same cross-network regions or the same domain-general hub located within the semantic network during semantic and social processing. Semantic word and event-level content engaged the same fronto-temporo-parietal network and a portion of the semantic hub in the anterior temporal lobe (ATL). Social word and event-level content engaged the supplementary motor area and right angular gyrus within the social network, but only social words engaged the domain-general semantic hub in left ATL. There was evidence of shared processing between the social and semantic systems in the dorsolateral portion of right ATL which was engaged by word and event-level semantic and social content. Overlap between the semantic and social word and event results was highly variable within and across participants, with the most consistent loci of overlap occurring in left inferior frontal, bilateral precentral and supramarginal gyri for social and semantic words and in bilateral superior temporal gyrus extending from ATL posteriorly into supramarginal gyri for social and semantic events. These results indicate a complex pattern of shared and distinct regions for social and semantic cognition during naturalistic processing. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on October 11, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/ACWQY .
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Semântica , Cognição Social , Humanos , Imageamento por Ressonância Magnética , Mapeamento Encefálico , Lobo Temporal/diagnóstico por imagem , CogniçãoRESUMO
Speech production in aphasia is often described as "effortful", though the consequences of consistent, high degrees of cognitive effort have not been explored. Using recent work on mental effort as a theoretical framework, the present study examined how effort-related fatigue produces decrements in performance in picture naming among participants with post-stroke aphasia. We analyzed three data sets from prior studies where participants completed a large picture naming test. Decreasing naming accuracy across trials was statistically significant in two of the three samples. There were also significant effects of practice (better performance on a second test administration), word frequency (better performance for more frequent words), and word length (better performance for shorter words). These results are the first concrete demonstration of fatigue affecting performance on a language task in post-stroke aphasia. They open a new avenue for research on mental effort/fatigue with potential implications for aphasia assessment, treatment, and management.
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Semantic relations include "taxonomic" relations based on shared features and "thematic" relations based on co-occurrence in events. The "dual-hub" account proposes that the anterior temporal lobe (ATL) is functionally specialized for taxonomic relations and the inferior parietal lobule (IPL) for thematic relations. This study examined this claim by analyzing the intra- and inter-region phase synchronization of intracranial EEG data from electrodes in the ATL, IPL, and two subregions of the semantic control network: left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG). Ten participants with epilepsy completed a semantic relatedness judgment task during intracranial EEG recording and had electrodes in at least one hub and at least one semantic control region. Theta band phase synchronization was partially consistent with the dual-hub account: synchronization between the ATL and IFG/pMTG increased when processing taxonomic relations, and synchronization within the IPL and between IPL and pMTG increased when processing thematic relations.
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Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Lobo Temporal/diagnóstico por imagem , Lobo Parietal , Julgamento , SemânticaRESUMO
Theories of word production and word recognition generally agree that multiple word candidates are activated during processing. The facilitative and inhibitory effects of these "lexical neighbors" have been studied extensively using behavioral methods and have spurred theoretical development in psycholinguistics, but relatively little is known about the neural basis of these effects and how lesions may affect them. This study used voxel-wise lesion overlap subtraction to examine semantic and phonological neighbor effects in spoken word production following left hemisphere stroke. Increased inhibitory effects of near semantic neighbors were associated with inferior frontal lobe lesions, suggesting impaired selection among strongly activated semantically related candidates. Increased inhibitory effects of phonological neighbors were associated with posterior superior temporal and inferior parietal lobe lesions. In combination with previous studies, these results suggest that such lesions cause phonological-to-lexical feedback to more strongly activate phonologically related lexical candidates. The comparison of semantic and phonological neighbor effects and how they are affected by left hemisphere lesions provides new insights into the cognitive dynamics and neural basis of phonological, semantic, and cognitive control processes in spoken word production.
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Mapeamento Encefálico , Encéfalo/fisiologia , Inibição Psicológica , Fonética , Semântica , Vocabulário , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estimulação Luminosa , Tempo de Reação/fisiologia , Tomografia Computadorizada por Raios X , Percepção VisualRESUMO
Deficits in fluent speech production following left hemisphere stroke are a central concern because of their impact on patients' lives and the insight they provide about the neural organization of language processing. Fluent speech production requires the rapid coordination of phonological, semantic, and syntactic processing, so this study examined how deficits in connected speech relate to these language sub-systems. Behavioural data (N = 69 participants with aphasia following left hemisphere stroke) consisted of a diverse and comprehensive set of narrative speech production measures and measures of overall severity, semantic deficits, and phonological deficits. These measures were entered into a principal component analysis with bifactor rotation-a latent structure model where each item loads on a general factor that reflects what is common among the items, and orthogonal factors that explain variance not accounted for by the general factor. Lesion data were available for 58 of the participants, and each factor score was analysed with multivariate lesion-symptom mapping. Effects of connectivity disruption were evaluated using robust regression with tract disconnection or graph theoretic measures of connectivity as predictors. The principal component analysis produced a four-factor solution that accounted for 70.6% of the variance in the data, with a general factor corresponding to the overall severity and length and complexity of speech output (complexity factor), a lexical syntax factor, and independent factors for Semantics and Phonology. Deficits in the complexity of speech output were associated with a large temporo-parietal region, similar to overall aphasia severity. The lexical syntax factor was associated with damage in a relatively small set of fronto-parietal regions which may reflect the recruitment of control systems to support retrieval and correct usage of lexical items that primarily serve a syntactic rather than semantic function. Tract-based measures of connectivity disruption were not statistically associated with the deficit scores after controlling for overall lesion volume. Language network efficiency and average clustering coefficient within the language network were significantly associated with deficit scores after controlling for overall lesion volume. These results highlight overall severity as the critical contributor to fluent speech in post-stroke aphasia, with a dissociable factor corresponding to lexical syntax.
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Taxonomic and thematic relations are major components of semantic representation but their neurocognitive underpinnings are still debated. We hypothesised that taxonomic relations preferentially activate parts of anterior temporal lobe (ATL) because they rely more on colour and shape features, while thematic relations preferentially activate temporoparietal cortex (TPC) because they rely more on action and location knowledge. We first conducted activation likelihood estimation (ALE) meta-analysis to assess evidence for neural specialisation in the existing fMRI literature (Study 1), then used a primed semantic judgement task to examine if the two relations are primed by different feature types (Study 2). We find that taxonomic relations show minimal feature-based specialisation but preferentially activate the lingual gyrus. Thematic relations are more dependent on action and location features and preferentially engage TPC. The meta-analysis also showed that lateral ATL is preferentially engaged by Thematic relations, which may reflect their greater reliance on verbal associations.
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Imageamento por Ressonância Magnética , Semântica , Humanos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Córtex Cerebral , Julgamento/fisiologia , Mapeamento EncefálicoRESUMO
Aphasia is a common consequence of stroke with severe impacts on employability, social interactions and quality of life. Producing discourse-relevant information in a real-world setting is the most important aspect of recovery because it is critical to successful communication. This study sought to identify the lesion correlates of impaired production of relevant information in spoken discourse in a large, unselected sample of participants with post-stroke aphasia. Spoken discourse (n = 80) and structural brain scans (n = 66) from participants with aphasia following left hemisphere stroke were analysed. Each participant provided 10 samples of spoken discourse elicited in three different genres, and 'correct information unit' analysis was used to quantify the informativeness of speech samples. The lesion correlates were identified using multivariate lesion-symptom mapping, voxel-wise disconnection and tract-wise analyses. Amount and speed of relevant information were highly correlated across different genres and with total lesion size. The analyses of lesion correlates converged on the same pattern: impaired production of relevant information was associated with damage to anterior dorsal white matter pathways, specifically the arcuate fasciculus, frontal aslant tract and superior longitudinal fasciculus. Damage to these pathways may be a useful biomarker for impaired informative spoken discourse and informs development of neurorehabilitation strategies.
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BACKGROUND: The volumetric size of a brain lesion is a frequently used stroke biomarker. It stands out among most imaging biomarkers for being a one-dimensional variable that is applicable in simple statistical models. In times of machine learning algorithms, the question arises of whether such a simple variable is still useful, or whether high-dimensional models on spatial lesion information are superior. METHODS: We included 753 first-ever anterior circulation ischemic stroke patients (age 68.4±15.2 years; NIHSS at 24 h 4.4±5.1; modified Rankin Scale (mRS) at 3-months median[IQR] 1[0.75;3]) and traced lesions on diffusion-weighted MRI. In an out-of-sample model validation scheme, we predicted stroke severity as measured by NIHSS 24 h and functional stroke outcome as measured by mRS at 3 months either from spatial lesion features or lesion size. RESULTS: For stroke severity, the best regression model based on lesion size performed significantly above chance (p < 0.0001) with R2 = 0.322, but models with spatial lesion features performed significantly better with R2 = 0.363 (t(752) = 2.889; p = 0.004). For stroke outcome, the best classification model based on lesion size again performed significantly above chance (p < 0.0001) with an accuracy of 62.8%, which was not different from the best model with spatial lesion features (62.6%, p = 0.80). With smaller training data sets of only 150 or 50 patients, the performance of high-dimensional models with spatial lesion features decreased up to the point of being equivalent or even inferior to models trained on lesion size. The combination of lesion size and spatial lesion features in one model did not improve predictions. CONCLUSIONS: Lesion size is a decent biomarker for stroke outcome and severity that is slightly inferior to spatial lesion features but is particularly suited in studies with small samples. When low-dimensional models are desired, lesion size provides a viable proxy biomarker for spatial lesion features, whereas high-precision prediction models in personalised prognostic medicine should operate with high-dimensional spatial imaging features in large samples.