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1.
Cereb Cortex ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39123309

RESUMEN

The functional importance of the anterior temporal lobes (ATLs) has come to prominence in two active, albeit unconnected literatures-(i) face recognition and (ii) semantic memory. To generate a unified account of the ATLs, we tested the predictions from each literature and examined the effects of bilateral versus unilateral ATL damage on face recognition, person knowledge, and semantic memory. Sixteen people with bilateral ATL atrophy from semantic dementia (SD), 17 people with unilateral ATL resection for temporal lobe epilepsy (TLE; left = 10, right = 7), and 14 controls completed tasks assessing perceptual face matching, person knowledge and general semantic memory. People with SD were impaired across all semantic tasks, including person knowledge. Despite commensurate total ATL damage, unilateral resection generated mild impairments, with minimal differences between left- and right-ATL resection. Face matching performance was largely preserved but slightly reduced in SD and right TLE. All groups displayed the familiarity effect in face matching; however, it was reduced in SD and right TLE and was aligned with the level of item-specific semantic knowledge in all participants. We propose a neurocognitive framework whereby the ATLs underpin a resilient bilateral representation system that supports semantic memory, person knowledge and face recognition.


Asunto(s)
Epilepsia del Lóbulo Temporal , Reconocimiento Facial , Semántica , Lóbulo Temporal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Lóbulo Temporal/cirugía , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Adulto , Reconocimiento Facial/fisiología , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/psicología , Epilepsia del Lóbulo Temporal/fisiopatología , Reconocimiento en Psicología/fisiología , Lateralidad Funcional/fisiología , Pruebas Neuropsicológicas , Memoria/fisiología , Anciano , Cara
2.
Brain ; 146(5): 1950-1962, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-36346107

RESUMEN

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.


Asunto(s)
Afasia , Trastornos del Lenguaje , Accidente Cerebrovascular , Humanos , Encéfalo/patología , Accidente Cerebrovascular/complicaciones , Afasia/etiología , Trastornos del Lenguaje/etiología , Lenguaje , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico
3.
Cereb Cortex ; 33(9): 5135-5147, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36222614

RESUMEN

Although memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unusual versus stereotypical patterns of retrieval. More creative responses to strongly associated word-pairs were associated with greater engagement of episodic memory: in highly familiar situations, semantic, and episodic stores converge on the same information enabling participants to form a personal link between items. This pattern of retrieval was associated with greater engagement of core default mode network (DMN). In contrast, more creative responses to weakly associated word-pairs were associated with the controlled retrieval of less dominant semantic information and greater recruitment of the semantic control network, which overlaps with the dorsomedial subsystem of DMN. Although both controlled semantic and episodic patterns of retrieval are associated with activation within DMN, these processes show little overlap in activation. These findings demonstrate that controlled aspects of semantic cognition play an important role in verbal creativity.


Asunto(s)
Memoria Episódica , Semántica , Humanos , Cognición/fisiología , Creatividad , Memoria a Largo Plazo , Imagen por Resonancia Magnética , Mapeo Encefálico , Encéfalo/fisiología
4.
Hum Brain Mapp ; 44(10): 4064-4076, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37145963

RESUMEN

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.


Asunto(s)
Conectoma , Imagen de Difusión Tensora , Humanos , Imagen de Difusión Tensora/métodos , Encéfalo/diagnóstico por imagen , Conectoma/métodos
5.
Cereb Cortex ; 32(16): 3392-3405, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34875018

RESUMEN

The Complementary Learning Systems (CLS) theory provides a powerful framework for considering the acquisition, consolidation, and generalization of new knowledge. We tested this proposed neural division of labor in adults through an investigation of the consolidation and long-term retention of newly learned native vocabulary with post-learning functional neuroimaging. Newly learned items were compared with two conditions: 1) previously known items to highlight the similarities and differences with established vocabulary and 2) unknown/untrained items to provide a control for non-specific perceptual and motor speech output. Consistent with the CLS, retrieval of newly learned items was supported by a combination of regions associated with episodic memory (including left hippocampus) and the language-semantic areas that support established vocabulary (left inferior frontal gyrus and left anterior temporal lobe). Furthermore, there was a shifting division of labor across these two networks in line with the items' consolidation status; faster naming was associated with more activation of language-semantic areas and lesser activation of episodic memory regions. Hippocampal activity during naming predicted more than half the variation in naming retention 6 months later.


Asunto(s)
Mapeo Encefálico , Vocabulario , Mapeo Encefálico/métodos , Lenguaje , Imagen por Resonancia Magnética , Semántica
6.
J Cogn Neurosci ; 33(12): 2494-2511, 2021 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-34407196

RESUMEN

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.


Asunto(s)
Afasia , Semántica , Adulto , Afasia/etiología , Humanos , Corteza Insular , Lenguaje , Habla
7.
Brain ; 143(5): 1541-1554, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32330940

RESUMEN

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.


Asunto(s)
Afasia/etiología , Afasia/fisiopatología , Encéfalo/fisiopatología , Modelos Neurológicos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen
8.
Brain ; 143(10): 3121-3135, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32940648

RESUMEN

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.


Asunto(s)
Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/psicología , Análisis de Componente Principal/métodos , Semántica , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/psicología , Anciano , Afasia Progresiva Primaria/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Fonética , Accidente Cerebrovascular/complicaciones
9.
Brain ; 142(10): 3202-3216, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31504247

RESUMEN

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.


Asunto(s)
Afasia/fisiopatología , Accidente Cerebrovascular/fisiopatología , Anciano , Anciano de 80 o más Años , Atención/fisiología , Encéfalo/patología , Mapeo Encefálico , Cognición , Comprensión/fisiología , Función Ejecutiva/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lenguaje , Pruebas del Lenguaje , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Análisis de Componente Principal , Semántica , Habla/fisiología , Accidente Cerebrovascular/complicaciones
11.
Brain ; 141(6): 1815-1827, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29672757

RESUMEN

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.


Asunto(s)
Afasia/rehabilitación , Terapia del Lenguaje/métodos , Recuerdo Mental/fisiología , Nombres , Aprendizaje Verbal/fisiología , Vocabulario , Anciano , Afasia/diagnóstico por imagen , Afasia/etiología , Encéfalo/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Generalización Psicológica , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Semántica , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen
13.
Neuroimage ; 122: 214-21, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26037055

RESUMEN

The 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.


Asunto(s)
Mapeo Encefálico/métodos , Comprensión/fisiología , Imagen por Resonancia Magnética/métodos , Percepción del Habla/fisiología , Lóbulo Temporal/fisiología , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Procesamiento de Señales Asistido por Computador , Adulto Joven
14.
Hum Brain Mapp ; 35(8): 4118-28, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24677506

RESUMEN

Magnetic susceptibility differences at tissue interfaces lead to signal loss in conventional gradient-echo (GE) EPI. This poses a problem for fMRI in language and memory paradigms, which activate the most affected regions. Two methods proposed to overcome this are spin-echo EPI and dual GE EPI, where two EPI read-outs are serially collected at a short and longer echo time. The spin-echo method applies a refocusing pulse to recover dephased MR signal due to static field inhomogeneities, but is known to have a relatively low blood oxygenation level dependant (BOLD) sensitivity. In comparison, GE has superior BOLD sensitivity, and by employing an additional shorter echo, in a dual GE sequence, it can reduce signal loss due to spin dephasing. We directly compared dual GE and spin-echo fMRI during a semantic categorization task, which has been shown to activate the inferior temporal region-a region known to be affected by magnetic susceptibility. A whole brain analysis showed that the dual GE resulted in significantly higher activation within the left inferior temporal fusiform (ITF) cortex, compared to spin-echo. The inferior frontal gyrus (IFG) was activated for dual GE, but not spin-echo. Regions of interest analysis was carried out on the anterior and posterior ITF, left and right IFG, and part of the cerebellum. Dual GE outperformed spin-echo in the anterior and posterior ITF and bilateral IFG regions, whilst being equal in the cerebellum. Hence, dual GE should be the method of choice for fMRI studies of inferior temporal regions.


Asunto(s)
Circulación Cerebrovascular/fisiología , Imagen por Resonancia Magnética/métodos , Oxígeno/sangre , Lóbulo Temporal/fisiología , Encéfalo/fisiología , Mapeo Encefálico/métodos , Femenino , Humanos , Juicio/fisiología , Masculino , Pruebas Neuropsicológicas , Estimulación Luminosa , Semántica , Procesamiento de Señales Asistido por Computador , Percepción Visual/fisiología , Adulto Joven
15.
Cortex ; 179: 103-111, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39167916

RESUMEN

Anomia is a common consequence following brain damage and a central symptom in semantic dementia (SD) and post-stroke aphasia (PSA), for instance. Picture naming tests are often used in clinical assessments and experience suggests that items vary systematically in their difficulty. Despite clinical intuitions and theoretical accounts, however, the existence and determinants of such a naming difficulty gradient remain to be empirically established and evaluated. Seizing the unique opportunity of two large-scale datasets of semantic dementia and post-stroke aphasia patients assessed with the same picture naming test, we applied an Item Response Theory (IRT) approach and we (a) established that an item naming difficulty gradient exists, which (b) partly differs between patient groups, and is (c) related in part to a limited number of psycholinguistic properties - frequency and familiarity for SD, frequency and word length for PSA. Our findings offer exciting future avenues for new, adaptive, time-efficient, and patient-tailored approaches to naming assessment and therapy.

16.
Neurology ; 103(4): e209679, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39042846

RESUMEN

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) spans heterogeneous typical and atypical phenotypes. Posterior cortical atrophy (PCA) is a striking example, characterized by prominent impairment in visual and other posterior functions in contrast to typical, amnestic AD. The primary study objective was to establish how the similarities and differences of cognition and brain volumes within AD and PCA (and by extension other AD variants) can be conceptualized as systematic variations across a transdiagnostic, graded multidimensional space. METHODS: This was a cross-sectional, single-center, observational, cohort study performed at the National Hospital for Neurology & Neurosurgery, London, United Kingdom. Data were collected from a cohort of patients with PCA and AD, matched for age, disease duration, and Mini-Mental State Examination (MMSE) scores. There were 2 sets of outcome measures: (1) scores on a neuropsychological battery containing 22 tests spanning visuoperceptual and visuospatial processing, episodic memory, language, executive functions, calculation, and visuospatial processing and (2) measures extracted from high-resolution T1-weighted volumetric MRI scans. Principal component analysis was used to extract the transdiagnostic dimensions of phenotypical variation from the detailed neuropsychological data. Voxel-based morphometry was used to examine associations between the PCA-derived clinical phenotypes and the structural measures. RESULTS: We enrolled 93 participants with PCA (mean: age = 59.9 years, MMSE = 21.2; 59/93 female) and 58 AD participants (mean: age = 57.1 years, MMSE = 19.7; 22/58 female). The principal component analysis for PCA (sample adequacy confirmed: Kaiser-Meyer-Olkin = 0.865) extracted 3 dimensions accounting for 61.0% of variance in patients' performance, reflecting general cognitive impairment, visuoperceptual deficits, and visuospatial impairments. Plotting AD cases into the PCA-derived multidimensional space, and vice versa, revealed graded, overlapping variations between cases along these dimensions, with no evidence for categorical-like patient clustering. Similarly, the relationship between brain volumes and scores on the extracted dimensions was overlapping for PCA and AD cases. DISCUSSION: These results provide evidence supporting a reconceptualization of clinical and radiologic variation in these heterogenous AD phenotypes as being along shared phenotypic continua spanning PCA and AD, arising from systematic graded variations within a transdiagnostic, multidimensional neurocognitive geometry.


Asunto(s)
Enfermedad de Alzheimer , Atrofia , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Femenino , Masculino , Atrofia/patología , Anciano , Estudios Transversales , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Cohortes
17.
Trends Cogn Sci ; 27(3): 258-281, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36631371

RESUMEN

A key goal for cognitive neuroscience is to understand the neurocognitive systems that support semantic memory. Recent multivariate analyses of neuroimaging data have contributed greatly to this effort, but the rapid development of these novel approaches has made it difficult to track the diversity of findings and to understand how and why they sometimes lead to contradictory conclusions. We address this challenge by reviewing cognitive theories of semantic representation and their neural instantiation. We then consider contemporary approaches to neural decoding and assess which types of representation each can possibly detect. The analysis suggests why the results are heterogeneous and identifies crucial links between cognitive theory, data collection, and analysis that can help to better connect neuroimaging to mechanistic theories of semantic cognition.


Asunto(s)
Encéfalo , Semántica , Humanos , Encéfalo/diagnóstico por imagen , Memoria , Cognición , Neuroimagen , Imagen por Resonancia Magnética
18.
Alzheimers Res Ther ; 15(1): 219, 2023 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-38102724

RESUMEN

BACKGROUND: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. METHODS: Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). RESULTS: Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. CONCLUSIONS: Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.


Asunto(s)
Afasia Progresiva Primaria , Humanos , Afasia Progresiva Primaria/diagnóstico por imagen , Afasia Progresiva Primaria/patología , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cognición , Lingüística
19.
Neuropsychologia ; 177: 108413, 2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36336090

RESUMEN

It is increasingly acknowledged that patients with aphasia following a left-hemisphere stroke often have difficulties in other cognitive domains. One of these domains is attention, the very fundamental ability to detect, select, and react to the abundance of stimuli present in the environment. Basic and more complex attentional functions are usually distinguished, and a variety of tests has been developed to assess attentional performance at a behavioural level. Attentional performance in aphasia has been investigated previously, but often only one specific task, stimulus modality, or type of measure was considered and usually only group-level analyses or data based on experimental tasks were presented. Also, information on brain-behaviour relationships for this cognitive domain and patient group is scarce. We report detailed analyses on a comprehensive dataset including patients' performance on various subtests of two well-known, standardised neuropsychological test batteries assessing attention. These tasks allowed us to explore: 1) how many patients show impaired performance in comparison to normative data, in which tasks and on what measure; 2) how the different tasks and measures relate to each other and to patients' language abilities; 3) the neural correlates associated with attentional performance. Up to 32 patients with varying aphasia severity were assessed with subtests from the Test of Attentional Performance (TAP) as well as the Test of Everyday Attention (TEA). Performance was compared to normative data, relationships between attention measures and other background data were explored with principal component analyses and correlations, and brain-behaviour relationships were assessed by means of voxel-based correlational methodology. Depending on the task and measure, between 3 and 53 percent of the patients showed impaired performance compared to normative data. The highest proportion of impaired performance was noted for complex attention tasks involving auditory stimuli. Patients differed in their patterns of performance and only the performance in the divided attention tests was (weakly) associated with their overall language impairment. Principal components analyses yielded four underlying factors, each being associated with distinct neural correlates. We thus extend previous research in characterizing different aspects of attentional performance within one sample of patients with chronic post stroke aphasia. Performance on a broad range of attention tasks and measures was variable and largely independent of patients' language abilities, which underlines the importance of assessing this cognitive domain in aphasic patients. Notably, a considerable proportion of patients showed difficulties with attention allocation to auditory stimuli. The reasons for these potentially modality-specific difficulties are currently not well understood and warrant additional investigations.


Asunto(s)
Afasia , Accidente Cerebrovascular , Humanos , Imagen por Resonancia Magnética/métodos , Afasia/etiología , Afasia/complicaciones , Encéfalo/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/psicología , Mapeo Encefálico , Pruebas Neuropsicológicas
20.
Brain Commun ; 4(3): fcac107, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35602650

RESUMEN

It is increasingly acknowledged that, often, patients with post-stroke aphasia not only have language impairments but also deficits in other cognitive domains (e.g. executive functions) that influence recovery and response to therapy. Many assessments of executive functions are verbally based and therefore usually not administered in this patient group. However, the performance of patients with aphasia in such tests might provide valuable insights both from a theoretical and clinical perspective. We aimed to elucidate (i) if verbal executive tests measure anything beyond the language impairment in patients with chronic post-stroke aphasia, (ii) how performance in such tests relates to performance in language tests and nonverbal cognitive functions, and (iii) the neural correlates associated with performance in verbal executive tests. In this observational study, three commonly used verbal executive tests were administered to a sample of patients with varying aphasia severity. Their performance in these tests was explored by means of principal component analyses, and the relationships with a broad range of background tests regarding their language and nonverbal cognitive functions were elucidated with correlation analyses. Furthermore, lesion analyses were performed to explore brain-behaviour relationships. In a sample of 32 participants, we found that: (i) a substantial number of patients with aphasia were able to perform the verbal executive tests; (ii) variance in performance was not explained by the severity of an individual's overall language impairment alone but was related to two independent behavioural principal components per test; (iii) not all aspects of performance were related to the patient's language abilities; and (iv) all components were associated with separate neural correlates, some overlapping partly in frontal and parietal regions. Our findings extend our clinical and theoretical understanding of dysfunctions beyond language in patients with aphasia.

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