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1.
Brain ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38889230

RESUMEN

There is a rich tradition of research on the neuroanatomical correlates of spoken language production in aphasia using constrained tasks (e.g., picture naming), which offer controlled insights into the distinct processes that govern speech and language (i.e., lexical-semantic access, morphosyntactic construction, phonological encoding, speech motor programming/execution). Yet these tasks do not necessarily reflect everyday language use. In contrast, naturalistic language production (also referred to as connected speech or discourse) more closely approximates typical processing demands, requiring the dynamic integration of all aspects of speech and language. The brain bases of naturalistic language production remain relatively unknown, however, in part because of the difficulty in deriving features that are salient, quantifiable, and interpretable relative to both speech-language processes and the extant literature. The present cross-sectional observational study seeks to address these challenges by leveraging a validated and comprehensive auditory-perceptual measurement system that yields four explanatory dimensions of performance-Paraphasia (misselection of words and sounds), Logopenia (paucity of words), Agrammatism (grammatical omissions), and Motor speech (impaired speech motor programming/execution). We used this system to characterize naturalistic language production in a large and representative sample of individuals with acute post-stroke aphasia (n = 118). Scores on each of the four dimensions were correlated with lesion metrics, and multivariate associations among the dimensions and brain regions were then explored. Our findings revealed distinct yet overlapping neuroanatomical correlates throughout the left-hemisphere language network. Paraphasia and Logopenia were associated primarily with posterior regions, spanning both dorsal and ventral streams, which are critical for lexical-semantic access and phonological encoding. In contrast, Agrammatism and Motor speech were associated primarily with anterior regions of the dorsal stream that are involved in morphosyntactic construction and speech motor planning/execution respectively. Collectively, we view these results as constituting a brain-behavior model of naturalistic language production in aphasia, aligning with both historical and contemporary accounts of the neurobiology of spoken language production.

2.
Brain ; 146(3): 1021-1039, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35388420

RESUMEN

Most individuals who experience aphasia after a stroke recover to some extent, with the majority of gains taking place in the first year. The nature and time course of this recovery process is only partially understood, especially its dependence on lesion location and extent, which are the most important determinants of outcome. The aim of this study was to provide a comprehensive description of patterns of recovery from aphasia in the first year after stroke. We recruited 334 patients with acute left hemisphere supratentorial ischaemic or haemorrhagic stroke and evaluated their speech and language function within 5 days using the Quick Aphasia Battery (QAB). At this initial time point, 218 patients presented with aphasia. Individuals with aphasia were followed longitudinally, with follow-up evaluations of speech and language at 1 month, 3 months, and 1 year post-stroke, wherever possible. Lesions were manually delineated based on acute clinical MRI or CT imaging. Patients with and without aphasia were divided into 13 groups of individuals with similar, commonly occurring patterns of brain damage. Trajectories of recovery were then investigated as a function of group (i.e. lesion location and extent) and speech/language domain (overall language function, word comprehension, sentence comprehension, word finding, grammatical construction, phonological encoding, speech motor programming, speech motor execution, and reading). We found that aphasia is dynamic, multidimensional, and gradated, with little explanatory role for aphasia subtypes or binary concepts such as fluency. Patients with circumscribed frontal lesions recovered well, consistent with some previous observations. More surprisingly, most patients with larger frontal lesions extending into the parietal or temporal lobes also recovered well, as did patients with relatively circumscribed temporal, temporoparietal, or parietal lesions. Persistent moderate or severe deficits were common only in patients with extensive damage throughout the middle cerebral artery distribution or extensive temporoparietal damage. There were striking differences between speech/language domains in their rates of recovery and relationships to overall language function, suggesting that specific domains differ in the extent to which they are redundantly represented throughout the language network, as opposed to depending on specialized cortical substrates. Our findings have an immediate clinical application in that they will enable clinicians to estimate the likely course of recovery for individual patients, as well as the uncertainty of these predictions, based on acutely observable neurological factors.


Asunto(s)
Afasia , Accidente Cerebrovascular , Humanos , Afasia/patología , Lóbulo Temporal/patología , Habla , Lenguaje , Imagen por Resonancia Magnética
3.
Neurocase ; 27(1): 97-105, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33666124

RESUMEN

Unexpected absence of aphasia after left-hemisphere perisylvian damage is often assumed to reflect right-hemisphere language lateralization, but other potential explanations include bilateral language representation, or sparing of critical left-hemisphere regions due to individual variability. We describe the case of a left-handed gentleman who presented with no aphasia after a left temporal hemorrhage. We used functional neuroimaging to determine how his language network had been spared. In this case, we observed unequivocal right-hemisphere lateralization of language function, explaining his lack of aphasia. We discuss the variability of language organization and highlight outstanding questions about the implications of damage in different scenarios.


Asunto(s)
Afasia , Lenguaje , Afasia/diagnóstico por imagen , Afasia/etiología , Lateralidad Funcional , Neuroimagen Funcional , Hemorragia , Humanos , Imagen por Resonancia Magnética
4.
Cereb Cortex ; 30(2): 618-627, 2020 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-31241149

RESUMEN

Speech perception involves mapping from a continuous and variable acoustic speech signal to discrete, linguistically meaningful units. However, it is unclear where in the auditory processing stream speech sound representations cease to be veridical (faithfully encoding precise acoustic properties) and become categorical (encoding sounds as linguistic categories). In this study, we used functional magnetic resonance imaging and multivariate pattern analysis to determine whether tonotopic primary auditory cortex (PAC), defined as tonotopic voxels falling within Heschl's gyrus, represents one class of speech sounds-vowels-veridically or categorically. For each of 15 participants, 4 individualized synthetic vowel stimuli were generated such that the vowels were equidistant in acoustic space, yet straddled a categorical boundary (with the first 2 vowels perceived as [i] and the last 2 perceived as [i]). Each participant's 4 vowels were then presented in a block design with an irrelevant but attention-demanding level change detection task. We found that in PAC bilaterally, neural discrimination between pairs of vowels that crossed the categorical boundary was more accurate than neural discrimination between equivalently spaced vowel pairs that fell within a category. These findings suggest that PAC does not represent vowel sounds veridically, but that encoding of vowels is shaped by linguistically relevant phonemic categories.


Asunto(s)
Corteza Auditiva/fisiología , Fonética , Percepción del Habla/fisiología , Estimulación Acústica , Adulto , Mapeo Encefálico , Discriminación en Psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto Joven
5.
Neuroimage ; 189: 368-379, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30665008

RESUMEN

Phonological encoding depends on left-lateralized regions in the supramarginal gyrus and the ventral precentral gyrus. Localization of these phonological regions in individual participants-including individuals with language impairments-is important in several research and clinical contexts. To localize these regions, we developed two paradigms that load on phonological encoding: a rhyme judgment task and a syllable counting task. Both paradigms relied on an adaptive staircase design to ensure that each individual performed each task at a similarly challenging level. The goal of this study was to assess the validity and reliability of the two paradigms, in terms of their ability to consistently produce left-lateralized activations of the supramarginal gyrus and ventral precentral gyrus in neurologically normal individuals with presumptively normal language localization. Sixteen participants were scanned with fMRI as they performed the rhyme judgment paradigm, the syllable counting paradigm, and an adaptive semantic paradigm that we have described previously. We found that the rhyme and syllable paradigms both yielded left-lateralized supramarginal and ventral precentral activations in the majority of participants. The rhyme paradigm produced more lateralized and more reliable activations, and so should be favored in future applications. In contrast, the semantic paradigm did not reveal supramarginal or precentral activations in most participants, suggesting that the recruitment of these regions is indeed driven by phonological encoding, not language processing in general. In sum, the adaptive rhyme judgment paradigm was effective in localizing left-lateralized phonological encoding regions in individual participants, and, in conjunction with the adaptive semantic paradigm, can be used to map individual language networks.


Asunto(s)
Mapeo Encefálico/métodos , Lóbulo Frontal/fisiología , Lateralidad Funcional/fisiología , Lenguaje , Lóbulo Parietal/fisiología , Psicolingüística , Adulto , Anciano , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Parietal/diagnóstico por imagen , Lectura , Reproducibilidad de los Resultados , Adulto Joven
6.
Curr Neurol Neurosci Rep ; 19(8): 53, 2019 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-31250125

RESUMEN

PURPOSE OF REVIEW: Aphasia is often characterized in terms of subtype and severity, yet these constructs have limited explanatory power, because aphasia is inherently multifactorial both in its neural substrates and in its symptomatology. The purpose of this review is to survey current and emerging multivariate approaches to understanding aphasia. RECENT FINDINGS: Techniques such as factor analysis and principal component analysis have been used to define latent underlying factors that can account for performance on batteries of speech and language tests, and for characteristics of spontaneous speech production. Multivariate lesion-symptom mapping has been shown to outperform univariate approaches to lesion-symptom mapping for identifying brain regions where damage is associated with specific speech and language deficits. It is increasingly clear that structural damage results in functional changes in wider neural networks, which mediate speech and language outcomes. Multivariate statistical approaches are essential for understanding the complex relationships between the neural substrates of aphasia, and resultant profiles of speech and language function.


Asunto(s)
Afasia/etiología , Encéfalo/fisiopatología , Anciano , Mapeo Encefálico , Femenino , Humanos , Lenguaje , Pruebas del Lenguaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Habla/fisiología , Accidente Cerebrovascular/complicaciones
7.
Brain ; 141(6): 1799-1814, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29718131

RESUMEN

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.


Asunto(s)
Afasia Progresiva Primaria/fisiopatología , Afasia Progresiva Primaria/rehabilitación , Afasia de Wernicke/fisiopatología , Logopedia/métodos , Habla/fisiología , Anciano , Afasia Progresiva Primaria/diagnóstico por imagen , Afasia de Wernicke/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Resultado del Tratamiento
8.
J Cogn Neurosci ; 30(3): 411-420, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29211650

RESUMEN

Cortical stimulation mapping (CSM) has provided important insights into the neuroanatomy of language because of its high spatial and temporal resolution, and the causal relationships that can be inferred from transient disruption of specific functions. Almost all CSM studies to date have focused on word-level processes such as naming, comprehension, and repetition. In this study, we used CSM to identify sites where stimulation interfered selectively with syntactic encoding during sentence production. Fourteen patients undergoing left-hemisphere neurosurgery participated in the study. In 7 of the 14 patients, we identified nine sites where cortical stimulation interfered with syntactic encoding but did not interfere with single word processing. All nine sites were localized to the inferior frontal gyrus, mostly to the pars triangularis and opercularis. Interference with syntactic encoding took several different forms, including misassignment of arguments to grammatical roles, misassignment of nouns to verb slots, omission of function words and inflectional morphology, and various paragrammatic constructions. Our findings suggest that the left inferior frontal gyrus plays an important role in the encoding of syntactic structure during sentence production.


Asunto(s)
Lingüística , Corteza Prefrontal/fisiología , Habla/fisiología , Adulto , Anciano , Mapeo Encefálico , Craneotomía , Estimulación Eléctrica , Femenino , Humanos , Monitorización Neurofisiológica Intraoperatoria , Masculino , Persona de Mediana Edad , Corteza Prefrontal/cirugía , Percepción Visual/fisiología , Adulto Joven
9.
Neuroimage ; 171: 62-74, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29277646

RESUMEN

Spoken and written language processing streams converge in the superior temporal sulcus (STS), but the functional and anatomical nature of this convergence is not clear. We used functional MRI to quantify neural responses to spoken and written language, along with unintelligible stimuli in each modality, and employed several strategies to segregate activations on the dorsal and ventral banks of the STS. We found that intelligible and unintelligible inputs in both modalities activated the dorsal bank of the STS. The posterior dorsal bank was able to discriminate between modalities based on distributed patterns of activity, pointing to a role in encoding of phonological and orthographic word forms. The anterior dorsal bank was agnostic to input modality, suggesting that this region represents abstract lexical nodes. In the ventral bank of the STS, responses to unintelligible inputs in both modalities were attenuated, while intelligible inputs continued to drive activation, indicative of higher level semantic and syntactic processing. Our results suggest that the processing of spoken and written language converges on the posterior dorsal bank of the STS, which is the first of a heterogeneous set of language regions within the STS, with distinct functions spanning a broad range of linguistic processes.


Asunto(s)
Comprensión/fisiología , Lectura , Percepción del Habla/fisiología , Lóbulo Temporal/fisiología , Escritura , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Encefálico/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Neuroimage ; 178: 574-582, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29860083

RESUMEN

Speech sounds are encoded by distributed patterns of activity in bilateral superior temporal cortex. However, it is unclear whether speech sounds are topographically represented in cortex, or which acoustic or phonetic dimensions might be spatially mapped. Here, using functional MRI, we investigated the potential spatial representation of vowels, which are largely distinguished from one another by the frequencies of their first and second formants, i.e. peaks in their frequency spectra. This allowed us to generate clear hypotheses about the representation of specific vowels in tonotopic regions of auditory cortex. We scanned participants as they listened to multiple natural tokens of the vowels [ɑ] and [i], which we selected because their first and second formants overlap minimally. Formant-based regions of interest were defined for each vowel based on spectral analysis of the vowel stimuli and independently acquired tonotopic maps for each participant. We found that perception of [ɑ] and [i] yielded differential activation of tonotopic regions corresponding to formants of [ɑ] and [i], such that each vowel was associated with increased signal in tonotopic regions corresponding to its own formants. This pattern was observed in Heschl's gyrus and the superior temporal gyrus, in both hemispheres, and for both the first and second formants. Using linear discriminant analysis of mean signal change in formant-based regions of interest, the identity of untrained vowels was predicted with ∼73% accuracy. Our findings show that cortical encoding of vowels is scaffolded on tonotopy, a fundamental organizing principle of auditory cortex that is not language-specific.


Asunto(s)
Corteza Auditiva/fisiología , Mapeo Encefálico/métodos , Fonética , Percepción del Habla/fisiología , Estimulación Acústica , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino
11.
Hum Brain Mapp ; 39(8): 3285-3307, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29665223

RESUMEN

Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia.


Asunto(s)
Afasia/diagnóstico , Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Lenguaje , Pruebas Neuropsicológicas , Adulto , Anciano , Anciano de 80 o más Años , Afasia/etiología , Afasia/fisiopatología , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Enfermedad Crónica , Estudios de Factibilidad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología
12.
Ann Neurol ; 81(3): 430-443, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28133816

RESUMEN

OBJECTIVE: To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. METHODS: Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms. RESULTS: A clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with transactive response DNA-binding protein (TDP) inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer disease (AD) pathology in 19% of cases. Each variant was associated with 1 typical pathology; 24 of 29 (83%) svPPA showed FTLD-TDP type C, 22 of 25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants. INTERPRETATION: Each PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo. Ann Neurol 2017;81:430-443.


Asunto(s)
Enfermedad de Alzheimer , Afasia Progresiva Primaria , Degeneración Lobar Frontotemporal , Sustancia Gris/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Afasia Progresiva Primaria/clasificación , Afasia Progresiva Primaria/patología , Afasia Progresiva Primaria/fisiopatología , Atrofia/patología , Femenino , Degeneración Lobar Frontotemporal/clasificación , Degeneración Lobar Frontotemporal/patología , Degeneración Lobar Frontotemporal/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Pick/patología , Enfermedad de Pick/fisiopatología , Afasia Progresiva Primaria no Fluente/patología , Afasia Progresiva Primaria no Fluente/fisiopatología , Máquina de Vectores de Soporte , Proteínas tau/metabolismo
13.
Neurocase ; 24(1): 31-40, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29350575

RESUMEN

Phonological deficits are common in aphasia after left-hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals improve through treatment, the neural substrates supporting improvements are poorly understood. We measured brain activation during pseudoword reading in an individual through two treatment phases. Improvements were associated with greater activation in residual left dorsal language regions and bilateral regions supporting attention and effort. Gains were maintained, while activation returned to pre-treatment levels. This case demonstrates the neural support for improved phonology after damage to critical regions and that improvements may be maintained without markedly increased effort.


Asunto(s)
Agrafia/rehabilitación , Encéfalo/diagnóstico por imagen , Dislexia/rehabilitación , Imágenes en Psicoterapia/métodos , Fonética , Anciano , Agrafia/diagnóstico por imagen , Agrafia/etiología , Dislexia/diagnóstico por imagen , Dislexia/etiología , Humanos , Procesamiento de Imagen Asistido por Computador , Terapia del Lenguaje/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Tiempo de Reacción , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento
14.
Brain ; 139(11): 2994-3006, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27554388

RESUMEN

Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network.


Asunto(s)
Afasia Progresiva Primaria/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Comprensión/fisiología , Semántica , Conducta Verbal/fisiología , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Oxígeno/sangre , Reconocimiento en Psicología/fisiología
15.
J Cogn Neurosci ; 28(2): 210-22, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26544920

RESUMEN

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.


Asunto(s)
Afasia Progresiva Primaria/patología , Encéfalo/patología , Fonética , Habla , Anciano , Afasia Progresiva Primaria/clasificación , Afasia Progresiva Primaria/psicología , Femenino , Humanos , Pruebas del Lenguaje , Modelos Logísticos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Lectura , Escritura
16.
J Cogn Neurosci ; 26(5): 970-85, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24345172

RESUMEN

Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA; also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the ATLs is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA to determine which regions normally involved in syntactic processing are damaged in semantic PPA and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural MRI and fMRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that, in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, whereas anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the ATLs but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left ATL did show abnormal functionality in semantic PPA patients; however, this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the ATL in sentence processing is less likely to relate to syntactic structure-building and more likely to relate to higher-level processes such as combinatorial semantic processing.


Asunto(s)
Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/fisiopatología , Comprensión/fisiología , Lenguaje , Semántica , Lóbulo Temporal/fisiología , Estimulación Acústica/métodos , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/métodos
17.
Hum Brain Mapp ; 35(8): 4049-63, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24452906

RESUMEN

The left superior temporal sulcus (STS) has been shown in numerous functional imaging studies to be a critical region for language processing, as it is reliably activated when language comprehension is compared with acoustically matched control conditions. Studies in non-human primates have demonstrated several subdivisions in the STS, yet the precise region(s) within the STS that are important for language remain unclear, in large part because the presence of draining veins in the sulcus makes it difficult to determine whether neural activity is localized to the dorsal or ventral bank of the sulcus. We used functional MRI to localize language regions, and then acquired several additional sequences in order to account for the impact of vascular factors. A breath-holding task was used to induce hypercapnia in order to normalize voxel-wise differences in blood oxygen level-dependent (BOLD) responsivity, and veins were identified on susceptibility-weighted and T2*-weighted BOLD images, and masked out. We found that the precise locations of language areas in individual participants were strongly influenced by vascular factors, but that these vascular effects could be ameliorated by hypercapnic normalization and vein masking. After these corrections were applied, the majority of regions activated by language processing were localized to the dorsal bank of the STS.


Asunto(s)
Circulación Cerebrovascular/fisiología , Lenguaje , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/fisiología , Adulto , Algoritmos , Mapeo Encefálico , Contencion de la Respiración , Femenino , Humanos , Hipercapnia/fisiopatología , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Adulto Joven
18.
Brain ; 136(Pt 4): 1260-73, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23471694

RESUMEN

Progressive alexia is an acquired reading deficit caused by degeneration of brain regions that are essential for written word processing. Functional imaging studies have shown that early processing of the visual word form depends on a hierarchical posterior-to-anterior processing stream in occipito-temporal cortex, whereby successive areas code increasingly larger and more complex perceptual attributes of the letter string. A region located in the left lateral occipito-temporal sulcus and adjacent fusiform gyrus shows maximal selectivity for words and has been dubbed the 'visual word form area'. We studied two patients with progressive alexia in order to determine whether their reading deficits were associated with structural and/or functional abnormalities in this visual word form system. Voxel-based morphometry showed left-lateralized occipito-temporal atrophy in both patients, very mild in one, but moderate to severe in the other. The two patients, along with 10 control subjects, were scanned with functional magnetic resonance imaging as they viewed rapidly presented words, false font strings, or a fixation crosshair. This paradigm was optimized to reliably map brain regions involved in orthographic processing in individual subjects. All 10 control subjects showed a posterior-to-anterior gradient of selectivity for words, and all 10 showed a functionally defined visual word form area in the left hemisphere that was activated for words relative to false font strings. In contrast, neither of the two patients with progressive alexia showed any evidence for a selectivity gradient or for word-specific activation of the visual word form area. The patient with mild atrophy showed normal responses to both words and false font strings in the posterior part of the visual word form system, but a failure to develop selectivity for words in the more anterior part of the system. In contrast, the patient with moderate to severe atrophy showed minimal activation of any part of the visual word form system for either words or false font strings. Our results suggest that progressive alexia is associated with a dysfunctional visual word form system, with or without substantial cortical atrophy. Furthermore, these findings demonstrate that functional MRI has the potential to reveal the neural bases of cognitive deficits in neurodegenerative patients at very early stages, in some cases before the development of extensive atrophy.


Asunto(s)
Dislexia/fisiopatología , Lóbulo Occipital/patología , Lóbulo Occipital/fisiopatología , Reconocimiento Visual de Modelos/fisiología , Lóbulo Temporal/fisiopatología , Escritura , Anciano , Afasia Progresiva Primaria/patología , Afasia Progresiva Primaria/fisiopatología , Atrofia , Dislexia/patología , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Persona de Mediana Edad , Psicolingüística/métodos , Lóbulo Temporal/patología
19.
Brain ; 136(Pt 6): 1929-41, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23576128

RESUMEN

Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.


Asunto(s)
Encéfalo/fisiología , Demencia Frontotemporal/fisiopatología , Principios Morales , Red Nerviosa/fisiología , Pensamiento/fisiología , Anciano , Estudios de Cohortes , Femenino , Demencia Frontotemporal/psicología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/métodos
20.
Neurocase ; 20(1): 100-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23171151

RESUMEN

We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement. Findings support the view that left and right anterior temporal lobes serve as semantic hubs that may be affected differentially in semantic variant by early, relatively unilateral damage.


Asunto(s)
Demencia Frontotemporal/diagnóstico , Lóbulo Temporal/patología , Anciano , Femenino , Humanos , Estudios Longitudinales , Pruebas Neuropsicológicas
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