RESUMEN
INTRODUCTION: Eye movement studies can uncover subtle aspects of language processing impairment in individuals with primary progressive aphasia (PPA), who may have difficulty understanding words. This study examined eye movement patterns on a word-object matching task in response to varying levels of word-knowledge in PPA. METHODS: Participants with semantic and non-semantic PPA completed an object-matching task, where a word was presented and participants then selected the corresponding pictured object from an array. Afterwards, participants defined words for trials to which they incorrectly pointed. Linear mixed-effects analyses examined fixation differences on targets and related and unrelated foils. RESULTS: On incorrectly-pointed trials, participants demonstrated greater fixation duration on related foils, demonstrating intra-category blurring. For words that could not be defined, there was similar fixation duration on related and unrelated foils, demonstrating inter-category semantic blurring. DISCUSSION: This study demonstrated that fixation patterns reflect varying levels of word knowledge in PPA.
Asunto(s)
Afasia Progresiva Primaria , Movimientos Oculares , Comprensión/fisiología , Humanos , Pruebas Neuropsicológicas , SemánticaRESUMEN
Primary progressive aphasia (PPA) is a clinical syndrome diagnosed when three core criteria are met. First, there should be a language impairment (i.e., aphasia) that interferes with the usage or comprehension of words. Second, the neurological work-up should determine that the disease is neurodegenerative, and therefore progressive. Third, the aphasia should arise in relative isolation, without equivalent deficits of comportment or episodic memory. The language impairment can be fluent or non-fluent and may or may not interfere with word comprehension. Memory for recent events is preserved although memory scores obtained in verbally mediated tests may be abnormal. This distinctive clinical pattern is most conspicuous in the initial stages of the disease, and reflects a relatively selective atrophy of the language network, usually located in the left hemisphere. There are different clinical variants of PPA, each with a characteristic pattern of atrophy. Clinicoanatomical correlations in patient with these variants have led to new insights on the organization of the large-scale language network in the human brain. For example, the left anterior temporal lobe, which was not part of the classic language network, has been shown to play a critical role in word comprehension and object naming. Furthermore, patients with PPA have shown that fluency can be dissociated from grammaticality. The underlying neuropathological diseases are heterogeneous and can include Alzheimer's disease as well as frontotemporal lobar degeneration. The clinician's task is to recognize PPA and differentiate it from other neurodegenerative phenotypes, use biomarkers to surmise the nature of the underlying neuropathology, and institute the most fitting multimodal interventions.
Asunto(s)
Humanos , Enfermedad de Alzheimer , Afasia , Afasia Progresiva Primaria , Atrofia , Biomarcadores , Encéfalo , Comprensión , Demencia , Degeneración Lobar Frontotemporal , Memoria , Memoria Episódica , Neuropatología , Fenotipo , Lóbulo TemporalRESUMEN
Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.
Asunto(s)
Anciano , Animales , Humanos , Envejecimiento , Genética , Metabolismo , Patología , Esclerosis Amiotrófica Lateral , Genética , Metabolismo , Patología , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Drosophila melanogaster , Genética , Metabolismo , Expresión Génica , Microscopía Electrónica de Rastreo , Neuronas Motoras , Metabolismo , Patología , Cuerpos Pedunculados , Metabolismo , Patología , Proteínas Mutantes , Genética , Metabolismo , Mutación , Células Fotorreceptoras de Invertebrados , Metabolismo , Patología , Plásmidos , Proteína FUS de Unión a ARN , Genética , Metabolismo , Proteínas Recombinantes de Fusión , Genética , Metabolismo , Degeneración Retiniana , Patología , TransfecciónRESUMEN
Functional magnetic resonance imaging (fMRI) was used to examine differences between children (9-12 years) and adults (21-31 years) in the distribution of brain activation during word processing. Orthographic, phonologic, semantic and syntactic tasks were used in both the auditory and visual modalities. Our two principal results were consistent with the hypothesis that development is characterized by increasing specialization. Our first analysis compared activation in children versus adults separately for each modality. Adults showed more activation than children in the unimodal visual areas of middle temporal gyrus and fusiform gyrus for processing written word forms and in the unimodal auditory areas of superior temporal gyrus for processing spoken word forms. Children showed more activation than adults for written word forms in posterior heteromodal regions (Wernicke's area), presumably for the integration of orthographic and phonologic word forms. Our second analysis compared activation in the visual versus auditory modality separately for children and adults. Children showed primarily overlap of activation in brain regions for the visual and auditory tasks. Adults showed selective activation in the unimodal auditory areas of superior temporal gyrus when processing spoken word forms and selective activation in the unimodal visual areas of middle temporal gyrus and fusiform gyrus when processing written word forms.