Primary Progressive aphasia (PPA) is a disorder characterized by gradual decline in language functions, with relative sparing of other cognitive abilities. This behavioral profile results from neurodegenerative disease that preferentially affects language cortex. As is the case in aphasia resulting from stroke, any of several critical language processing domains may be affected in PPA, including syntax, semantics, phonology, and orthography. In stroke-induced aphasia, traditional lesion mapping approaches have provided important insight into the localization of cortical regions supporting these domains. Specifically, left perisylvian cortex has been implicated in syntactic and phonological aspects of language, whereas left extrasylvian cortical regions are associated with lexical-semantic and orthographic functions. The goal of the present study was to seek converging evidence for the role of left hemisphere cortical regions in language using a voxel-based imaging technique in individuals with PPA. Fifteen individuals with progressive aphasia and fifteen normal controls were given a comprehensive language battery comprising tasks in the domains of syntax, semantics, phonology, and orthography. A subset of patients and all normal controls underwent high-resolution structural MRI scanning. Voxel-based morphometry (VBM) was used to characterize patterns of regional cortical atrophy in the patients relative to controls and to correlate language tasks with gray matter volumes. Results confirm a key role for left perisylvian cortex in phonological and syntactic processes, and indicate that left temporal regions are critically involved in semantic processes. Findings shed light on the veracity of the "primary systems" hypothesis of written language, which posits that written language impairments arise from core cognitive deficits affecting semantic and phonological systems.

Orientador: Rosana do Carmo Novaes Pinto / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Estudos da Linguagem / Made available in DSpace on 2018-08-21T11:43:18Z (GMT). No. of bitstreams: 1 Mazuchelli_LarissaPicinato_M.pdf: 6512450 bytes, checksum: 12e5034b7c0e50fcb0d9ea53f571bdf4 (MD5) Previous issue date: 2012 / Resumo: Ao retomarmos a história da afasiologia, observamos que a linguagem oral, até o século XIX, era reduzida a um ato motor e a escrita era vista unicamente como simulacro da fala. Essas concepções ainda estão presentes, contudo, na literatura neurolinguística tradicional, que não apenas dicotomiza a relação entre oralidade e escrita, mas baseia-se em características de uma escrita normativa padrão para avaliar a linguagem de sujeitos afásicos - geralmente de forma superficial e com a consequente patologização de fenômenos que caracterizam processos normais. Na contramão dessas tendências, este estudo de caso fundamenta-se na Neurolinguística de orientação enunciativo-discursiva, em que a linguagem é concebida como um fenômeno sócio-histórico, uma atividade humana, lugar de interação e interlocução de sujeitos, indeterminada, incompleta e passível de (re)interpretação, em que tanto o sujeito quanto ela própria se constituem em um movimento dinâmico. Tendo esses princípios como cenário, o objetivo deste trabalho é discutir o impacto dos episódios neurológicos na vida do sujeito AJ que há mais de dez anos dribla as dificuldades impostas por uma afasia progressiva - assim caracterizada uma vez que prevalecem os indícios do agravamento dos sinais (sintomas) reconhecidamente relacionados ao chamado "declínio cognitivo", na literatura neuropsicológica. A reflexão, realizada por meio da análise qualitativa das produções escritas anteriores aos eventos neurológicos de AJ e de suas produções orais e escritas posteriores a eles - nas sessões de atendimento individual e coletivo do Grupo III do CCA (Centro de Convivência de Afásicos) -, trata (i) do efeito das práticas sociais com a linguagem (especialmente com as atividades de leitura e escrita) na (re)organização linguístico-cognitiva, o que possibilita, ainda que sob o impacto da afasia e do severo comprometimento cognitivo, que AJ se mantenha na língua(gem) e nas relações sociais; (ii) da inter-relação entre oralidade e escrita, que tem maior visibilidade em um caso-limite como o de AJ, para quem a escrita é lugar de (re)encontros e ponto de apoio para seu querer-dizer. Assim, buscamos contribuir para o desenvolvimento teórico acerca do funcionamento da linguagem nas patologias e para o acompanhamento terapêutico de sujeitos com comprometimentos linguísticocognitivos / Abstract: Considering the history of aphasiology, we observe that the oral language, up to the 19th century, was reduced to a motor act, while writing was seen as a simulacrum of the speech. Such concepts are still present, however, in the traditional neurolinguistics literature, which not only dichotomizes the relation between orality and writing, but is based on characteristics of a standard normative writing to evaluate the language of aphasic subjects - generally in a superficial way and with the consequent act of considering pathological phenomena that characterize normal processes. Opposing such tendencies, this case study is based on the discursive-enunciative Neurolinguistics, which conceives language as a socio-historic phenomenon, a human activity, locus of interaction and interlocution of subjects, indeterminate, incomplete and capable of (re)interpretation, in which both subject and the language constitute each other in a dynamic movement. Having these principles as scenery, the objective of this work is discuss the impact of the neurologic episodes in AJ's life, who has been struggling, for over ten years, with the difficulties imposed by the so-called progressive aphasia - characterized by the continuous aggravation of the signs (symptoms) and by being closely related to "cognitive decline" in the neuropsychological literature. The research - guided by a qualitative analysis of AJ's writings produced before the neurological events, and of his oral and written productions after the strokes in individual and collective sessions of the Group III of CCA (Centro de Convivência de Afásicos) - discusses (i) the effect of social practices with language (especially with the activities of reading and writing) in the cognitive-linguistic (re)organization, which enables AJ, despite the impact of the aphasia and of the severe cognitive compromising, to dwell in the language and in social relations; (ii) the interrelation between orality and writing, which has higher visibility in a limit-case as AJ's, to whom writing is the locus of (re)encounter and as a keystone to his will of speech. Thus, we aim to contribute to the theoretical development of language functioning in pathologies and to the therapeutic follow-up of subjects with cognitive-linguistic compromising / Mestrado / Linguistica / Mestra em Linguística

Background: Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by impairments in language. The presence of Alzheimer disease (AD) neuropathology has been observed in approximately 40% of PPA cases. Cross-sectional and longitudinal features of cortical atrophy in PPA are emerging but less is known about the integrity of subcortical structures, particularly the thalamus. As a major relay station in the brain, the thalamus is implicated in language functioning given its reciprocal connections with perisylvian regions in the cortex. High-dimensional brain mapping was used to characterize thalamic morphology in individuals with and without non-semantic PPA. Further, shape differences were compared between PPA participants with suspected AD pathology (PPAAβ +) and those without suspected AD pathology (PPAAβ -) as determined by amyloid PET scans. The relationship between shape and specific language deficits were also investigated. Method: Thalamic integrity was examined in 57 PPA participants relative to cognitively healthy controls (N=44) with similar demographics. MR scans were acquired using high-resolution T1-weighted MPRAGE volumes following the ADNI protocol. Thalamic shape features were estimated using Large Deformation Diffeomorphic Metric Mapping. Thalamic nuclei of interest included mediodorsal, pulvinar, and anterior regions. General linear models compared differences in thalamic shape between groups. Pearson models characterized relationships between thalamic nuclei and language function. Results: After controlling for whole brain volume, thalamic volume did not differ between groups [F(1, 99)=0.80, p=0.80]. However, PPA participants exhibited significant bilateral inward shape deformation in dorsal and ventral regions that extended in an anterior to posterior fashion, and unilateral outward deformation in medial and lateral regions only in the left thalamus relative to controls [F(9, 91)=5.75, p<0.001, Wilk's Λ=0.64]. There were no shape differences between PPAAβ + and PPAAβ – groups. Pearson models revealed significant correlations between confrontation naming and shape deformation in the left pulvinar (r=0.59, p<0.01) and left anterior (r=0.55, p<0.01) thalamic nuclei for the PPAAβ + group only, such that lower language scores reflected greater localized volume loss. Conclusions: In the absence of volumetric differences, shape measures were able to capture unique aspects of localized morphologic differences in PPA that corresponded to worse naming performance only in those with suspected AD pathology. Thalamic changes appear to be a contributing and unrecognized component to the presentation and language characterization of PPA.

This study used an item-based approach to explore the full range of lexical-semantic (word frequency and imageability) and sublexical characteristics (regularity and consistency) of stimulus items. Oral reading and spelling-to-dictation data from 72 adults with acquired alexia/agraphia due to stroke or progressive aphasia were analyzed to determine unique influences of lexical-semantic and sublexical variables on performance. Multiple regression analyses were performed for each etiology and lesion group (i.e., perisylvian stoke, extrasylvian stroke, perisylvian atrophy, and extrasylvian atrophy). As expected, word frequency had a significant influence on reading and spelling performance in almost all contexts. Of particular interest was the consistent finding that written language performance associated with left perisylvian damage was moderated primarily by lexical-semantic features of stimuli (frequency and imageability), whereas performance by those with left extrasylvian damage was strongly influenced by sublexical features of sound-spelling regularity and, to a lesser extent, consistency.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Introdução: Indíviduos com danos cerebrais podem apresentar dissociação na produção de verbos e substantivos. Há uma maior diversidade de transtornos neurológicos que apresentam prejuízo na produção de verbos do que de substantivos, e esses transtornos normalmente apresentam danos em circuitos cerebrais frontais. No entanto, pouco se sabe sobre a natureza do prejuízo na produção de verbos em cada transtorno neurológico. Objetivo: A presente tese de doutorado teve como objetivo investigar a produção de verbos em diferentes doenças neurodegenerativas e no envelhecimento normal através das tarefas de fluência e nomeação de verbos. Métodos: para atingir o objetivo geral, foram realizados três estudos que originaram três artigos científicos. O primeiro artigo realizou uma adaptação da tarefa de fluência de verbos para o português brasileiro, obteve a performance de 62 brasileiros idosos saudáveis para esta tarefa e a influência de fatores demográficos, clínicos e da aplicação de outras tarefas de fluência verbal previamente à fluência de verbos. O segundo artigo investigou a natureza dos déficits da produção de verbos na doença de Alzheimer (DA). Para isso 35 pacientes com DA em fase leve e moderada foram avaliados para as tarefas de fluência e nomeação de verbos, assim como 35 idosos saudáveis (controles). Também analisou-se a influência da frequência das palavras nas tarefas estudadas. O terceiro artigo, investigou a natureza dos déficits na produção de verbos na Afasia Progressiva Primária (APP) não-fluente. Foram avaliados 12 pacientes com APP não-fluente e 9 sujeitos controle. Todos partcipantes foram avaliados através de tarefas de nomeação e fluência de verbos e de substantivos. Um efeito de manipulabilidade foi estudado na tarefa de nomeação. Correlatos neurais foram investigados utilizado a técnica de Voxel Based Morphometry (VBM) a partir de imagens de ressonância magnética (RM) estrutural dos pacientes. Resultados: No primeiro artigo obteve-se a performance dos idosos saudáveis na fluência de verbos (11,73±5,80), a correlação com a escolaridade (r=0,616), MEEM escore total (r=0,399), MEEM Atenção e Cálculo (r=0,393), e MEEM Linguagem (r=0,322). Não houve influência da aplicação prévia de tarefas de fluência verbal na fuência de verbos. No segundo artigo, os pacientes com DA mostraram prejuízo tanto na tarefa de nomeação de verbos (p<0,000; F=36,983) quanto na fluência de verbos (p<0,000; F=21,460), porém a primeira foi mais comprometida que a segunda. A performance dos pacientes com DA na nomeação de verbos foi influenciada pela severidade da doença e pela frequência das palavras. No terceiro artigo, os pacientes com APP não-fluente foram comprometidos em todas tarefas de nomeação e de fluência verbal, porém foram significativamente piores em verbos do que em substantivos. Não houve efeito de manipulabilidade. As áreas atróficas Broadmann 44 (p<0,001) e giro pré-central (p<0,001) se correlacionaram com o prejuízo na nomeação de verbos, enquanto as áreas atróficas 44 e 45 de Broadman (p<0,001, ambas) se correlacionaram com o prejuízo na fluência de verbos. Conclusões: Nossos achados indicam que o prejuízo na produção de verbos parece ter uma natureza predominantemente semântica na DA e prodominantemente gramatical na APP não fluente. As evidências levantam questões importantes também para a neurobiologia da linguagem. / Background: Individuals with brain damage may show dissociation in the verb and noun production. There is a larger diversity of neurological disorders that show impairment in verbs rather in nouns, and these disorders use to present damage in the frontal brain circuits. However, little is known about the nature of the verb production impairment in each one of these neurological disorders. Objective: The current doctoral thesis had the aim of investigating the verb production in different neurodegenerative diseases and in the normal elderly, using verb fluency and verb naming tasks. Methods: to reach the main aim, we carried out three studies that resulted in three articles. In the first article we adapted the verb fluency task for Brazilian Portuguese, we obtained the performance of 62 healthy elderly people for this task, and we verified the influence of demographic and clinical factors as well as of the previous application of other verbal fluency tasks. The second article investigated the nature of the verb production deficits in the Alzheimer’s disease (AD). Thirty-five mild and moderate AD patients and 35 healthy controls were evaluated for verb fluency and verb naming tasks. It also analyzed the influence of word frequency in the used tasks. The third article investigated the nature of verb production deficits in the nonfluent variant of Primary Progressive Aphasia (nfPPA). Twelve patients with nfPPA and 9 healthy controls were evaluated for verb and noun fluency and naming tasks. A manipulability effect was studied in the naming task. Neural correlates were investigated by Voxel Based Morphometry (VBM) of structural Magnetic Ressonance Imaging (MRI) of the patients. Results: The first article obtained the healthy elderly people performance for verb fluency (11.73±5.80), a correlation with education (r=0.616), MMSE total score (r=0.399), MMSE Attention and Calculation (r=0.393), and with MMSE Language (r=0.322). There was no influence of previous application of verbal fluency tasks on the verb fluency. In the second article, the AD patients showed deficits in the verb naming (p<0.000; F=36.983) and in the verb fluency (p<0.000; F=21.460), however the first task was more impaired than the second one. The AD patients performance in the verb naming was influenced by the disease severity and by word frequency. In the third article, the nfPPA patients were impaired in all naming and fluency tasks, however they were significantly worse in verbs than in nouns. There was no effect of manipulability. Atrophy on BA 44 (p<0.001) and on precentral gyrus (p<0.001) correlated with impairment in verb naming. Atrophy on BA 44 and 45 (p<0.001 for both) correlated with impairment in verb fluency. Conclusions: Our findings indicate the verb production deficits seem to have a more predominant semantic nature in AD and more predominant grammatical nature in nfPPA. This evidence brings up important questions for the neurobiology of language.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Background: The presence of AD pathology can result in diverse behavioral phenotypes, including the typical amnestic variant characterized by memory deficits, and an atypical aphasic variant characterized by language deficits. Previous research has identified unique cortical atrophy patterns in each phenotype, though less focus has been drawn to subcortical involvement. The current study sought to dissociate these behavioral phenotypes by characterizing their thalamic volume and shape features using high-dimensional brain mapping procedures. Relationships between brain metrics and specific language and memory deficits were also investigated in aphasic AD and amnestic AD, respectively. Method: Thalamic integrity was examined in aphasic AD (n = 25), amnestic AD (n = 21), and healthy control participants (n = 44). Age and supratentorial volume (STV) were used as covariates in all analyses. MR scans were acquired using high-resolution T1-weighted MPRAGE volumes following the ADNI protocol. Thalamic shape features were estimated using Large Deformation Diffeomorphic Metric Mapping. General linear models compared differences in thalamic shape between groups. Pearson correlation coefficients characterized relationships between thalamic nuclei (pulvinar, anterior, and mediodorsal) and language and memory performance in aphasic AD and amnestic AD, respectively. Results: After controlling for age and STV, thalamic volume did not differ between groups [F (2,85) = 2.55, p = 08]. However, AD phenotypes exhibited bilateral inward shape deformation in dorsal and ventral regions extending in an anterior to posterior fashion [left: F(20, 154) = 2.61, p < .001; right: F(20,154)= 2.26, p < .01]. Amnestic AD demonstrated right ventrolateral localized volume loss relative to aphasic AD. Pearson models revealed lower confrontation naming was correlated with localized volume loss of bilateral pulvinar (left: r = .59, p < .01; right: r = .55, p < .01), and bilateral anterior (left: r = .50, p = .01; right: r = .49, p = .01) thalamic nuclei for aphasic AD; lower delayed recall was significantly correlated with localized volume loss in left anterior (r = .46, p = .04) thalamic nuclei in amnestic AD. Conclusions: In the absence of volumetric differences, shape measures captured distinct patterns of localized volume loss in aphasic AD and amnestic AD behavioral phenotypes relative to control participants. Comparisons of AD variants demonstrated inward deformation in amnestic AD, particularly in right ventrolateral regions. Thalamic changes appear to be implicated in AD pathology, with relationships to the expected cognitive impairments, although thalamic atrophy patterns are unable to fully dissociate behavioral phenotypes.

Η παρούσα εργασία εστιάζει στον τρόπο επεξεργασίας των σύνθετων λέξεων της Νέας Ελληνικής (ΝΕ) στην Πρωτοπαθή Προοδευτική Αφασία με αγραμματικό λόγο (ΠΠΑ-α). Οι μέχρι τώρα έρευνες επικεντρώνονται κυρίως σε κλινικές περι- πτώσεις αφασίας από κάποια εστιακή εγκεφαλική βλάβη (ΕΑ), ενώ η ΠΠΑ δεν έχει μελετηθεί ως προς το ζήτημα αυτό τόσο στη ΝΕ όσο και διαγλωσσικά. Στόχο, λοι- πόν, της συγκεκριμένης εργασίας αποτελεί η εξέταση του κατά πόσο ελληνόφωνοι ασθενείς με ΠΠΑ-α παρουσιάζουν ελλείμματα στην κατονομασία σύνθετων λέξεων. Μέθοδος: Διεξαγωγή πειράματος κατονομασίας μέσω ορισμού (naming on definition task), το οποίο αφορά την κατονομασία σύνθετων λέξεων της ΝΕ. Συμμετέχοντες: 2 ΠΠΑ-α ασθενείς (ο πρώτος σε πιο πρώιμο στάδιο της ΠΠΑ-α σε σχέση με το δεύτερο) και 2 άτομα που συνιστούν την ομάδα ελέγχου (controls). Πειραματικό υλικό: 71 σύνθετα της ΝΕ, 45 υποτακτικά (π.χ. μολυβοθήκη, μαυροπί- νακας, σιγοτραγουδώ), 15 παρατακτικά (π.χ. αλατοπίπερο, βορειοδυτικός) και 11 εξωκεντρικά (π.χ. κοκκινομάλλης, κακόγουστος).Υποθέσεις: Σύμφωνα με τα πορίσματα της τρέχουσας βιβλιογραφίας, ασθενείς με αγραμματικού τύπου ΕΑ και ΠΠΑ-α εμφανίζουν παρόμοια επίδοση σε πειράματα που ελέγχουν τη μορφοσύνταξη (Thompson et al.). Έτσι, αναμένεται να έχουν εξί- σου παρόμοια επίδοση και όσον αφορά την επεξεργασία συνθέτων, αφού η σύνθεση αποτελεί μία αμιγώς μορφολογική διαδικασία. Βάσει του παραπάνω παραλληλι- σμού, υποθέτουμε πως οι ΠΠΑ-α ασθενείς θα κατονομάζουν ευκολότερα τα σημα- σιολογικά διαφανή σύνθετα (πρώτη υπόθεση), θα διατηρούν τη γνώση της δομής του συνθέτου (δεύτερη υπόθεση), θα διατηρούν τα όρια των επιμέρους συστατικών σε πιθανά λάθη υποκατάστασης ή παράλειψης (τρίτη υπόθεση), και θα προβαίνουν σε ανάκληση του συνθέτου μέσω τεμαχισμού στα επιμέρους συστατικά του (τέταρτηυπόθεση). Τέλος, αν το συστατικό-κεφαλή έχει κάποιο βασικό ρόλο στη διαδικασία της κατονομασίας, αναμένονται συστηματικά περισσότερα λάθη σε αυτό το συστα- τικό (πέμπτη υπόθεση). Ακόμη, στο επίκεντρο του ενδιαφέροντος βρίσκονται και κάποια επιπλέον ερωτήματα που αφορούν το αν και κατά πόσο υπάρχει όντως σύ- γκλιση μεταξύ της ΠΠΑ-α και της ΕΑ-α στην κατονομασία σύνθετων λέξεων, το αν υπάρχει συσχέτιση μεταξύ του είδους/αριθμού των λαθών και του τύπου συνθέτου και το αν υφίστανται πρόβλημα με συστατικά συγκεκριμένης γραμματικής κατηγο- ρίας. Αποτελέσματα: Τα αποτελέσματα του πειράματος ανέδειξαν σημαντικές διαφορές στην επίδοση των δύο ασθενών. Ειδικότερα, ο πρώτος ασθενης είχε περισσότερα λάθη υποκατάστασης, τα οποία σηματοδοτούν επίγνωση της σύνθετης δομής και ανάκληση του συνθέτου μέσω τεμαχισμού στα επιμέρους συστατικά του. Αντίθετα, η δεύτερη ασθενής είχε περισσότερα λάθη περίφρασης και απάντησης με μία λέξη- λέξημα, ενώ ο στόχος ήταν η απάντηση με σύνθετη λέξη. Έτσι, τα λάθη της δεύ- τερης ασθενούς παραπέμπουν σε μη επίγνωση της σύνθετης δομής και σε μία πιο ολιστική διαδικασία ανάκλησης του συνθέτου. Τέλος, τα περισσότερα λάθη και των δύο ασθενών έγιναν σε υποτακτικά σύνθετα της γραμματικής κατηγορίας του ονό- ματος, ενώ δεν εντοπίστηκε επίδραση τόσο της σημασιολογικής διαφάνειας όσο και της μορφολογικής κεφαλής. Συμπεράσματα: Από την ανάλυση των αποτελεσμάτων γίνεται σαφές πως το στά- διο της διαταραχής καθορίζει και το είδος των γλωσσικών ελλειμμάτων. Συγκεκρι- μένα, στα πρώιμα στάδια της ΠΠΑ-α εμφανίζονται γλωσσικά ελλείμματα τα οποία συγκλίνουν με αυτά της ΕΑ-α, ενώ σε μετέπειτα στάδια η ικανότητα κατονομασίας πλήττεται σοβαρά διαμορφώνοντας ένα ιδιαίτερο κλινικό προφίλ, το οποίο δεν φαί- νεται να συγκλίνει ξεκάθαρα με κάποιον άλλο παθολογικό πληθυσμό. Αναλυτικό- τερα, στα αρχικά στάδια το πρόβλημα εδράζεται στην ενεργοποίηση της φωνολο- γικής μορφής της λέξης, ενώ οι μορφολογικοί κανόνες φαίνεται ότι διατηρούνται (γνώση της σύνθετης δομής, ορίων των συστατικών). Αντίθετα, σε μετέπειτα στά- δια το πρόβλημα εντοπίζεται στην ενεργοποίηση τόσο της φωνολογικής όσο και της μορφολογικής δομής του συνθέτου. Σε ό,τι αφορά τα υποτακτικά σύνθετα, η αυξη- μένη δυσκολία που δημιουργούν μπορεί να συσχετιστεί με τη λειτουργική σχέση των επιμέρους συστατικών τους. Εν κατακλείδι, η παρούσα εργασία αποτελεί μία πρώτη προσπάθεια μελέτης της σύνθεσης στην ΠΠΑ-α. Η ανάλυση των αποτελεσμάτων έφερε στο φως μία σειρά από γλωσσικά ελλείμματα, τα οποία αναμένεται να ελεγχθούν σε μεγαλύτερο δείγμα ΠΠΑ-α ασθενών για τον καθορισμό ασφαλέστερων συμπερασμάτων. / The present study is focused on the agrammatic variant of Primary Progressive Aphasia (PPA-a), which is a language impairment caused by neurodegenerative disease and characterized by difficulties in processing the grammatical aspects of speech (Mesulam, 2013). PPA-a has not examined about the grammatical deficits in Modern Greek (MG). Therefore, the aim of the present study is to examine if the Greek-speaking individuals with PPA-a have problems in naming compound words in MG. Procedure: Naming definition task of compound words in MG. Participants: Two patients with PPA-a (the first patient is in earlier stage of the disease than the other patient). Stimulus set: 71 compounds in MG, 45 subordinate compounds (e.g. [molivo’θici]>pencil case, [mavro’pinakas]>blackboard), 15 coordinate compounds (e.g. [alato’pipero]>salt and pepper, [vorioδiti’kos]>northwest) and 11 exocentric compounds (e.g. [kokkino’malis]>redhead, [ka’koγustos]>vulgar/tasteless). Hypotheses: According to the recent bibliography, agrammatic patients caused by stroke (StrAgr) and PPA-a patients have common performance in tasks which examine the morphosyntax (Thompson et al. 2013). So, PPA-a is expected to have the same deficits with StrAgr in naming compounds, given that compounding is a pure morphological procedure. Specifically, we expected compound effect, semantic transparency effect and lexical access through decomposition. Results: The error analysis showed differences in the performance of the two patients respect to the stage of the disease. Specifically, in the early stage substitution errors were occurred, supporting compound effect and a view of lexical access through decomposition. On the contrary, noncomposed semantic paraphasias and single words errors were occurred mainly at a later stage , indicating a more holistic access. Finally, the most errors were in subordinate compounds, whereas no effect of headedness and semantic transparency were found. Discussion: The results produce clear evidence that the stage of the PPA-a can affect the kind of the linguistic deficits. Specifically, in the initial stages, the linguistic deficits resemble with those of StrAgr patients with problems in the activation of the phonological form of the compound, whereas the morphological rules are intact. On the other hand, the naming competence is more impaired and distinctly different from other pathological populations at a later stage. Specifically, there are problems in the activation of both the phonological and the morphological compound forms. Finally, the increased difficulty with subordinate compounds will be correlated with the grammatical relations holding between the constituents.