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1.
Cereb Cortex ; 33(11): 6959-6989, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36758954

RESUMO

The purpose of this study is to identify consistencies across functional neuroimaging studies regarding common and unique brain regions/networks for individuals with reading difficulties (RD) and math difficulties (MD) compared to typically developing (TD) individuals. A systematic search of the literature, utilizing multiple databases, yielded 116 functional magnetic resonance imaging and positron emission tomography studies that met the criteria. Coordinates that directly compared TD with either RD or MD were entered into GingerALE (Brainmap.org). An activation likelihood estimate (ALE) meta-analysis was conducted to examine common and unique brain regions for RD and MD. Overall, more studies examined RD (n = 96) than MD (n = 20). Across studies, overactivation for reading and math occurred in the right insula and inferior frontal gyrus for atypically developing (AD) > TD comparisons, albeit in slightly different areas of these regions; however, inherent threshold variability across imaging studies could diminish overlying regions. For TD > AD comparisons, there were no similar or overlapping brain regions. Results indicate there were domain-specific differences for RD and MD; however, there were some similarities in the ancillary recruitment of executive functioning skills. Theoretical and practical implications for researchers and educators are discussed.


Assuntos
Dislexia , Leitura , Humanos , Dislexia/patologia , Funções Verossimilhança , Encéfalo , Cognição , Imageamento por Ressonância Magnética
2.
JAMA Netw Open ; 5(10): e2236102, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36301547

RESUMO

Importance: Developmental dyslexia is a heritable learning disability affecting 7% to 10% of the general population and can have detrimental impacts on mental health and vocational potential. Individuals with dyslexia show altered functional organization of the language and reading neural networks; however, it remains unknown how early in life these neural network alterations might emerge. Objective: To determine whether the early emergence of large-scale neural functional connectivity (FC) underlying long-term language and reading development is altered in infants with a familial history of dyslexia (FHD). Design, Setting, and Participants: This cohort study included infants recruited at Boston Children's Hospital between May 2011 and February 2019. Participants underwent structural and resting-state functional magnetic resonance imaging in the Department of Radiology at Boston Children's Hospital. Infants with FHD were matched with infants without FHD based on age and sex. Data were analyzed from April 2019 to June 2021. Exposures: FHD was defined as having at least 1 first-degree relative with a dyslexia diagnosis or documented reading difficulties. Main Outcomes and Measures: Whole-brain FC patterns associated with 20 predefined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific FC patterns that differentiated between infants with vs without FHD. For classification performance estimates, 99% CIs were calculated as the classification accuracy minus chance level. Results: A total of 98 infants (mean [SD] age, 8.5 [2.3] months; 51 [52.0%] girls) were analyzed, including 35 infants with FHD and 63 infants without FHD. Multivariate pattern analyses identified distinct FC patterns between infants with vs without FHD in the left fusiform gyrus (classification accuracy, 0.55 [99% CI, 0.046-0.062]; corrected P < .001; Cohen d = 0.76). Connections linking left fusiform gyrus to regions in the frontal and parietal language and attention networks were among the paths with the highest contributions to the classification performance. Conclusions and Relevance: These findings suggest that on the group level, FHD was associated with an early onset of atypical FC of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading abilities will be essential to further elucidate the ontogenetic mechanisms underlying the development of dyslexia.


Assuntos
Mapeamento Encefálico , Dislexia , Criança , Lactente , Feminino , Humanos , Masculino , Predisposição Genética para Doença , Estudos de Coortes , Dislexia/diagnóstico por imagem , Dislexia/patologia , Leitura
3.
Ann N Y Acad Sci ; 1516(1): 222-233, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35899373

RESUMO

Handwriting is a vital skill for everyday human activities. It has a wealth of information about writers' characteristics and can hint toward underlying neurological conditions, such as Parkinson's disease, autism, dyslexia, and attention-deficit/hyperactivity disorder (ADHD). Many previous studies have reported a link between personality and individual differences in handwriting, but the evidence for the relationship tends to be anecdotal in nature. Using functional magnetic resonance imaging (fMRI), we examined whether the association between personality traits and handwriting was instantiated at the neural level. Results showed that the personality trait of conscientiousness modulated brain activation in the left premotor cortex and right inferior/middle frontal gyrus, which may reflect the impact of personality on orthography-to-grapheme transformation and executive control involved in handwriting. Such correlations were not observed in symbol-drawing or word-reading tasks, suggesting the specificity of the link between conscientiousness and handwriting in these regions. Moreover, using a connectome-based predictive modeling approach, we found that individuals' conscientiousness scores could be predicted based on handwriting-related functional brain networks, suggesting that the influence of personality on handwriting may occur within a broader network. Our findings provide neural evidence for the link between personality and handwriting processing, extending our understanding of the nature of individual differences in handwriting.


Assuntos
Conectoma , Dislexia , Encéfalo , Mapeamento Encefálico , Dislexia/patologia , Escrita Manual , Humanos , Imageamento por Ressonância Magnética/métodos , Personalidade/fisiologia
4.
Neuroimage ; 249: 118909, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35033675

RESUMO

Reading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for transmitting information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 686 children ages 5-18 using state-of-the-art neuroimaging acquisitions and processing techniques. We searched for associations between fractional anisotropy (FA) and single-word and single-nonword reading skills in children with diverse reading abilities across multiple tracts previously thought to contribute to reading. We also looked for group differences in tract FA between typically reading children and children with reading disabilities. FA of the white matter increased with age across all participants. There were no significant correlations between overall reading abilities and tract FAs across all children, and no significant group differences in tract FA between children with and without reading disabilities. There were associations between FA and nonword reading ability in older children (ages 9 and above). Higher FA in the right superior longitudinal fasciculus (SLF) and left inferior cerebellar peduncle (ICP) correlated with better nonword reading skills. These results suggest that letter-sound correspondence skills, as measured by nonword reading, are associated with greater white matter coherence among older children in these two tracts, as indexed by higher FA.


Assuntos
Imagem de Tensor de Difusão , Dislexia/patologia , Leitura , Substância Branca/anatomia & histologia , Adolescente , Criança , Pré-Escolar , Dislexia/diagnóstico por imagem , Feminino , Humanos , Masculino , Substância Branca/diagnóstico por imagem
5.
Dev Sci ; 25(2): e13160, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34278658

RESUMO

Reading disorders are common in children and can impact academic success, mental health, and career prospects. Reading is supported by network of interconnected left hemisphere brain regions, including temporo-parietal, occipito-temporal, and inferior-frontal circuits. Poor readers often show hypoactivation and reduced gray matter volumes in this reading network, with hyperactivation and increased volumes in the posterior right hemisphere. We assessed gray matter development longitudinally in pre-reading children aged 2-5 years using magnetic resonance imaging (MRI) (N = 32, 110 MRI scans; mean age: 4.40 ± 0.77 years), half of whom had a family history of reading disorder. The family history group showed slower proportional growth (relative to total brain volume) in the left supramarginal and inferior frontal gyri, and faster proportional growth in the right angular, right fusiform, and bilateral lingual gyri. This suggests delayed development of left hemisphere reading areas in children with a family history of dyslexia, along with faster growth in right homologues. This alternate development pattern may predispose the brain to later reading difficulties and may later manifest as the commonly noted compensatory mechanisms. The results of this study further shows our understanding of structural brain alterations that may form the neurological basis of reading difficulties.


Assuntos
Dislexia , Substância Cinzenta , Encéfalo/patologia , Mapeamento Encefálico/métodos , Criança , Pré-Escolar , Dislexia/patologia , Humanos , Imageamento por Ressonância Magnética/métodos
6.
Commun Biol ; 4(1): 1413, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34931059

RESUMO

For over 150 years, the study of patients with acquired alexia has fueled research aimed at disentangling the neural system critical for reading. An unreached goal, however, relates to the determination of the fiber pathways that root the different visual and linguistic processes needed for accurate word reading. In a unique series of neurosurgical patients with a tumor close to the visual word form area, we combine direct electrostimulation and population-based streamline tractography to map the disconnectivity fingerprints characterizing dissociated forms of alexia. Comprehensive analyses of disconnectivity matrices establish similarities and dissimilarities in the disconnection patterns associated with pure, phonological and lexical-semantic alexia. While disconnections of the inferior longitudinal and posterior arcuate fasciculi are common to all alexia subtypes, disconnections of the long arcuate and vertical occipital fasciculi are specific to phonological and pure alexia, respectively. These findings provide a strong anatomical background for cognitive and neurocomputational models of reading.


Assuntos
Dislexia/patologia , Leitura , Substância Branca/patologia , Adulto , Alexia Pura/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/patologia , Adulto Jovem
7.
PLoS One ; 16(12): e0259986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34910756

RESUMO

We compared the performance of dyslexic and typical readers on two perceptual tasks, the Vanderbilt Holistic Face Processing Task and the Holistic Word Processing Task. Both yield a metric of holistic processing that captures the extent to which participants automatically attend to information that is spatially nearby but irrelevant to the task at hand. Our results show, for the first time, that holistic processing of faces is comparable in dyslexic and typical readers but that dyslexic readers show greater holistic processing of words. Remarkably, we show that these metrics predict the performance of dyslexic readers on a standardized reading task, with more holistic processing in both tasks associated with higher accuracy and speed. In contrast, a more holistic style on the words task predicts less accurate reading of both words and pseudowords for typical readers. We discuss how these findings may guide our conceptualization of the visual deficit in dyslexia.


Assuntos
Dislexia/psicologia , Reconhecimento Visual de Modelos/fisiologia , Adulto , Estudos de Casos e Controles , Dislexia/patologia , Humanos , Tempo de Reação , Leitura , Adulto Jovem
8.
Sci Rep ; 11(1): 23000, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837013

RESUMO

Faces and words are traditionally assumed to be independently processed. Dyslexia is also traditionally thought to be a non-visual deficit. Counter to both ideas, face perception deficits in dyslexia have been reported. Others report no such deficits. We sought to resolve this discrepancy. 60 adults participated in the study (24 dyslexic, 36 typical readers). Feature-based processing and configural or global form processing of faces was measured with a face matching task. Opposite laterality effects in these tasks, dependent on left-right orientation of faces, supported that they tapped into separable visual mechanisms. Dyslexic readers tended to be poorer than typical readers at feature-based face matching while no differences were found for global form face matching. We conclude that word and face perception are associated when the latter requires the processing of visual features of a face, while processing the global form of faces apparently shares minimal-if any-resources with visual word processing. The current results indicate that visual word and face processing are both associated and dissociated-but this depends on what visual mechanisms are task-relevant. We suggest that reading deficits could stem from multiple factors, and that one such factor is a problem with feature-based processing of visual objects.


Assuntos
Cognição/fisiologia , Dislexia/patologia , Reconhecimento Facial/fisiologia , Leitura , Transtornos da Visão/fisiopatologia , Percepção Visual/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Auxiliares Sensoriais , Processamento de Texto , Adulto Jovem
9.
Hum Brain Mapp ; 42(14): 4580-4596, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34219304

RESUMO

The importance of (inherited) genetic impact in reading development is well established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance after controlling for a number of confounds-including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring's diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research.


Assuntos
Dislexia , Rede Nervosa , Idade Paterna , Leitura , Tálamo , Criança , Pré-Escolar , Estudos Transversais , Dislexia/diagnóstico por imagem , Dislexia/etiologia , Dislexia/patologia , Dislexia/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/crescimento & desenvolvimento , Pulvinar/anatomia & histologia , Pulvinar/diagnóstico por imagem , Pulvinar/crescimento & desenvolvimento , Tálamo/anatomia & histologia , Tálamo/diagnóstico por imagem , Tálamo/crescimento & desenvolvimento
10.
Hum Brain Mapp ; 42(14): 4497-4509, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197028

RESUMO

Primary education is the incubator for learning academic skills that help children to become a literate, communicative, and independent person. Over this learning period, nonlinear and regional changes in the brain occur, but how these changes relate to academic performance, such as reading ability, is still unclear. In the current study, we analyzed longitudinal T1 MRI data of 41 children in order to investigate typical cortical development during the early reading stage (end of kindergarten-end of grade 2) and advanced reading stage (end of grade 2-middle of grade 5), and to detect putative deviant trajectories in children with dyslexia. The structural brain change was quantified with a reliable measure that directly calculates the local morphological differences between brain images of two time points, while considering the global head growth. When applying this measure to investigate typical cortical development, we observed that left temporal and temporoparietal regions belonging to the reading network exhibited an increase during the early reading stage and stabilized during the advanced reading stage. This suggests that the natural plasticity window for reading is within the first years of primary school, hence earlier than the typical period for reading intervention. Concerning neurotrajectories in children with dyslexia compared to typical readers, we observed no differences in gray matter development of the left reading network, but we found different neurotrajectories in right IFG opercularis (during the early reading stage) and in right isthmus cingulate (during the advanced reading stage), which could reflect compensatory neural mechanisms.


Assuntos
Córtex Cerebral , Desenvolvimento Infantil , Dislexia , Rede Nervosa , Neuroimagem , Leitura , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Dislexia/diagnóstico por imagem , Dislexia/patologia , Dislexia/fisiopatologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/crescimento & desenvolvimento
11.
Neuroimage ; 237: 118087, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878382

RESUMO

Although the neural basis of dyslexia has intensively been investigated, results are still unclear about the existence of a white matter deficit in the arcuate fasciculus (AF) throughout development. To unravel this ambiguity, we examined the difference in fractional anisotropy (FA) of the AF between children developing dyslexia and children developing typical reading skills in a longitudinal sample with three MRI time points throughout reading development: the pre-reading stage (5-6 years old), the early reading stage (7-8 years old) and the advanced reading stage (9-10 years old). Applying along-the-tract analyses of white matter organization, our results confirmed that a white matter deficit existed in the left AF prior to the onset of formal reading instruction in children who developed dyslexia later on. This deficit was consistently present throughout the course of reading development. Additionally, we evaluated the use of applying a continuous approach on the participants' reading skills rather than the arbitrary categorization in individuals with or without dyslexia. Our results confirmed the predictive relation between FA and word reading measurements later in development. This study supports the use of longitudinal approaches to investigate the neural basis of the developmental process of learning to read and the application of triangulation, i.e. using multiple research approaches to help gain more insight and aiding the interpretation of obtained results.


Assuntos
Córtex Cerebral/patologia , Desenvolvimento Infantil , Imagem de Tensor de Difusão , Dislexia/patologia , Substância Branca/patologia , Córtex Cerebral/diagnóstico por imagem , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Dislexia/diagnóstico por imagem , Dislexia/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Leitura , Substância Branca/diagnóstico por imagem
12.
Hum Mol Genet ; 30(12): 1160-1171, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-33864365

RESUMO

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N = 42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N = 1825; minimum P = 0.002 for non-word reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.


Assuntos
ATPases Transportadoras de Cálcio/genética , Dislexia/genética , Predisposição Genética para Doença , Transtorno Específico de Linguagem/genética , Adenosina Trifosfatases/genética , Adolescente , Adulto , Criança , Dislexia/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Mutação de Sentido Incorreto , Linhagem , Polimorfismo de Nucleotídeo Único , Transtorno Específico de Linguagem/epidemiologia , Transtorno Específico de Linguagem/patologia , Sequenciamento do Exoma , Adulto Jovem
13.
PLoS One ; 16(3): e0249016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33760863

RESUMO

We report on developmental vowel dyslexia, a type of dyslexia that selectively affects the reading aloud of vowel letters. We identified this dyslexia in 55 Turkish-readers aged 9-10, and made an in-depth multiple-case analysis of the reading of 17 participants whose vowel dyslexia was relatively selective. These participants made significantly more vowel errors (vowel substitution, omission, migration, and addition) than age-matched controls, and significantly more errors in vowel letters than in consonants. Vowel harmony, a pivotal property of Turkish phonology, was intact and the majority of their vowel errors yielded harmonic responses. The transparent character of Turkish orthography indicates that vowel dyslexia is not related to ambiguity in vowel conversion. The dyslexia did not result from a deficit in the phonological-output stage, as the participants did not make vowel errors in nonword repetition or in repeating words they had read with a vowel error. The locus of the deficit was not in the orthographic-visual-analyzer either, as their same-different decision on words differing in vowels was intact, and so was their written-word comprehension. They made significantly more errors on nonwords than on words, indicating that their deficit was in vowel processing in the sublexical route. Given that their single-vowels conversion was intact, and that they showed an effect of the number of vowels, we conclude that their deficit is in a vowel-specific buffer in the sublexical route. They did not make vowel errors within suffixes, indicating that suffixes are converted as wholes in a separate sublexical sub-route. These results have theoretical implications for the dual-route model: they indicate that the sublexical route converts vowels and consonants separately, that the sublexical route includes a vowel buffer, and a separate morphological conversion route. The results also indicate that types of dyslexia can be detected in transparent languages given detailed error-analysis and dyslexia-relevant stimuli.


Assuntos
Dislexia/patologia , Idioma , Vocabulário , Criança , Humanos , Modelos Teóricos , Leitura , Turquia , Testes de Associação de Palavras , Redação
14.
Neuropathology ; 40(6): 559-569, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33073872

RESUMO

Tubular aggregate myopathy (TAM) is a progressive disorder characterized by muscle weakness, cramps, and myalgia. TAM clinically overlaps with Stormorken syndrome (STRMK), combining TAM with miosis, thrombocytopenia, hyposplenism, ichthyosis, short stature, and dyslexia. TAM and STRMK arise from gain-of-function mutations in STIM1 (stromal interaction molecule 1) or ORAI1, both encoding key regulators of Ca2+ homeostasis, and mutations in either gene result in excessive extracellular Ca2+ entry. The pathomechanistic similarities and differences between TAM and STRMK are only partially understood. Here we provide functional in vitro experiments demonstrating that STIM1 harboring the TAM D84G or the STRMK R304W mutation similarly cluster and exert a dominant effect on the wild-type protein. Both mutants recruit ORAI1 to the clusters, increase cytosolic Ca2+ levels, promote major nuclear import of the Ca2+ -dependent transcription factor NFAT (nuclear factor of activated T cells), and trigger the formation of circular membrane stacks. In conclusion, the analyzed TAM and STRMK mutations have a comparable impact on STIM1 protein function and downstream effects of excessive Ca2+ entry, highlighting that TAM and STRMK involve a common pathomechanism.


Assuntos
Transtornos Plaquetários/genética , Dislexia/genética , Ictiose/genética , Transtornos de Enxaqueca/genética , Miose/genética , Miopatias Congênitas Estruturais/genética , Proteínas de Neoplasias/genética , Baço/anormalidades , Molécula 1 de Interação Estromal/genética , Animais , Transtornos Plaquetários/metabolismo , Transtornos Plaquetários/patologia , Células Cultivadas , Dislexia/metabolismo , Dislexia/patologia , Eritrócitos Anormais/metabolismo , Eritrócitos Anormais/patologia , Humanos , Ictiose/metabolismo , Ictiose/patologia , Camundongos , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/patologia , Miose/metabolismo , Miose/patologia , Fadiga Muscular/genética , Mutação , Miopatias Congênitas Estruturais/metabolismo , Miopatias Congênitas Estruturais/patologia , Fatores de Transcrição NFATC/metabolismo , Proteína ORAI1/metabolismo , Baço/metabolismo , Baço/patologia , Transfecção
15.
Neurocase ; 26(6): 328-339, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33103577

RESUMO

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.


Assuntos
Apraxias/congênito , Ataxia , Hemorragia Cerebral , Síndrome de Cogan , Transtornos da Linguagem , Transtornos da Percepção , Idoso , Agnosia/etiologia , Agnosia/patologia , Agnosia/fisiopatologia , Agrafia/etiologia , Agrafia/patologia , Agrafia/fisiopatologia , Apraxias/etiologia , Apraxias/patologia , Apraxias/fisiopatologia , Ataxia/etiologia , Ataxia/patologia , Ataxia/fisiopatologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Síndrome de Cogan/etiologia , Síndrome de Cogan/patologia , Síndrome de Cogan/fisiopatologia , Dislexia/etiologia , Dislexia/patologia , Dislexia/fisiopatologia , Humanos , Transtornos da Linguagem/etiologia , Transtornos da Linguagem/patologia , Transtornos da Linguagem/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Lobo Occipital/patologia , Lobo Parietal/patologia , Transtornos da Percepção/etiologia , Transtornos da Percepção/patologia , Transtornos da Percepção/fisiopatologia , Síndrome , Lobo Temporal/patologia , Percepção do Tato/fisiologia , Percepção Visual/fisiologia
16.
Genes (Basel) ; 11(6)2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32560373

RESUMO

Dyslexia, or reading disability, is found to have a genetic basis, and several related genes have been reported. We investigated whether natural selection has acted on single nucleotide polymorphisms (SNPs) that were reported to be associated with risk/non-risk for the reading disability of Chinese characters. We applied recently developed 2D SFS-based statistics to SNP data of East Asian populations to examine whether there is any sign of selective sweep. While neutrality was not rejected for most SNPs, significant signs of selection were detected for two linkage disequilibrium (LD) regions containing the reported SNPs of GNPTAB and DCDC2. Furthermore, we searched for a selection target site among the SNPs in these LD regions, because a causal site is not necessarily a reported SNP but could instead be a tightly linked site. In both LD regions, we found candidate target sites, which may have an effect on expression regulation and have been selected, although which genes these SNPs affect remains unknown. Because most people were not engaged in reading until recently, it is unlikely that there has been selective pressure on reading ability itself. Consistent with this, our results suggest a possibility of genetic hitchhiking, whereby alleles of the reported SNPs may have increased in frequency together with the selected target, which could have functions for other genes and traits apart from reading ability.


Assuntos
Dislexia/genética , Proteínas Associadas aos Microtúbulos/genética , Seleção Genética/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Alelos , Povo Asiático , Evolução Biológica , Dislexia/patologia , Feminino , Humanos , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Leitura
17.
BMC Med Genet ; 21(1): 87, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357925

RESUMO

BACKGROUND: Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies. CASE PRESENTATION: Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. CONCLUSIONS: We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.


Assuntos
Dineínas do Axonema/genética , Dislexia/genética , Situs Inversus/genética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/patologia , Dineínas/genética , Dislexia/diagnóstico por imagem , Dislexia/patologia , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Situs Inversus/diagnóstico por imagem , Situs Inversus/patologia
18.
Hum Brain Mapp ; 41(10): 2827-2845, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32166830

RESUMO

Developmental dyslexia affects 40-60% of children with a familial risk (FHD+) compared to a general prevalence of 5-10%. Despite the increased risk, about half of FHD+ children develop typical reading abilities (FHD+Typical). Yet the underlying neural characteristics of favorable reading outcomes in at-risk children remain unknown. Utilizing a retrospective, longitudinal approach, this study examined whether putative protective neural mechanisms can be observed in FHD+Typical at the prereading stage. Functional and structural brain characteristics were examined in 47 FHD+ prereaders who subsequently developed typical (n = 35) or impaired (n = 12) reading abilities and 34 controls (FHD-Typical). Searchlight-based multivariate pattern analyses identified distinct activation patterns during phonological processing between FHD+Typical and FHD-Typical in right inferior frontal gyrus (RIFG) and left temporo-parietal cortex (LTPC) regions. Follow-up analyses on group-specific classification patterns demonstrated LTPC hypoactivation in FHD+Typical compared to FHD-Typical, suggesting this neural characteristic as an FHD+ phenotype. In contrast, RIFG showed hyperactivation in FHD+Typical than FHD-Typical, and its activation pattern was positively correlated with subsequent reading abilities in FHD+ but not controls (FHD-Typical). RIFG hyperactivation in FHD+Typical was further associated with increased interhemispheric functional and structural connectivity. These results suggest that some protective neural mechanisms are already established in FHD+Typical prereaders supporting their typical reading development.


Assuntos
Encéfalo , Desenvolvimento Infantil/fisiologia , Conectoma , Imagem de Tensor de Difusão , Dislexia , Leitura , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Dislexia/diagnóstico por imagem , Dislexia/patologia , Dislexia/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Desenvolvimento da Linguagem , Estudos Longitudinais , Masculino , Estudos Retrospectivos
19.
Behav Brain Res ; 381: 112382, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31917238

RESUMO

Prefrontal volume reductions commonly are demonstrated in ADHD, but the literature examining prefrontal volume in reading disorders (RD) is scant despite their also having executive functioning (EF) deficits. Furthermore, only a few anatomical studies have examined the frontal lobes in comorbid RD/ADHD, though they have EF deficits similar to RD and ADHD. Hence, we examined frontal gyri volume in children with RD, ADHD, RD/ADHD and controls, as well as their relationship to EF for gyri found to differ between groups. We found right inferior frontal (RIF) volume was smaller in ADHD, and smaller volume was related to worse behavioral regulation. Left superior frontal (LSF) volume was larger in RD than ADHD, and its size was negatively related to basic reading ability. Left middle frontal (LMF) volume was largest in RD/ADHD overall. Further, its volume was not related to basic reading nor behavioral regulation but was related to worse attentional control, suggesting some specificity in its EF relationship. When examining hypotheses on the etiology of RD/ADHD, RD/ADHD was commensurate with ADHD in RIF volume and both RD and ADHD in LSF volume (being midway between the groups), consistent with the common etiology hypothesis. Nevertheless, they also had an additional gyrus affected: LMF, consistent with the cognitive subtype hypothesis in its specificity to RD/ADHD. The few other frontal aMRI studies on RD/ADHD supported both hypotheses as well. Given this, future research should continue to focus on frontal morphology in its endeavors to find neurobiological contributors to the comorbidity between RD and ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Dislexia/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Dislexia/complicações , Dislexia/patologia , Dislexia/fisiopatologia , Função Executiva/fisiologia , Feminino , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia
20.
PLoS One ; 14(5): e0215560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048844

RESUMO

A child's school achievement is influenced by environmental factors. The environmental factors, when represented by socio-economic status (SES) of the family, have been demonstrated to be related to the reading skills of a child. The neural correlates of the relation between SES and reading have been less thoroughly investigated. The present study expands current research by exploring the relation between SES, quantified by paternal educational level, reading of the offspring and the structure of white matter pathways in the left hemisphere as derived from DTI-based tractography analyses. Therefore, three dorsal white matter pathways, i.e. the long, anterior and posterior segments of the arcuate fasciculus (AF), and three ventral white matter pathways, i.e. the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the uncinate fasciculus (UF), were manually dissected in the left hemisphere of 34 adolescents with a wide range of reading skills. The results demonstrated a relation between word reading, SES quantified by paternal educational level, and fractional anisotropy (FA) within the left dorsal AF segment and the left ventral UF. Thus, the present study proposes a relationship between paternal educational level and a specific white matter pathway that is important for reading, aiming to guide future research that can determine processes underlying this relationship.


Assuntos
Escolaridade , Leitura , Classe Social , Substância Branca/fisiologia , Adolescente , Dislexia/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Fatores de Risco , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem
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