Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 108
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Cereb Cortex ; 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240317

RESUMO

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

3.
Neuroimage ; 200: 704-705, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30959191
4.
Genes Brain Behav ; 18(5): e12572, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30950222

RESUMO

Most people have left-hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic-developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole-genome-sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left-right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population-genetic data sets, as well as 34 subjects (14 left-handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un-mutated in controls. A hypothesis derived from invertebrate mechanisms of left-right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.

5.
Brain ; 142(4): 1009-1023, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30859180

RESUMO

We report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, nWESextremes = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (nWES = 2,868, nWESextremes = 956) and genome-wide genotypes (nGW = 9924, nGWextremes = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (Pdiscovery = 8.21 × 10-5, Preplication = 5.25 × 10-3, Pcombined = 4.72 × 10-5) and of NOTCH3 using gene-based tests (Pdiscovery = 1.61 × 10-2, Preplication = 3.99 × 10-2, Pcombined = 5.31 × 10-3). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease.

6.
Neurology ; 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651383

RESUMO

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

7.
Brain Struct Funct ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30460551

RESUMO

With the advances in diffusion MRI and tractography, numerous atlases of the human pyramidal tract (PyT) have been proposed, but the inherent limitation of tractography to resolve crossing bundles within the centrum semiovale has so far prevented the complete description of the most lateral PyT projections. Here, we combined a precise manual positioning of individual subcortical regions of interest along the descending pathway of the PyT with a new bundle-specific tractography algorithm. This later is based on anatomical priors to improve streamlines tracking in crossing areas. We then extracted both left and right PyT in a large cohort of 410 healthy participants and built a population-based atlas of the whole-fanning PyT with a complete description of its most corticolateral projections. Clinical applications are envisaged, the whole-fanning PyT atlas being likely a better marker of corticospinal integrity metrics than those currently used within the frame of prediction of poststroke motor recovery. The present population-based PyT, freely available, provides an interesting tool for clinical applications to locate specific PyT damage and its impact to the short- and long-term motor recovery after stroke.

8.
Mol Psychiatry ; 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463886

RESUMO

Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech.

9.
Stroke ; 49(2): 282-287, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29311265

RESUMO

BACKGROUND AND PURPOSE: The genetic contribution to dilated perivascular space (dPVS) burden-an emerging MRI marker of cerebral small vessel disease-is unknown. We measured the heritability of dPVS burden and its shared heritability with other MRI markers of cerebral small vessel disease. METHODS: The study sample comprised 1597 participants from the population-based Three City (3C) Dijon Study, with brain MRI and genome-wide genotyping (mean age, 72.8±4.1 years; 61% women). dPVS burden and lacunar brain infarcts were rated on a semiquantitative scale, whereas an automated algorithm generated white matter hyperintensity volume (WMHV). We estimated dPVS burden heritability and shared heritability with WMHV and lacunar brain infarcts using the genome-wide complex trait analysis tool, on unrelated participants, adjusting for age, sex, intracranial volume, and principal components of population stratification. RESULTS: dPVS burden was significantly correlated with WMHV and lacunar brain infarcts, the strongest correlation being found between WMHV and dPVS in basal ganglia. Heritability estimates were h2=0.59±0.24 (P=0.007) for dPVS burden, h2=0.54±0.24 (P=0.010) for WMHV, and h2=0.48±0.81 (P=0.278) for lacunar brain infarcts. We found a nonsignificant trend toward shared heritability between dPVS and WMHV (rg=0.41±0.28; P=0.096), which seemed driven by dPVS in basal ganglia (rg=0.72±0.61; P=0.126) and not dPVS in white matter (rg=-0.10±0.36; P=0.393). A genetic risk score for WMHV based on published loci was associated with increased dPVS burden in basal ganglia (P=0.031). CONCLUSIONS: We provide evidence for important genetic contribution to dPVS burden in older community-dwelling people, some of which may be shared with WMHV. Differential heritability patterns for dPVS in white matter and basal ganglia suggest at least partly distinct underlying biological processes.


Assuntos
Encéfalo/irrigação sanguínea , Doenças de Pequenos Vasos Cerebrais/genética , Acidente Vascular Cerebral Lacunar/genética , Idoso , Idoso de 80 Anos ou mais , Doenças de Pequenos Vasos Cerebrais/complicações , Feminino , Genótipo , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Fatores de Risco , Acidente Vascular Cerebral Lacunar/complicações
10.
Brain Struct Funct ; 223(3): 1217-1228, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29101522

RESUMO

We investigated the association between the left planum temporale (PT) surface area or asymmetry and the hemispheric or regional functional asymmetries during language production and perception tasks in 287 healthy adults (BIL&GIN) who were matched for sex and handedness. The measurements of the PT surface area were performed after manually delineating the region using brain magnetic resonance images (MRI) and considering the Heschl's gyrus (HG) duplication pattern; the measurements either included (PTtot) or did not include (PTpost) the second gyrus. A region encompassing both the PT and HG (HGPT) was also studied. Regardless of the ROI measured, 80% of the sample had a positive left minus right PT asymmetry. We first tested whether the PTtot, PTpost and HGPT surface areas in the left or right hemispheres or PT asymmetries differed in groups of individuals varying in language lateralization by assessing their hemispheric index during a sentence production minus word list production task. We then investigated the association between these different measures of the PT anatomy and the regional asymmetries measured during the task. Regardless of the anatomical definition used, we observed no correlations between the left surface areas or asymmetries and the hemispheric or regional functional asymmetries during the language production task. We then performed a similar analysis using the same sample measuring language functional lateralization during speech listening tasks (i.e., listening to sentences and lists of words). Although the hemispheric lateralization during speech listening was not correlated with the left PTtot, PTpost or HGPT surface areas or the PT asymmetries, significant positive correlations were observed between the asymmetries in these regions and the regional functional asymmetries measured in areas adjacent to the end of the Sylvian fissure while participants listened to the word lists or sentences. The PT asymmetry thus appears to be associated with the local functional asymmetries in auditory areas but is not a marker of inter-individual variability in language dominance.

11.
Hum Brain Mapp ; 38(12): 5871-5889, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28868791

RESUMO

We used a Support Vector Machine (SVM) classifier to assess hemispheric pattern of language dominance of 47 individuals categorized as non-typical for language from their hemispheric functional laterality index (HFLI) measured on a sentence minus word-list production fMRI-BOLD contrast map. The SVM classifier was trained at discriminating between Dominant and Non-Dominant hemispheric language production activation pattern on a group of 250 participants previously identified as Typicals (HFLI strongly leftward). Then, SVM was applied to each hemispheric language activation pattern of 47 non-typical individuals. The results showed that at least one hemisphere (left or right) was found to be Dominant in every, except 3 individuals, indicating that the "dominant" type of functional organization is the most frequent in non-typicals. Specifically, left hemisphere dominance was predicted in all non-typical right-handers (RH) and in 57.4% of non-typical left-handers (LH). When both hemisphere classifications were jointly considered, four types of brain patterns were observed. The most often predicted pattern (51%) was left-dominant (Dominant left-hemisphere and Non-Dominant right-hemisphere), followed by right-dominant (23%, Dominant right-hemisphere and Non-Dominant left-hemisphere) and co-dominant (19%, 2 Dominant hemispheres) patterns. Co-non-dominant was rare (6%, 2 Non-Dominant hemispheres), but was normal variants of hemispheric specialization. In RH, only left-dominant (72%) and co-dominant patterns were detected, while for LH, all types were found, although with different occurrences. Among the 10 LH with a strong rightward HFLI, 8 had a right-dominant brain pattern. Whole-brain analysis of the right-dominant pattern group confirmed that it exhibited a functional organization strictly mirroring that of left-dominant pattern group. Hum Brain Mapp 38:5871-5889, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Lateralidade Funcional , Linguagem , Imagem por Ressonância Magnética , Máquina de Vetores de Suporte , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
12.
Am J Geriatr Psychiatry ; 25(12): 1311-1321, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28688824

RESUMO

OBJECTIVE: Evidence is mixed as to whether periventricular or deep white matter hyperintensities (WMHs) increase the risk for depressive symptoms, partly because of heterogeneity in depression measurement, short follow-up, and confounding by prodromal dementia. The study objective was to evaluate WMH volume in relation to discrete depressive symptoms over 10 years, stratifying by incident depression and dementia. METHODS: In this prospective longitudinal cohort study of a representative population sample from Dijon, France, 1,440 participants aged 65-80 years (median age: 72 years; 59.5% women) without depression, dementia, or stroke at baseline were studied. Baseline T2-weighted images were obtained in a 1.5-T scanner to quantify WMHs (log cm3). Clinic visits were performed up to five times in a 10-year period to assess incident neurologic diseases and comorbidities. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale and converted to factor z scores, representing somatic symptoms, depressed affect, low positive affect, and interpersonal problems. RESULTS: Periventricular WMH volume was uniquely associated with low positive affect among incident depression cases (ß = 0.15; 95% confidence interval [CI]: 0.02-0.29; p = 0.026). Deep WMH volume was uniquely associated with depressed affect among incident dementia cases (ß = 0.36; 95% CI: 0.05-0.68; p = 0.025). WMH volume (periventricular, deep, and total) was associated with interpersonal problems among persons who developed dementia with depression. CONCLUSION: The findings highlight that regional WMH volumes and specific depressive symptoms have clinical and prognostic relevance to help differentiate between persons at risk for depression and dementia.


Assuntos
Demência/patologia , Depressão/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Demência/epidemiologia , Depressão/epidemiologia , Feminino , França/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagem
13.
Neuroimage ; 153: 399-409, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28232121

RESUMO

Brain imaging is now ubiquitous in clinical practice and research. The case for bringing together large amounts of image data from well-characterised healthy subjects and those with a range of common brain diseases across the life course is now compelling. This report follows a meeting of international experts from multiple disciplines, all interested in brain image biobanking. The meeting included neuroimaging experts (clinical and non-clinical), computer scientists, epidemiologists, clinicians, ethicists, and lawyers involved in creating brain image banks. The meeting followed a structured format to discuss current and emerging brain image banks; applications such as atlases; conceptual and statistical problems (e.g. defining 'normality'); legal, ethical and technological issues (e.g. consents, potential for data linkage, data security, harmonisation, data storage and enabling of research data sharing). We summarise the lessons learned from the experiences of a wide range of individual image banks, and provide practical recommendations to enhance creation, use and reuse of neuroimaging data. Our aim is to maximise the benefit of the image data, provided voluntarily by research participants and funded by many organisations, for human health. Our ultimate vision is of a federated network of brain image biobanks accessible for large studies of brain structure and function.


Assuntos
Bases de Dados Factuais , Disseminação de Informação/métodos , Neuroimagem , Sistemas de Gerenciamento de Base de Dados , Humanos , Armazenamento e Recuperação da Informação
14.
Cortex ; 86: 314-339, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27321148

RESUMO

This review synthesizes anatomo-functional variability of language hemispheric representation and specialization (hemispheric specialization for language, HSL) as well as its modulation by several variables (demographic, anatomical, developmental, genetic, clinical, and psycholinguistic) in physiological and pathological conditions. The left hemisphere (LH) dominance for language, observed in approximately 90% of healthy individuals and in 70% of patients, is grounded by intra-hemispheric connections mediated by associative bundles such as the arcuate fasciculus and inter-hemispheric transcallosal connections mediated by the corpus callosum that connects homotopic regions of the left and right hemispheres (RH). In typical brains, inter-hemispheric inhibition, exerted from the LH to the RH, permits the LH to maintain language dominance. In pathological conditions, inter- and intra-hemispheric inhibition is decreased, inducing modifications on the degree of HSL and of language networks. HSL evaluation is classically performed in clinical practice with the Wada test and electro-cortical stimulation, gold standard methods. The advent of functional neuroimaging has allowed a more detailed assessment of the language networks and their lateralization, consistent with the results provided by the gold standard methods. In the first part, we describe anatomo-functional support for HSL in healthy conditions, its developmental course, its relationship with cognitive skills, and the various modulatory factors acting on HSL. The second section is devoted to the assessment of HSL in patients with focal and drug-resistant epilepsy (FDRE). FDRE is considered a neurological model associated with patterns of language plasticity, both before and after surgery: FDRE patients show significant modification of language networks induced by changes mediated by transcallosal connections (explaining inter-hemispheric patterns of language reorganization) or collateral connections (explaining intra-hemispheric patterns of language reorganization). Finally, we propose several predictive and explicative models of language organization and reorganization.


Assuntos
Encéfalo/fisiologia , Epilepsia/fisiopatologia , Lateralidade Funcional/fisiologia , Plasticidade Neuronal/fisiologia , Mapeamento Encefálico , Humanos , Linguagem , Imagem por Ressonância Magnética , Modelos Neurológicos
15.
Psychosom Med ; 79(1): 14-23, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27428856

RESUMO

OBJECTIVE: Low socioeconomic position (SEP) has been linked to an increased risk of dementia and cognitive decline. However, little is known about the association between SEP and morphologic brain changes in older age. This study examines the relationships between indicators of life-course SEP with both hippocampal volume (HcV) and HcV loss in a population-based cohort of 1328 older adults aged 65 to 80 years. METHODS: Multivariable linear regression models were used to estimate the associations of SEP with baseline HcV and the annual rate of HcV atrophy according to three life-course conceptual models: the sensitive/critical periods model (which explored SEP in specific periods: in childhood [using parental education], early adulthood [based on participants' education], and midlife [based on participants' socioprofessional group]); the accumulation-of-risk model (life-course cumulative SEP), and the social mobility model (life-course SEP trajectories). RESULTS: Participants with lower midlife SEP had smaller HcV (-0.08 cm; 95% confidence interval, -0.15 to -0.01) and 0.17% (95% confidence interval, 0.04%-0.30%) faster hippocampal atrophy than participants with higher midlife SEP. Childhood and early adulthood SEPs were not related to hippocampal measures. The accumulation-of-risk and the social mobility models revealed that the accumulation of socioeconomic disadvantage and declining socioeconomic trajectories were related to faster hippocampal atrophy. CONCLUSIONS: In this cohort of older adults, lower socioprofessional attainment in midlife and disadvantageous life-course socioeconomic position were associated with faster hippocampal atrophy, a cerebral change linked to cognitive disorders. Results support the hypothesized links between socioenvironmental exposures related to stress and/or cognitive enrichment and brain/cognitive reserve capacities.


Assuntos
Escolaridade , Hipocampo/diagnóstico por imagem , Desenvolvimento Humano , Classe Social , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Atrofia/patologia , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Mobilidade Social
16.
Neuropsychologia ; 94: 75-83, 2017 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-27916670

RESUMO

The objective of this study was to validate a line bisection judgement (LBJ) task for use in investigating the lateralized cerebral bases of spatial attention in a sample of 51 right-handed healthy participants. Using functional magnetic resonance imaging (fMRI), the participants performed a LBJ task that was compared to a visuomotor control task during which the participants made similar saccadic and motoric responses. Cerebral lateralization was determined using a voxel-based functional asymmetry analysis and a hemispheric functional lateralization index (HFLI) computed from fMRI contrast images. Behavioural attentional deviation biases were assessed during the LBJ task and a "paper and pencil" symbol cancellation task (SCT). Individual visuospatial skills were also evaluated. The results showed that both the LBJ and SCT tasks elicited leftward spatial biases in healthy subjects, although the biases were not correlated, which indicated their independence. Neuroimaging results showed that the LBJ task elicited a right hemispheric lateralization, with rightward asymmetries found in a large posterior occipito-parietal area, the posterior calcarine sulcus (V1p) and the temporo-occipital junction (TOJ) and in the inferior frontal gyrus, the anterior insula and the superior medial frontal gyrus. The comparison of the LBJ asymmetry map to the lesion map of neglect patients who suffer line bisection deviation demonstrated maximum overlap in a network that included the middle occipital gyrus (MOG), the TOJ, the anterior insula and the inferior frontal region, likely subtending spatial LBJ bias. Finally, the LBJ task-related cerebral lateralization was specifically correlated with the LBJ spatial bias but not with the SCT bias or with the visuospatial skills of the participants. Taken together, these results demonstrated that the LBJ task is adequate for investigating spatial lateralization in healthy subjects and is suitable for determining the factors underlying the variability of spatial cerebral lateralization.


Assuntos
Atenção/fisiologia , Encéfalo/fisiologia , Lateralidade Funcional/fisiologia , Julgamento/fisiologia , Percepção Espacial/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Movimentos Sacádicos/fisiologia , Percepção da Fala/fisiologia
17.
Brain Struct Funct ; 222(4): 1645-1662, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27581617

RESUMO

Despite its significant functional and clinical interest, the anatomy of the uncinate fasciculus (UF) has received little attention. It is known as a 'hook-shaped' fascicle connecting the frontal and anterior temporal lobes and is believed to consist of multiple subcomponents. However, the knowledge of its precise connectional anatomy in humans is lacking, and its subcomponent divisions are unclear. In the present study, we evaluate the anatomy of the UF and provide its detailed normative description in 30 healthy subjects with advanced particle-filtering tractography with anatomical priors and robustness to crossing fibers with constrained spherical deconvolution. We extracted the UF by defining its stem encompassing all streamlines that converge into a compact bundle, which consisted not only of the classic hook-shaped fibers, but also of straight horizontally oriented. We applied an automatic-clustering method to subdivide the UF bundle and revealed five subcomponents in each hemisphere with distinct connectivity profiles, including different asymmetries. A layer-by-layer microdissection of the ventral part of the external and extreme capsules using Klingler's preparation also demonstrated five types of uncinate fibers that, according to their pattern, depth, and cortical terminations, were consistent with the diffusion-based UF subcomponents. The present results shed new light on the UF cortical terminations and its multicomponent internal organization with extended cortical connections within the frontal and temporal cortices. The different lateralization patterns we report within the UF subcomponents reconcile the conflicting asymmetry findings of the literature. Such results clarifying the UF structural anatomy lay the groundwork for more targeted investigations of its functional role, especially in semantic language processing.


Assuntos
Lobo Frontal/anatomia & histologia , Lobo Temporal/anatomia & histologia , Substância Branca/anatomia & histologia , Adulto , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Microdissecção , Vias Neurais/anatomia & histologia , Adulto Jovem
18.
BMJ Open ; 7(12): e018328, 2017 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-29289936

RESUMO

OBJECTIVES: The objective was to develop and validate a risk model for the likelihood of extensive white matter lesions (extWML) to inform clinicians on whether to proceed with or forgo diagnostic MRI. DESIGN: Population-based cohort study and multivariable prediction model. SETTING: Two representative samples from France. PARTICIPANTS: Persons aged 60-80 years without dementia or stroke. Derivation sample n=1714; validation sample n=789. PRIMARY AND SECONDARY OUTCOME MEASURES: Volume of extWML (log cm3) was obtained from T2-weighted images in a 1.5 T scanner. 20 candidate risk factors for extWML were evaluated with the C-statistic. Secondary outcomes in validation included incident stroke over 12 years follow-up. RESULTS: The multivariable prediction model included six clinical risk factors (C-statistic=0.61). A cut-off of 7 points on the multivariable prediction model yielded the optimum balance in sensitivity 63.7% and specificity 54.0% and the negative predictive value was high (81.8%), but the positive predictive value was low (31.5%). In further validation, incident stroke risk was associated with continuous scores on the multivariable prediction model (HR 1.02; 95% CI 1.01 to 1.04, P=0.02) and dichotomised scores from the multivariable prediction model (HR 1.28; 95% CI 1.02 to 1.60, P=0.03). CONCLUSIONS: A simple clinical risk equation for WML constituted by six variables can inform decisions whether to proceed with or forgo brain MRI. The high-negative predictive value demonstrates potential to reduce unnecessary MRI in the population aged 60-80 years.


Assuntos
Encefalopatias/diagnóstico , Modelos Biológicos , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/diagnóstico por imagem , Demência , Feminino , França , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia
19.
Neuroimage ; 145(Pt B): 389-408, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-26658930

RESUMO

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.


Assuntos
Encefalopatias , Estudo de Associação Genômica Ampla , Transtornos Mentais , Estudos Multicêntricos como Assunto , Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/genética , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia
20.
Front Hum Neurosci ; 10: 628, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27999536

RESUMO

The aim of this study was to characterize, using fMRI, the functional asymmetries of hand laterality task (HLT) in a sample of 295 participants balanced for handedness. During HLT, participants have to decide whether the displayed picture of a hand represent a right or a left hand. Pictures of hands' back view were presented for 150 ms in the right or left hemifield. At the whole hemisphere level, we evidenced that the laterality of the hand and of the hemifield in which the picture was displayed combined their effects on the hemispheric asymmetry in an additive way. We then identified a set of 17 functional homotopic regions of interest (hROIs) including premotor, motor, somatosensory and parietal regions, whose activity and asymmetry varied with the laterality of the presented hands. When the laterality of a right hand had to be evaluated, these areas showed stronger leftward asymmetry, the hROI located in the primary motor area showing a significant larger effect than all other hROIs. In addition a subset of six parietal regions involved in visuo-motor integration together with two postcentral areas showed a variation in asymmetry with hemifield of presentation. Finally, while handedness had no effect at the hemispheric level, two regions located in the parietal operculum and intraparietal sulcus exhibited larger leftward asymmetry with right handedness independently of the hand of presentation. The present results extend those of previous works in showing a shift of asymmetries during HLT according to the hand presented in sensorimotor areas including primary motor cortex. This shift was not affected by manual preference. They also demonstrate that the coordination of visual information and handedness identification of hands relied on the coexistence of contralateral motor and visual representations in the superior parietal lobe and the postcentral gyrus.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA