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1.
J Neurophysiol ; 124(5): 1415-1448, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32965153

RESUMO

Using procedures optimized to explore network organization within the individual, the topography of a candidate language network was characterized and situated within the broader context of adjacent networks. The candidate network was first identified using functional connectivity and replicated across individuals, acquisition tasks, and analytical methods. In addition to classical language regions near the perisylvian cortex and temporal pole, regions were also observed in dorsal posterior cingulate, midcingulate, and anterior superior frontal and inferior temporal cortex. The candidate network was selectively activated when processing meaningful (as contrasted with nonword) sentences, whereas spatially adjacent networks showed minimal or even decreased activity. Results were replicated and triplicated across two prospectively acquired cohorts. Examined in relation to adjacent networks, the topography of the language network was found to parallel the motif of other association networks, including the transmodal association networks linked to theory of mind and episodic remembering (often collectively called the default network). The several networks contained juxtaposed regions in multiple association zones. Outside of these juxtaposed higher-order networks, we further noted a distinct frontotemporal network situated between language regions and a frontal orofacial motor region and a temporal auditory region. A possibility is that these functionally related sensorimotor regions might anchor specialization of neighboring association regions that develop into a language network. What is most striking is that the canonical language network appears to be just one of multiple similarly organized, differentially specialized distributed networks that populate the evolutionarily expanded zones of human association cortex.NEW & NOTEWORTHY This research shows that a language network can be identified within individuals using functional connectivity. Organizational details reveal that the language network shares a common spatial motif with other association networks, including default and frontoparietal control networks. The language network is activated by language task demands, whereas closely juxtaposed networks are not, suggesting that similarly organized but differentially specialized distributed networks populate association cortex.

2.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

3.
J Neurophysiol ; 123(3): 1144-1179, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32049593

RESUMO

Association cortex is organized into large-scale distributed networks. One such network, the default network (DN), is linked to diverse forms of internal mentation, opening debate about whether shared or distinct anatomy supports multiple forms of cognition. Using within-individual analysis procedures that preserve idiosyncratic anatomical details, we probed whether multiple tasks from two domains, episodic projection and theory of mind (ToM), rely on the same or distinct networks. In an initial experiment (6 subjects, each scanned 4 times), we found evidence that episodic projection and ToM tasks activate separate regions distributed throughout the cortex, with adjacent regions in parietal, temporal, prefrontal, and midline zones. These distinctions were predicted by the hypothesis that the DN comprises two parallel, interdigitated networks. One network, linked to parahippocampal cortex (PHC), is preferentially recruited during episodic projection, including both remembering and imagining the future. A second juxtaposed network, which includes the temporoparietal junction (TPJ), is differentially engaged during multiple forms of ToM. In two prospectively acquired independent experiments, we replicated and triplicated the dissociation (each with 6 subjects scanned 4 times). Furthermore, the dissociation was found in all zones when analyzed independently, including robustly in midline regions previously described as hubs. The TPJ-linked network is interwoven with the PHC-linked network across the cortex, making clear why it is difficult to fully resolve the two networks in group-averaged or lower-resolution data. These results refine our understanding of the functional-anatomical organization of association cortex and raise fundamental questions about how specialization might arise in parallel, juxtaposed association networks.NEW & NOTEWORTHY Two distributed, interdigitated networks exist within the bounds of the canonical default network. Here we used repeated scanning of individuals, across three independent samples, to provide evidence that tasks requiring episodic projection or theory of mind differentially recruit the two networks across multiple cortical zones. The two distributed networks thus appear to preferentially subserve distinct functions.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32033921

RESUMO

BACKGROUND: Individuals with either deletion or duplication of the BP4-BP5 segment of chromosome 16p11.2 have varied behavioral phenotypes that may include autistic features, mild to moderate intellectual disability, and/or language impairment. However, the neurophysiological correlates of auditory language discrimination processing in individuals with 16p11.2 deletion and 16p11.2 duplication have not been investigated. METHODS: Magnetoencephalography was used to measure magnetic mismatch fields (MMFs) arising from the left and right superior temporal gyrus during an auditory oddball paradigm with vowel stimuli (/a/ and /u/) in children and adolescents with 16p11.2 deletion or 16p11.2 duplication and in typically developing peers. One hundred twenty-eight participants ranging from 7 to 17 years of age were included in the final analysis (typically developing: n = 61, 12.08 ± 2.50 years of age; 16p11.2 deletion: n = 45, 11.28 ± 2.51 years of age; and 16p11.2 duplication: n = 22, 10.73 ± 2.49 years of age). RESULTS: Delayed MMF latencies were found in both 16p11.2 deletion and 16p11.2 duplication groups compared with typically developing subjects. In addition, these delayed MMF latencies were associated with language and cognitive ability, with prolonged latency predicting greater impairment. CONCLUSIONS: Our findings suggest that auditory MMF response delays are associated with clinical severity of language and cognitive impairment in individuals with either 16p11.2 deletion or 16p11.2 duplication, indicating a correlate of their shared/overlapping behavioral phenotype (and not a correlate of gene dosage).

5.
Psychol Med ; 50(2): 273-283, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30744715

RESUMO

BACKGROUND: Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. METHODS: A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. RESULTS: Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. CONCLUSIONS: These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Delusões/psicologia , Medo/fisiologia , Córtex Visual/fisiopatologia , Adolescente , Delusões/diagnóstico , Medo/psicologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Análise de Regressão , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Adulto Jovem
6.
Nat Rev Neurosci ; 20(10): 593-608, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31492945

RESUMO

Discoveries over the past two decades demonstrate that regions distributed throughout the association cortex, often called the default network, are suppressed during tasks that demand external attention and are active during remembering, envisioning the future and making social inferences. This Review describes progress in understanding the organization and function of networks embedded within these association regions. Detailed high-resolution analyses of single individuals suggest that the default network is not a single network, as historically described, but instead comprises multiple interwoven networks. The multiple networks share a common organizational motif (also evident in marmoset and macaque anatomical circuits) that might support a general class of processing function dependent on internally constructed rather than externally constrained representations, with each separate interwoven network specialized for a distinct processing domain. Direct neuronal recordings in humans and monkeys reveal evidence for competitive relationships between the internally and externally oriented networks. Findings from rodent studies suggest that the thalamus might be essential to controlling which networks are engaged through specialized thalamic reticular neurons, including antagonistic subpopulations. These association networks (and presumably thalamocortical circuits) are expanded in humans and might be particularly vulnerable to dysregulation implicated in mental illness.


Assuntos
Aprendizagem por Associação/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem
7.
Nat Commun ; 10(1): 1976, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036823

RESUMO

Networks of widely distributed regions populate human association cortex. One network, often called the default network, is positioned at the apex of a gradient of sequential networks that radiate outward from primary cortex. Here, extensive anatomical data made available through the Marmoset Brain Architecture Project are explored to show a homologue exists in marmoset. Results reveal that a gradient of networks extend outward from primary cortex to progressively higher-order transmodal association cortex in both frontal and temporal cortex. The apex transmodal network comprises frontopolar and rostral temporal association cortex, parahippocampal areas TH / TF, the ventral posterior midline, and lateral parietal association cortex. The positioning of this network in the gradient and its composition of areas make it a candidate homologue to the human default network. That the marmoset, a physiologically- and genetically-accessible primate, might possess a default-network-like candidate creates opportunities for study of higher cognitive and social functions.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Callithrix , Cognição , Lobo Frontal/diagnóstico por imagem , Imagem por Ressonância Magnética , Neurociências
8.
J Neurophysiol ; 121(4): 1513-1534, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785825

RESUMO

Examination of large-scale distributed networks within the individual reveals details of cortical network organization that are absent in group-averaged studies. One recent discovery is that a distributed transmodal network, often referred to as the "default network," comprises two closely interdigitated networks, only one of which is coupled to posterior parahippocampal cortex. Not all studies of individuals have identified the same networks, and questions remain about the degree to which the two networks are separate, particularly within regions hypothesized to be interconnected hubs. In this study we replicate the observation of network separation across analytical (seed-based connectivity and parcellation) and data projection (volume and surface) methods in two individuals each scanned 31 times. Additionally, three individuals were examined with high-resolution (7T; 1.35 mm) functional magnetic resonance imaging to gain further insight into the anatomical details. The two networks were identified with separate regions localized to adjacent portions of the cortical ribbon, sometimes inside the same sulcus. Midline regions previously implicated as hubs revealed near complete spatial separation of the two networks, displaying a complex spatial topography in the posterior cingulate and precuneus. The network coupled to parahippocampal cortex also revealed a separate region directly within the hippocampus, at or near the subiculum. These collective results support that the default network is composed of at least two spatially juxtaposed networks. Fine spatial details and juxtapositions of the two networks can be identified within individuals at high resolution, providing insight into the network organization of association cortex and placing further constraints on interpretation of group-averaged neuroimaging data. NEW & NOTEWORTHY Recent evidence has emerged that canonical large-scale networks such as the "default network" fractionate into parallel distributed networks when defined within individuals. This research uses high-resolution imaging to show that the networks possess juxtapositions sometimes evident inside the same sulcus and within regions that have been previously hypothesized to be network hubs. Distinct circumscribed regions of one network were also resolved in the hippocampal formation, at or near the parahippocampal cortex and subiculum.


Assuntos
Encéfalo/fisiologia , Conectoma , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética
9.
Neuroimage ; 185: 335-348, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30332613

RESUMO

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018).


Assuntos
Envelhecimento , Encéfalo , Conectoma/métodos , Longevidade , Rede Nervosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Imagem Multimodal , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Neuroimagem/métodos , Projetos de Pesquisa
10.
Cereb Cortex ; 29(3): 1251-1262, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29425267

RESUMO

White matter degradation has been proposed as one possible explanation for age-related cognitive decline. In the present study, we examined 2 main questions: 1) Do diffusion characteristics predict longitudinal change in cognition independently or synergistically with amyloid status? 2) Are the effects of diffusion characteristics on longitudinal cognitive change tract-specific or global in nature? Cognitive domains of executive function, episodic memory, and processing speed were measured annually (mean follow-up = 3.93 ± 1.25 years). Diffusion tensor imaging and Pittsburgh Compound-B positron emission tomography were performed at baseline in 265 clinically normal older adults (aged 63-90). Tract-specific diffusion was measured as the mean fractional anisotropy (FA) for 9 major white matter tracts. Global diffusion was measured as the mean FA across the 9 white matter tracts. Linear mixed models demonstrated independent, rather than synergistic, effects of global FA and amyloid status on cognitive decline. After controlling for amyloid status, lower global FA was associated with worse longitudinal performance in episodic memory and processing speed, but not executive function. After accounting for global FA, none of the individual tracts predicted a significant change in cognitive performance. These findings suggest that global, rather than tract-specific, diffusion characteristics predict longitudinal cognitive decline independently of amyloid status.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Cognição/fisiologia , Substância Branca/anatomia & histologia , Substância Branca/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
11.
Proc Natl Acad Sci U S A ; 115(40): 10160-10165, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30224467

RESUMO

Age-related changes in striatal function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.


Assuntos
Envelhecimento/fisiologia , Córtex Cerebral , Corpo Estriado , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Imagem por Ressonância Magnética , Memória/fisiologia , Núcleo Inferior Caudal do Nervo Trigêmeo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Inferior Caudal do Nervo Trigêmeo/diagnóstico por imagem , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo
12.
Neuroimage ; 183: 972-984, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30261308

RESUMO

The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5-21), and HCP-A is enrolling 1200+ healthy adults (ages 36-100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22-35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.


Assuntos
Envelhecimento , Encéfalo , Conectoma/métodos , Longevidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Neuroimage ; 183: 456-468, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30142446

RESUMO

Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5-21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9-17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Protocolos Clínicos , Conectoma/métodos , Desenvolvimento Humano/fisiologia , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Criança , Pré-Escolar , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Adulto Jovem
14.
Biol Psychiatry ; 84(4): 253-264, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29778275

RESUMO

BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV. RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results. CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.


Assuntos
Encéfalo/patologia , Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Variações do Número de Cópias de DNA , Adolescente , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/genética , Criança , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Feminino , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/genética , Idioma , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/genética , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Adulto Jovem
15.
Radiology ; 286(1): 217-226, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28786752

RESUMO

Purpose To identify developmental neuroradiologic findings in a large cohort of carriers who have deletion and duplication at 16p11.2 (one of the most common genetic causes of autism spectrum disorder [ASD]) and assess how these features are associated with behavioral and cognitive outcomes. Materials and Methods Seventy-nine carriers of a deletion at 16p11.2 (referred to as deletion carriers; age range, 1-48 years; mean age, 12.3 years; 42 male patients), 79 carriers of a duplication at 16p11.2 (referred to as duplication carriers; age range, 1-63 years; mean age, 24.8 years; 43 male patients), 64 unaffected family members (referred to as familial noncarriers; age range, 1-46 years; mean age, 11.7 years; 31 male participants), and 109 population control participants (age range, 6-64 years; mean age, 25.5 years; 64 male participants) were enrolled in this cross-sectional study. Participants underwent structural magnetic resonance (MR) imaging and completed cognitive and behavioral tests. MR images were reviewed for development-related abnormalities by neuroradiologists. Differences in frequency were assessed with a Fisher exact test corrected for multiple comparisons. Unsupervised machine learning was used to cluster radiologic features and an association between clusters and cognitive and behavioral scores from IQ testing, and parental measures of development were tested by using analysis of covariance. Volumetric analysis with automated segmentation was used to confirm radiologic interpretation. Results For deletion carriers, the most prominent features were dysmorphic and thicker corpora callosa compared with familial noncarriers and population control participants (16%; P < .001 and P < .001, respectively) and a greater likelihood of cerebellar tonsillar ectopia (30.7%; P < .002 and P < .001, respectively) and Chiari I malformations (9.3%; P < .299 and P < .002, respectively). For duplication carriers, the most salient findings compared with familial noncarriers and population control participants were reciprocally thinner corpora callosa (18.6%; P < .003 and P < .001, respectively), decreased white matter volume (22.9%; P < .001, and P < .001, respectively), and increased ventricular volume (24.3%; P < .001 and P < .001, respectively). By comparing cognitive assessments to imaging findings, the presence of any imaging feature associated with deletion carriers indicated worse daily living, communication, and social skills compared with deletion carriers without any radiologic abnormalities (P < .005, P < .002, and P < .004, respectively). For the duplication carriers, presence of decreased white matter, callosal volume, and/or increased ventricle size was associated with decreased full-scale and verbal IQ scores compared with duplication carriers without these findings (P < .007 and P < .004, respectively). Conclusion In two genetically related cohorts at high risk for ASD, reciprocal neuroanatomic abnormalities were found and determined to be associated with cognitive and behavioral impairments. © RSNA, 2017 Online supplemental material is available for this article.


Assuntos
Transtorno Autístico , Encéfalo/diagnóstico por imagem , Deleção Cromossômica , Transtornos Cromossômicos , Variações do Número de Cópias de DNA/genética , Deficiência Intelectual , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Transtorno Autístico/diagnóstico por imagem , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Encéfalo/patologia , Criança , Pré-Escolar , Transtornos Cromossômicos/diagnóstico por imagem , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 16/genética , Análise por Conglomerados , Estudos Transversais , Feminino , Deleção de Genes , Duplicação Gênica/genética , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Neuron ; 95(2): 457-471.e5, 2017 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-28728026

RESUMO

Certain organizational features of brain networks present in the individual are lost when central tendencies are examined in the group. Here we investigated the detailed network organization of four individuals each scanned 24 times using MRI. We discovered that the distributed network known as the default network is comprised of two separate networks possessing adjacent regions in eight or more cortical zones. A distinction between the networks is that one is coupled to the hippocampal formation while the other is not. Further exploration revealed that these two networks were juxtaposed with additional networks that themselves fractionate group-defined networks. The collective networks display a repeating spatial progression in multiple cortical zones, suggesting that they are embedded within a broad macroscale gradient. Regions contributing to the newly defined networks are spatially variable across individuals and adjacent to distinct networks, raising issues for network estimation in group-averaged data and applied endeavors, including targeted neuromodulation.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiologia , Hipocampo/fisiologia , Rede Nervosa/patologia , Vias Neurais/fisiologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos
18.
Proc Natl Acad Sci U S A ; 114(21): 5521-5526, 2017 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-28484032

RESUMO

Heritability, defined as the proportion of phenotypic variation attributable to genetic variation, provides important information about the genetic basis of a trait. Existing heritability analysis methods do not discriminate between stable effects (e.g., due to the subject's unique environment) and transient effects, such as measurement error. This can lead to misleading assessments, particularly when comparing the heritability of traits that exhibit different levels of reliability. Here, we present a linear mixed effects model to conduct heritability analyses that explicitly accounts for intrasubject fluctuations (e.g., due to measurement noise or biological transients) using repeat measurements. We apply the proposed strategy to the analysis of resting-state fMRI measurements-a prototypic data modality that exhibits variable levels of test-retest reliability across space. Our results reveal that the stable components of functional connectivity within and across well-established large-scale brain networks can be considerably heritable. Furthermore, we demonstrate that dissociating intra- and intersubject variation can reveal genetic influence on a phenotype that is not fully captured by conventional heritability analyses.


Assuntos
Técnicas Genéticas , Característica Quantitativa Herdável , Adolescente , Adulto , Encéfalo/fisiologia , Simulação por Computador , Feminino , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
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.
Nat Genet ; 49(1): 27-35, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27869829

RESUMO

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.


Assuntos
Variações do Número de Cópias de DNA/genética , Loci Gênicos/genética , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Esquizofrenia/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fatores de Risco
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