Cellular, molecular, and functional imaging approaches to understanding early neurodevelopment in autism
了解自闭症早期神经发育的细胞、分子和功能成像方法
基本信息
- 批准号:10240556
- 负责人:
- 金额:$ 217.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-07 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:12 year oldAddressAffectAgeAnatomyAttentionBehaviorBehavioralBiologicalBiological ModelsBirthBrainBrain imagingCellsCharacteristicsChildChildhoodDataDevelopmentDiagnosisDiagnosticDiseaseEvaluationFemaleFetal DevelopmentFunctional ImagingFunctional Magnetic Resonance ImagingGeneticImageImpairmentInfantIntellectual functioning disabilityInterdisciplinary StudyInterventionInvestigationLearningLifeLinkMeasuresMethodologyMethodsMolecularNeonatalNeurobiologyNeurologyNeuronal PlasticityNeuronsNeurosciencesNewborn InfantOrganizational ChangeOrganoidsPatientsPatternPerinatalPhotonsPlayPregnancyPrognostic MarkerProspective cohortPsychopathologyRadiology SpecialtyReportingResearch Project GrantsResolutionRiskRisk FactorsRoleSchool-Age PopulationScientistSecond Pregnancy TrimesterSeveritiesSex DifferencesSiblingsSocial ValuesSymptomsSynapsesSystemTestingThird Pregnancy TrimesterTimeToddlerTrainingautism spectrum disorderautistic childrenbasebehavioral studycellular imagingcohortconnectomeconnectome based predictive modelingdensitydiagnostic biomarkerdisorder riskefficacy testingexecutive functionfetalhigh riskhuman modelimaging approachinduced pluripotent stem cellinfancyinhibitory neuroninnovationmalemolecular imagingmultidisciplinaryneonatal periodneural modelneural networkneurodevelopmentneuroimagingneuromechanismneurophysiologynovelnovel diagnosticsoutcome predictionpredicting responsepredictive modelingprenatalprognosticprogramsprotective factorsrecruitrelating to nervous systemresilienceresponserisk sharingsexstatisticsstem cell biomarkers
项目摘要
The Yale Center represents a multidisciplinary research program consisting of five inter-related research
projects and four cores dedicated to advancing understanding of early neurobiology of ASD. The proposal
brings together a team of experts from the fields of developmental psychopathology and neurobiology,
genetics, neurology, radiology, neuroscience, and statistics to identify the molecular, cellular, and neural
mechanisms related to ASD from prenatal stages to childhood. We focus our investigation on two cohorts of
younger siblings of children with ASD who, due to familial factors, are at high risk (HR) for developing the
disorder: a prospective cohort recruited pre- and perinatally and followed through 24 months, and a cohort of
HR siblings who was well-characterized at 24 months through our past studies and will reach the age of 12
years during the life of the Yale ACE. These cohorts enable our search for neural signatures of ASD during
fetal, neonatal, and school-age periods, as well as to examine the connectome across the spectrum of risk for
ASD both in males and females. Although neural and behavioral markers of ASD have been reported in 6-
month-old infants later diagnosed with ASD, to our best knowledge, this is the first investigation into both fetal
and neonatal functional connectivity in ASD. Emerging data suggest that male, but not female, ASD subjects
demonstrate significant alterations in neural networks, and – for the first time – the proposed studies will
identify not only the changes in connectivity in ASD but also the impact of fetal/neonatal sex upon these
changes. Since recent studies demonstrate neuroplasticity in the developing brain across the late second and
third trimesters of gestation, it is essential to understand if the factors associated with ASD are developing in
this same time frame and to understand any sex differences that may be apparent even at that early age. The
iPSC derived organoid system models human fetal development, allowing us to investigate neurobiological risk
and protective factors that play a unique role in this period and may enable the discovery of patient-specific
neuronal or stem cell biomarkers that could be used as predictors of risk or resilience in ASD. The Yale ACE
aims rely on application of cutting-edge approaches to the analysis the connectome, fetal and neonatal
imaging modeling neural development using the iPSC methodology with high resolution dual photon imaging
approaches, the development of early markers for ASD, studying early attention and learning, novel predictive
models relating brain organization to behavior, and statistical approaches for integrating the spectrum of data
types across to address these aims. Results from the combined projects have a great potential to identify novel
diagnostic and prognostic markers at the time of birth, identify neural, cellular, and molecular bases of risk and
protective mechanisms in ASD, and clarify neural bases of sex differences in ASD.
耶鲁中心代表了一个多学科研究项目,由五项相互关联的研究组成
项目和四个核心致力于增进对自闭症谱系障碍早期神经生物学的理解。提案
汇集了来自发展精神病理学和神经生物学领域的专家团队,
遗传学、神经学、放射学、神经科学和统计学来识别分子、细胞和神经
从产前阶段到儿童期与 ASD 相关的机制。我们的调查重点是两个群体
患有自闭症谱系障碍 (ASD) 儿童的弟弟妹妹,由于家庭因素,他们有患上自闭症谱系障碍 (ASD) 的高风险 (HR)
障碍:在产前和围产期招募并随访 24 个月的前瞻性队列,以及
根据我们过去的研究,HR 兄弟姐妹在 24 个月大时就已经表现良好,并将年满 12 岁
在耶鲁大学 ACE 的一生中。这些队列使我们能够在
胎儿、新生儿和学龄期,以及检查跨风险范围的连接组
自闭症谱系障碍(ASD)在男性和女性中均有发生。尽管 ASD 的神经和行为标记已在 6-
一个月大的婴儿后来被诊断出患有自闭症谱系障碍,据我们所知,这是对胎儿和婴儿的首次调查
和自闭症谱系障碍 (ASD) 中的新生儿功能连接。新数据表明,自闭症谱系障碍对象是男性,而非女性
展示了神经网络的重大改变,并且首次提出的研究将
不仅确定自闭症谱系障碍连通性的变化,还确定胎儿/新生儿性别对这些变化的影响
变化。由于最近的研究表明,发育中的大脑在第二和第二阶段具有神经可塑性
在妊娠晚期,有必要了解与自闭症谱系障碍 (ASD) 相关的因素是否正在发生
在同一时间范围内,了解即使在很小的时候也可能出现的任何性别差异。这
iPSC 衍生的类器官系统模拟人类胎儿发育,使我们能够研究神经生物学风险
和保护因素在这一时期发挥独特的作用,可能有助于发现患者特异性的
神经元或干细胞生物标志物可用作 ASD 风险或恢复力的预测因子。耶鲁王牌
目标依赖于应用尖端方法来分析胎儿和新生儿的连接组
使用 iPSC 方法和高分辨率双光子成像对神经发育进行成像建模
方法、自闭症谱系障碍 (ASD) 早期标记的开发、研究早期注意力和学习、新颖的预测
将大脑组织与行为相关的模型,以及整合数据范围的统计方法
打字来实现这些目标。联合项目的结果具有识别新颖的潜力的巨大潜力
出生时的诊断和预后标记,识别风险和风险的神经、细胞和分子基础
自闭症谱系障碍的保护机制,并阐明自闭症谱系障碍性别差异的神经基础。
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol.
- DOI:10.1038/s41598-020-78885-z
- 发表时间:2020-12-14
- 期刊:
- 影响因子:4.6
- 作者:Horien C;Fontenelle S 4th;Joseph K;Powell N;Nutor C;Fortes D;Butler M;Powell K;Macris D;Lee K;Greene AS;McPartland JC;Volkmar FR;Scheinost D;Chawarska K;Constable RT
- 通讯作者:Constable RT
Hypoconnectivity between anterior insula and amygdala associates with future vulnerabilities in social development in a neurodiverse sample of neonates.
- DOI:10.1038/s41598-022-20617-6
- 发表时间:2022-09-28
- 期刊:
- 影响因子:4.6
- 作者:Scheinost, Dustin;Chang, Joseph;Lacadie, Cheryl;Brennan-Wydra, Emma;Foster, Rachel;Boxberger, Alexandra;Macari, Suzanne;Vernetti, Angelina;Constable, R. Todd;Ment, Laura R.;Chawarska, Katarzyna
- 通讯作者:Chawarska, Katarzyna
Attention to audiovisual speech does not facilitate language acquisition in infants with familial history of autism
- DOI:10.1111/jcpp.13595
- 发表时间:2022-03-04
- 期刊:
- 影响因子:7.6
- 作者:Chawarska, Katarzyna;Lewkowicz, David;Vernetti, Angelina
- 通讯作者:Vernetti, Angelina
A guide to the measurement and interpretation of fMRI test-retest reliability.
- DOI:10.1016/j.cobeha.2020.12.012
- 发表时间:2021-08
- 期刊:
- 影响因子:5
- 作者:Noble S;Scheinost D;Constable RT
- 通讯作者:Constable RT
Atypical Intrinsic Hemispheric Interaction Associated with Autism Spectrum Disorder Is Present within the First Year of Life.
- DOI:10.1093/cercor/bhab284
- 发表时间:2022-03-04
- 期刊:
- 影响因子:0
- 作者:Rolison M;Lacadie C;Chawarska K;Spann M;Scheinost D
- 通讯作者:Scheinost D
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KATARZYNA CHAWARSKA其他文献
KATARZYNA CHAWARSKA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('KATARZYNA CHAWARSKA', 18)}}的其他基金
Multimodal investigation of emotional reactivity as a predictor of later psychopathology in infants at risk for ASD
情绪反应作为自闭症谱系障碍婴儿后期精神病理学预测因子的多模式研究
- 批准号:
10296223 - 财政年份:2021
- 资助金额:
$ 217.95万 - 项目类别:
Multimodal investigation of emotional reactivity as a predictor of later psychopathology in infants at risk for ASD
情绪反应作为自闭症谱系障碍婴儿后期精神病理学预测因子的多模式研究
- 批准号:
10613533 - 财政年份:2021
- 资助金额:
$ 217.95万 - 项目类别:
Multimodal investigation of emotional reactivity as a predictor of later psychopathology in infants at risk for ASD
情绪反应作为自闭症谱系障碍婴儿后期精神病理学预测因子的多模式研究
- 批准号:
10430237 - 财政年份:2021
- 资助金额:
$ 217.95万 - 项目类别:
Attentional, temperamental, and physiological process underlying anxiety in preschoolers with ASD
患有自闭症谱系障碍 (ASD) 的学龄前儿童焦虑的注意力、气质和生理过程
- 批准号:
9217354 - 财政年份:2017
- 资助金额:
$ 217.95万 - 项目类别:
Neonatal connectome as a predictor of social and attentional impairment in ASD
新生儿连接组作为 ASD 社交和注意力障碍的预测因子
- 批准号:
10240559 - 财政年份:2017
- 资助金额:
$ 217.95万 - 项目类别:
Preliminary efficacy of social reward value training in toddlers with elevated symptoms of autism
社会奖励价值训练对自闭症症状加重的幼儿的初步效果
- 批准号:
10240563 - 财政年份:2017
- 资助金额:
$ 217.95万 - 项目类别:
Cellular, molecular, and functional imaging approaches to understanding early neurodevelopment in autism
了解自闭症早期神经发育的细胞、分子和功能成像方法
- 批准号:
9560923 - 财政年份:2017
- 资助金额:
$ 217.95万 - 项目类别:
Cellular, molecular, and functional imaging approaches to understanding early neurodevelopment in autism
了解自闭症早期神经发育的细胞、分子和功能成像方法
- 批准号:
9767864 - 财政年份:2017
- 资助金额:
$ 217.95万 - 项目类别:
A Multimedia Screening System for Early ASD Identification in Diverse Populations
用于不同人群早期 ASD 识别的多媒体筛查系统
- 批准号:
8893574 - 财政年份:2015
- 资助金额:
$ 217.95万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 217.95万 - 项目类别:
Research Grant