Functional Neuroimaging of Individual Differences in Affect and Motivation
情感和动机个体差异的功能神经影像
基本信息
- 批准号:8605554
- 负责人:
- 金额:$ 18.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-02-01 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAmygdaloid structureAnteriorAuditoryBehavioralBiologyBiomedical EngineeringBrainBrain imagingCerebral cortexClinicalComputational TechniqueCorpus striatum structureDataDevelopmentDoctor of PhilosophyElectrophysiology (science)EmotionalEmotionsEnvironmentFellowshipFunctional Magnetic Resonance ImagingFundingGene ExpressionGenesGeneticGenetic Predisposition to DiseaseGenetic RiskGenetic VariationGenotypeHaplotypesHealthHearingHumanIndividualIndividual DifferencesInstitutesInvestigationK-Series Research Career ProgramsMagnetic Resonance ImagingMajor Depressive DisorderMedialMediatingMental DepressionMentored Patient-Oriented Research Career Development AwardMentorsMethodologyMichiganMissionModelingMolecularMolecular GeneticsMood DisordersMotivationNeural PathwaysNeurobiologyNeurosciencesNeurosciences ResearchNeurotic DisordersOpioidOutcomePainParticipantPatternPeptidesPhenotypePhysiciansPhysicsPlasmaPositioning AttributePre-Clinical ModelPrefrontal CortexProcessPsychiatristPsychiatryPsychologyPublic HealthPublishingRadiology SpecialtyRecruitment ActivityRecurrenceResearchResearch PersonnelResidenciesResourcesRestRewardsRiskRoleSamplingSchizophreniaScientistStimulusStressSystemTestingTimeTrainingTraining and EducationTranslational ResearchUnited States National Institutes of HealthUniversitiesVariantVentral StriatumWashingtonWorkapproach behavioravoidance behaviorcareercareer developmentcingulate cortexclinically relevantdesigndisorder riskendophenotypeexperiencegenetic varianthuman datainterestmotivated behaviorneural circuitneurobiological mechanismneuroimagingneuropeptide Ypatient orientedpre-clinicalprofessorpublic health prioritiesrelating to nervous systemresearch studyresilienceresponsereward circuitryreward processingrisk variantstress resiliencetraittranslational neuroscience
项目摘要
DESCRIPTION (provided by applicant): The proposed K23 career development award aims to train a promising candidate to become an independent investigator in neuroimaging, genetics, and mood disorders while characterizing neurobiological mechanisms that underlie genetic risk for depression. Candidate. The candidate's education and training have prepared him well for this project. His interest in neuroscience emerged as an undergraduate at the University of Washington, where he majored in Physics and Biology. He subsequently earned his MD and PhD in Neuroscience at the University of Michigan. For his thesis project, he employed electrophysiology and computational techniques to study activity in the cerebral cortex that underlies sound perception, and in a related study, he investigated auditory processing in schizophrenia. He continued his training in psychiatry residency and fellowship at the University of Michigan, during which he was introduced to functional neuroimaging and the neurobiology of mood disorders. He was recently appointed Assistant Professor of Psychiatry at the University of Michigan. As a trained neuroscientist and psychiatrist, he is well positioned for a career in patient-oriented psychiatric neuroscience research. To achieve full research independence, he has identified three key Training Objectives: (1) experience directing a translational neuroscience research study on affective disorders, (2) training in the design, execution, and analysis of functional magnetic resonance imaging (fMRI) experiments, and (3) development of methodological expertise in molecular genetics. Environment. The proposed K23 project will take place within the Department of Psychiatry and the Molecular & Behavioral Neuroscience Institute at the University of Michigan. The Department and Institute benefit from close collaborative relationships with other units including Bioengineering, Psychology, Radiology, and the CTSA-funded Michigan Institute for Clinical and Health Research. This vigorous research environment includes ample access to fMRI facilities, genotyping resources, and clinical samples, and it nurtures an expanding group of translational psychiatric researchers. The primary mentor, Jon-Kar Zubieta MD PhD, is a productive and well-funded neuroscientist who has more than 15 years of experience with neuroimaging and genetics, and an established track record of mentoring junior investigators, including three recent K awardees. The candidate will also benefit from two local co-mentors, geneticist Margit Burmeister PhD and MRI physicist Robert Welsh PhD, and three carefully chosen consultants. Research. The K23 project focuses on neurobiological vulnerability to major depressive disorder (MDD), a common, debilitating, recurrent brain illness, and a significant public health problem worldwide. MDD is thought to arise from the interaction of environmental and genetic factors within multiple neural pathways, but progress has been hindered by our limited understanding of circuit-level endophenotypes in humans. Our recent findings implicate functional genetic variation of neuropeptide Y (NPY) in negative emotional processing and risk for MDD, suggesting a way forward. While NPY has been consistently implicated in avoidance behavior and circuitry, preclinical data have also indicated a role in approach behavior and circuitry (reward, motivated behavior, and appetitive drive). Our preliminary fMRI data suggest that NPY influences approach circuitry in humans as well, specifically implicating ventral striatum, medial prefrontal cortex, and the interaction of these regions. The impact of NPY variation on approach circuitry and functional connectivity deserves further investigation. Specific Aim 1: NPY genotyping, plasma NPY, and behavioral characterization. We propose to recruit 240 healthy participants and classify them by NPY genotype. We will characterize the effects of NPY variation on plasma NPY levels, motivated behavior, and emotional traits. (Aligns with Training Objectives 1 and 3.) Specific Aim 2: Effects of NPY on reward circuitry and connectivity. We will characterize NPY effects on reward processing and functional connectivity in healthy participants classified as low- or high-expression (n=30 per group). We will test whether NPY influences (i) activation of reward circuitry differentially during processing of monetary loss versus gain and (ii) patterns of functional connectivity at rest. (Aligns with Training Objective 2.) Summary. The proposed K23 award is well aligned with the missions of the NIH and PHS. The project will train a promising early investigator to become a clinical translational neuroscientist. At the same time, the project will address important, testable questions about the neurobiology of genetic vulnerability to MDD, an identified public health priority.
拟议的K23职业发展奖旨在培养一名有前途的候选人成为神经影像学,遗传学和情绪障碍的独立研究者,同时表征抑郁症遗传风险的神经生物学机制。 候选人候选人的教育和培训使他为这个项目做好了充分的准备。他在华盛顿大学主修物理学和生物学时,就对神经科学产生了兴趣。随后,他在密歇根大学获得了神经科学的医学博士和博士学位。在他的论文项目中,他采用了电生理学和计算技术来研究大脑皮层的活动,这些活动是声音感知的基础,在一项相关研究中,他调查了精神分裂症的听觉处理。他继续在密歇根大学接受精神病学住院医师培训和奖学金培训,在此期间,他了解了功能神经成像和情绪障碍的神经生物学。他最近被任命为密歇根大学精神病学助理教授。作为一名训练有素的神经科学家和精神病学家,他在以患者为导向的精神神经科学研究中处于有利地位。为了实现完全的研究独立性,他确定了三个关键的培训目标:(1)指导情感障碍转化神经科学研究的经验,(2)功能性磁共振成像(fMRI)实验的设计,执行和分析的培训,以及(3)分子遗传学方法专业知识的发展。 环境拟议的K23项目将在密歇根大学精神病学系和分子与行为神经科学研究所内进行。该部门和研究所受益于与其他单位,包括生物工程,心理学,放射学,和CTSA资助的密歇根临床和健康研究所密切的合作关系。这种充满活力的研究环境包括充分利用功能磁共振成像设备,基因分型资源和临床样本,它培育了一个不断扩大的翻译精神病学研究人员群体。主要导师Jon-Kar Zubieta MD PhD是一位富有成效且资金充足的神经科学家,在神经影像学和遗传学方面拥有超过15年的经验,并且在指导初级研究人员(包括三位最近的K获奖者)方面拥有良好的记录。候选人还将受益于两位当地的共同导师,遗传学家Margit Burmeister博士和MRI物理学家Robert Welsh博士,以及三位精心挑选的顾问。 Research. K23项目的重点是神经生物学对重度抑郁症(MDD)的脆弱性,这是一种常见的、使人衰弱的、复发性脑部疾病,也是一个重大的全球公共卫生问题。MDD被认为是由多个神经通路内的环境和遗传因素的相互作用引起的,但由于我们对人类回路水平内表型的了解有限,进展受到阻碍。我们最近的研究结果表明,神经肽Y(NPY)的功能性遗传变异在负面情绪处理和抑郁症的风险,提出了一个前进的方向。 虽然NPY一直与回避行为和电路有关,但临床前数据也表明了它在接近行为和电路(奖励,动机行为和食欲驱动)中的作用。我们初步的功能磁共振成像数据表明,神经肽Y影响的方法在人类的电路,以及,特别是涉及腹侧纹状体,内侧前额叶皮层,以及这些地区的相互作用。神经肽Y的变化对接近电路和功能连接的影响值得进一步研究。 具体目标1:NPY基因分型、血浆NPY和行为特征。我们建议招募240名健康受试者,并按NPY基因型对他们进行分类。我们将描述血浆NPY水平,动机行为和情绪特征的影响,神经肽Y的变化。(符合培训目标1和3。) 具体目标2:NPY对奖励回路和连接的影响。我们将描述NPY对低表达或高表达的健康参与者(每组n=30)的奖励处理和功能连接的影响。我们将测试神经肽Y是否影响(i)在处理金钱损失与收益期间奖励回路的激活差异,以及(ii)休息时功能连接的模式。(符合培训目标2) 摘要拟议的K23奖与NIH和PHS的使命保持一致。该项目将培养一名有前途的早期研究人员成为临床转化神经科学家。与此同时,该项目将解决有关遗传易感性MDD的神经生物学的重要,可测试的问题,这是一个确定的公共卫生优先事项。
项目成果
期刊论文数量(0)
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Brian James Mickey其他文献
Brian James Mickey的其他文献
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{{ truncateString('Brian James Mickey', 18)}}的其他基金
Functional Neuroimaging of Individual Differences in Affect and Motivation in Maj
情感和动机个体差异的功能神经影像学研究
- 批准号:
8240800 - 财政年份:2012
- 资助金额:
$ 18.23万 - 项目类别:
Functional Neuroimaging of Individual Differences in Affect and Motivation
情感和动机个体差异的功能神经影像
- 批准号:
8411962 - 财政年份:2012
- 资助金额:
$ 18.23万 - 项目类别:
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