Core 3: Translational Neuroimaging Core
核心 3:转化神经影像核心
基本信息
- 批准号:10090538
- 负责人:
- 金额:$ 16.07万
- 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:2017-02-15 至 2022-01-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAddressAffectAgeAlcohol abuseAlcohol consumptionAlcoholic beverage heavy drinkerAlcoholsAnatomyAnimalsAppearanceAreaAutopsyBiologicalBrainChronicControl AnimalCorpus striatum structureDataData AnalysesDiffusion Magnetic Resonance ImagingEthanolEthicsFrequenciesFunctional Magnetic Resonance ImagingGlucocorticoidsGoalsGrantHumanKnowledgeLigandsLinkLogisticsMacaca mulattaMagnetic Resonance ImagingMeasurementMeasuresMethodsMonitorMonkeysMotorNatureNeurobiologyNeuronsNeurophysiology - biologic functionOregonPatternPharmaceutical PreparationsPhysiologicalPlaguePrimatesProceduresRecoveryResearchResearch PersonnelResearch SubjectsRestRodentSelf AdministrationSeriesSignal TransductionStressStructureTechniquesTranslatingValidationWithdrawalalcohol abstinencealcohol effectalcohol exposurealcohol use initiationblood oxygen level dependentbrain circuitrybrain healthbrain tissuecohortdata acquisitiondesigndesigner receptors exclusively activated by designer drugsdrinkingdrinking behaviorexperimental studyflexibilityhuman subjectin vivoindexinginsightmultiple drug useneural stimulationneuroimagingneuromechanismneurophysiologynonhuman primatenutritionproblem drinkerputamenreceptorrelating to nervous systemresponsetoolwhite matter
项目摘要
Project Summary
Non-invasive neuroimaging procedures have provided instrumental insights into our understanding of how
chronic exposure to ethanol can affect brain structure and function. Through comparisons of brain macroscopic
structure in alcoholics and age-matched controls, it has been possible to detect changes in brain tissue
volume, and its recovery following abstinence from alcohol. Diffusion tensor imaging (DTI) experiments have
provided information on cellular-level changes in white matter microstructure that result from chronic exposure
to ethanol, often prior to the appearance of macroscopic changes. In addition to these structural changes, it
has also been possible to characterize physiological changes associated with brain function in functional MRI
experiments. However, in all of these neuroimaging approaches, consistent systematic confounding factors
plague the biological interpretations of findings. First, it is not possible to accurately quantify ethanol exposure,
beginning at the initiation of drinking, in human subjects. Second, confounding factors such as polydrug use,
nutrition, frequency of withdrawals, and other environmental insults are difficult to discern from the effects of
ethanol exposure on brain structure and function. Third, the interpretation of functional neuroimaging
experiments can be difficult to cast in terms of neural function, e.g., as measured using traditional
neurophysiological methods. In order to address these deficits in knowledge, we propose a Translational
Neuroimaging Core to perform MRI experiments on nonhuman primate research subjects at the Oregon
National Primate Research Center's nonhuman-primate-dedicated MRI facility. These experiments have been
designed to directly support projects in the INIA-S as well as the INIA-N consortia. Aim 1 is to provide data to
buttress INIA-S project 8, in which glucocorticoid antagonists will be administered to nonhuman primate
research subjects, and the resting-state functional MRI changes associated with the resulting changes in
drinking patterns will be determined. Aim 2 is to support an INIA-N project proposed by A. Pfefferbaum, E.
Sullivan, and N. Zahr, in which brain structural and functional changes associated with repeated episodes of
abstinence and drinking will be determined in rhesus macaques to bridge data acquired in rodent and human
species. Aim 3 is to support INIA-S project 7, to use functional MRI to directly monitor changes in brain circuitry
induced through the influence of designer receptors exclusively activated by designer drugs (DREADDs) in the
striatum, and to characterize the effects of DREADDs-induced neural activity changes on functional
connectivity measurements. Last, in a subset of control animals, quantitative comparisons will be performed
between MRI-determined functional connectivity and connectivity assessed with focal infrared neural
stimulation of regions known to be sensitive to previous exposure to ethanol, with the goal of assessing the
validity of common interpretations of resting-state fMRI experiments.
Project Summary
Non-invasive neuroimaging procedures have provided instrumental insights into our understanding of how
chronic exposure to ethanol can affect brain structure and function. Through comparisons of brain macroscopic
structure in alcoholics and age-matched controls, it has been possible to detect changes in brain tissue
volume, and its recovery following abstinence from alcohol. Diffusion tensor imaging (DTI) experiments have
provided information on cellular-level changes in white matter microstructure that result from chronic exposure
to ethanol, often prior to the appearance of macroscopic changes. In addition to these structural changes, it
has also been possible to characterize physiological changes associated with brain function in functional MRI
experiments. However, in all of these neuroimaging approaches, consistent systematic confounding factors
plague the biological interpretations of findings. First, it is not possible to accurately quantify ethanol exposure,
beginning at the initiation of drinking, in human subjects. Second, confounding factors such as polydrug use,
nutrition, frequency of withdrawals, and other environmental insults are difficult to discern from the effects of
ethanol exposure on brain structure and function. Third, the interpretation of functional neuroimaging
experiments can be difficult to cast in terms of neural function, e.g., as measured using traditional
neurophysiological methods. In order to address these deficits in knowledge, we propose a Translational
Neuroimaging Core to perform MRI experiments on nonhuman primate research subjects at the Oregon
National Primate Research Center's nonhuman-primate-dedicated MRI facility. These experiments have been
designed to directly support projects in the INIA-S as well as the INIA-N consortia. Aim 1 is to provide data to
buttress INIA-S project 8, in which glucocorticoid antagonists will be administered to nonhuman primate
research subjects, and the resting-state functional MRI changes associated with the resulting changes in
drinking patterns will be determined. Aim 2 is to support an INIA-N project proposed by A. Pfefferbaum, E.
Sullivan, and N. Zahr, in which brain structural and functional changes associated with repeated episodes of
abstinence and drinking will be determined in rhesus macaques to bridge data acquired in rodent and human
species. Aim 3 is to support INIA-S project 7, to use functional MRI to directly monitor changes in brain circuitry
induced through the influence of designer receptors exclusively activated by designer drugs (DREADDs) in the
striatum, and to characterize the effects of DREADDs-induced neural activity changes on functional
connectivity measurements. Last, in a subset of control animals, quantitative comparisons will be performed
between MRI-determined functional connectivity and connectivity assessed with focal infrared neural
stimulation of regions known to be sensitive to previous exposure to ethanol, with the goal of assessing the
validity of common interpretations of resting-state fMRI experiments.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christopher D Kroenke其他文献
Christopher D Kroenke的其他文献
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{{ truncateString('Christopher D Kroenke', 18)}}的其他基金
Characterizing the FASD cerebral cortex in utero with DTI
用 DTI 表征子宫内 FASD 大脑皮层
- 批准号:
8431246 - 财政年份:2012
- 资助金额:
$ 16.07万 - 项目类别:
Characterizing the FASD cerebral cortex in utero with DTI
用 DTI 表征子宫内 FASD 大脑皮层
- 批准号:
8598852 - 财政年份:2012
- 资助金额:
$ 16.07万 - 项目类别:
Characterizing the FASD cerebral cortex in utero with DTI
用 DTI 表征子宫内 FASD 大脑皮层
- 批准号:
8963409 - 财政年份:2012
- 资助金额:
$ 16.07万 - 项目类别:
Characterizing the FASD cerebral cortex in utero with DTI
用 DTI 表征子宫内 FASD 大脑皮层
- 批准号:
8806487 - 财政年份:2012
- 资助金额:
$ 16.07万 - 项目类别:
TIM UPGRADE FOR NONHUMAN-PRIMATE-DEDICATED MAGNETOM TRIO
非人类灵长类专用 Magnetom Trio 的 TIM 升级
- 批准号:
8357869 - 财政年份:2011
- 资助金额:
$ 16.07万 - 项目类别:
ETHANOL TOLERANCE: IN VIVO SPECTROSCOPY AND DRINKING IN MONKEYS
乙醇耐受性:猴子体内光谱学和饮酒
- 批准号:
8357788 - 财政年份:2011
- 资助金额:
$ 16.07万 - 项目类别:
ETHANOL TOLERANCE: IN VIVO SPECTROSCOPY AND DRINKING IN MONKEYS
乙醇耐受性:猴子体内光谱学和饮酒
- 批准号:
8173271 - 财政年份:2010
- 资助金额:
$ 16.07万 - 项目类别:
Structural determinants of DTI observations in developing cortex and white matter
发育中皮层和白质 DTI 观察结果的结构决定因素
- 批准号:
8039920 - 财政年份:2010
- 资助金额:
$ 16.07万 - 项目类别:
Tim Upgrade for Nonhuman-Primate-Dedicated Magnetom Trio
蒂姆升级非人类灵长类专用磁力三重奏
- 批准号:
7792912 - 财政年份:2010
- 资助金额:
$ 16.07万 - 项目类别:
Structural determinants of DTI observations in developing cortex and white matter
发育中皮层和白质 DTI 观察结果的结构决定因素
- 批准号:
8627659 - 财政年份:2010
- 资助金额:
$ 16.07万 - 项目类别:
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