A multimodal investigation of positive and negative modulators of the medial temporal hippocampal system

内侧颞海马系统正负调节器的多模式研究

基本信息

批准号：
10480796
负责人：
Michael Anthony Rosario
金额：
$ 4.78万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480796
关键词：
Acute Address Affective Amygdaloid structure Animal Model Anterior Area Attenuated Award BRAIN initiative Behavior Behavioral Behavioral Model Biological Black American Black race Black, Indigenous, People of Color Brain Chronic Chronic stress Cognitive Collaborations Communication Communities Conscious Data Data Analyses Development Elderly Exercise Experimental Designs Feedback Fellowship Functional Magnetic Resonance Imaging Funding Future Goals Hippocampus (Brain)Human Individual Intervention Interview Investigation Lead Learning Left Link Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manuscripts Measures Medial Mediation Memory Mental Health Mentors Mentorship Methods Modality Modeling Mood Disorders National Institute of Mental Health Neurobiology Neurocognitive Neurocognitive Deficit Neurosciences Research Outcome Participant Pattern Peer Review Grants Performance Policies Policy Maker Positron-Emission Tomography Postdoctoral Fellow Process Proxy Psychosocial Stress Public Health Publications Race Regulation Research Research Domain Criteria Research Personnel Research Priority Research Project Grants Resolution Resources Risk Factors Sampling Science Scientist Services Severities Social Environment Statistical Data Interpretation Statistical Models Stimulus Stress Students System Testing Thick Training United States United States National Institutes of Health Universities Women&apos s Health Work Writing acute traumatic stress disorder age related arterial stiffness base biological adaptation to stress black women brain health cardiorespiratory fitness cardiovascular disorder risk cardiovascular health career development dentate gyrus diversity and inclusion emerging adulthood experimental study health equity improved memory encoding modifiable risk multimodal neuroimaging multimodality neuroimaging neuroinflammation perceived discrimination physical conditioning racism relating to nervous system skills social social health determinants socioenvironmental factor stress resilience stressor symposium translational neuroscience underserved community young adult

项目摘要

PROJECT SUMMARY/ABSTRACT The United States is grappling with racism as an ongoing public health crisis. A salient socioenvironmental chronic stressor in the lives of Black Americans, racism is associated with negative mental and physical health outcomes. The integrity of the medial temporal hippocampal (MTH) system is modifiable by extrinsic experiential factors, which can also increase its vulnerability. Opposite modulators of this system include cardiorespiratory fitness and chronic stress, which are differentially associated with pattern separation, a neurocomputational pro- cess reliant on the hippocampus that is vital for disambiguating highly similar stimuli during memory encoding. Our lab has shown that increased cardiorespiratory fitness positively impacts the MTH system in both young and older adults. In contrast, animal models and human neuroimaging studies of socioenvironmental chronic stress have shown extensive structural and functional reorganization of this system. The hippocampal long-axis also shows affective (anterior) and cognitive (posterior) differentiation, suggesting a neural substrate perturbed in mood disorders and by chronic stress. There is evidence of MTH neurocognitive deficits in young adulthood related to acute stress and mood disorders, but this has not been investigated as a consequence of chronic stress. The negative impact of racism may explain disparities in the severity and chronicity of mood disorders in Black Americans. In Aim 1, we demonstrate that 1) greater cardiorespiratory fitness predicts increased MTH cortical thickness in young but not older adults and 2) greater perceived discrimination predicts reduced MTH volume in a diverse group of older adults. In Aim 2 we hypothesize that greater perceived racism will be associ- ated with MTH neurocognitive deficits in Black young adults. Technical training will focus on gaining expertise in task-based high-resolution fMRI and advanced multivariate statistical modeling of behavioral and fMRI data. Thus, in relation to greater perceived racism, we seek to behaviorally examine associations with spatial and non- spatial pattern separation performance. Next, we will conduct advanced multivariate statistical modeling to quan- tify whether greater perceived racism modulates fMRI activity associated with a NIMH Research Domain Criteria correlate of hippocampal function, the Mnemonic Similarity Task. Finally, in Aim 3 we propose to identify a post- doctoral mentor with expertise in mood disorders, chronic stress, and/or neuroinflammation who can train me in experimental design and data analysis using modalities such as Positron Emission Tomography to investigate neuroinflammation, due to its well-established link to stressors.The broad, long term goal is to build brain health equity research capacity, identifying modifiable or mitigating factors of chronic stress due to intersecting margin- alized identities. Finally, this proposal seeks to address the BRAIN Initiative’s Scientific Review and High Priority Research Area for using multimodal methods to investigate the human brain in relation to behavioral and cogni- tive outcomes, answers a recent call by the NIMH to investigate socioenvironmental stressors and mitigating factors, and a push by the NIH to investigate how social determinants of health impact healthy living.

项目摘要/摘要美国正在与种族主义斗争，这是一种持续的公共卫生危机。一个显着的社会环境黑人美国人生活中的长期压力源，种族主义与负面的身心健康有关结果。外部专家可以修改媒体临时海马（MTH）系统的完整性因素，这也会增加其脆弱性。该系统的相反调节器包括心肺适应性和慢性应激，与模式分离有不同的相关性，一种神经计算的促值 CESS依赖于海马，这对于在记忆编码过程中消除高度相似的刺激至关重要。我们的实验室表明，增加心肺适应性对年轻和老年人。相反，动物模型和人类神经影像学研究已经显示了该系统的广泛结构和功能重组。海马长轴也显示情感（前）和认知（后）分化，表明神经底物干扰情绪障碍和慢性压力。有证据表明成年后的神经认知缺陷与急性压力和情绪障碍有关，但由于慢性压力。种族主义的负面影响可能解释了情绪障碍的严重性和慢性性差异黑人美国人。在AIM 1中，我们证明1）更大的心肺适应性预测增加了MTH 年轻人但不是老年人的皮质厚度，2）更大的感知歧视预测降低了mth 一组老年人的潜水员组。在AIM 2中，我们假设更大的种族主义将是相关的黑人年轻人中有MTH神经认知缺陷。技术培训将着重于获得专业知识基于任务的高分辨率fMRI和行为和fMRI数据的高级多元统计建模。关于种族主义，我们试图在行为上研究与空间和非 - 空间模式分离性能。接下来，我们将进行先进的多元统计建模认为更大的感知种族主义是否调节与NIMH研究领域标准相关的fMRI活动海马功能的相关性，助记符相似性任务。最后，在AIM 3中，我们建议确定一个后可以在情绪障碍，慢性压力和/或神经炎症方面具有专业知识的博士心理知识，可以训练我实验设计和数据分析使用诸如正电子发射断层扫描的模态进行研究神经炎症，由于其公认的压力链接，长期的长期目标是建立大脑健康股权研究能力，确定由于边缘相交而导致的可修改或减轻慢性应激因素身份的身份。最后，该建议旨在解决大脑倡议的科学审查和高度优先级研究领域，用于研究与行为和认知有关的人脑的研究领域结局，回答NIMH最近的呼吁调查社会环境压力并减轻压力因素，以及NIH的推动，以调查社会对健康的决定如何影响健康的生活。