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

项目摘要/摘要 美国正在努力应对种族主义这一持续的公共卫生危机。突出的社会环境 在美国黑人的生活中，种族主义与消极的心理和身体健康有关 结果。内侧颞叶海马体(MTH)系统的完整性可以通过外在经验来改变 因素，这也可能增加其脆弱性。这个系统的相反调节器包括心肺。 健康和慢性压力与模式分离有不同的关联，这是一种神经计算程序。 CESS依赖于海马体，在记忆编码过程中，海马体对消除高度相似的刺激至关重要。 我们的实验室已经表明，增加心肺健康对青少年和青少年的MTH系统都有积极的影响 上了年纪的人。相比之下，社会环境慢性应激的动物模型和人类神经成像研究 已经显示出这一系统在结构和功能上的广泛重组。海马体长轴也 显示情感(前部)和认知(后部)分化，表明神经底物受到干扰 情绪障碍和慢性压力。有证据表明MTH在青年时期存在神经认知缺陷 与急性应激和情绪障碍有关，但这还没有作为慢性疾病的结果进行调查 压力。种族主义的负面影响可能解释了情绪障碍在严重程度和慢性程度上的差异。 美国黑人。在目标1中，我们论证了1)心肺健康状况越好，MTH越高。 年轻人而不是老年人的皮质厚度和2)更大的辨别力预测MTH降低 一组不同的老年人的音量。在目标2中，我们假设更大的种族主义将与 患有MTH神经认知缺陷的黑人青年。技术培训将侧重于获得以下方面的专业知识 基于任务的高分辨率功能磁共振成像以及先进的行为和功能磁共振数据多元统计建模。 因此，关于更严重的种族主义，我们寻求从行为上考察与空间和非空间的联系 空间模式分离性能。接下来，我们将对权值进行高级多元统计建模。 确定更大的种族主义是否会调节与NIMH研究领域标准相关的fMRI活动 海马区功能与记忆相似性任务的相关性。最后，在目标3中，我们建议确定一个职位- 在情绪障碍、慢性压力和/或神经炎方面有专业知识的博士导师，他可以培训我 用正电子发射断层扫描等方式进行研究的实验设计和数据分析 神经炎，因为它与压力的联系已经确立。广泛的、长期的目标是建立大脑健康 股票研究能力，确定因交叉边际而导致的慢性压力的可修改或缓解因素- 将身份具体化。最后，这项提案寻求解决大脑倡议的科学审查和高度优先事项 使用多模式方法研究人脑与行为和认知的关系的研究领域 积极的结果，回应了NIMH最近关于调查社会环境应激源和缓解压力的呼吁 因素，以及美国国立卫生研究院推动调查健康的社会决定因素如何影响健康生活。

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.