Tackling Memory Deficits in Neurodegenerative Dementias using 7T-fMRI Investigations of Hippocampal Subfield Connectivity

使用 7T-fMRI 研究海马亚区连接来解决神经退行性痴呆症的记忆缺陷

• 批准号: 471863045
• 负责人: Privatdozentin Dr. Cornelia McCormick
• 金额: --
• 依托单位: Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/471863045?language=en
• 关键词: Tackling; Memory; Deficits; Neurodegenerative; Dementias

Neurodegenerative Dementias (NDs), including Alzheimer’s Dementia (AD) and Frontotemporal Dementia (FTD) are progressive, lethal diseases affecting more than 10 million people in Europe. Memory impairment, an early hallmark of NDs, represents a major burden. Especially devastating to individuals and their families are deficits in autobiographical memory (AM), by which patients lose the ability to recall moments from the past. Despite its huge impact on daily life, AM deficits are not being standardly assessed in memory clinics, and there is a gap in understanding the neural mechanisms involved. The neural network subserving AM is centered on the hippocampus, alongside a brain-wide network including the ventromedial prefrontal cortex (vmPFC) and the posterior neocortex. All of these regions are differentially affected in NDs. In particular, the hippocampus is affected in AD, the vmPFC in the behavioural variant of FTD (bvFTD), and the posterior neocortex in posterior cortical atrophy (PCA). Whereas general mnemonic deficits have been described in all of these NDs, there has been no systematic investigation of AM deficits in relation to disease-specific patterns of neuropathology. We know that the hippocampus, a central player in AM, is a heterogeneous brain structure comprising several anatomically distinct subfields which contribute differently to AM. Furthermore, hippocampal subfields are differentially affected in early AD, and likely in bvFTD and PCA. Nonetheless, there are no data on how hippocampal subfield activation or connectivity during AM are differently affected in NDs.Functional magnetic resonance imaging (fMRI) allows the investigation of whole-brain networks. However, the resolution of standard whole-brain 3 Tesla fMRI is limited to approx. 3 mm. This relatively low spatial resolution places severe limitations on neural network analysis. By comparison, recent advances in 7T-fMRI allow submillimeter resolution across the whole brain. This high resolution allows investigation of network interactions between neocortex and small substructures such as hippocampal subfields. Thus, the specific goals of the proposed research are: 1. To exploit 7 Tesla fMRI to investigate neuronal network dysfunction underlying AM impairment in several neuroanatomically distinct NDs;2. To relate the neuroanatomical patterns of network dysfunction to the specific neurocognitive deficits seen in these disorders.The proposed research facilitates an in-depth dissection of the functional roles of crucial memory structures. In doing so, this work permits testable new theoretical models of AM network mechanisms, potentially transforming our understanding of the neuronal underpinnings of human memory. In addition, this work will aid in the characterization of AM deficits and network dysfunction in several NDs enabling promising clinically-relevant outcomes valuable in early differential diagnosis, and assessment of disease progression.

神经退行性痴呆（ND），包括阿尔茨海默氏痴呆（AD）和额颞叶痴呆（FTD），是影响欧洲1000多万人的进行性致命疾病。记忆障碍，ND的早期标志，是一个主要的负担。对个人及其家庭来说，尤其具有毁灭性的是自传体记忆（AM）的缺陷，患者失去了回忆过去时刻的能力。尽管它对日常生活有着巨大的影响，但AM缺陷在记忆诊所中并没有得到标准的评估，并且在理解所涉及的神经机制方面存在差距。 辅助AM的神经网络以海马为中心，旁边是包括腹内侧前额叶皮层（vmPFC）和后部新皮层的全脑网络。所有这些区域在ND中受到不同的影响。特别是，AD中的海马、FTD行为变体（bvFTD）中的vmPFC和后皮质萎缩（PCA）中的后新皮质受到影响。虽然一般记忆缺陷已被描述在所有这些ND，一直没有系统的调查AM赤字与疾病特异性的神经病理学模式。我们知道，海马，在AM的中央球员，是一个异质性的大脑结构，包括几个解剖学上不同的子字段，有助于AM。此外，海马子场在早期AD中受到不同影响，并且可能在bvFTD和PCA中。尽管如此，有没有关于如何海马子场激活或连接在AM不同影响NDs.Functional磁共振成像（fMRI）允许全脑网络的调查数据。然而，标准的全脑3特斯拉功能磁共振成像的分辨率仅限于约。这种相对较低的空间分辨率对神经网络分析造成了严重的限制。相比之下，7 T-fMRI的最新进展允许整个大脑的亚毫米分辨率。这种高分辨率允许研究新皮层和小的子结构（如海马子场）之间的网络相互作用。因此，本研究的具体目标是：1. 目的：1.利用7 T fMRI研究神经解剖学上不同的ND中AM损伤的神经网络功能障碍。 将网络功能障碍的神经解剖模式与这些障碍中所见的特定神经认知缺陷联系起来。拟议的研究有助于深入剖析关键记忆结构的功能作用。在这样做的过程中，这项工作允许可测试的AM网络机制的新理论模型，可能会改变我们对人类记忆的神经元基础的理解。此外，这项工作将有助于表征AM缺陷和网络功能障碍的几个ND，使有前途的临床相关的结果在早期鉴别诊断和评估疾病进展。