Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Department of Physics, Goteborg University, Goteborg, Sweden.
Elife. 2023 Aug 31;12:RP87188. doi: 10.7554/eLife.87188.
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
蓝斑核（LC）是一个重要的去甲肾上腺素能核团，由于其在认知和精神障碍中的新兴作用，最近引起了很多关注。尽管之前的组织学研究表明 LC 具有异质性的连接和细胞特征，但尚无研究评估其在体内的功能拓扑结构、这种异质性如何随年龄变化，以及它是否与认知和情绪有关。在这里，我们使用基于梯度的方法，使用来自 18 至 88 岁人群的 3T 静息态 fMRI（剑桥衰老与神经科学中心队列，n=618）来描述 LC 随年龄变化的功能异质性。我们发现 LC 在其纵轴上表现出一个从前往后的功能梯度，这在一个独立数据集（人类连接组计划[HCP]7T 数据集，n=184）中得到了复制。尽管该梯度的主要前后方向在不同年龄组中是一致的，但随着年龄的增长、情绪记忆和情绪调节，其空间特征会发生变化。更具体地说，与年龄较大和行为表现较差相关的是，丧失类似头端的连接、更集中的功能拓扑和右左 LC 梯度之间更大的不对称性。此外，医院焦虑和抑郁量表（HADS）评分高于正常的参与者也表现出梯度的改变，表现为更大的不对称性。这些结果提供了 LC 功能拓扑结构随年龄变化的体内描述，并暗示这种组织的空间特征是与 LC 相关的行为测量和精神病理学相关的标记物。
