Pedersen Robin, Johansson Jarkko, Salami Alireza
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden.
Aging Brain. 2023 Jun 15;3:100079. doi: 10.1016/j.nbas.2023.100079. eCollection 2023.
Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age.
以往的研究表明，随着个体年龄增长，脑网络内连接性下降，而脑网络间连接性增加，这种模式被称为功能去分化。虽然脑网络分隔减少背后的机制尚未完全明确，但有证据表明多巴胺（DA）系统中与年龄相关的差异可能起关键作用。多巴胺D1受体（D1DR）是多巴胺能系统中含量最丰富且对年龄敏感的受体亚型，已知其可调节突触活动并增强神经元信号的特异性。在这项来自动态网络与衰老认知（DyNAMiC）项目的研究中（N = 180，年龄20 - 79岁），我们着手探究年龄、功能连接性和多巴胺D1DR可用性之间的相互作用。通过多元偏最小二乘法（PLS）的一种新应用，我们发现年龄较大以及D1DR可用性较低，均与脑网络内连接性下降和脑网络间连接性增加的模式同时相关。表现出大规模脑网络更显著差异的个体工作记忆效率更高。与维持假说一致，我们发现与尾状核中D1DR较少的年龄匹配个体相比，尾状核中D1DR较多的老年个体脑连接组的去分化程度较低，且工作记忆能力更强。这些发现表明，多巴胺能神经传递在衰老过程中的功能去分化中起重要作用，对老年时的工作记忆功能产生影响。
