Objective.在最近的研究中,网络控制理论已被应用于阐明大脑状态之间的转变,强调评估大脑网络的可控性在促进从一个状态到另一个状态的转变中的重要性。尽管取得了这些进步,与阿尔茨海默病(AD)相关的功能网络可控性的潜在改变,以及导致这些改变的潜在遗传机制,仍然不清楚。方法。我们对AD患者(n=64)和匹配的正常对照(NCs,n=64)。我们调查了AD中可控性测量改变与认知功能之间的关联。此外,我们结合Allen人脑图谱进行了相关分析,以确定其表达与AD中功能网络可控性变化相关的基因。然后对鉴定基因的功能特征进行了一系列分析。主要结果。与NC相比,AD患者的平均可控性降低,主要在默认模式网络(DMN)内(63%的分区),边缘(LIM)网络内的平均可控性增加(占部分的33%)。相反,AD患者在LIM网络中表现出模态可控性的降低(27%的分组)和在DMN中表现出模态可控性的增加(80%的分组)。在AD患者中,显著性网络的平均可控性与小精神状态考试成绩之间存在显著正相关。可控性测量的变化与转录组概况表现出空间相关性。鉴定的重要基因在神经生物学相关途径中表现出富集,并在各种组织中表现出优先表达。细胞类型,和发展时期。意义。我们的发现有可能为AD中功能网络可控性改变的遗传机制提供新的见解。此外,这些结果为更深入地了解AD的发病机制和治疗策略的发展提供了前景.
Objective. In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network
controllability associated with Alzheimer\'s disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear.Approach. We conducted a comparative analysis of functional network
controllability measures between patients with AD (n= 64) and matched normal controls (NCs,n= 64). We investigated the association between altered
controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes.Main results. In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal
controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in
controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods.Significance. Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.