Murai Shota A, Mano Tatsuo, Sanes Jerome N, Watanabe Takamitsu
International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, Bunkyo City, Tokyo 113-0033, Japan.
Department of Degenerative Neurological Diseases, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.
Brain Commun. 2024 Jul 11;6(4):fcae199. doi: 10.1093/braincomms/fcae199. eCollection 2024.
Alzheimer's disease is characterized by cognitive impairment and progressive brain atrophy. Recent human neuroimaging studies reported atypical anatomical and functional changes in some regions in the default mode network in patients with Alzheimer's disease, but which brain area of the default mode network is the key region whose atrophy disturbs the entire network activity and consequently contributes to the symptoms of the disease remains unidentified. Here, in this case-control study, we aimed to identify crucial neural regions that mediated the phenotype of Alzheimer's disease, and as such, we examined the intrinsic neural timescales-a functional metric to evaluate the capacity to integrate diverse neural information-and grey matter volume of the regions in the default mode network using resting-state functional MRI images and structural MRI data obtained from individuals with Alzheimer's disease and cognitively typical people. After confirming the atypically short neural timescale of the entire default mode network in Alzheimer's disease and its link with the symptoms of the disease, we found that the shortened neural timescale of the default mode network was associated with the aberrantly short neural timescale of the left angular gyrus. Moreover, we revealed that the shortened neural timescale of the angular gyrus was correlated with the atypically reduced grey matter volume of this parietal region. Furthermore, we identified an association between the neural structure, brain function and symptoms and proposed a model in which the reduced grey matter volume of the left angular gyrus shortened the intrinsic neural time of the region, which then destabilized the entire neural timescale of the default mode network and resultantly contributed to cognitive decline in Alzheimer's disease. These findings highlight the key role of the left angular gyrus in the anatomical and functional aetiology of Alzheimer's disease.
阿尔茨海默病的特征是认知障碍和进行性脑萎缩。最近的人类神经影像学研究报告称，阿尔茨海默病患者默认模式网络的某些区域存在非典型的解剖和功能变化，但默认模式网络的哪个脑区是关键区域，其萎缩扰乱了整个网络活动，进而导致疾病症状，目前仍未明确。在此病例对照研究中，我们旨在确定介导阿尔茨海默病表型的关键神经区域，因此，我们使用静息态功能磁共振成像图像和从阿尔茨海默病患者及认知正常者获得的结构磁共振成像数据，研究了默认模式网络区域的内在神经时间尺度——一种评估整合不同神经信息能力的功能指标——以及灰质体积。在确认阿尔茨海默病患者整个默认模式网络的神经时间尺度非典型缩短及其与疾病症状的关联后，我们发现默认模式网络缩短的神经时间尺度与左侧角回异常缩短的神经时间尺度相关。此外，我们还发现角回缩短的神经时间尺度与该顶叶区域非典型减少的灰质体积相关。此外，我们确定了神经结构、脑功能与症状之间的关联，并提出了一个模型，即左侧角回灰质体积减少缩短了该区域的内在神经时间，进而破坏了默认模式网络的整个神经时间尺度，最终导致阿尔茨海默病患者的认知衰退。这些发现突出了左侧角回在阿尔茨海默病解剖和功能病因学中的关键作用。
