Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2010 Nov 1;5(11):e13788. doi: 10.1371/journal.pone.0013788.
Local network connectivity disruptions in Alzheimer's disease patients have been found using graph analysis in BOLD fMRI. Other studies using MEG and cortical thickness measures, however, show more global long distance connectivity changes, both in functional and structural imaging data. The form and role of functional connectivity changes thus remains ambiguous. The current study shows more conclusive data on connectivity changes in early AD using graph analysis on resting-state condition fMRI data.
METHODOLOGY/PRINCIPAL FINDINGS: 18 mild AD patients and 21 healthy age-matched control subjects without memory complaints were investigated in resting-state condition with MRI at 1.5 Tesla. Functional coupling between brain regions was calculated on the basis of pair-wise synchronizations between regional time-series. Local (cluster coefficient) and global (path length) network measures were quantitatively defined. Compared to controls, the characteristic path length of AD functional networks is closer to the theoretical values of random networks, while no significant differences were found in cluster coefficient. The whole-brain average synchronization does not differ between Alzheimer and healthy control groups. Post-hoc analysis of the regional synchronization reveals increased AD synchronization involving the frontal cortices and generalized decreases located at the parietal and occipital regions. This effectively translates in a global reduction of functional long-distance links between frontal and caudal brain regions.
CONCLUSIONS/SIGNIFICANCE: We present evidence of AD-induced changes in global brain functional connectivity specifically affecting long-distance connectivity. This finding is highly relevant for it supports the anterior-posterior disconnection theory and its role in AD. Our results can be interpreted as reflecting the randomization of the brain functional networks in AD, further suggesting a loss of global information integration in disease.
在 BOLD fMRI 中使用图分析发现阿尔茨海默病患者的局部网络连接中断。然而，其他使用 MEG 和皮质厚度测量的研究显示，在功能和结构成像数据中，存在更多的全局远距离连接变化。因此，功能连接变化的形式和作用仍然不清楚。本研究使用静息状态 fMRI 数据的图分析，对早期 AD 患者的连接变化提供了更具结论性的数据。
方法/主要发现：在 1.5 Tesla 的 MRI 上，对 18 名轻度 AD 患者和 21 名无记忆主诉的年龄匹配健康对照者进行了静息状态研究。基于区域时间序列之间的成对同步，计算脑区之间的功能耦合。定量定义局部（簇系数）和全局（路径长度）网络度量。与对照组相比，AD 功能网络的特征路径长度更接近随机网络的理论值，而簇系数没有显著差异。阿尔茨海默病组和健康对照组之间的全脑平均同步性没有差异。对区域同步性的事后分析显示，AD 同步性增加涉及额叶皮质，而位于顶叶和枕叶的同步性普遍减少。这有效地转化为额叶和尾部脑区之间功能长程连接的全局减少。
结论/意义：我们提供了 AD 引起的大脑整体功能连接变化的证据，特别是影响远距离连接的证据。这一发现具有重要意义，因为它支持了前部-后部断开连接理论及其在 AD 中的作用。我们的结果可以解释为反映了 AD 中大脑功能网络的随机化，进一步表明疾病中全局信息整合的丧失。
