Amnestic mild cognitive impairment (aMCI) is considered as a transitional stage between normal aging and Alzheimer’s disease (AD), which has high risk of deteriorating into AD. Due to the irreversibility of AD, researchers pay more attention to this aMCI stage and try to investigate the underlying pathological mechanism.Disconnection hypothesis is one of the popular hypotheses about pathological mechanism of aMCI. Previous studies revealed either local or remote functional connectivity disruptions in aMCI patients, however, no study systematically investigated the intrinsic pattern of distance-related functional connectivity alterations in aMCI patients.
To investigate the local-to-remote functional connectivity alterations in aMCI, Dr. Hui-Jie Li from Institute of Psychology, and Dr. Kuncheng Li from Xuanwu Hospital cooperated to explore distance-related connectional changes in aMCI. They used a novel surface-based regional homogeneity method to investigate the functional synchronization at local scale. Further, they employed seed-based functional connectivity method to investigate the disrupted remote functional connectivity across whole-cortex brain regions associated with abnormal regional functional homogeneity. This work revealed the reduced functional synchronizationin the default mode network (right posterior cingulate cortex) and increased functional synchronization in the somatomotor network (left precentralgyrus and postcentral sulcus) (Fig. 1C).
Fig. 1. MCI alters local synchronizations in the default and somatomotor networks.
Seeded by regions with abnormal local functional connectivity, this work revealed a spatially distributed profile of reduced remote connectivity across the default network and strengthened remote functional connectivity between the right posterior cingulate cortex (default mode network core node) and a set of brain areas within the somatomotor and attention networks in aMCI patients (Fig. 2C). They also analyzed the functional covariance between local and remote functional connectivity at both global and regional levels by using inter-participant correlation approaches, and revealed local-remote functional associations in region-specific scale (Fig. 3).The results showed that remotefunctional connectivity exhibitedpredictive value for behavioral performance measured by auditoryverbal learning tests on theindividual performance of episodicmemory (Fig. 4).
Fig. 2. Dysfunctional remote functional connectivity in aMCI patients.
Fig. 3. Functional covariance between local and remote connectivity.
Fig. 4. Connectivity dysfunction and behavioral performance.
The current local and remote dysfunctional connectivity showed that the dysfunctional pattern of the abnormal cortical connectomic profile might be an underlying neurodegenerative feature in aMCI patients. Thiswork highlighted the importance of examiningchanges in distance-related functional connectomics of aMCI.
This study was supported by National Basic Research Program (973Program) (2015CB351702), Chinese Academy of Sciences YouthInnovation Promotion Association (2016084), National NaturalScience Foundation of China and Beijing Municipal Science & Technology Commission.
The paper is now available online from Neurobiology of aging. Yi-Wen Zhang#, Zhi-Lian Zhao#, Zhi-Gang Qi, Yang Hu, Yin-Shan Wang, Can Sheng, Yu Sun, Xiao-Ni Wang, Li-Li Jiang, Chao-Gan Yan, Kun-Cheng Li*, Hui-Jie Li*, Xi-NianZuo. Local-to-remote cortical connectivity in amnestic mild cognitive impairment. 2017. Neurobiology of Aging. https://doi.org/10.1016/j.neurobiolaging.2017.04.016