Functional Disconnection and Compensation in Mild Cognitive Impairment: Evidence from DLPFC Connectivity Using Resting-State fMRI

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in mild cognitive impairment (MCI) has given prominence to its importance in studies on the disconnection associated with MCI. The purpose of the current study was to examine the DLPFC functional connectivity patterns during rest in MCI patients and the impact of regional grey matter (GM) atrophy on the functional results. Structural and functional MRI data were collected from 14 MCI patients and 14 age, gender-matched healthy controls. We found that both the bilateral DLPFC showed reduced functional connectivity with the inferior parietal lobule (IPL), superior/medial frontal gyrus and sub-cortical regions (e.g., thalamus, putamen) in MCI patients when compared with healthy controls. Moreover, the DLPFC connectivity with the IPL and thalamus significantly correlated with the cognitive performance of patients as measured by mini-mental state examination (MMSE), clock drawing test (CDT), and California verbal learning test (CVLT) scores. When taking GM atrophy as covariates, these results were approximately consistent with those without correction, although there may be a decrease in the statistical power. These results suggest that the DLPFC disconnections may be the substrates of cognitive impairments in MCI patients. In addition, we also found enhanced functional connectivity between the left DLPFC and the right prefrontal cortex in MCI patients. This is consistent with previous findings of MCI-related increased activation during cognitive tasks, and may represent a compensatory mechanism in MCI patients. Together, the present study demonstrated the coexistence of functional disconnection and compensation in MCI patients using DLPFC functional connectivity analysis, and thus might provide insights into biological mechanism of the disease.背外侧前额叶皮层（dorsolateral prefrontal cortex, DLPFC）在轻度认知障碍（mild cognitive impairment, MCI）中已知的区域异常及其在各类神经环路中的作用，凸显了其在与MCI相关的神经断开研究中的重要地位。本研究旨在探讨轻度认知障碍患者静息状态下背外侧前额叶皮层的功能连接模式，以及区域灰质（grey matter, GM）萎缩对该功能连接结果的影响。我们收集了14名轻度认知障碍患者与14名年龄、性别匹配的健康对照者的结构磁共振成像与功能磁共振成像数据。研究发现，与健康对照相比，轻度认知障碍患者的双侧背外侧前额叶皮层与顶下小叶（inferior parietal lobule, IPL）、额上/内侧回以及丘脑、壳核等皮层下区域的功能连接均显著减弱。此外，背外侧前额叶皮层与顶下小叶、丘脑的功能连接强度，与患者通过简易精神状态检查表（mini-mental state examination, MMSE）、画钟测验（clock drawing test, CDT）以及加州语言学习测验（California verbal learning test, CVLT）测得的认知评分显著相关。当将区域灰质萎缩作为协变量进行校正后，上述结果与未校正时大体一致，尽管统计效力可能有所下降。上述结果表明，背外侧前额叶皮层的功能断开可能是轻度认知障碍患者认知损害的病理基础。此外，我们还发现轻度认知障碍患者左侧背外侧前额叶皮层与右侧前额叶皮层之间的功能连接显著增强。这与此前关于轻度认知障碍患者在认知任务中激活增强的研究结果一致，或可代表轻度认知障碍患者的一种代偿机制。综上，本研究通过背外侧前额叶皮层功能连接分析，证实了轻度认知障碍患者同时存在功能断开与代偿机制，从而为阐明该疾病的生物学机制提供了新的见解。