Harrington Deborah L, Shen Qian, Castillo Gabriel N, Filoteo J Vincent, Litvan Irene, Takahashi Colleen, French Chelsea
Cognitive Neuroimaging Laboratory, Research Service, VA San Diego Healthcare System, San DiegoCA, United States.
Department of Radiology, University of California, San Diego, La JollaCA, United States.
Front Aging Neurosci. 2017 Jun 19;9:197. doi: 10.3389/fnagi.2017.00197. eCollection 2017.
Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.
静息态功能磁共振成像（rsfMRI）期间内在活动的紊乱在帕金森病（PD）中很常见，但大多是在特定子网络中进行研究。异常内在活动的认知意义以及轻度认知障碍发作之前的异常情况也知之甚少。为了解决这些局限性，我们采用了三种不同的分析方法来识别31名认知正常的PD患者（PD-CN）和30名健康成年人的rsfMRI指标紊乱情况。使用运动障碍协会特别工作组二级标准对受试者进行轻度认知障碍筛查。全脑数据驱动的分析方法首先分析低频内在波动幅度（ALFF）和区域同质性（ReHo），后者是功能相似区域之间局部连通性的一种度量。然后我们检查这些指标中的区域紊乱是否改变了与其他脑区的功能连接。我们还研究了PD-CN中异常的rsfMRI指标是否与脑萎缩以及执行功能、视觉组织和情景记忆功能有关。结果显示，在默认模式网络（后扣带回、顶下小叶、海马旁回、内嗅皮质）、感觉运动皮质（初级运动区、中央前/后回）、基底神经节（壳核、尾状核）以及介导认知的小脑后叶VII中，PD-CN患者的ALFF和ReHo出现异常增加和减少。对于默认模式网络区域，我们还观察到ALFF和ReHo改变的复合特征。ALFF和ReHo中的大多数区域紊乱与PD-CN中增强的长程相互作用有关，特别是与不同网络中的区域有关。PD-CN中更强的长程功能连接也部分扩展到了对照组网络之外的连接。异常增加的活动和功能连接似乎对本研究中测试的认知能力产生了病理性而非代偿性影响。受试者工作特征曲线分析表明，rsfMRI变量在区分患者和对照组方面具有出色的敏感性（≥90%），但脑容量和认知变量的准确性较差。总之，这些结果为临床显著认知障碍之前异常内在活动和连接的拓扑结构、认知相关性和敏感性提供了新的见解。需要进行纵向研究以确定这些神经认知关联是否预示着未来轻度认知障碍或痴呆的发展。
