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Chinese Journal of Alzheimer's Disease and Related Disorders

Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders      Editor in chief: Jun WANG

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Chinese Journal of Alzheimer's Disease and Related Disorders >

2020 , Vol. 3 >Issue 4: 267 - 273

DOI: https://doi.org/10.3969/j.issn.2096-5516.2020.04.002

Study of fMRI of brain networks of patients with Parkinson's disease accompanied by cognition impairment

  • PENG Qiaojun , 1, 2 ,
  • WANG Yufeng 1, 2 ,
  • TAN Juan 1, 2 ,
  • HOU Changyue 1, 2 ,
  • WANG Yinxu 1, 2 ,
  • WANG Xiaoming , 1, 2
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  • 1 Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
  • 2 Institute of Neurological Diseases, Northern Sichuan Medical College, Nanchong 637000

Received date: 2020-08-30

  Revised date: 2020-09-03

  Online published: 2020-12-25

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Abstract

Objective: Investigate the changes of brain networks in patients with Parkinson's disease accompanied by cognitive impairment(PD-CI) in order to provide valuable information for the study of its neuroimaging mechanisms. Methods: A total of 22 patients with primary PD who visited neurology clinic of the Affiliated Hospital of North Sichuan Medical College from May 2019 to May 2020 were included. MoCA and MMSE were used to evaluate all subjects, divided them into 12 Parkinson's Disease with Cognitive Impairment (PD-CI), 10 Parkinson's disease with normal cognitive function(PD-NC), and 25 healthy controls (HC) matched with their age, sex, and years of education. Standard clinical feature assessment and Rs-fMRI scan were performed for all subjects. SPASS21.0 software was used to perform statistical analysis on the experimental data, and statistical methods such as independent sample t-test, one-way analysis of variance and chi-square test statistical methods were used. Regional homogeneity was adopted to analyze the Rs-fMRI data of patients in the three groups respectively, and brain regions with differences in ReHo values between each group were selected as region of interest (ROI), and then whole-brain FC analysis was conducted by using ROI-based functional connectivity (FC) method. Results: (1) ReHo value result analysis: compared with the HC group, the ReHo values of left cerebellar Angle 1, right orbital superior frontal gyrus, left medial superior frontal gyrus, right dorsolateral superior frontal gyrus, left inferior marginal angular gyrus, left medial and side cingulate gyrus were decreased in the PD-CI group, while those of right tongue gyrus were increased. Compared with the HC group, the values of ReHo in the left cerebellar Angle 1, right orbital superior frontal gyrus, left medial superior frontal gyrus, and left acromial inferior margin angular gyrus were decreased in the PD-NC group, and no regions with higher ReHo values were found. Compared with the PD-NC group, the right dorsolateral superior frontal gyrus had lower ReHo value and the right lingual gyrus had higher ReHo value in the PD-CI group. (2) FC result analysis: Compared with the HC group, in the PD-CI group, the functional connections between left medial superior frontal gyrus and left parahippocampal gyrus were weakened, the functional connections between left inferior marginal gyrus, left central sulcus lid and left triangular inferior frontal gyrus were weakened too, while that between right dorsolateral superior frontal gyrus and right precuneus and between left inferior marginal gyrus and right superior pillow gyrus were strengthened. Compared with the HC group, in the PD-NC group, the functional connection between left medial superior frontal gyrus and left parahippocampal gyrus and between left inferior marginal Angle gyrus and left triangular inferior frontal gyrus were weakened, while that between right dorsolateral superior frontal gyrus and right precuneus was strengthened. Compared with the PD-NC group, in the PD-CI group, the functional connections between the left inferior parietal gyrus and the left middle temporal gyrus and the left posterior central gyrus were weakened. Conclusion: (1) The decreasing of ReHo values of left cerebellar Angle 1, right orbitofrontal superior gyrus, left medial superior gyrus, right dorsolateral superior gyrus, left inferior marginal gyrus, left medial and paracingulate gyrus of PD-CI patients were associated with cognitive impairment of PD patients, while the increasing of ReHo values of right tongue gyrus may be the compensatory performance of cognitive function. (2) The default mode network (DMN) functional connections of PD-CI patients was changed and the change of DMN functional connections may be the key to their cognitive decline.These conclusions may help to further study the potential mechanism of PD-related cognitive impairment, and provide new ideas for the treatment of PD patients and their cognitive dysfunction.

Key words： Parkinson's disease; Cognition impairment; Resting-state functional magnetic resonance imaging; Brain network

Cite this article

PENG Qiaojun , WANG Yufeng , TAN Juan , HOU Changyue , WANG Yinxu , WANG Xiaoming . Study of fMRI of brain networks of patients with Parkinson's disease accompanied by cognition impairment[J]. Chinese Journal of Alzheimer's Disease and Related Disorders, 2020 , 3(4) : 267 -273 . DOI: 10.3969/j.issn.2096-5516.2020.04.002

帕金森病（Parkinson's disease, PD）是最常见的中枢神经系统退行性疾病之一,主要临床表现运动迟缓、静止性震颤、肌强直和姿势步态异常等运动症状外,非运动症状（non-motor symptoms, NMS）如认知障碍（cognitive impairment, CI）、感觉障碍、自主神经功能障碍、神经精神障碍等贯穿整个病程,可早于运动症状出现。CI是PD常见的非运动症状,60%的PD患者存在一个或多个认知领域受损,且尚缺乏明确有效的治疗手段[1]。静息态功能磁共振成像（resting-state functional magnetic resonance imaging, rs-fMRI）是一种非侵入性技术,目前已成为探索大脑活动和连接性的重要工具,在轻度认知功能障碍及痴呆中得到广泛运用[2]。其中区域一致性（regional homogeneity, ReHo）提供了一种基于体素与相邻体素间的时间相关性的局部功能连通方法,可以衡量区域内体素之间的活动协调性。而目前国内尚未见采用Rs-fMR探索PD-CI患者相关脑网络的报道;因此本研究运用Rs-fMRI观察PD-CI相关脑网络,以期为其神经影像机制探讨提供有价值的信息。

1 资料与方法

1.1 研究对象

纳入2019年5月到2020年5月就诊于川北医学院附属医院神经内科门诊的原发性PD患者共例22例,所有受试者均行蒙特利尔认知功能评估量表（Montreal Cognitive Assessment, MoCA）、简易智能评定量表（Mini-Mental State Examination, MMSE)评估,将其分为帕金森病伴认知功能障碍患者（Parkinson's Disease with Cognitive Impairment, PD-CI）12例,帕金森病认知功能正常患者（Parkinson's Disease with Normal Cognitive Function, PD-NC）)10例,以及与之年龄、性别、受教育年限相匹配的健康对照者（HC）25例。纳入标准：（1）符合2016年中国PD诊断标准,扫描前抗PD药物无调整且扫描前12 h临时停用抗PD药物;（2）所有患者能配合完成临床量表评估及长时间的磁共振扫描;（3）无MRI禁忌证,已签署同意书。排除标准：（1）排除各种原因引起的继发性帕金森综合征,排除PD以外的神经系统疾病;（2）有头部外伤史、卒中史、颅内感染等神经精神疾病;（3）糖尿病、严重的精神疾病,酒精或药物滥用史;（4）排除中-重度头部震颤者。所有受试者均签署知情同意书。

1.2 研究方法

收集PD患者的一般情况,包括：性别、年龄、文化程度、发病年龄、起病形式等。所有患者进行MMSE、MoCA评分、H-Y分级评估,将MoCA< 26分且MMSE> 24分的PD患者归为PD-IC组,将MoCA≥26分且MMSE> 24分的PD归为PD-NC组,静息态功能磁共振检查均于同一时间段内进行;HC组年龄、性别、受教育年限与PD患者组相匹配,亦均为右利手。所有健康对照者经病史询问无神经、精神疾病及药物依赖、成瘾的病史。先进行常规TIWI及T2WI扫描,排除有异常影像学表现者。
所有影像数据均在川北医学院附属医院3.0T磁共振室采集。采用美国GE公司生产的GE HD-X3.0T（DISCOVERY MR750,USA）超导性磁共振扫描仪,32通道相控阵头颅线圈接收信号。首先进行常规TIWI及CS-FMR T2WI扫描,然后进行rs-fMRI扫描,成像覆盖全脑。rs-fMR扫描参数如下：通过梯度回波平面成像（echo planar imaging, EPI）技术获得,扫描时间8分20秒,扫描参数：TR=2000 ms, TE=30 ms, FA=90°,层数=35层,层厚=4 mm,矩阵=64×64,视野（field of view, FOV）=240 mm×240 mm。

1.3 数据处理与统计学分析

Rs-fMRI数据预处理：使用SPM 8.0软件包（Statistical Parametric Mapping 8.0）进行。主要包括：去除前5个时间点,然后进行时间校正、头动校正（去除平动大于3 mm或转动大于3°的患者数据）、空间标准化、空间平滑等预处理。
ReHo分析：对没有空间平滑的图像进行去线性漂移、滤波和利用多元线性回归去除脑白质、脑脊液和六个运动信号在内的干扰信号对数据的影响。用REST软件计算数据的肯德尔和谐系数（Kendall's coefficient concordance, KCC）,即ReHo值,然后将得到的每一体素的ReHo值除以全脑ReHo的平均值以标准化。每个受试者的影像数据均获得一个相应的ReHo图像,然后再行高斯（Gausian）平滑、剔除空间标准化产生的微小差异。
FC分析：预处理后,利用多元线性回归去除脑白质、脑脊液和全脑信号以及六个运动参数在内的干扰信号对数据的影响,滤波（0.01-0.08 Hz）和去除线性趋势。将具有明显ReHo值差异的认知相关脑区定义为ROI,利用REST软件提取每个ROI内的BOLD信号,将各ROI的信号分别与全脑每个体素的信号进行FC分析,得到相关系数r,将其转换为符合正态分布的Z值后进一步进行统计学分析。
采用SPSS 21.0统计学软件。三组患者的性别、年龄等一般资料分别采用卡方检验及独立样本t检验采用、单因素方差分析的统计学方法。用“均数±标准差”表示,P< 0.05为差异有统计学意义。

2 结果

2.1 一般资料

PD患者共22例纳入本研究,根据MoCA及MMSE评分将PD患者分为PD-CI组12例（男性5例,女性7例,年龄范围58~75岁）和PD-NC组10 例（男性6例,女性4例,年龄范围53~79岁）。HC组共纳入25例符合条件的受试者（男性11例,女性14例,年龄范围54~73岁）。PD-CI组、PD-NC组及HC组在年龄、性别比例、教育年限部分,差异无统计学意义（P> 0.05）,PD-CI组和PD-NC组在病程、MMSE、H-Y分级、左旋多巴等效剂量部分,差异无统计学意义（P> 0.05）,PD-CI组和PD-NC组在MoCA量表评分比较,差异具有统计学意义（P< 0.05）。见表1。
表1 PD-CI组和PD-CN组及HC组一般资料及临床量表评分（ $\bar{x} \pm s$）
项目 PD-CI组 PD-NC组 HC组 P值
性别（男/女） 12（5/7） 10（4/6） 25（11/14） 0.974
年龄（岁） 66.66±6.34 65.50±7.46 63.12±4.76 0.197
病程（年） 4.41±1.64 4.20±1.14 0.665
教育年限（年） 6.16±3.13 6.10±2.77 6.32±2.63 0.973
MMSE 25.66±1.30 26.20±1.62 26.08±1.55 0.662
MoCA 21.08±2.15 26.90±0.88 26.96±1.02 0.000
H-Y分级 2.25±0.50 2.00±0.47 0.960
左旋多巴等效剂量(mg/d) 472.91±134.19 470.00±136.83 0.870

2.2 三组ReHo值结果

2.2.1 三组间差异

主要在右背外侧额上回、左侧小脑角1区、右舌回、左内侧额上回、右眶内额上回、左内侧和旁扣带脑回、左顶下缘角回,差异具有统计学意义（P< 0.05）,见图1,图2,表2。
图1 各组ReHo值差异脑区（不同的颜色深度代表不同的激活强度,由红转黄代表激活强度由弱到强）
图2 PD-CI组（PD伴认知障碍）、PC-NC组（PD不伴认知障碍）及HC组（正常对照）各脑区ReHo值比较
表2 三组间组ReHo值差异脑区
差异脑区 MNI坐标 F值 团块大小（体素）
X Y Z
右背外侧额上回 21 18 51 25.57 503
左小脑角1区 -9 -78 -27 13.27 401
右舌回 21 -72 0 15.27 296
左内侧额上回 0 45 24 11.27 234
右眶内额上回 33 57 -6 11.87 167
左内侧和旁扣带脑回 -6 -9 39 10.76 86
左顶下缘角回 -60 -33 42 9.71 67

Note: MNI:montreal neurological institute.

与HC组相比,PD-CI组左侧小脑角1区、右眶内额上回、左内侧额上回、右背外侧额上回、左顶下缘角回、左内侧和旁扣带脑回的ReHo值降低,右舌回的ReHo值增高（P< 0.05）,见图2,表3。
表3 PD-CI组与HC组ReHo值差异脑区
差异脑区 MNI坐标 F值 团块大小（体素）
X Y Z
PD-CI组<HC组
右背外侧额上回 21 18 51 25.57 503
左小脑角1区 -9 -78 -27 13.27 401
左内侧额上回 0 45 24 11.27 234
右眶内额上回 33 57 -6 11.87 167
左内侧和旁扣带脑回 -6 -9 39 10.76 86
左顶下缘角回 -60 -33 42 9.71 67
PD-CI组>HC组
右舌回 21 -72 0 15.27 296
PD-NC组与HC组相比,PD-NC组左侧小脑角1区、右眶内额上回、左内侧额上回、左顶下缘角回ReHo值降低,未发现ReHo值增高的区域（P< 0.05）,见图2,表4。
表4 PD-NC组与HC组ReHo值差异脑区
差异脑区 MNI坐标 F值 团块大小（体素）
X Y Z
PD-NC组<HC组
左小脑角1区 -9 -78 -27 13.27 401
左内侧额上回 0 45 24 11.27 234
右眶内额上回 33 57 -6 11.87 167
左顶下缘角回 -60 -33 42 9.71 67
与PD-NC组相比,PD-CI组右背外侧额上回ReHo值降低,右舌回ReHo值增高（P< 0.05）,见图2,表5。
表5 PD-CI组与PD-NC组ReHo值差异脑区
差异脑区 MNI坐标 F值 团块大小（体素）
X Y Z
PD-CI组<PD-NC组
右背外侧额上回 21 18 51 25.57 503
PD-CI组>PD-NC组
右舌回 21 -72 0 15.27 296

2.3 三组间差异脑区的功能连接

根据ReHo值选择以下3个脑区进行FC分析：左内侧额上回、右背外侧额上回、左顶下缘角回。
与HC组相比,PD-CI组和PD-NC组左内侧额上回与左海马旁回功能连接减弱;PD-CI组与PD-NC组相比左内侧额上回功能连接无明显差异（P< 0.05）,见图3。
图3 三组间左内侧颞上回功能连接差异
与HC组相比,PD-CI组和PD-NC组右背外侧额上回与右楔前叶连接增强;PD-CI组与PD-NC组右背外侧额上回功能连接无明显差异（P< 0.05）,见图4。
图4 三组间右背外侧额上回功能连接差异
与HC组相比,PD-CI组左顶下缘角回与左中央沟盖、左三角部额下回功能连接减弱;与HC组相比,PD-NC组左顶下缘角回与左三角部额下回连接减弱;与HC组相比,PD-CI组左顶下缘角回与右枕上回连接增强;与PD-NC组相比,PD-CI组左顶下缘角回与左颞中回、左中央后回功能连接减弱（P< 0.05）,见图5。
图5 三组间左顶下缘角回功能连接差异

3 讨论

2012年MDS工作组提出了PD-MCI的诊断标准和诊断程序指南[3],旨在提高对PD患者认知功能障碍的早期认识及早期干预,降低发展为PDD风险。PD患者可以出现多种认知领域损害,包括：执行功能、注意力及工作记忆力、语言能力、视空间能力和记忆,目前PD-CI发病机制尚不明确。rs-fMRI技术的发展为探索PD患者认知功能障碍的发病机制提供了新的途径,并可能有助于为其影像诊断提供帮助。Meta分析显示PD患者的ReHo值在很大程度上不受年龄、疾病持续时间和扫描仪场强的潜在混杂变量的影响,进一步证实研究结果的可靠性[4]。

3.1 区域一致性分析

本研究结果显示,与HC组相比,PD-CI和PD-NC组左侧小脑角1区、右眶内额上回、左内侧额上回、左顶下缘角回ReHo值降低,提示这些脑区的神经元活动一致性下降,可能存在脑功能异常。据报道,枕叶和舌回涉及视觉识别,并认为在情景记忆巩固中起作用。先前的研究表明不伴痴呆的PD患者经常会出现各种认知异常,尤其是视空间障碍,且视觉相关区域局部脑血流量减少[5-6]。枕叶视觉皮层损害与整体认知功能下降有关,且发生痴呆的风险更高,既往研究也证实在PD患者视觉皮层观察到ReHo值的广泛下降[7],本研究发现PD-CI组与PD-CN组及HC组相比,右舌回ReHo值增高,提示PD-CI组患者右舌回神经元活动一致性增强,可能与PD患者枕叶视觉皮层损害导致其舌回适应性补偿效应有关。额上回已被报道广泛参与多种认知和运动控制任务,背外侧前额叶皮层从黑质致密部和腹侧被盖区接收多巴胺投射,并且与工作记忆和注意力执行相关[8⇓-10]。本研究发现PD-CI组右背外侧额上回ReHo值降低,推测PD-CI认知障碍可能与多巴胺缺乏有关。

3.2 功能连接分析

研究发现PD患者整个大脑及不同脑网络内的连接发生变化,其中DMN的改变是PD-CI患者Rs-fMRI的主要标志,其主要包括内侧前额叶皮层（medial prefrontal cortex, MPFC）、后扣带回皮层、楔前叶、内侧颞叶（medial temporal lobe, MTL）和下顶叶皮层,在静息状态下具有很高的代谢活性[11]。多项研究证实PD患者DMN区域之间的功能性连接受到破坏,且与认知功能相关[12⇓-14]。MPFC是DMN的关键节点,已被证明在执行功能中起着至关重要的作用[15],且该区域在背侧注意力网络和DMN不同模式的转换发挥了关键作用[16]。PD患者认知障碍主要表现为额皮层下的注意执行障碍[17],可能与PD患者前额叶内葡萄糖代谢下降有关[18]。有学者发现,即使无认知受损的PD患者其DMN内功能连接性已有所降低,并且DMN连接性降低与认知参数（包括执行、记忆、视觉空间能力等方面）显著相关,与患病时间、运动障碍严重程度以及使用左旋多巴治疗并无相关性,从而推测DMN连接功能障碍可能是导致PD认知功能减退的关键因素[19]。
本研究发现,与HC组相比,PD-CI组和PD-NC组左内侧额上回与左海马旁回功能连接减弱,左顶下缘角回与左三角部额下回功能连接减弱,而左内侧额上回、左顶下缘角回属于DMN,表明即使PD患者无认知功能下降,DMN连接功能已发生障碍,与既往研究一致[19];顶下小叶包括缘回和角上回,与人的痛觉、触觉、味觉、认知、空间感觉处理等有关。楔前叶是DMN的核心功能脑区,与许多高级认知功能相关,例如情境记忆、自我相关信息处理及意识[19]。其葡萄糖代谢比大脑其他区域高35%,与前额叶、顶叶、运动前区、补充运动区之间存在广泛联系[20]。其选择性与顶叶脑区相连,参与视觉空间信息处理[21];本研究发现,与HC组相比,PD-CI组和PD-NC组右背外侧额上回与右楔前叶连接增强,PD-CI组左顶下缘角回与右枕上回连接增强,这可能与PD患者视觉空间、视觉感知表现更差而导致的补偿效应有关。颞叶主要涉及视觉感知、感觉信息处理、记忆、语音理解和情感活动,是语义网络的一部分[22]。PD患者的内侧颞叶损伤与较差的记忆表现有关[19];与顶下小叶皮质的功能连接性降低与PD患者视觉空间性能相关[23]。本研究发现与PD-NC组相比,PD-CI组左顶下缘角回与左颞中回、左中央后回功能连接减弱,可能与PD-CI患者较PD-NC患者视空间能力、运动功能进一步加重有关。
由于样本量较小,本研究未对PD患者认知功能障碍损害细分亚组,未将PD患者MoCA评分与其功能连接差异进行相关性分析。在未来的研究中,需进一步扩大样本,对PD认知功能损害患者细分亚组,进一步探索PD-CI不同认知领域损害相关脑网络。可运用EEG-fMRI、PET和DTI等多种神经影像学方法进行研究,将有助于进一步明确 PD-CI病理生理机制或核心网络。

References

Publishing order | Descend order by publishing year | Descend order by cited within
[1]
Aarsland, D, Brønnick, K, Fladby, T, et al. Mild cognitive impairment in Parkinson's disease[J]. Curr Neurol Neurosci Rep, 2011, 11(4): 371-378.

DOI

[2]
Xie, CM, Bai, F, Yu, H, et al. Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment[J]. NeuroImage, 2012, 63(1): 320-327.

DOI

[3]
Litvan, I, Goldman, JG, Tröster, AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines[J]. Mov Disord, 2012, 27(3): 349-356.

DOI

[4]
Pan, PL, Zhan, H, Xia, MX, et al. Aberrant regional homogeneity in Parkinson's disease: A voxel-wise meta-analysis of resting-state functional magnetic resonance imaging studies[J]. Neurosci Biobehav Rev, 2017, 72: 223-231.

DOI

[5]
Seichepine, DR, Neargarder, S, Davidsdottir, S, et al. Side and type of initial motor symptom influences visuospatial functioning in Parkinson's disease[J]. J Parkinsons Dis, 2015, 1(5): 75-83.

[6]
Abe, Y, Kachi, T, Kato, T, et al. Occipital hypoperfusion in Parkinson's disease without dementia: correlation to impaired cortical visual processing[J]. J Neurol Neurosurg Psychiatry, 2003, 74(4): 419-422.

DOI

[7]
Hu, J, Xiao, CY, Gong, DW, et al. Regional homogeneity analysis of major Parkinson’s disease subtypes based on functional magnetic resonance imaging[J]. Neurosci Lett, 2019, 706: 81-87.

DOI

[8]
Corbetta, M, Shulman, GL. Control of goal-directed and stimulus-driven attention in the brain[J]. Nat Rev Neurosci, 2002, 3: 201-215.

[9]
Baggio, HC, Segura, B, Garrido-Millan, JL, et al. Resting-state frontostriatal functional connectivity in Parkinson's disease-related apathy[J]. Mov Disord, 2015, 30(5): 671-679.

DOI

[10]
Hatz, F, Meyer, A, Zimmermann, R, et al. Apathy in patients with Parkinson's disease correlates with alteration of left fronto-polar electroencephalographic connectivity[J]. Front Aging Neurosci, 2017, 9: 262.

DOI

[11]
Marcus, ER, Ann, MM, Abraham, ZS, et al. A default mode of brain function[J]. Proc Natl Acad Sci U S A, 2001, 98(2): 676-682.

DOI

[12]
Olaia, LJ, Natalia, O, Javier, P, et al. Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson's disease[J]. Parkinsonism Relat Disord, 2016, 33: 58-64.

DOI

[13]
Aracil, BI, Sampedro, F, Marín, LJ, et al. A divergent breakdown of neurocognitive networks in Parkinson's Disease mild cognitive impairment[J]. Hum Brain Mapp, 2019, 40(11): 3233-3242.

DOI PMID

[14]
Zhan, ZW, Lin, LZ, Yu, EH, et al. Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia[J]. CNS Neurosci Ther, 2018, 24(10): 897-905.

DOI

[15]
Funahashi, S, Andreau, JM. Prefrontal cortex and neural mechanisms of executive function[J]. J Physiol Paris, 2013, 107(6): 471-482.

DOI PMID

[16]
Sridharan, D, Levitin, DJ, Menon, V, et al. A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks[J]. Proc Natl Acad Sci U S A, 2008, 105(34): 12569-12574.

DOI

[17]
Kehagia, AA, Barker, RA, Robbins, TW, et al. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease[J]. Lancet Neurol, 2010, 9(12): 1200-1213.

DOI PMID

[18]
Chaorui, H, Chengke, T, Andrew, F, et al. Changes in network activity with the progression of Parkinson's disease[J]. Brain, 2007, 130(7): 1834-1846.

DOI

[19]
Tessitore, A, Esposito, F, Vitale, C, et al. Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease[J]. Neurology, 2012, 79(23): 2226-2232.

DOI

[20]
Cavanna, AE, Trimble, MR. The precuneus: a review of its functional anatomy and behavioural correlates[J]. Brain, 2006, 129(3): 564-583.

DOI

[21]
Cavada, C, Goldman-Rakic, PS. Posterior parietal cortex in rhesus monkey: Ⅱ. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe[J]. J Comp Neurol, 1989, 4(287): 422-445.

[22]
Zhan, ZW, Lin, LZ, Yu, EH, et al. Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia[J]. CNS Neurosci Ther, 2018, 24(10): 897-905.

DOI

[23]
Baggio, HC, Junqué, C. Functional MRI in Parkinson's disease cognitive impairment[J]. Int Rev Neurobiol, 2019, 144: 29-58.

DOI PMID

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