帕金森病伴姿势不稳/步态障碍患者大脑动态功能网络连接模式改变的研究

Altered brain dynamic functional network connectivity in Parkinson's disease patients with postural instability/gait difficulty

目的探讨帕金森病(PD)中姿势不稳/步态障碍(PIGD)亚型患者大脑动态功能网络连接模式的改变及意义。方法收集南京医科大学第一附属医院神经内科自2016年5月至2019年8月收治的90例PD患者以及性别、年龄相匹配的54例健康对照的临床资料及静息态功能磁共振成像(rs-fMRI)数据,根据统一帕金森病评定量表(UPDRS)相关评分将PD患者分为PD伴姿势不稳/步态障碍(PD-PIGD)组(49例)和非PIGD(PD-non-PIGD)组(41例)。采用独立成分分析(ICA)法、滑动窗口法和k-means聚类法进行大脑动态功能网络连接分析及组间比较,使用偏相关分析检验动态功能连接属性和临床量表之间的相关性。结果共识别出4个重复出现的功能连接状态,PD-PIGD患者在低连通模式的状态3(44%)和状态2(23%)中出现频率较高。时间属性方面,PD-PIGD组患者在状态3中的平均停留时间明显高于PD-non-PIGD组,转化次数明显低于PD-non-PIGD组患者及健康对照组,差异均有统计学意义[P<0.05,错误发现率(FDR)校正];PD-PIGD组在状态2中的时间分数和平均停留时间均明显高于健康对照组,差异均有统计学意义(P<0.05,FDR校正)。功能连接强度方面,状态2中PD-PIGD组受试者默认模式网络中的内侧额上回(IC17)和楔前叶(IC30)、听觉网络中的颞上回(IC16)和颞中回(IC33)之间的连接明显减弱,默认模式网络(DMN)中的楔前叶(IC30)与感觉运动网络中的辅助运动区(IC25)之间的连接显著增强;差异均有统计学意义(P<0.05,FDR校正)。偏相关分析显示PD-PIGD组在状态3中的平均停留时间与PIGD评分呈正相关关系(r=0.450,P=0.039)。结论PD-PIGD患者存在特异性的动态功能网络连接模式,主要表现为大脑功能网络的低连通性及更长的停留时间;DMN、听觉网络、感觉运动网络间和网络内存在局部功能网络域间分离特性。

Objective To investigate the alterations in brain dynamic functional network connectivity(dFNC)and their significance in Parkinson's disease(PD)patients with postural instability/gait difficulty(PIGD).Methods Ninety PD patients admitted to Department of Neurology,First Affiliated Hospital of Nanjing Medical University from May 2016 to August 2019 were recruited,and 54 healthy controls matched with gender and age were chosen;their clinical data and resting-state functional MRI(rs-fMRI)data were collected.PD patients were divided into PD with PIGD(PD-PIGD)group(n=49)and PD without PIGD(PD-non-PIGD)group(n=41)according to Unified Parkinson's Disease Rating Scale(UPDRS)scores.Independent component analysis(ICA),sliding window method and k-means clustering were used to analyze the dFNC and compare among groups.Correlations of dFNC alterations with clinical scales were verified by partial correlation analysis.Results Four repeated recurring functional connectivity states were identified,and PD-PIGD patients had high frequency in state 3(44%)and state 2(23%)of the low dFNC.In terms of dFNC time attributes,PD-PIGD patients had longer mean dwell time in state 3 than PD-non-PIGD patients and had lower number of transitions in state 3 than PD-non-PIGD patients and healthy controls,with significant differences(P<0.05);PD-PIGD patients had significantly higher fractional windows and statistically longer mean dwell time in state 2 than healthy controls(P<0.05).In terms of dFNC strengths,compared with healthy controls,PD-PIGD patients showed significantly decreased functional connectivity within default mode network(DMN,between medial superior frontal gyrus and precuneus)and auditory network(AN,between superior temporal gyrus and middle temporal gyrus),but significantly increased functional connectivity between sensorimotor network(SMN,supplementary motor area)and DMN(precuneus)in state 2(P<0.05,false discovery rate[FDR]-corrected).Partial correlation analysis indicated positive correlation between mean dwell time in state 3 and PIGD scores in PD-PIGD patients(r=0.450,P=0.039).Conclusion PD-PIGD patients exhibit specific dFNC,mainly characterized by low connectivity of the brain functional network and prolonged dwell time;local functional network domains often separate between DMN,AN and SMN networks and within the networks.