帕金森病患者运动网络的频率特异性静息态功能磁共振成像研究

Resting state functional connectivity alterations in motor networks of Parkinson’s disease in different frequency bands

目的基于静息态功能磁共振成像(resting state functional magnetic resonance imaging,rs-fMRI)系统性探究帕金森病(Parkinson’s disease,PD)患者运动网络的功能连接(functional connectivity,FC)改变,并观察频率特异性FC模式。材料与方法经过严格质控,最终前瞻性纳入28例PD患者与34例性别、年龄、受教育年限匹配的健康对照者。整合来自模板的双侧小脑(Ⅳ~Ⅴ、Ⅵ、Ⅷ小叶)、黑质、基底节(尾状核、壳核、苍白球)、丘脑、运动皮层(中央前回、中央后回、中央旁小叶)共计36个感兴趣区(regions of interest,ROI)组成PD特异性运动网络,使用常规低频(0.01~0.1 Hz)以及slow-3(0.073~0.198 Hz)、slow-4(0.027~0.073 Hz)、slow-5(0.01~0.027 Hz)子频段下的FC分别构建连边。经过基于网络的统计分析,探究频率特异性FC改变模式。使用Spearman偏相关分析观察异常FC与临床运动及认知评分的相关性。结果PD患者在常规低频下展现了广泛的FC减低。在P=0.01的连边阈值与P=0.05的子图阈值下,观察到包含22个ROI和29条连边的子图(P=0.017),其中网络间连接以丘脑-小脑-基底节为著,以及黑质-壳核、中央后回-小脑的连接。网络内连接主要集中于小脑双侧Ⅵ小叶间、双侧壳核间、双侧中央旁小叶与右侧中央后回。在P=0.05的连边与子图阈值下与常规低频对比,slow-4展现了更多的丘脑-基底节的FC改变。slow-5频段的特异连边主要集中在“小脑-黑质-基底节-丘脑”的网络间连接。slow-3频段未发现异常FC。常规低频下,丘脑-苍白球及壳核间FC与统一帕金森病评分量表第三部分(Unified Parkinson’s Disease Rating ScaleⅢ,UPDRS-Ⅲ)呈负相关(P_(corrected)=0.04及P_(corrected)<0.01)。结论PD患者表现了整合运动网络复杂且广泛的FC受损,并且具有频率特异性改变模式。包含“小脑黑质-基底节-丘脑-运动皮层”多环路的脑网络功能异常可能是PD运动障碍的神经病理学机制之一,而纹状体、丘脑等皮层下结构可能具有疾病诊断与监测的潜在生物学价值。

Objective:Based on resting state functional magnetic resonance imaging(rs-fMRI),to investigate the functional connectivity(FC)of motor networks in Parkinson’s disease(PD)patients and to explore frequency-specific FC patterns.Materials and Methods:Twenty-eight PD patients and 34 healthy controls(HCs)matched for gender,age,and education were enrolled.A total of 36 regions of interest(ROI)containing the bilateral cerebellum(Ⅳ-Ⅴ,Ⅵ,Ⅷlobules),substantia nigra(SN),basal ganglia(BG)(caudate nucleus,putamen,pallidum),thalamus,and motor cortex(precentral and postcentral gyrus,paracentral lobule)were selected from atlases to form a PD-specific motor network,using FC in conventional band(0.01-0.1 Hz),slow-3(0.073-0.198 Hz),slow-4(0.027-0.073 Hz)and slow-5(0.01-0.027 Hz)as edges.After network-based statistical analysis,the frequency-specific FC change patterns were explored.Correlations between abnormal FC and clinical motor and cognitive scores were calculated using Spearman’s partial correlation analysis.Results:PD patients demonstrated extensive FC reduction at conventional band.In the threshold of P_(edge)=0.01 and P_(component)=0.05,the component containing 22 ROIs and 29 edges were observed(P=0.017),where inter-network connections were dominated between thalamo-cerebello-BG circuits,as well as connections between SN-putamen and postcentral gyrus-cerebellum.Compared with typical band at the threshold of Pedge=0.05,slow-4 showed more thalamo-BG FC changes,while slow-5 specific FC was mainly the"cerebello-SN-BG-thalamo"related circuits.No statistically aberrant FC was detected in slow-3.The FC between thalamus-pallidum,also between inter-putamina,were negatively correlated with the Unified Parkinson’s Disease Rating ScaleⅢ(UPDRS-Ⅲ)(P_(corrected)=0.04 and P_(corrected)<0.01).Conclusions:PD patients showed a complex and extensive FC impairment of the integrative motor network,with frequency-specific changes.Alterations in brain functional networks containing"cerebello-SN-BG-thalamo-motor cortical"circuits may be one of the neuropathological mechanisms of PD movement dysfunction.The striatum,thalamus and other subcortical regions may be served as potential biomarkers for disease diagnosis and monitoring.