精神分裂症患者中脑多巴胺区亚频段静息态功能连接异常研究

Aberrations of Sub⁃band Resting⁃State Functional Connectivity Associated with Dopaminergic Midbrain Regions in Schizophrenia

目的探讨精神分裂症(SZ)患者中脑多巴胺区[腹侧被盖部(VTA)和黑质致密区(SNc)]不同亚频段(Slow⁃5:0.01~0.027 Hz,Slow⁃4:0.027~0.073 Hz)下静息态功能连接(rsFC)的异常。方法纳入91例SZ患者和91名健康志愿者对照组(HC)。所有被试均进行静息态功能磁共振成像(rs⁃fMRI)扫描。将中脑多巴胺区划分为四个亚区(左、右侧VTA和SNc),全脑其他区域划分为272个脑区,分析SZ组和HC组在Slow⁃5和Slow⁃4频段上双侧VTA和SNc各自与全脑其他脑区的rsFC的组间差异,进一步分析这些异常rsFC是否具有频率特异性,并考察SZ组异常rsFC值与临床症状之间的相关性。结果两个频段下SZ患者右侧VTA与小脑蚓8区的rsFC均降低。此外,Slow⁃5频段SZ患者右侧SNc与小脑蚓7区的rsFC降低;Slow⁃4频段SZ患者右侧SNc与左侧腹侧尾状核的rsFC降低,右侧SNc与左侧舌前回和左侧中央后回的rsFC升高。其中,右侧SNc与小脑蚓8区和左侧腹侧尾状核的rsFC异常在两个频段间的差异具有统计学意义。与临床症状的相关性分析表明,Slow⁃5频段SZ组右侧SNc与小脑蚓7区的rsFC和阳性与阴性症状量表(PANSS)中的阳性症状分、思维障碍分、激活性分和攻击性(补充)分均呈正相关;Slow⁃4频段SZ组右侧SNc与左侧舌前回的rsFC和PANSS量表中的思维障碍分呈负相关。结论SZ患者中脑特定多巴胺区与小脑蚓、尾状核、舌前回和中央后回存在亚频段rsFC异常,且部分rsFC异常具有频率依赖性,这为SZ的神经生理机制研究提供了新思路。

Objective This study aims to investigate resting⁃state functional connectivity(rsFC)abnormalities of the dopaminergic midbrain regions,specifically the ventral tegmental area(VTA)and substantia nigra pars compacta(SNc),across different sub⁃frequency bands(Slow⁃5:0.01-0.027 Hz,Slow⁃4:0.027-0.073 Hz)in patients with schizophrenia(SZ).Methods Ninety⁃one SZ patients and ninety⁃one healthy controls(HC)were included in this study.All partici⁃pants underwent resting⁃state functional MRI scans.The dopaminergic midbrain regions were delineated into four subregions(bilateral VTA and SNc)and the the other parts of the brain were segmented into 272 regions.The rsFC between each of the 4 dopaminergic regions and each of the other 272 brain regions was compared between patients and controls for two frequency bands separately(Slow⁃5 and Slow⁃4).Further statistical comparisons were conducted to test whether these rsFC alterations in patients were dependent on frequency.In addition,correlations between the abnormal rsFCs and clinical symp⁃tomsassessed by the Positive and Negative Syndrome Scale(PANSS)were examined.Results In both frequency bands,SZ patients exhibited reduced rsFC between the right VTA and the cerebellar vermis 8 region.Furthermore,in Slow⁃5,SZ patients exhibited decreased rsFC between the right SNc and the cerebellar vermis 7 region.In Slow⁃4,SZ patients exhibited reduced rsFC between the right SNc and the left ventral caudate nucleus and increased rsFC between the right SNc and the left rostral lingual gyrus and between the right SNc and the leftpostcentral gyrus.Notably,the differences in two of these identifiedrsFCs(“right SNc⁃the cerebellar vermis 7 region”,“the right SNc and the left ventral caudate nucleus”)were significantly changed in patients compared with controls.Correlation analyses between the altered rsFCs and clinical symptoms indicated positive correlations between the rsFC between the right SNc and the cerebellar vermis 7 region in Slow⁃5 and the scores of positive symptoms,thought disorder,activation,and supplementary aggression;in contrast,the rsFC between the right SNc and the left rostral lingualgyrusin Slow⁃4 was negatively correlated with the score of thought disorder.Conclusion This study revealed sub⁃band rsFC abnormalities of dopaminergic midbrain regions with several other regionsin SZ patients.Some of these rsFCabnormalitieswere frequency⁃dependent,and were associated with clinical symptoms.These find⁃ings might offer new insights on the neurophysiological mechanisms underlying SZ.