肝豆状核变性伴认知损害的尾状核静息态功能连接改变的fMRI研究

A resting-state fMRI study of altered functional connectivity of caudate nucleus in Wilson’s disease patients with cognitive impairment

目的:利用静息态fMRI分析肝豆状核变性(WD)伴认知损害患者的尾状核功能连接改变。方法:选取19例WD患者(WD组)及24例健康志愿者(对照组)为研究对象,并行静息态fMRI检查;采用简明智力状态量表(MMSE)、言语流畅性测验(VFT)、数字广度测验(DST)、前瞻记忆(PM)测试法评估患者认知功能;利用AFNI软件,分别以双侧尾状核为种子点(ROI),与全脑其他体素行功能连接分析,得到2组功能连接的差异脑区,对差异脑区的功能连接强度值与基于事件的前瞻性记忆(EBPM)评分及基于时间的前瞻性记忆(TBPM)评分行相关性分析。结果:WD组的MMSE评分、VFT评分、DST评分、TBPM评分和EBPM评分均较对照组低,差异均有统计学意义(均P<0.05)。与对照组相比,WD组左侧尾状核与双侧丘脑、双侧额上回、右侧额中回功能连接减低,右侧尾状核与小脑蚓部、双侧豆状核、双侧丘脑、双侧额上回、右侧角回功能连接减低。WD组右侧尾状核和右侧额上回间的功能连接强度值与EBPM评分呈正相关(r=0.508,P=0.028);右侧尾状核和右侧丘脑间的功能连接强度值与TBPM评分呈正相关(r=0.473,P=0.041);左侧尾状核和左侧丘脑间的功能连接强度值与TBPM评分呈正相关(r=0.462,P=0.047)。结论:WD患者认知障碍与纹状体-丘脑-皮质连接受损有关,尤其是尾状核与丘脑及额上回的功能连接减低有关。fMRI可作为WD患者脑功能障碍的重要研究手段。

Objective:To analyze the functional connectivity changes in the caudate nucleus in patients with Wilson’s disease(WD)and cognitive impairment by using resting-state fMRI.Methods:19 patients with WD(WD group)and 24 normal healthy volunteers(the control group)were recruited,all of them underwent resting-state fMRI.Multiple methods,including the mini-mental status examination(MMSE),the verbal fluency test(VFT),the digit span test(DST)and the prospective memory(PM)test,were used to evaluate the cognitive function.Using AFNI software,the functional connectivity between the bilateral caudate nucleus and the other voxels in the whole brain was analyzed.In addition,the brain regions with different functional connectivity between the two groups were analyzed.Then,the correlations between the abnormal functional connectivity brain regions and the prospective memory scores(EBPM and TBPM scores)were analyzed.Results:The MMSE,VFT,DST,TBPM and EBPM scores in WD group were significantly lower than the control group(all P<0.05).Compared with the control group,the functional connectivity between the left caudate nucleus and bilateral thalamus,bilateral superior frontal gyrus,right middle frontal gyrus were decreased in WD group,and the functional connectivity between the right caudate nucleus and cerebellar vermis,bilateral lenticular nucleus,bilateral thalamus,bilateral superior frontal gyrus,right angular gyrus decreased as well.The value of the functional connectivity in WD group between the right caudate nucleus and right superior frontal gyrus was positively correlated with EBPM score(r=0.508,P=0.028),and that between the right caudate nucleus and right thalamus was positively correlated with TBPM score(r=0.473,P=0.041).The value of the functional connectivity between the left caudate nucleus and left thalamus was positively correlated with TBPM score(r=0.462,P=0.047).Conclusions:Cognitive impairment in WD patients is closely related to impaired striatum-thalamus-cortex connectivity,especially the decreased functional connectivity between the caudate nucleus and thalamus,superior frontal gyrus.And fMRI can be used as an important research method for assessing brain dysfunction in WD patients.