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基础研究
重度抑郁症患者用药治疗后全脑低频振幅和度中心性功能成像研究
李颖娜 李慧 赵立营 王志仁

Cite this article as: Li YN, Li H, Zhao LY, et al. Functional imaging analysis of the whole brain ALFF and DC in MDD after medication treatment[J]. Chin J Magn Reson Imaging, 2022, 13(1): 64-69.本文引用格式:李颖娜, 李慧, 赵立营, 等. 重度抑郁症患者用药治疗后全脑低频振幅和度中心性功能成像研究[J]. 磁共振成像, 2022, 13(1): 64-69. DOI:10.12015/issn.1674-8034.2022.01.013.


[摘要] 目的 比较重度抑郁症(major depressive disorder,MDD)患者用药治疗改善前后全脑低频振幅(amplitude of low-frequency fluctuation,ALFF)和度中心性(degree centrality, DC)值的变化情况,探讨其脑功能异常的潜在机制。材料与方法 纳入诊断符合国际疾病与相关健康问题统计分类第十版(the International Statistical Classification of Diseases and Related Health Problems 10th Revision,ICD-10)诊断标准的重度抑郁症患者17例(男8例,女9例)。采用汉密尔顿抑郁量表(17-item Hamilton Rating Scale for Depression,HAMD17)和神经心理状态评定量表(Repeatable Battery for the Assessment of Neuropsychological Status,RBANS)评价所有患者的抑郁症状严重程度和认知功能。应用静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)技术,分别在用药治疗前和用药治疗8周后,采集所有患者rs-fMRI数据,基于DPABI V2.3 (Data Processing & Analysis of Brain Imaging,DPABI)软件,对数据进行预处理后得到ALFF和DC图,采用配对样本t检验比较治疗前后的临床量表和脑功能图像差异。提取治疗后全脑的ALFF、DC值与所有患者的临床量表评分进行Pearson相关分析。结果 所有MDD患者用药治疗前后HAMD17评分(27.59±3.89 vs. 8.18±5.81,P<0.001)、即刻记忆(88.94±18.71 vs. 102.77±13.18,P<0.001)和注意(108.41±18.66 vs. 113.12±17.61,P=0.014)均有明显改善。用药治疗后左侧壳核、右侧额中回/背外侧额上回的ALFF值增高[均经高斯随机场(Gaussian random field,GRF)校正,体素水平P<0.01,团块水平P<0.05)]。用药治疗后左侧距状回/右侧小脑Ⅵ区的DC值增高,而右侧背外侧额上回/额中回的DC值减低(均经GRF校正,体素水平P<0.01,团块水平P<0.05)。Pearson相关分析显示,MDD患者症状改善后右侧额中回的ALFF值与教育年限之间呈正相关(r2=0.27,P=0.03);治疗后右侧颞上回的DC值与延迟记忆呈负相关(r2=0.672,P<0.0001,GRF校正),右侧缘上回/颞上回的DC值与即刻记忆呈负相关(r2=0.668,P<0.0001,GRF校正)。结论 本研究显示经过药物治疗后的MDD患者静息态脑活动(ALFF,DC)与认知能力具有较强的相关性,此结果可能作为疾病进展的新指标。我们的研究结果预示ALFF和DC可能帮助探索MDD的潜在病理机制。
[Abstract] Objective To evaluate the altered functional change in patients with major depressive disorder (MDD) before and after medication treatment using the whole brain amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) levels, and investigate the potential mechanism of brain functional change.Materials and Methods: Seventeen participants (male 8/female 9) diagnosed with MDD were included in the study and underwent one brain functional image scan. The same rs-fMRI scan was undergone again after 8-week medication treatment. The progression of disease of patients was measured by 17-item Hamilton Rating Scale for Depression (HAMD17) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) following each MRI scan. The significant difference of clinical scales and ALFF and DC levels before and after medication treatment were determined using paired t-test. The relationship between ALFF and DC levels in the whole brain regions and HAMD17 and RBANS scores were based on Pearson correlation coefficient. All data were corrected by Gaussian random field theory (GRF, voxel-wise P<0.01, cluster-wise P<0.05, and two-tailed test).Results The paired t-test found that the scores of HAMD17 after medication treatment were significantly lower than that before (P<0.001), while immediate memory and attention scores were significantly higher than before (P<0.001). Moreover, the ALFF values after medication treatment were higher than that before in the Putamen_L (AAL) and Frontal_Mid_R/Frontal_Sup_R (AAL) (GRF correction, voxel level P<0.01, cluster level P<0.05). The DC values after medication treatment were higher in the Calcarine_L/Cerebelum_6_R and lower in the Frontal_Sup_R/Frontal_Mid_R (AAL) (GRF correction, voxel level P<0.01, cluster level P<0.05). Pearson correlation showed that there was a positive correlation found between ALFF values and education (r2=0.27, P=0.03) in the Frontal_Mid_R (AAL) (GRF correction, voxel level P<0.01, cluster level P<0.05).The after treatment DC values were negatively corelated with RBANS-delayed memory score (r2=0.672, P<0.0001) in the Temporal_Sup_R (AAL), and RBANS-Immediate Memory score (r2=0.668, P<0.0001) in the SupraMarginal_R/Temporal_Sup_R (GRF correction, voxel level P<0.01, cluster level P<0.05), respectively.Conclusions The present study demonstrated that the resting-state functional brain activity (ALFF, DC) had strong relationship with cognitive ability (RBANS scores) in patients with MDD after medication treatment, which might provide new imaging markers as progression of MDD. Our results indicated that the ALFF and DC might help detect the underlying pathological mechanism in MDD continuum.
[关键词] 重度抑郁症;药物治疗;低频振幅;度中心性;磁共振成像;静息态功能磁共振成像
[Keywords] major depressive disorder;medication treatment;amplitude of low-frequency fluctuation;degree centrality;magnetic resonance imaging;resting-state functional magnetic resonance imaging

李颖娜 1   李慧 2   赵立营 1   王志仁 2*  

1 北京回龙观医院医学影像中心,北京 100096

2 北京回龙观医院精神医学研究中心,北京 100096

王志仁,E-mail:zhiren75@163.com

全部作者均声明无利益冲突。


基金项目: 北京市科技计划 Z171100001017022 北京市属医院科研培育计划 PX2018069 北京市医院管理局“登峰”计划专项经费资助 DFL20182001
收稿日期:2021-08-04
接受日期:2021-11-10
中图分类号:R445.2  R749.4 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.01.013
本文引用格式:李颖娜, 李慧, 赵立营, 等. 重度抑郁症患者用药治疗后全脑低频振幅和度中心性功能成像研究[J]. 磁共振成像, 2022, 13(1): 64-69. DOI:10.12015/issn.1674-8034.2022.01.013

       重度抑郁症(major depressive disorder,MDD)是一种发病非常普遍、严重损害身心健康的疾病,常见于青壮年人群,高自杀风险给家庭和社会带来了沉重的经济负担[1]。研究发现MDD是一种多维、系统性、影响多神经环路的疾病[2],然而对于MDD的神经机制目前尚不十分清楚。静息态功能磁共振成像(resting-state functional magnetic resonance imaging, rs-fMRI)是一种研究人脑功能的方法,具有无创性且空间分辨率非常高,广泛应用于脑神经科学等多个领域。rs-fMRI被广泛应用于探索MDD患者局部自发脑活动。既往研究主要集中在比较MDD患者与健康对照的脑功能及结构的差异,发现MDD患者脑网络的功能及结构异常,而针对MDD患者用药治疗前后的脑功能改变的研究相对较少。因此,本研究欲采用rs-fMRI评估MDD患者用药治疗前后脑功能改变,并探索脑功能改变与临床症状潜在的相关性。

1 材料与方法

1.1 研究对象

       本研究是前瞻性研究,选择2018年10月至2019年12月就诊于北京回龙观医院门诊的MDD患者。纳入标准:(1)由2名主治及以上职称医师根据国际疾病与相关健康问题统计分类第十版(the International Statistical Classification of Diseases and Related Health Problem 10th Revision,ICD-10)中抑郁障碍的诊断标准,符合抑郁发作的诊断;(2)年龄18~50岁;(3)包括本次抑郁发作共抑郁发作3次以上,且期间无躁狂或轻躁狂发作;(4)汉密尔顿抑郁量表(17-item Hamilton Rating Scale for Depression,HAMD17)评分≥17;(5)愿意接受抗抑郁治疗;(6)入组前8周内未服用抗抑郁药物治疗;(7)右利手;(8)自愿参与研究,并签署知情同意书。排除标准:(1)患者有下列任何疾病的现病史或既往病史:①精神分裂症或者其他精神病性障碍;②双相障碍;③痴呆或者任何其他神经退行性疾病;④酒精或物质依赖;⑤有躯体疾病或药物所致的任何精神疾病;(2)患者为孕妇或者产后≤6个月的女性或者处于哺乳期的女性;(3)患者有严重的自杀倾向;(4)既往接受过无抽搐电休克治疗治疗或因疾病严重,未来2月内有可能需要进行无抽搐电休克治疗者;(5) MRI检查禁忌证者。按照纳入/排除标准,最终纳入17人。本研究经北京回龙观医院伦理委员会审查批准(批号:2017-72)。所有受试者及其监护人均签署知情同意书。

1.2 一般临床资料收集及量表评估

       收集MDD患者年龄、性别、教育年限、病程、首发年龄、发作次数等一般临床资料。由2名主治及以上职称精神科医师分别在用药前(产品名称:心达悦-氢溴酸伏硫西汀;型号:CN-179-22-10-23002;生产厂家及国别:H.Lundbeck A/S,丹麦;用药剂量、频次:10 mg/d)及用药8周后对所有研究对象进行量表评价,HAMD17用于测量患者的抑郁严重程度,神经心理状态评定量表(Repeatable Battery for the Assessment of Neuropsychological Status,RBANS)包括即刻记忆(immediate memory)、视觉广度(visuospatial)、语言功能(language)、注意(attention)、延迟记忆(delayed memory)用于评估患者的认知功能。采用的测量工具由统一培训后的精神科医生进行评估。

1.3 扫描方法及技术参数

       检查采用Siemens Prisma MRI 3.0 T磁共振扫描仪(德国西门子公司)和64通道头颅磁共振线圈,对所有研究对象进行两次rs-fMRI扫描,两次扫描时间间隔为8周。采用磁化准备梯度(MPRAGE)序列获取高分辨率的3D-T1WI解剖像。扫描参数:重复时间(repetition time, TR) 2400 ms,回波时间(echo time, TE) 2.22 ms,翻转角(flip angle,FA) 8°,层数182层,矩阵(matrix size) 320×300,层厚(thickness) 1 mm,体素0.8 mm×0.8 mm×0.8 mm。采用梯度平面回波序列(GRE-EPI)获取rs-fMRI序列图像。扫描参数:TR=2000 ms,TE=30 ms,FA=90°,矩阵64×64,层厚3.5 mm,间隔4 mm,层数33层,采集240个时间点,扫描时间8 min。扫描过程中,要求受试者在大脑清醒的状态下保持宁静、闭眼、勿动以及正常呼吸[3]

1.4 图像分析和诊断方法

1.4.1 rs-fMRI数据预处理

       rs-fMRI数据的预处理基于MATLAB 2017b平台的DPABI V2.3 (Data Processing & Analysis of Brain Imaging,DPABI;http://rfmri.org/dpabi)软件包进行。具体流程:(1)格式转换:将医学数字成像和通信图像(digital imaging and communications in medicine,DICOM)转换为NIFIT格式;(2)滤掉前10个时间点;(3)时间校正;(4)头动校正:排除平移超过3 mm或旋转超过3°者;(5)空间标准化:采用DARTEL方法,先把结构像配到功能像空间,然后把结构像分割成灰质、白质及脑脊液,最后再标准化MNI空间;(6)去线性漂移、滤波和去协变量:标准化后的数据经过0.01~0.08 Hz的带通滤波器去除低频漂移和高频生理噪声,其中计算低频振幅(amplitude of low-frequency fluctuation,ALFF)时,则滤波放在ALFF之后选;(7)空间平滑:为减小空间噪声和局部的解剖结构伪影,进行空间平滑的处理,半峰全宽(full width at half maximum,FWHM)值为6 mm[3]

1.4.2 ALFF和度中心性(degree centrality, DC)计算

       rs-fMRI数据经预处理后,采用DPABI软件计算ALFF和DC。使用快速傅里叶变换(fast Fourier transform,FFT)算法将预处理的时域信号转化到频域得到功率谱,功率谱求平方根得到ALFF。DC是以每个体素为节点,计算该节点与全脑其他节点的相关,定义相关系数r>0.25的连接边[4]

1.5 统计学处理

       采用SPSS 20.0软件对一般临床资料和临床相关量表进行统计学分析。符合正态分布的计量资料以均数±标准差(x¯±s)表示,不符合正态分布的计量资料以中位数(四分位数)表示。MDD患者用药前后量表变化采用配对样本t检验,P<0.05为差异有统计学意义。采用DPABI对用药前后标准化的ALFF和DC参数图进行配对样本t检验,多重比较采用GRF校正,阈值设置为体素水平P<0.01,团块水平P<0.05,体素值>30;分别对所有患者用药前后各量表与脑功能成像的变化值进行Pearson相关性分析,多重比较采用GRF校正,阈值设置为体素水平P<0.01,团块水平P<0.05,体素值>30。组水平统计分析时,均控制了年龄、性别等协变量。

2 结果

2.1 一般人口学资料

       本研究共收集MDD患者17例,其中男8例,女9例,平均年龄28岁,所有患者均右利手。所有患者一般人口学资料见表1

表1  一般人口学资料
Tab. 1  General data of patient in major depressive disorder

2.2 MDD患者用药前后临床症状量表比较

       MDD患者用药前后临床症状量表比较发现HAMD17、即刻记忆和注意差异具有统计学意义,详见表2

表2  重度抑郁症患者用药前后临床症状量表比较
Tab. 2  Comparison of clinical scales before and after medication treatment in MDD

2.3 MDD患者用药治疗前后全脑ALFF值比较

       MDD患者用药治疗前后全脑ALFF值比较发现,用药后左侧壳核(Putamen_L)、右侧额中回(Frontal_Mid_R)/背外侧额上回(Frontal_Sup_R)的ALFF值增高(GRF校正,体素水平P<0.01,团块水平P<0.05,体素值>30),详见表3图1。MDD患者用药治疗前后全脑DC值比较发现,用药后左侧距状回/右侧小脑Ⅳ区的DC值增高;而用药后右侧背外侧额上回/额中回的DC值减低,详见表4、图2。

图1  重度抑郁症患者用药前后配对t检验ALFF差异脑区图。黄色代表ALFF值用药后>用药前。ALFF:低频振幅。
图2  重度抑郁症患者用药前后配对t检验DC差异脑区图。红色代表DC值用药后>用药前,蓝色代表DC值用药后<用药前。DC:度中心性。
图3  重度抑郁症患者症状改善后右侧额中回ALFF值与教育年限相关性。ALFF:低频振幅。
图4  A~B:重度抑郁症患者症状改善后右侧颞上回DC值与延迟记忆呈负相关性,A为相关脑区,B为相关散点图;C~D:重度抑郁症患者症状改善后右侧缘上回/颞上回DC值与即刻记忆呈负相关性,C为相关脑区,D为相关散点图。DC:度中心性。
Fig. 1  Brain regions with significant ALFF difference were displayed in major depressive disorder compared between before and after medication treatment. Yellow areas mean higher ALFF in after medication treatment. ALFF: amplitude of low frequency fluctuation.
Fig. 2  Brain regions with significant DC difference were displayed in major depressive disorder compared between before and after medication treatment. Red areas mean higher DC after medication treatment, while blue areas mean lower DC after medication treatment. DC: degree centrality.
Fig. 3  Correlation of the ALFF levels of Temporal_Sup_R (AAL) and education. ALFF: amplitude of low-frequency fluctuation.
Fig. 4  A-B: The DC value of Temporal_Sup_R (AAL) was negatively correlated with delayed memory in MDD after medication treatment (A: DC map, B: scatter plot.). C-D: The DC value of SupraMarginal_R / Temporal_Sup_R (AAL) was negatively correlated with immediate memory in MDD after medication treatment (C: DC map, D: scatter plot.). DC: degree centrality.
表3  重度抑郁症患者用药前后全脑ALFF显著差异的脑区
Tab. 3  Brain regions with significant ALFF difference in major depressive disorder compared between before and after medication treatment
表4  重度抑郁症患者用药治疗前后全脑DC显著差异的脑区
Tab. 4  Brain regions with significant DC difference in major depressive disorder compared between before and after medication treatment

2.4 Pearson相关分析结果

       Pearson相关分析结果显示,MDD患者症状改善后右侧额中回的ALFF值与教育年限之间呈正相关(r2=0.27,P=0.03),见图3。同时发现,用药治疗后MDD患者DC值与延迟记忆呈负相关,相关脑区为右侧颞上回(Temporal_Sup_R) (r2=0.672,P<0.0001) (GRF校正,体素水平P<0.01,团块水平P<0.05);用药治疗后MDD患者DC值与即刻记忆呈负相关,相关脑区为右侧颞上回(Temporal_Sup_R)/右侧缘上回(SupraMarginal_R) (r2=0.668,P<0.0001) (GRF校正,体素水平P<0.01,团块水平P<0.05),见表5、图4。

表5  重度抑郁症患者用药治疗后全脑DC值与延迟记忆和即刻记忆的相关性分析
Tab. 5  Correlation of DC level and delayed memory or immediate memory in major depressive disorder after medication treatment

3 讨论

       本研究采用rs-fMRI前瞻性评估重度抑郁症患者用药治疗前后脑功能及临床症状改善情况,本研究MDD患者用药前后全脑ALFF值和DC值比较发现,患者症状缓解后左侧壳核、右侧额中回/右侧背外侧额上回的ALFF值增高;患者用药后左侧距状回/右侧小脑Ⅵ区的DC值增高;而用药后右侧背外侧额上回/额中回的DC值减低,同时,用药治疗后临床症状明显改善,抑郁严重程度明显降低、即刻记忆增加、注意力提高、认知功能明显提高。基于rs-fMRI方法,本研究创新性分析MDD患者用药治疗前后脑功能的变化情况,有助于临床预测药物治疗的反应,以及了解有效治疗后大脑功能的改变情况,同时本研究还有可能用于阐明药物治疗反应的影像生物学标志物。

3.1 MDD患者治疗前后全脑ALFF值变化特征

       ALFF是脑功能指标之一,能从能量的角度反应各个体素在低频段内神经活动的同步化强度[5],ALFF指数在描述自发脑活动方面具有稳定、可信度及可用性高等特点,常用于多种精神疾病的诊疗中[6, 7, 8, 9]。本研究通过比较重度抑郁症患者用药治疗前后ALFF值发现,治疗症状改善后的左侧壳核、右侧额中回/背外侧额上回的ALFF值增高,表明该差异脑区的神经元活动幅度增强。

       壳核是一个组成基底神经节的重要结构,基底神经节-丘脑-皮质回路对于认知和情绪的调节至关重要,因此是参与精神疾病和情绪生成的核心回路[10, 11]。壳核是该回路中的一个关键节点,它与皮层和丘脑以及杏仁核等边缘区域进行通信[12]。国内研究显示抑郁症患者基底核可通过与额叶之间的信号交流来影响认知及记忆等活动[13]。rs-fMRI研究表明,精神分裂症中壳核相关的网络功能缺陷与主要的阳性症状以及认知障碍相关[14, 15, 16]。本研究提示MDD患者用药治疗后壳核ALFF值增加,进一步为MDD患者症状改善后情绪加工功能增强提供了证据支持。背外侧额上回/额中回属于背外侧前额环路的重要脑区,主要参与执行功能,参与久远记忆的检索等神经活动[2]。因此,治疗后右侧额中回/背外侧额上回的ALFF值增加可能预示患者记忆和认知能力的增强。这与相应的临床量表改变情况基本一致。但是本文的研究对象样本量相对较小,这导致了本研究中尚未发现ALFF值的改变与临床症状相关评估量表改变之间的相关性。

3.2 MDD患者临床症状改善后右侧额中回/背外侧额上回的ALFF值与教育年限的相关性分析

       在分析教育对认知影响的机制方面,大多数学者支持“认知储备”假说,它认为教育可能会延迟脑损伤受试者的认知表现[17]。右侧额中回/背外侧额上回主要参与认知加工及有意识的情绪管理[18, 19],同时额中回与一些皮下组织有较高的功能连接[20]。故而当MDD患者临床症状改善后,其早期教育年限越高则其右侧额中回及背外侧额上回的脑活动恢复越良好。

3.3 MDD患者治疗前后全脑DC值变化特征。

       DC是脑网络拓扑属性之一,常用来表征大脑网络节点的重要性。DC值的改变预示着该节点与脑网络中其他节点之间的功能同步性出现了异常,即相互联系的程度改变了,那么脑区的功能相应就会出现损伤[21]。在本文中,通过所有节点DC值的计算,找到MDD患者临床症状改善前后脑网络DC值变化的节点及其DC值变化的差异,以更好地观察MDD患者临床症状改善前后大脑神经机制的异同,从而用于MDD的早期诊断及治疗后疗效的评价。

       距状回属于边缘系统与小脑半球的Ⅵ区主要参与执行功能及情绪加工[22],研究显示小脑半球与参与大脑活动的皮质区域相连[23, 24]。Gong等[25]的meta分析发现MDD患者左侧小脑半球Ⅵ区和crus Ⅰ区的ALFF值减低,这表明MDD患者小脑半球固有活性受损。较多研究发现MDD患者中常发现小脑结构和功能的异常,尤其是小脑半球Ⅵ,Ⅶ,Ⅸ区等[26],包括灰质体积[26, 27],功能活性和连接异常[28, 29, 30, 31]。小脑功能障碍可能会减慢察觉情绪状态所需的数据集成过程,导致小脑功能受损患者不能明确认识他们的情绪状态[32]。本研究发现,用药治疗后MDD患者左侧距状回/右侧小脑后叶DC连接增强,这表明MDD患者在用药前存在注意力的减退,而用药治疗后这种功能连接增强。因此,我们的研究结果提供了额外的证据,证明小脑功能障碍参与MDD情感障碍的病理生理学。

       背外侧前额叶(dorsolateral prefrontal cortex, DLPFC)是参与情绪、执行功能、认知控制的重要脑区[33]。无创DLPFC刺激的抗抑郁治疗功效与远端大脑区域的影响和多个内在大脑网络的重组有关,表明网络级效应对治疗效果的重要作用[34]。本研究发现MDD患者用药治疗后背外侧前额叶/额中回较用药前DC值减低,这说明在用药治疗前这些脑区在调节情感相关的主观情绪状态和活动的效果不足,这可能是因为它们的相关连接出现了损伤。因此,进一步的研究需要验证降低的抑制效果究竟是否是由于前额皮层的目标情感相关区域的输出功能增强导致的。

3.4 MDD患者临床症状改善后右侧颞上回及右侧缘上回的DC值与延迟记忆、即刻记忆的相关性分析

       Golby等[35]报道了内侧颞叶及前额叶等脑区是与情景记忆相关的重要区域。左侧的损伤与言语记忆的损害相关[36],而右侧的损伤与情景记忆的损害相关[37]。缘上回是额顶控制网络的重要组成部分,与情绪及认知加工密切相关,Silani等[38]研究显示右侧缘上回是控制情绪的关键脑区。本研究中MDD患者用药治疗后右侧颞上回的DC值与即刻记忆、延迟记忆呈负相关可能为用药治疗前一种功能代偿可能的提示。

       本研究的局限性与展望:(1)本研究的样本量相对较少,接下来的研究中将扩大样本量,以求更精确地反映MDD患者脑损伤的相关影像学机制;(2)本研究中主要研究静息态脑功能的改变,且脑功能指标仅分析ALFF与DC,下一步要纳入更多的脑功能指标,同时分析MDD患者在用药治疗前后脑结构的变化情况,多模型态多角度探索MDD患者症状改善的可能病理生理基础;(3)本研究的研究对象主要是MDD患者,尚未分析MDD患者与正常健康对照之间的脑功能和认知功能的差异,因此,未来的研究中要进一步分析用药改善后的MDD患者与健康对照之间的异同,为MDD患者的临床治愈/缓解进一步提供影像学证据。

       综上所述,本研究基于rs-fMRI方法分析重度抑郁症患者临床症状改善前后全脑ALFF值和DC值的变化特征。本研究发现,经过药物治疗后的MDD患者的功能性ALFF的改变主要集中于额叶-基底节环路,而其神经元活性的减低可能是MDD患者认知功能异常的病理基础;其次,药物治疗前后MDD患者左侧距状回/右侧小脑和右侧背外侧额上回/额中回功能网络异常可能是MDD患者症状改善的重要病理生理机制;此外,药物治疗后的MDD患者DC值与认知能力具有较强的相关性,此结果预示DC值可能成为MDD患者临床症状改善的新依据。

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