本文選題：靜息態(tài)功能磁共振成像　切入點(diǎn)：重性抑郁癥　出處：《第四軍醫(yī)大學(xué)》2017年博士論文

【摘要】：重性抑郁障礙(major depressive disorder,MDD)是一種常見的精神疾病。隨著對(duì)于抑郁癥的認(rèn)識(shí)逐漸深入,目前的觀點(diǎn)認(rèn)為MDD是大腦中異常連接所導(dǎo)致的多腦區(qū)功能紊亂�；诠δ艽殴舱癯上�(functional magnetic resonance imaging,fMRI)的研究發(fā)現(xiàn)大腦可以被分解為不同的功能網(wǎng)絡(luò),各個(gè)功能網(wǎng)絡(luò)覆蓋的腦區(qū)在結(jié)構(gòu)上不相連,然而在功能上卻存在緊密聯(lián)系。功能網(wǎng)絡(luò)在大腦處于任務(wù)狀態(tài)和靜息狀態(tài)下都具有相似的分布模式。以功能網(wǎng)絡(luò)為基礎(chǔ)研究大腦功能的重組和交互,能夠從網(wǎng)絡(luò)連接的角度解釋多腦區(qū)功能紊亂。因此靜息態(tài)功能網(wǎng)絡(luò)連接分析對(duì)精神疾病研究具有重要意義。MDD患者功能網(wǎng)絡(luò)內(nèi)的功能連接異常已經(jīng)被許多研究報(bào)道過。默認(rèn)網(wǎng)絡(luò)(default mode network,DMN)、凸顯網(wǎng)絡(luò)(salience network,SN)和中央執(zhí)行網(wǎng)絡(luò)(central executive network,CEN)在MDD患者中均存不同程度的異常。腦區(qū)的異常能夠通過神經(jīng)連接傳遞到另外的腦區(qū),因此研究異常腦區(qū)之間神經(jīng)活動(dòng)的作用方向,對(duì)理解疾病發(fā)病機(jī)制具有重要意義。功能連接反映腦區(qū)活動(dòng)的相關(guān)性,卻不能提供神經(jīng)活動(dòng)的方向信息。有效連接分析方法能夠估計(jì)神經(jīng)活動(dòng)的連接方向及強(qiáng)度,但是需要基于先驗(yàn)知識(shí)構(gòu)建模型。因此探究不同功能網(wǎng)絡(luò)內(nèi)部節(jié)點(diǎn)間的有效連接是功能網(wǎng)絡(luò)研究的熱點(diǎn)問題。大腦處于不同的功能狀態(tài)時(shí),功能網(wǎng)絡(luò)的活躍程度也存在差異。比較功能網(wǎng)絡(luò)的活躍程度在時(shí)間上的變化關(guān)系,能夠得到網(wǎng)絡(luò)之間的連接關(guān)系。功能網(wǎng)絡(luò)之間的連接關(guān)系反映不同大腦功能之間的協(xié)同性。這種大腦功能網(wǎng)絡(luò)的協(xié)同性在許多精神疾病中都發(fā)生了異常。功能網(wǎng)絡(luò)之間的協(xié)同作用也是大腦功能網(wǎng)絡(luò)研究的一個(gè)熱點(diǎn)問題。皮層下深部腦區(qū)對(duì)大腦皮層具有廣泛的神經(jīng)投射。深部腦區(qū)與皮層腦區(qū)在功能上的連接模式被稱為功能投射網(wǎng)絡(luò)。深部腦區(qū)對(duì)功能投射網(wǎng)絡(luò)的活動(dòng)具有調(diào)節(jié)作用。根據(jù)深部腦區(qū)與功能投射網(wǎng)絡(luò)的連接關(guān)系,能夠?qū)ι畈磕X區(qū)進(jìn)行功能劃分。研究疾病相關(guān)腦區(qū)與功能投射網(wǎng)絡(luò)的連接關(guān)系,以此進(jìn)行腦區(qū)的功能劃分,對(duì)深部腦刺激技術(shù)(deep brain stimulation,DBS)等疾病干預(yù)技術(shù)有重要的指導(dǎo)作用。針對(duì)上面提出的三個(gè)問題,本文的研究主要從功能網(wǎng)絡(luò)內(nèi)、功能網(wǎng)絡(luò)間和深部腦區(qū)的功能投射網(wǎng)絡(luò)三個(gè)角度研究了MDD患者的功能網(wǎng)絡(luò)異常。論文的主要工作包括:第一章為靜息態(tài)功能網(wǎng)絡(luò)的有效連接分析。前期研究表明MDD患者在DMN、CEN和SN均出現(xiàn)連接異常。為了發(fā)現(xiàn)這些網(wǎng)絡(luò)異常腦區(qū)間神經(jīng)活動(dòng)的作用方向和因果關(guān)系。本文首次采用頻譜動(dòng)態(tài)因果模型(spectral dynamic causal modeling,spDCM)分析方法對(duì)功能網(wǎng)絡(luò)內(nèi)的有效連接進(jìn)行分析,并對(duì)比了MDD患者治療前、治療后和健康對(duì)照組之間的差異。通過獨(dú)立成分分析(independent component analysis,ICA)方法分解出靜息態(tài)功能網(wǎng)絡(luò),并選擇出與MDD密切相關(guān)的靜息態(tài)功能網(wǎng)絡(luò)。再根據(jù)靜息態(tài)功能網(wǎng)絡(luò)的空間分布模式,分別選擇出網(wǎng)絡(luò)內(nèi)部的關(guān)鍵節(jié)點(diǎn)。最后根據(jù)網(wǎng)絡(luò)內(nèi)部關(guān)鍵節(jié)點(diǎn)構(gòu)建DCM模型,使用spDCM估計(jì)功能網(wǎng)絡(luò)內(nèi)關(guān)鍵節(jié)點(diǎn)之間的有效連接。結(jié)果發(fā)現(xiàn)MDD患者SN和DMN內(nèi)部均存在有效連接異常。有效連接的結(jié)果表明,MDD患者DMN左側(cè)頂葉皮層(left parietal cortex,LPC)神經(jīng)活動(dòng)的調(diào)控作用降低。SN腹側(cè)子網(wǎng)絡(luò)內(nèi)的右側(cè)前腦島(right anterior insula,RAI)區(qū)域的神經(jīng)活動(dòng)調(diào)控能力降低。SN前部子網(wǎng)絡(luò)的左側(cè)額葉皮層(left frontal cortex,LFC)存在異常的調(diào)控作用。第二章引入DCM方法對(duì)SN前部子網(wǎng)絡(luò)、SN腹側(cè)子網(wǎng)絡(luò)、DMN前部子網(wǎng)絡(luò)、DMN后部子網(wǎng)絡(luò)、CEN左側(cè)子網(wǎng)絡(luò)和CEN右側(cè)子網(wǎng)絡(luò)之間的有效連接進(jìn)行建模,分別使用隨機(jī)DCM(stochastic dynamic causal modeling,sDCM)和spDCM對(duì)模型參數(shù)進(jìn)行估計(jì)。并與Pearson相關(guān)法和最大延遲相關(guān)在MDD患者治療前、治療后和健康對(duì)照組的結(jié)果進(jìn)行了對(duì)比。DCM模型選擇的結(jié)果顯示,治療前MDD組、治療后MDD組和健康對(duì)照組的功能網(wǎng)絡(luò)之間均存在因果聯(lián)系。DCM的結(jié)果驗(yàn)證了SN對(duì)DMN與CEN相反的調(diào)節(jié)作用在MDD患者中出現(xiàn)異常,發(fā)現(xiàn)了SN與CEN之間的調(diào)節(jié)回路,以及SN與DMN后部子網(wǎng)絡(luò)對(duì)DMN前部子網(wǎng)絡(luò)相反的調(diào)控作用。同時(shí)也發(fā)現(xiàn)治療前MDD患者的DMN后部子網(wǎng)絡(luò)對(duì)CEN左側(cè)子網(wǎng)絡(luò)和CEN右側(cè)子網(wǎng)絡(luò)的異常激勵(lì)作用,這種異常調(diào)節(jié)作用在治療后也得到改善。第三部分使用功能投射網(wǎng)絡(luò)分析方法研究了丘腦內(nèi)體素與功能投射網(wǎng)絡(luò)的連接關(guān)系。首先計(jì)算丘腦內(nèi)每個(gè)體素的功能連接圖。再使用ICA方法估計(jì)出丘腦的全腦功能投射模式,并從這些模式中選擇出SN前部子網(wǎng)絡(luò)、SN腹側(cè)子網(wǎng)絡(luò)、DMN前部子網(wǎng)絡(luò)、DMN后部子網(wǎng)絡(luò)、CEN左側(cè)子網(wǎng)絡(luò)、CEN右側(cè)子網(wǎng)絡(luò)和運(yùn)動(dòng)網(wǎng)絡(luò)。對(duì)原有方法進(jìn)行改進(jìn),使用有約束的多變量回歸模型估計(jì)每個(gè)丘腦體素與各個(gè)功能投射網(wǎng)絡(luò)的連接關(guān)系。最后根據(jù)丘腦體素與各個(gè)網(wǎng)絡(luò)連接的分布情況,對(duì)比MDD和健康對(duì)照組的丘腦的功能分區(qū)差異。結(jié)果發(fā)現(xiàn)MDD組右側(cè)丘腦內(nèi)側(cè)前部區(qū)域與CEN右側(cè)子網(wǎng)絡(luò)的連接出現(xiàn)異常降低。丘腦腹部后側(cè)部分區(qū)域與運(yùn)動(dòng)網(wǎng)絡(luò)之間的連接在MDD患者中也低于健康對(duì)照組,但是該結(jié)果在經(jīng)過多重比較校正后并不顯著。本文針對(duì)大腦功能網(wǎng)絡(luò)分析問題,使用功能網(wǎng)絡(luò)內(nèi)有效連接分析、功能網(wǎng)絡(luò)間的連接分析和深部腦區(qū)的功能投射網(wǎng)絡(luò)分析方法,研究MDD患者的大腦功能網(wǎng)絡(luò)異常。功能網(wǎng)絡(luò)內(nèi)有效連接分析定位了導(dǎo)致網(wǎng)絡(luò)異常的關(guān)鍵節(jié)點(diǎn)。功能網(wǎng)絡(luò)間的連接分析研究了網(wǎng)絡(luò)間的異常調(diào)控作用關(guān)系。功能投射網(wǎng)絡(luò)分析研究了丘腦內(nèi)功能投射發(fā)生異常的區(qū)域。這三個(gè)種分析方法構(gòu)成了一個(gè)較為全面的功能網(wǎng)絡(luò)分析框架。
[Abstract]:Major depressive disorder (major depressive, disorder, MDD) is a common mental disease. As for depression gradually deepening understanding, the current view is that MDD is dysfunction in multiple brain areas caused by abnormal connections in the brain. Based on functional magnetic resonance imaging (functional magnetic resonance imaging, fMRI) the study found that the brain can be the network function is decomposed into different brain regions, each functional coverage of the network is not connected in the structure, but in function are closely linked. Functional networks have similar distribution patterns of task state and resting state in brain function. In the network as the foundation to the study of brain function reorganization and interaction, from the network the connection point of interpretation function of multiple regions of the brain disorder. Resting state functional connectivity so it is important to analyze the function of patients with.MDD in the network research work on mental illness Can an abnormal connection has been proved by many studies reported. The default network (default mode network DMN (salience), network SN, highlighting the network) and the central executive network (central executive network, CEN) in the patients with MDD were abnormal in different degrees. The abnormal brain regions by neural connections can transfer to other brain regions therefore, the direction of neural activities between abnormal brain regions, has important significance in understanding the pathogenesis of diseases. The correlation of functional connectivity reflects brain activity, but can not provide the direction information of neural activity. Effective connectivity analysis method to estimate the connection direction and strength of neural activity, but the need to model construction based on the prior knowledge. Therefore explore the effective connection of internal nodes of different function between networks is a hot topic in the research function of the network. The brain in different functional states, active function of the network also There are differences between the degree of active function. The changes of network in time, can get the network connections between the connection between the network function. Reflect the synergy between different brain functions. The brain functional network coordination in many psychiatric disorders are abnormal. A hot issue between the function of the network the synergistic effect is the brain functional network research. Subcortical deep brain regions with extensive neural projection to the cerebral cortex. The connection mode of deep brain area and cortex function is called functional projection activities on the network. The network function mapping in deep brain regions play a role in the regulation of the network connections. According to the deep Department of brain and the function of projection, can be divided the function of deep brain regions. The connection network of brain areas related to disease and function of projection, the brain function of stroke Points of deep brain stimulation (deep brain stimulation, DBS) and other disease intervention technology has an important guiding role. Aiming at the three problems mentioned above, this paper mainly from the function of network, network function and deep brain function network projection three angles to research the function of network with MDD abnormal. The main work includes: the first chapter is the effective connectivity of resting state functional network analysis. Previous studies showed that MDD patients in DMN, CEN and SN showed abnormal connections. In order to find these network abnormal brain nerve activity interval direction and causal relationship. For the first time by the spectrum of dynamic causal model (spectral dynamic causal modeling, spDCM) were effective connection to function in the network analysis, and compares the differences between the MDD patients before treatment, after treatment and healthy control group. Through independent component analysis (in Dependent component analysis, ICA) method of decomposition of resting state functional network, and the choice of the resting state functional network closely related with MDD. According to the distribution pattern of resting state functional network space, respectively select key nodes within the network. Finally, according to the internal network of key nodes to build DCM model, using spDCM to estimate the effective connection between the key function of nodes within the network. The internal SN and DMN in patients with MDD were abnormal. The effective connection of effective connection. The results showed that MDD patients with DMN left parietal cortex (left parietal cortex, LPC) Regulation of neural activity decreased.SN ventral sub network in the right anterior insula (right anterior, insula, RAI) nerve regulating the activities of regional capacity to reduce.SN sub network in front of the left frontal cortex (left frontal cortex, LFC) in regulation of anomalies. The second chapter introduces the method of DCM SN Sub network, SN ventral sub network, DMN front DMN rear sub network, sub network between CEN and CEN on the right side of the left sub network connection sub network effectively modeled respectively using stochastic DCM (stochastic dynamic causal modeling, sDCM and spDCM). The model parameters were estimated and correlated with Pearson method and the maximum delay in MDD patients before treatment, after treatment and healthy control group compared.DCM model selection showed that MDD group before treatment, there was a causal relationship between the function of.DCM network of MDD group and control group after treatment, the results show that the SN of DMN and CEN opposite role in abnormal MDD patients, were found between SN and CEN and SN and the DMN loop, the rear sub network regulation of DMN front sub network opposite. Also found before treatment in patients with MDD DMN CEN on the left rear sub network subnet The abnormal incentive effect of collaterals and the right of CEN sub network, the abnormal regulation is also improved after treatment. The third part studies the connection between the use and function of the thalamus voxel projection network analysis function mapping network. First calculate the function within the thalamus of each voxel connected graph. Then use the ICA method to estimate the total brain function projection patterns of the thalamus, and the choice of the SN front sub network from these patterns, SN ventral sub network, DMN front sub network, DMN CEN left rear sub network, sub network, CEN network and sub network. The right movement for improvement on the original method, using the constrained multivariable regression model estimation connection between each voxel and thalamus each function projection network. Finally according to the distribution of thalamic voxel connected to each network, function zoning difference comparison between MDD and thalamus in healthy control group. The results showed that MDD group On the right side of the front area of the medial thalamus and CEN right sub network is abnormal. Between the posterior portion of the thalamus decreased abdominal area and the movement of network connection in MDD patients was lower than that of the control group, but the results after correction for multiple comparisons was not significant after. According to the brain functional network analysis, network connection function analysis, link analysis and deep brain function mapping network function between the network analysis method, the brain functional network of MDD patients with abnormal function in the network. The network connection effective positioning analysis leads to different key nodes. The abnormal regulation of the relationship between the network connection between the network analysis function. The function of projection network analysis of the abnormal region of the thalamus. These three functional projection methods constitute a comprehensive analysis framework. The function of network

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R445.2;R749.4
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本文編號(hào)：1677589