本文選題：精神分裂癥 + 幻聽　； 參考：《第四軍醫(yī)大學(xué)》2017年博士論文

【摘要】：精神分裂癥(SZ)是一種嚴(yán)重的精神疾病,臨床上往往表現(xiàn)為癥狀各異的綜合征,涉及感知覺、思維、情感和行為等多方面的障礙以及精神活動與環(huán)境的不協(xié)調(diào),人群終生發(fā)病率約為1%,其患者約占我國住院精神病患者的50%,慢性精神病患者的60%左右。幻聽(AVHs)是精神分裂癥主要癥狀之一,也是診斷精神分裂癥的重要臨床指標(biāo),是指在沒有相應(yīng)的外部聲音刺激作用于聽覺器官的情況下而產(chǎn)生聽覺,幻聽是聽覺對大腦的不服從,精神分裂癥患者有幻聽癥狀的占60%-80%�；寐牭膬�(nèi)容常常威脅病人、命令病人,或談?wù)摬∪说乃枷?評論病人的行為,給病人帶來極大的痛苦。特別是在命令性幻聽支配下會導(dǎo)致患者爆發(fā)出強大的攻擊性和破壞性行為,其自傷或傷人暴力行為會危及病人及其家屬,甚至危害社會。精神分裂癥幻聽仍然是病因未明的重性精神病。揭示幻聽的神經(jīng)機制,不但有顯著的臨床意義,也對研究精神分裂癥的病理生理機制有重要意義。近年來,各種神經(jīng)影像技術(shù)開始用于精神分裂癥幻聽相關(guān)的研究并取得了很多突破性的成果,為精神分裂癥幻聽診斷以及治療提供了重要的依據(jù),同時也為揭示AVHs產(chǎn)生的機理提供了重要的支撐。通過一系列的研究,幻聽產(chǎn)生的神經(jīng)機制也取得了重要的進(jìn)展。研究發(fā)現(xiàn),幻聽與語音生成和感知相關(guān)的腦區(qū)結(jié)構(gòu)和功能改變高度相關(guān)。相關(guān)研究結(jié)果已經(jīng)證明聽覺幻覺的形成主要與左中顳回、左顳-頂葉區(qū)域和左下額葉有關(guān)。最近的研究也進(jìn)一步表明,AVHs患者在額葉和顳葉皮質(zhì)區(qū)的皮質(zhì)厚度變薄�；隗w素的形態(tài)學(xué)研究報告,聽覺幻覺的嚴(yán)重性與包括初級和次級聽覺皮質(zhì)的顳葉相關(guān)。f MRI研究發(fā)現(xiàn),幻聽現(xiàn)象與左下額葉皮層和左中顳葉皮層的過度激活有關(guān),meta分析也顯示,AVHs與左下額葉和左下頂葉高度相關(guān)。然而,精神分裂癥是一種具有未知病因和病理生理學(xué)的疾病,幻聽的發(fā)病原因遠(yuǎn)比局部的腦區(qū)異常更為復(fù)雜。大量的神經(jīng)影像學(xué)研究認(rèn)為,認(rèn)知功能異常不能簡單地歸因于單一腦區(qū)或某幾個腦區(qū)的結(jié)構(gòu)病變與功能紊亂,認(rèn)知功能障礙往往是由腦區(qū)之間的連接異常引起的。因此,僅限于研究精神分裂癥幻聽患者表現(xiàn)出的特定腦區(qū)異常已經(jīng)不足以理解幻聽的發(fā)病機理。研究表明,幻聽的產(chǎn)生與大腦語言網(wǎng)絡(luò)的連接異常高度相關(guān)。擴散張量成像(DTI)研究已經(jīng)發(fā)現(xiàn),連接額葉和顳頂葉語言區(qū)域的纖維完整性降低,這項研究也進(jìn)一步表明,精神分裂癥患者聽覺幻覺的產(chǎn)生是由大腦皮層語言網(wǎng)絡(luò)的異常連接引起的。f MRI研究也顯示,幻聽的出現(xiàn)是大腦額葉和顳葉語言區(qū)之間的功能連接異常的結(jié)果。額葉和顳葉語言區(qū)域之間的功能連接異常在精神分裂癥幻聽患者句子完成任務(wù)、外部語音處理任務(wù)和說話聲音任務(wù)等試驗中都被發(fā)現(xiàn)。靜息態(tài)f MRI研究進(jìn)一步揭示了語言網(wǎng)絡(luò)的連接異常可能是精神分裂癥患者出現(xiàn)持續(xù)性幻聽的病理基礎(chǔ)。基于對大量幻聽病例研究的綜述也證實,幻聽相關(guān)病變的腦區(qū)基本上都位于大腦語言網(wǎng)絡(luò)通路上。雖然以前的研究表明幻聽的出現(xiàn)與大腦語言網(wǎng)絡(luò)連通性的改變有關(guān),但是都沒有系統(tǒng)研究精神分裂癥患者大腦語言區(qū)結(jié)構(gòu)連接和功能連接的改變?nèi)绾螌?dǎo)致幻聽的產(chǎn)生,這些異常是否有其內(nèi)在的關(guān)系,跟沒有進(jìn)一步研究這些腦區(qū)之間的有效連接。大腦有三種連接形式,第一種是結(jié)構(gòu)連接,指不同的腦區(qū)在解剖上的連接關(guān)系,是功能連接和有效連接的物質(zhì)基礎(chǔ);第二種是功能連接,反映腦區(qū)在動態(tài)生理活動中的相互關(guān)系,闡明腦區(qū)間是否存在功能關(guān)系以及其的強弱;第三種是有效連接,描述的是某一腦區(qū)是如何對另一腦區(qū)進(jìn)行作用的,闡述腦區(qū)之間信息傳遞的因果模式。我們認(rèn)為,只有系統(tǒng)研究大腦語言網(wǎng)絡(luò)的連通性才能真正揭示幻聽發(fā)生的神經(jīng)病理機理,對于精神分裂癥幻聽患者的診治也有非常重要的意義。本文以核磁共振數(shù)據(jù)為基礎(chǔ),通過腦連接分析方法,研究幻聽的產(chǎn)生與大腦連接異常的關(guān)系。在實驗一中,我們利用DTI技術(shù)研究對比了頻繁經(jīng)歷幻聽的精神分裂癥患者、未曾經(jīng)歷過幻聽的患者和健康對照三組被試白質(zhì)纖維的完整性。結(jié)果發(fā)現(xiàn)精神分裂癥非幻聽患者大腦顳葉區(qū)域白質(zhì)FA值異常。而在精神分裂癥幻聽患者中,顳葉、顳極、額葉、扣帶、小腦的腦白質(zhì)FA值都有降低,異常最大的腦區(qū)主要分布在額葉和顳葉的語言區(qū)域中。這些腦區(qū)最主要的連接是弓狀纖維束,也稱為弓形束。弓形束的破壞導(dǎo)致從額葉的布羅卡區(qū)到顳葉的韋尼克區(qū)神經(jīng)元連接的異常,這些異常會對語言流產(chǎn)生干擾。臨床觀測發(fā)現(xiàn),幻聽的內(nèi)容通常與患者自己的思想內(nèi)容密切相關(guān),這也說明了正是患者大腦神經(jīng)連接的異常,導(dǎo)致語言流不受控制地產(chǎn)生了混亂,引起了幻聽的產(chǎn)生。FA值的降低反映了該腦區(qū)纖維松散或交叉,纖維的完整性降低。我們的研究結(jié)果發(fā)現(xiàn)的顳葉和額葉語言區(qū)FA值的減少,反映了這些區(qū)域纖維束完整性的降低,而纖維束的異常導(dǎo)致語言區(qū)域連通性的改變,導(dǎo)致患者大腦語言區(qū)域功能障礙從而產(chǎn)生了幻聽癥狀。我們也發(fā)現(xiàn),幻聽患者扣帶回中的FA值異常。扣帶回被視為“情感和認(rèn)知之間的界面”,并且在精神分裂癥、強迫性障礙和重性抑郁癥等多種精神疾病如中均發(fā)現(xiàn)有損傷,我們的研究結(jié)果也與以前的研究相一致。在此項實驗中,我們以語言區(qū)的LIFG,LMTG和LIPL作為種子點進(jìn)行了纖維追蹤分析,結(jié)果顯示精神分裂癥幻聽患者語言區(qū)的纖維連接存在很多無序的連接和交叉,也反映了患者大腦語言區(qū)纖維完整性減低。在實驗一中我們發(fā)現(xiàn)在AVHs患者大腦白質(zhì)纖維結(jié)構(gòu)最大的改變正是位于語言網(wǎng)絡(luò)中額葉和顳葉之間的重要連接。這些改變很有可能正是幻聽產(chǎn)生的根源,并且有助于理解大腦內(nèi)部生成的信號如何被誤認(rèn)為是從外部生成的語音。我們認(rèn)為,異常結(jié)構(gòu)連接致使患者不能區(qū)分自己大腦內(nèi)部產(chǎn)生的信號和外部刺激。為了證實這個結(jié)論,我們在試驗二中對同一批被試在同一時間采集到的功能數(shù)據(jù)進(jìn)一步探索幻聽患者功能連接的異常。在實驗二中,對同一批被試,我們使用獨立成分分析的方法,研究了幻聽及非幻聽精神分裂癥患者語言網(wǎng)絡(luò)的功能連接異常。統(tǒng)計分析顯示,與正常對照組相比,兩組病人均在語言網(wǎng)絡(luò)的左側(cè)區(qū)域表現(xiàn)出功能連接的降低。同時,幻聽患者相對于非幻聽組及正常對照組,則在語言網(wǎng)絡(luò)右側(cè)多個腦區(qū)表現(xiàn)出功能連接的增強。本實驗發(fā)現(xiàn)兩組病人均在左側(cè)顳中回、顳上回、額下回功能連接降低,該結(jié)果提示,語言網(wǎng)絡(luò)左側(cè)功能連接的降低可能是精神分裂癥患者一個共同的病理改變。該結(jié)果與以往關(guān)于精神分裂癥的研究一致。同時,我們還發(fā)現(xiàn),與非幻聽病人及正常對照組相比,幻聽病人均表現(xiàn)出功能連接的減弱,相關(guān)的腦區(qū)包括左側(cè)額下回以及左側(cè)顳中回區(qū)域。該結(jié)果提示,這些腦區(qū)功能連接的異�？赡芘c幻聽癥狀的出現(xiàn)相關(guān)。我們在實驗一中,已經(jīng)發(fā)現(xiàn)精神分裂癥幻聽患者在這些腦區(qū)的結(jié)構(gòu)連接減弱,本實驗的結(jié)果與實驗一的結(jié)果相互印證,這說明幻聽的產(chǎn)生正是由于大腦語言區(qū)域功能和結(jié)構(gòu)連接產(chǎn)生了異常。在實驗三中,我們利用隨機動態(tài)因果模型(DCM)研究精神分裂癥幻聽患者與非幻聽患者大腦語言網(wǎng)絡(luò)中的有效連接。在此項靜息態(tài)f MRI研究中,被試與前面兩個實驗完全相同。語言處理中三個重要區(qū)域LIFG,LMTG和LIPL作為感興趣區(qū)(ROI),提取出這三個ROI的時間序列。對于每個被試,首先構(gòu)建全連接的DCM模型,然后使用網(wǎng)絡(luò)發(fā)現(xiàn)方案識別最優(yōu)(獲勝)模型。通過單因素ANOVA分析三組之間的統(tǒng)計學(xué)差異。結(jié)果表明,與非AVHs的患者相比,AVHs患者從LIFG到LMTG的有效連接顯著降低。同時,與健康對照相比,AVHs患者從LIPL到LMTG的有效連接顯著降低。我們的研究結(jié)果發(fā)現(xiàn)AVHs患者語言網(wǎng)絡(luò)中因果交互的模式異常,表明從額葉到顳葉語言區(qū)域的連通性降低或中斷可能是AVHs病理基礎(chǔ)的關(guān)鍵,這些結(jié)果也為精神分裂癥的“連接異常假說”提供了支撐。我們還發(fā)現(xiàn),與精神分裂癥非幻聽患者相比,幻聽患者從LIFG到LMTG的有效連接顯著降低。雖然持續(xù)幻聽是判定精神分裂癥的一個關(guān)鍵癥狀,但并不是所有的精神分裂癥患者都有幻聽癥狀。我們的研究結(jié)果也從一個側(cè)面證實,不同的神經(jīng)損傷導(dǎo)致精神分裂癥表現(xiàn)出不同的癥狀和亞型。在試驗一中,我們發(fā)現(xiàn)幻聽患者額葉與顳葉之間的纖維完整性明顯降低,在實驗二中,我們發(fā)現(xiàn)幻聽患者這些腦區(qū)。這些結(jié)果也為精神分裂癥的“連接異常假說”提供了支撐。在三個實驗中,我們均發(fā)現(xiàn)幻聽患者大腦語言區(qū)域連接存在異常,表明從語言區(qū)域的連通性降低或中斷可能是AVHs病理基礎(chǔ)的關(guān)鍵。
[Abstract]:Schizophrenia (SZ) is a serious mental illness. Clinical symptoms are often characterized by different symptoms, involving perception, thinking, emotion and behavior, as well as incoordination between mental activity and the environment. The lifetime incidence of the population is about 1%, and the patient accounts for about 50% of the patients in the hospital and the chronic psychosis. About 60%. Auditory hallucination (AVHs) is one of the main symptoms of schizophrenia and an important clinical indicator for the diagnosis of schizophrenia. It means that hearing is produced without the corresponding external sound stimulation in the hearing organ, auditory hallucination is disobedient to the brain, and the schizophrenic patients have auditory hallucinations in 60%-80%. auditory hallucinations. The content often threatens the patient, orders the patient, or talks about the patient's thoughts, reviews the behavior of the patient, and brings great pain to the patient. Especially under the command of auditory hallucination, it will cause the patient to break out powerful aggressive and destructive behavior, and its self injury or the violent behavior will jeopardize the patient and his family, or even harm the society. The auditory hallucination of cleft disease is still a serious psychosis of the unknown etiology. It is of significant significance not only to reveal the nervous mechanism of auditory hallucination, but also to the study of the pathophysiological mechanism of schizophrenia. In recent years, various neuroimaging techniques have been used to study the auditory hallucination of schizophrenia and have made many breakthroughs. It provides an important basis for the diagnosis and treatment of schizophrenia. It also provides important support to reveal the mechanism of AVHs production. Through a series of studies, the neural mechanism of auditory hallucination has also made important progress. The results of the study have shown that the formation of auditory hallucinations is mainly related to the left mesotemporal gyrus, the left temporal parietal region and the left inferior frontal lobe. Recent studies have further demonstrated that the cortical thickness of the frontal and temporal cortex is thinner in AVHs patients. The morphological study based on voxel, the severity of auditory hallucinations and the primary and secondary auditory hallucinations. The temporal lobe related.F MRI study found that auditory hallucinations were associated with excessive activation in the lower left frontal cortex and the left mesial temporal cortex. Meta analysis also showed that AVHs was associated with the lower left frontal lobe and the lower left parietal lobe. However, schizophrenia is a disease with unknown etiology and pathophysiology, and the cause of auditory hallucination is far more than the local brain. A large number of neuroimaging studies suggest that cognitive dysfunction can not be simply attributed to structural disorders and dysfunction in a single brain region or a few brain regions. Cognitive dysfunction is often caused by abnormal connections between the brain regions. Regional abnormalities are not enough to understand the pathogenesis of auditory hallucinations. Studies have shown that auditory hallucinations are associated with abnormal height in the brain's language network. Diffusion tensor imaging (DTI) studies have found that fibrous integrity in the frontal and temporal parietal language areas is reduced, and this study further suggests that the auditory hallucinations of schizophrenia patients are further demonstrated. .f MRI studies, caused by abnormal connections of the cerebral cortex language network, also show that the appearance of auditory hallucinations is the result of abnormal functional connections between the frontal and temporal lobe language areas. The functional connections between the frontal and temporal lobe language regions are abnormal in the sentences of the schizophrenic auditory patients and the external speech processing tasks and the tasks. The resting state f MRI study further revealed that the connection abnormalities of the language network may be the pathological basis for the occurrence of persistent auditory hallucinations in the schizophrenic patients. A review based on a large number of auditory hallucinations also confirms that the brain areas of auditory hallucinations are basically located on the brain's language network pathway. Although previous studies have shown that the appearance of auditory hallucination is related to changes in the connectivity of the brain's language network, there is no systematic study of how the changes in the structural connections and functional connections in the brain of the schizophrenic patients lead to the emergence of auditory hallucinations. The brain has three kinds of connection forms. The first is the structural connection, which refers to the anatomical connection of different brain regions, the material basis for functional connection and effective connection; the second is functional connection, reflects the relationship between the brain regions in the dynamic physiological activities, and explains the existence of functional relations and its strength in the brain region; The three is an effective connection, which describes how a certain brain area acts on another brain region and describes the causal mode of information transfer between the brain regions. We think that only systematic study of the connectivity of the brain's language network can truly reveal the neuropathic mechanism of the hallucination, and the diagnosis and treatment of schizophrenia patients with schizophrenia. On the basis of nuclear magnetic resonance data, this paper studies the relationship between the emergence of auditory hallucination and the abnormal brain connection through the method of brain connective analysis. In experiment one, we used DTI technique to compare the three groups of patients who had experienced auditory hallucinations, those who had never experienced auditory hallucinations and healthy control groups of white matter fibers. The results showed that the FA value of white matter in the temporal lobe region of the non auditory schizophrenic patients was abnormal. In the schizophrenic patients, the temporal lobe, the temporal pole, the frontal lobe, the cingulate band and the cerebellar white matter FA were reduced, the most abnormal brain areas were mainly distributed in the language areas of the frontal and temporal lobes. The most important connection in these brain areas was the bow. Fibrous bundles, also known as arcuate bundles. The destruction of the arcuate bundle leads to abnormal connections between the Broca and the temporal lobe neurons of the frontal lobe, which interfere with the language flow. Clinical observations have found that the content of the auditory hallucination is closely related to the content of the patient's own thought, which also indicates that it is the nerve connection of the patient's brain. The abnormality of the language leads to the confusion of the language flow without the control of the real estate. The decrease of the.FA value of the auditory hallucination reflects the loosening or intersecting of the fibers in the brain and the decrease in the integrity of the fibers. Our results show a decrease in the FA value of the temporal and frontal lobes, reflecting the decrease in the integrity of the fiber bundles in these regions and the abnormality of the fiber bundles. We also found that the FA value in the cingulate gyrus was abnormal. The cingulate gyrus was regarded as "the interface between emotion and cognition", and a variety of mental disorders such as schizophrenia, compulsive disorder, and heavy depressive disorder, such as schizophrenia, were also found. The results of our study were consistent with previous studies. In this experiment, we used LIFG, LMTG, and LIPL as seed points for fiber tracing analysis. The results showed that there were many disordered connections and intersections in the language area of schizophrenic auditory hallucinations, and the patient's brain was also reflected. In experiment one, we found that the largest changes in the white matter fiber structure in the brain of AVHs patients are the important connections between the frontal and temporal lobes in the language network. These changes are likely to be the root of the auditory hallucination, and help to understand how the signals generated within the brain are mistaken for the error. External generated speech. We think that abnormal structural connections cause patients to be unable to distinguish between signals and external stimuli within their own brain. In order to confirm this conclusion, we further explore the functional data of the same batch of subjects at the same time in test 2 to further explore the abnormal functional connection of the auditory hallucinations. In Experiment 2, In the same group, we used an independent component analysis to study the dysfunction of the functional connectivity of the language network of the patients with auditory hallucination and non auditory schizophrenia. Statistical analysis showed that compared with the normal control group, the two groups showed lower functional connectivity in the left area of the language network. At the same time, the auditory hallucinations were compared to non auditory groups. The results showed that the lower left functional connection of the language network may be a common pathological change in the schizophrenic patients. The results suggest that the decrease of the left functional connection in the language network may be a common pathological change in the patients with schizophrenia. The results suggest that the two groups of patients are likely to be a common pathological change in schizophrenia. The previous study of schizophrenia was consistent. At the same time, we also found that, compared with the non auditory hallucination patients and the normal control group, the auditory hallucination patients showed a weakening of the functional connection, and the related brain areas included the left inferior frontal gyrus and the left temporal gyrus. In our experiment, we have found that the structural connections of schizophrenic auditory hallucinations have weakened in these brain regions. The results of this experiment confirm with the results of experiment one. This shows that the auditory hallucination is due to the abnormal function of the brain region and the structural connection. In Experiment 3, we use random dynamic causality modules. DCM study the effective connection in the brain language network of schizophrenic auditory hallucinations and non auditory patients. In this resting state f MRI study, the subjects were exactly the same as the previous two experiments. Three important regions of language processing, LIFG, LMTG and LIPL as the region of interest (ROI), extracted the time series of the three ROI, for each of the subjects, First, a fully connected DCM model was constructed and the network discovery scheme was used to identify the optimal (winning) model. The statistical difference between the three groups was analyzed by a single factor ANOVA. The results showed that the effective connection between the AVHs patients from LIFG to LMTG was significantly lower than that of the non AVHs patients. At the same time, compared with the health control, the AVHs patients were from LIPL to LMTG. Our results show that the pattern abnormality in the causal interaction in the AVHs language network indicates that the reduction or interruption of connectivity from the frontal lobe to the temporal lobe may be the key to the pathological basis of AVHs, and these results also provide support for the "connection anomaly hypothesis" of schizophrenia. The effective connection of auditory hallucinations from LIFG to LMTG decreased significantly compared to non auditory hallucinations. Although persistent auditory hallucinations were a key symptom of schizophrenia, not all schizophrenic patients had hallucinations. Our findings also proved from a side side that different nerve injuries lead to schizophrenia. In trial one, we found that the fibrous integrity between the frontal and temporal lobes of the auditory hallucination patients decreased significantly. In the second experiment, we found the auditory hallucination of these brain regions. These results also supported the "connection abnormality hypothesis" of schizophrenia. In the three experiments, we all found auditory hallucination. Abnormal connectivity of brain brain regions indicates that the decrease or interruption of connectivity from the language area may be the key to the pathological basis of AVHs.

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R749.3
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本文編號：1772743