本文選題：語言 + 漢語�。� 參考：《復旦大學》2013年博士論文

【摘要】：近年,人類對腦功能的研究越來越重視。2013年初,美國和歐盟都推出了“人腦計劃”,希望通過10年繪制出人腦活動圖。語言是人腦獨有的高級認知功能。人類的一切心理活動都離不開語言。當前,腦病變患者對醫(yī)療質(zhì)量的要求日益提高,已不再是一味地追求生存,而是更加注重有尊嚴有質(zhì)量的生活。由于存在個體差異和受病變所致的腦功能移位、重組(reorganization)或塑形(plasticity),神經(jīng)外科手術(shù)借助傳統(tǒng)解剖標志來定位腦語言功能區(qū),不僅不準確,而且可誤腦語言皮質(zhì)和語言網(wǎng)絡(luò),導致術(shù)后病人失語及認知障礙。因此,迫切需要尋找效的技術(shù)以實現(xiàn)語言區(qū)的精確定位。然而,既往絕大多數(shù)語言定位的理論都是基于英語等拼音字母語言的研究結(jié)果,迄今,對漢語的語言定位仍缺乏系統(tǒng)的研究。因此,通過探索語言定位的新技術(shù)以及漢語語言分布和語言網(wǎng)絡(luò)既有助于拓寬現(xiàn)有的語言定位手段,又可以從宏觀上了解漢語語言的定位和分布特點。 本論文基于多模態(tài)的技術(shù)手段(術(shù)中皮質(zhì)電刺激、任務(wù)態(tài)功能磁共振、靜息態(tài)功能磁共振、彌散張量成像、術(shù)中磁共振),在國人漢語人群中進行了一系列探索和研究。第一部分通過55例患者的功能預后證實了喚醒麻醉下術(shù)中皮質(zhì)電刺激(金標準)定位語言中樞的可靠性,這是后面兩部分研究的立論基礎(chǔ)；第二部分提出了3種語言定位新技術(shù)和新方法,并經(jīng)金標準驗證,實現(xiàn)了技術(shù)創(chuàng)新；第三部分構(gòu)建了基于功能磁共振和電生理的漢語語言分布圖和語言網(wǎng)絡(luò),實現(xiàn)了理論創(chuàng)新。 第一部分：3T iMRI環(huán)境下喚醒麻醉聯(lián)合術(shù)中語言皮質(zhì)定位技術(shù)在語言區(qū)腦膠質(zhì)瘤手術(shù)中的應(yīng)用 喚醒手術(shù)和術(shù)中MRI兩種技術(shù)已被廣泛應(yīng)用于臨床,其應(yīng)用的可靠性和有效性并分別得到證實�？墒�,兩種復雜技術(shù)聯(lián)合應(yīng)用的經(jīng)驗和報道卻比較有限。我們在論文中報道了本單位在術(shù)中MRI環(huán)境下進行喚醒手術(shù)的經(jīng)驗和方法并且定量的評估了對語言區(qū)腫瘤患者的功能預后以及切除程度的影響。共55例(從2010年12月-2012年12月)語言區(qū)的腦膠質(zhì)瘤患者納入本研究。切除程度的評估通過體積分析法實現(xiàn),語言的評估采用漢語失語癥檢查表。手術(shù)中MRI掃描采用局部鋪巾法,語言皮質(zhì)定位采用自行研制的喚醒麻醉腦功能刺激設(shè)備(專利號：201220303939.1)。 結(jié)果發(fā)現(xiàn),共有22名患者(40%)在術(shù)后1周出現(xiàn)近期語言障礙,只有2名患者(3.6%)出現(xiàn)永久性(術(shù)后6月)語言障礙。由于術(shù)中MRI的參與,55名患者腫瘤的全切率從34.5%增加到63.6%。其中共有23名(41.8%)患者在術(shù)中MRI掃描后獲得進一步的切除。中位切除程度從91.6%(范圍45.7%-99.0%)增加到100%(范圍74.0%-100%),并具有統(tǒng)計學意義(P0.01)。局部鋪巾法不僅達到無菌手術(shù)操作要求,而且能夠滿足術(shù)中MRI掃描要求和克服喚醒麻醉的氣道管理難題。沒有發(fā)生與鋪巾法有關(guān)的并發(fā)癥。腦功能刺激裝置顯著提高了喚醒手術(shù)的工作效率。 本部分結(jié)果表明1)聯(lián)合術(shù)中MRI以及語言皮質(zhì)定位兩項技術(shù)應(yīng)用于語言區(qū)腫瘤手術(shù)有助于語言功能的保護的同時提高全切率；2)基于大樣本的病例預后隨訪證實喚醒麻醉下的術(shù)中語言皮質(zhì)定位是可靠的。 第二部分:漢語語言中樞定位的技術(shù)創(chuàng)新 術(shù)中語言皮質(zhì)定位技術(shù)是語言定位公認的金標準。然而,該技術(shù)具有下列不足,一是無法用于術(shù)前的計劃,且無法直觀的顯示與腫瘤的位置關(guān)系；二是只局限在骨窗有限的范圍內(nèi),無法全面的顯示整體語言網(wǎng)絡(luò)；三是需要患者的配合,無法應(yīng)用于兒童以及語言障礙或不合作患者。因此,迫切需要尋找和探索新的語言定位手段以彌補現(xiàn)有定位手段的不足。 本部分基于三種不同的影像學模態(tài)(彌散張量成像,任務(wù)態(tài)fMRI,靜息態(tài)fMRI),分別針對外科手術(shù)目前應(yīng)用的不足和缺陷,提出了三種語言定位的新技術(shù)和新方法。第一種技術(shù),將弓狀束纖維示蹤技術(shù)應(yīng)用于額葉皮質(zhì)的定位,并通過金標準對其定位的準確性進行驗證,定位的靈敏度是70.0%,特異度是97.6%,如果將弓狀束周圍1厘米作為標準,靈敏度和特異度分別為90.0%和96.0%,特異度未明顯下降的前提下靈敏度得到極大的提高。第二種技術(shù),我們將任務(wù)態(tài)fMRI與術(shù)中MRI結(jié)合,首先提出喚醒麻醉下術(shù)中功能磁共振技術(shù),克服了術(shù)前fMRI的腦移位問題。本論文探索了該技術(shù)定位的可行性,并在個體病例上通過電生理結(jié)果驗證了其可靠性。第三種是方法學的創(chuàng)新,獨立成分分析法進行靜息態(tài)fMRI分析的最大難題就是需要人為的判斷各個成分,我們引入了d’(d-prime)的計算方法成功的實現(xiàn)了分別基于組水平和個體水平的語言成分的篩選,同時將該技術(shù)應(yīng)用于腫瘤患者進行語言區(qū)定位,初步證實了該方法的可行性。 第三部分:基于功能磁共振和電生理的漢語語言皮質(zhì)分布圖和語言網(wǎng)絡(luò)的建立 越來越多的證據(jù)表明漢語語言的處理不同英語等語言。由于語言的復雜性和缺乏動物模型,現(xiàn)有的漢語語言的研究基本都局限于功能神經(jīng)影像的研究。神經(jīng)外科是唯一可以實現(xiàn)與大腦“面對面”交流的學科,這也就提供了一個獨特的機會通過術(shù)中語言皮質(zhì)定位技術(shù)構(gòu)建漢語語言的分布圖和拓撲結(jié)構(gòu)。本部分我們首先分別構(gòu)建了腦膠質(zhì)瘤患者三種任務(wù)模式(圖片命名,動詞產(chǎn)生和默讀詩歌)和正常志愿者的一種任務(wù)模式(圖片命名)的fMRI的語言分布圖；接下來,通過將55例患者術(shù)中語言皮質(zhì)電刺激的陽性位點進行合成,分別得到言語中止、命名性失語和閱讀性失語的皮質(zhì)分布圖；最后,以電生理的陽性位點作為種子點,通過功能連接,構(gòu)建基于金標準的漢語語言靜息網(wǎng)絡(luò)。 本部分的結(jié)果表明1)中央前回腹側(cè)部(BA6區(qū)的腹側(cè)部)和額葉島蓋部(BA44)對語言的產(chǎn)生具有至關(guān)重要的作用。我們推斷中央前回腹側(cè)部以及島蓋部應(yīng)當是語言產(chǎn)生的核心區(qū)域,較傳統(tǒng)的broca區(qū)要后移；2)左側(cè)額中回(BA9區(qū))在漢語的電生理定位中較英語更易出現(xiàn)語言任務(wù)的中止,證實BA9區(qū)是漢語語言處理中的一個特殊的節(jié)點；3)漢語的語言分布范圍較印歐語系更加廣泛,個體差異更大；4)單一一種任務(wù)的fMRI進行語言定位仍存缺陷,聯(lián)合多種任務(wù)進行定位可提高可靠性；5)基于金標準構(gòu)建漢語語言靜息網(wǎng)絡(luò)是可行的,可能更接近真實的語言網(wǎng)絡(luò)。 結(jié)論 本論文圍繞轉(zhuǎn)化醫(yī)學對漢語語言定位開展了一系列的研究,主要結(jié)論和價值如下： 1、通過多模態(tài)技術(shù)構(gòu)建了漢語語言分布圖和網(wǎng)絡(luò),發(fā)現(xiàn)了漢語語言的特殊性與共性,為漢語語言區(qū)手術(shù)提供理論指導。 2、通過技術(shù)和方法的創(chuàng)新,提出了多種可行且可靠的新技術(shù)方案進行語言定位,為語言定位提供技術(shù)指導。 3、基于語言定位的復雜性,單一的定位方案并不可靠,可通過多模態(tài)技術(shù)互相驗證。 創(chuàng)新點 1、首次報道喚醒手術(shù)和術(shù)中高場強MRI在語言區(qū)腫瘤的聯(lián)合應(yīng)用(國內(nèi)首次) 2、首次通過電生理驗證了弓狀束纖維示蹤定位漢語額葉語言區(qū)的有效性(國際首次) 3、首次提出喚醒麻醉下術(shù)中功能磁共振(ai-fMRI)的概念并應(yīng)用于臨床,證實了其可行性與可靠性(國際首次) 4、首次建立基于獨立成分分析法的語言網(wǎng)絡(luò)自動篩選方法并應(yīng)用于個體(國際首次) 5、首次建立具有自主知識產(chǎn)權(quán)的漢語語言皮質(zhì)分布圖(國際首次) 6、首次建立基于電生理的漢語語言靜息網(wǎng)絡(luò)(國際首次)
[Abstract]:In recent years, the research of human brain function has been paid more and more attention at the beginning of.2013. Both the United States and the European Union have launched the "human brain program", hoping to draw a human brain activity map through 10 years. Language is a unique high-level cognitive function of the human brain. All the psychological activities of human beings are inseparable from the language. It is no longer the pursuit of survival, but more emphasis on a life of dignity and quality. Because of the existence of individual differences and dislocations caused by the brain function shift, reorganization or plasticity, the Department of Neurosurgery surgery with the aid of traditional anatomical markers to locate the brain function area is not only inaccurate, but also mistaken brain language cortex And language network, resulting in postoperative patients aphasia and cognitive impairment. Therefore, there is an urgent need to find effective techniques to achieve the precise positioning of the language area. However, most of the previous theories of language localization are based on the results of the phonetic alphabet language such as English and so on. So far, the language localization of Chinese is still lacking systematic research. The exploration of the new technology of language positioning and the distribution of Chinese language and language network can not only help to broaden the existing language positioning means, but also understand the localization and distribution characteristics of the Chinese language from the macro level.
This paper is based on multimodal techniques (cortical electrical stimulation, task state functional magnetic resonance, resting state function magnetic resonance, diffusion tensor imaging, and intraoperative magnetic resonance). A series of studies and studies were carried out in Chinese people. The first part confirmed the cortical electrical stimulation (gold) during the wake anaesthesia in 55 patients. Standard) positioning the reliability of the language center, which is the foundation of the last two parts of the study; the second part puts forward 3 new techniques and new methods for language positioning, and realizes technical innovation through the verification of gold standard. The third part constructs a Chinese language distribution map and a language network based on functional magnetic resonance and electrophysiology. The theory has realized the theory. Innovation.
Part I: application of awaking anesthesia combined with intraoperative localization of language cortex in 3T iMRI brain glioma surgery
The two techniques of wake-up operation and intraoperative MRI have been widely used in clinical practice, and the reliability and effectiveness of their applications are confirmed. However, the experience and reports of the combined application of the two complex techniques are limited. In this paper we report the experience and methods of the unit in the operation of the wake-up operation under the operation of the MRI and quantitative A total of 55 patients with glioma in the language area (December 2010 -2012 December) were included in the study. The assessment of the degree of resection was achieved by volume analysis, and the language evaluation adopted the Chinese aphasia check list. In the operation, the MRI scan used the local napkin method. Cortical localization was performed by a self-developed wake-up anesthetic brain stimulation device (Patent No. 201220303939.1).
The results showed that a total of 22 patients (40%) had recent language disorders at 1 weeks after the operation, only 2 patients (3.6%) had permanent (postoperative June) language barriers. Due to the involvement of MRI, 55 patients increased the total tumor rate from 34.5% to 63.6%., of which 23 (41.8%) patients received further resection after MRI scanning. The degree increased from 91.6% (range 45.7%-99.0%) to 100% (range 74.0%-100%) and had statistical significance (P0.01). The local napkin method not only met the requirements of aseptic operation, but also met the requirements of MRI scan in the operation and overcome the airway management problem of wake up anesthesia. There was no complication associated with the napkin method. Brain function stimulation device The efficiency of the wake-up operation was significantly improved.
The results of this part show that 1) combined operation of MRI and two techniques of language cortex localization in language area tumor surgery can help to protect the language function while improving the total cut rate while 2) based on the prognosis of large sample cases, it is proved that the localization of the language cortex in the operation under the wake up anesthesia is reliable.
The second part: technological innovation of location of Chinese Language Center.
The technique of language cortical positioning is the golden standard of language positioning. However, the technique has the following shortcomings, one is that it can not be used before the operation and can not display the relationship with the tumor directly. Two it is limited to the limited scope of the bone window and can not show the overall language network in an all-round way; and the three is the need for the patient's coordination, It is impossible to apply to children, language disorders or non cooperative patients. Therefore, it is urgent to find and explore new language positioning methods to make up for the shortcomings of existing positioning methods.
This part is based on three different imaging modality (diffuse tensor imaging, mission state fMRI, resting state fMRI). In view of the shortcomings and shortcomings of the current application of surgical operations, three new techniques and new methods for the localization of language are proposed. The first technique is applied to the localization of the frontal cortex by the bow beam tracing technique and through the gold standard. The sensitivity of the location is verified by 70%, the sensitivity is 70%, the specificity is 97.6%. If the 1 cm around the bow bundle is the standard, the sensitivity and specificity are 90% and 96% respectively, the sensitivity is greatly improved under the condition that the specificity does not decrease obviously. Second techniques, we combine the task state fMRI with the intraoperative MRI, first of all. The functional magnetic resonance (fMRI) technique under wake up anesthesia was proposed to overcome the problem of brain displacement of fMRI before operation. The feasibility of this technique was explored in this paper, and its reliability was verified by electrophysiological results in individual cases. The third is the innovation of methodology and the biggest problem of the rest state fMRI analysis by independent component analysis is the need. In order to judge the individual components artificially, we introduced the d '(d-prime) method to successfully screen the language components based on the group level and the individual level, and applied the technique to the tumor patients to locate the language area, and initially confirmed the feasibility of the method.
The third part: the distribution of Chinese language cortex and the establishment of language network based on fMRI and electrophysiology.
More and more evidence shows that Chinese language is handled in different languages such as English and other languages. Due to the complexity of language and the lack of animal models, the study of the existing Chinese language is limited to the research of functional neuroimaging. The Department of neurosurgery is the only subject that can meet the "face-to-face" flow of the brain. This provides a unique feature. In this part, we first constructed the language distribution maps of the three tasks of the brain glioma patients (picture naming, verb generation and silent reading) and a task model of normal volunteers (the picture named) fMRI. The positive loci of the electrical stimulation of the language cortex of 55 patients were synthesized and the cortical distribution maps of speech discontinuation, named aphasia and reading aphasia were obtained respectively. Finally, the positive loci of electrophysiology were used as seed points, and the resting network of Chinese language based on gold standard was constructed by functional connection.
The results of this part show that 1) the anterior central ventral part of the central ventral region (the ventral part of BA6 region) and the frontal lobe Island (BA44) play a vital role in the production of language. We infer that the anterior central ventral side of the central region and the island cover should be the core region of the language, and the traditional Broca region should be moved back; 2) the left middle frontal gyrus (BA9 region) is in Chinese electrophysiology. It is easier to show the suspension of language tasks than English in physical location. It is proved that BA9 area is a special node in Chinese language processing; 3) Chinese language is more widely distributed than Indo European, and the individual difference is greater; 4) a single task of the language location still has defects, combining a variety of tasks can improve reliability. Sex; 5) constructing a resting network of Chinese language based on the golden standard is feasible and may be closer to the real language network.
conclusion
This thesis has carried out a series of studies on the location of Chinese language in translational medicine. The main conclusions and values are as follows:
1, the Chinese language distribution map and network were constructed through multi-modal technology, and the particularity and commonality of Chinese language were found, which provided theoretical guidance for Chinese language area surgery.
2, through the innovation of technology and method, we put forward various feasible and reliable new technology solutions for language localization, and provide technical guidance for language localization.
3, based on the complexity of language localization, a single localization scheme is not reliable and can be verified by multi-modal technology.
innovation point
1, we first reported the combined application of wake-up surgery and intraoperative high field MRI in the language area tumors (the first time in China).
2, for the first time, the validity of arcuate fiber tracer localization of Chinese frontal lobes was verified by electrophysiology.
3, we first proposed the concept of functional magnetic resonance imaging (ai-fMRI) during awake anesthesia and applied it in clinical practice, which confirmed its feasibility and reliability (the first time in the world).
4, it is the first time to set up an automatic language screening method based on independent component analysis (ICA) and apply it to individuals (the first time in the world).
5, the first time to establish a Chinese language cortical distribution map with independent intellectual property rights (the first time in the world).
6, the first Chinese language resting network based on electrophysiology has been established for the first time.
【學位授予單位】：復旦大學
【學位級別】：博士
【學位授予年份】：2013
【分類號】：R651.1

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2 陳安;BOLD fMRI技術(shù)結(jié)合非血流動力學響應(yīng)函數(shù)分析法檢測大鼠C6皮下膠質(zhì)瘤內(nèi)部氧合變化的可行性研究[D];蘇州大學;2014年

3 張東升;美沙酮維持治療的海洛因依賴者大腦抑制性控制功能的fMRI研究[D];第四軍醫(yī)大學;2014年

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