溫建斌，李小俚

北京師范大學(xué) 認(rèn)知神經(jīng)科學(xué)與學(xué)習(xí)國(guó)家重點(diǎn)實(shí)驗(yàn)室，北京 100875

腦皮層功能定位技術(shù)在臨床研究中的應(yīng)用發(fā)展

溫建斌，李小俚

北京師范大學(xué) 認(rèn)知神經(jīng)科學(xué)與學(xué)習(xí)國(guó)家重點(diǎn)實(shí)驗(yàn)室，北京 100875

皮層功能定位對(duì)于保證神經(jīng)外科手術(shù)的效果有重要作用，而皮層電刺激技術(shù)一直以來(lái)都被認(rèn)為是臨床皮層功能定位的“金標(biāo)準(zhǔn)”。隨著神經(jīng)成像技術(shù)和理論的發(fā)展，越來(lái)越多新的方法也開(kāi)始被應(yīng)用于神經(jīng)外科皮層功能定位，包括皮層腦電圖、正電子放射斷層掃描、功能核磁共振成像、腦磁圖、經(jīng)顱磁刺激以及皮層光學(xué)成像等。本文對(duì)這些技術(shù)的原理分別作了簡(jiǎn)單介紹，并從臨床可靠性、安全性、檢測(cè)效率、成本以及應(yīng)用現(xiàn)狀等方面對(duì)它們進(jìn)行比較。文章最后對(duì)臨床皮層功能定位技術(shù)的未來(lái)發(fā)展?fàn)顩r作出了展望。

皮層功能定位；神經(jīng)外科；功能核磁成像；經(jīng)顱磁刺激；皮層腦電圖

引言

神經(jīng)外科手術(shù)對(duì)于藥物難治性癲癇[1]、腦血管疾病[2]以及腦腫瘤等[3]均有較好的治愈效果。但是，當(dāng)大腦的重要功能區(qū)與病灶臨近或重合時(shí)，便會(huì)受到損毀手術(shù)的影響，從而引起功能損傷。大部分術(shù)后功能區(qū)受損的病人會(huì)在3個(gè)月內(nèi)得到恢復(fù)，但約有5%的病人會(huì)形成永久損傷[4]。因此，如何能準(zhǔn)確地對(duì)大腦重要的功能區(qū)進(jìn)行定位對(duì)手術(shù)方案的制定和病人的愈后有重要意義。皮層電刺激技術(shù)（Electrical Cortical Stimulation，ECS）一直以來(lái)被認(rèn)為是臨床上皮層功能定位的“金標(biāo)準(zhǔn)”，但隨著神經(jīng)信號(hào)采集以及神經(jīng)成像技術(shù)和理論的發(fā)展，越來(lái)越多的新方法也開(kāi)始被應(yīng)用于神經(jīng)外科皮層功能定位。除了皮層電刺激之外，目前可在臨床上用于皮層功能定位的技術(shù)包括：皮層腦電圖（Electrocorticography，ECoG）、正電子放射斷層掃描（Positron Emission Tomography，PET）、功能核磁共振成像（Functional Magnetic Resonance Imaging，fMRI）、腦磁圖（Magnetoencephalography，MEG）、經(jīng)顱磁刺激（Transcranial Magnetic Stimulation，TMS）和皮層光學(xué)成像（Optical Cortical Imaging，OCI）等。

總的來(lái)說(shuō)，皮層功能定位技術(shù)可采取的策略可大體分為兩種：① 觀測(cè)記錄相關(guān)腦區(qū)在特定認(rèn)知任務(wù)下的活動(dòng)狀態(tài)，如電/磁信號(hào)（ECoG和MEG）、光信號(hào)（OCI）或代謝強(qiáng)度（fMRI和PET）等指標(biāo)。采用這種策略可以說(shuō)明相關(guān)腦區(qū)參與了特定認(rèn)知過(guò)程，但無(wú)法證明其充分性和必要性；② 對(duì)相關(guān)皮層區(qū)域施加刺激并考察引起的后果（ECS和TMS）。如果刺激引起抑制性的效果，則可以暫時(shí)造成目標(biāo)皮層區(qū)域失活，從而直接模擬手術(shù)可能造成的認(rèn)知損傷，驗(yàn)證了該皮層區(qū)域?qū)τ谙嚓P(guān)功能的必要性；反之，如果刺激是興奮性的，則可以通過(guò)觀察其是否能引起相關(guān)的預(yù)期反應(yīng)而確定相關(guān)皮層區(qū)域的功能。除了總體技術(shù)策略，這些方法在原理上也各不相同，在臨床可靠性、檢測(cè)效率、安全性以及成本方面也存在差別，本文將分別對(duì)其作簡(jiǎn)單介紹，比較其應(yīng)用現(xiàn)狀，并就未來(lái)發(fā)展作出展望。

1 皮層功能定位技術(shù)簡(jiǎn)介

1.1 皮層電刺激技術(shù)

ECS的發(fā)展最早可以追溯到19世紀(jì)，于1910年前后開(kāi)始作為一種穩(wěn)定可靠的功能定位技術(shù)被應(yīng)用于神經(jīng)外科手術(shù)，一直至今。ECS需要開(kāi)顱進(jìn)行，通過(guò)直接放置在皮層表面的電極施加電流刺激而對(duì)相關(guān)皮層區(qū)域造成干擾，從而判斷其功能。作為臨床應(yīng)用時(shí)間最長(zhǎng)的皮層功能定位技術(shù)，ECS已經(jīng)使無(wú)數(shù)病人免受外科術(shù)后的功能損傷，其可靠性也得到諸多系統(tǒng)研究的支持[5-6]。實(shí)際上，盡管有很長(zhǎng)的歷史，幾十年來(lái)ECS本身并沒(méi)有很多實(shí)質(zhì)性的改變，臨床上甚至沒(méi)有一套嚴(yán)格的標(biāo)準(zhǔn)化操作規(guī)程[7]。由于是直接對(duì)皮層施加電刺激，在應(yīng)用于癲癇病人時(shí)，ECS有誘發(fā)后放電甚至發(fā)作的風(fēng)險(xiǎn)，另外，在應(yīng)用于兒科病人時(shí)，由于發(fā)育中的皮層對(duì)于電刺激的耐受性較差，往往不能取得理想效果。ECS的另外一個(gè)缺點(diǎn)是效率低，每個(gè)刺激點(diǎn)需要從弱電流開(kāi)始，重復(fù)若干次后再逐步加強(qiáng)，且刺激間需要留有充分間隔。這樣導(dǎo)致一個(gè)典型的術(shù)前硬膜下植入電極電刺激功能定位程序耗時(shí)經(jīng)常長(zhǎng)達(dá)數(shù)小時(shí)。盡管如此，ECS仍然是應(yīng)用最為廣泛的皮層功能定位技術(shù)，其也經(jīng)常被用作標(biāo)準(zhǔn)來(lái)評(píng)估其他功能定位技術(shù)的效果。

1.2 皮層功能定位法-皮層腦電信號(hào)定位法

相較而言，用皮層腦電定位重要功能區(qū)可以免除電刺激帶來(lái)的風(fēng)險(xiǎn)，且能夠同步處理所有電極通道來(lái)源的數(shù)據(jù)，提高了效率。而且由于其高信噪比和高時(shí)空分辨率，很多研究者開(kāi)發(fā)出基于皮層高頻伽馬活動(dòng)的快速或?qū)崟r(shí)功能定位系統(tǒng)[19-22]。利用皮層腦電信號(hào)確定功能區(qū)的缺點(diǎn)在于，它不能夠反映全腦的信息，也不能記錄（或刺激）到大腦溝回里面和深部（如內(nèi)側(cè)顳葉和海馬）皮層組織，電極之間的區(qū)域也可能被漏測(cè)，而這些也幾乎是所有侵入性功能定位技術(shù)都面臨的問(wèn)題。

1.3 正電子放射斷層掃描技術(shù)

PET技術(shù)發(fā)展于上世紀(jì)50年代，其基本原理是將能夠被人體正常代謝的分子用能夠進(jìn)行正β衰變的同位素標(biāo)記，然后在特定的時(shí)間窗口內(nèi)，通過(guò)記錄同位素衰變引起的物理效應(yīng)來(lái)確定相關(guān)分子在空間中的密度分布，從而達(dá)到對(duì)人體組織進(jìn)行結(jié)構(gòu)成像和功能成像的目的。神經(jīng)功能成像常用的標(biāo)的物有15O標(biāo)記的水分子和氟代脫氧葡萄糖（18F-FDG），前者通過(guò)皮層血流量來(lái)反映神經(jīng)細(xì)胞的活動(dòng)強(qiáng)度，后者與細(xì)胞對(duì)于葡萄糖攝取的情況相關(guān)，從而反映細(xì)胞活動(dòng)水平。PET技術(shù)可以用于多種功能定位，如軀體感覺(jué)、運(yùn)動(dòng)和語(yǔ)言等[23-25]。但此項(xiàng)技術(shù)的缺點(diǎn)有很多，其空間分辨率最高僅能達(dá)到4 mm，而其信號(hào)本身也不能反映隨時(shí)間變化的情況[26]。PET設(shè)備部署成本較高，圖像采集時(shí)需要的放射性顯像劑相對(duì)昂貴，并且顯像劑的注射和在體內(nèi)駐留都可能對(duì)人體造成不良影響。

1.4 腦磁圖技術(shù)

MEG技術(shù)發(fā)展于上世紀(jì)60年代，其依靠探測(cè)由神經(jīng)電活動(dòng)引起的空間磁場(chǎng)變化來(lái)記錄腦活動(dòng)。由于神經(jīng)電活動(dòng)很微弱，產(chǎn)生的磁場(chǎng)變化也很難探測(cè)，因此MEG需要及其靈敏的超導(dǎo)量子干涉探頭才能捕捉到有效信號(hào)。早期的MEG主要利用軀體感覺(jué)誘發(fā)磁場(chǎng)對(duì)軀體感覺(jué)區(qū)進(jìn)行定位[27-28]，隨后類似的原理也被應(yīng)用于運(yùn)動(dòng)和語(yǔ)言等[29-30]相關(guān)功能的定位。近年來(lái)也有許多研究者開(kāi)始關(guān)注MEG記錄到的不同頻段的皮層活動(dòng)與認(rèn)知任務(wù)之間的關(guān)系[31-32]。MEG是一種非侵入性的腦成像設(shè)備，其空間分辨率可以達(dá)到毫米級(jí)，時(shí)間分辨率可以達(dá)到毫秒級(jí)，因此除了功能定位之外，在臨床上也多用于記錄分析某些異常放電活動(dòng)，如癲癇[33]。但此種技術(shù)的缺點(diǎn)在于設(shè)備部署和采集成本很高，而其對(duì)于相關(guān)溯源算法的依賴也使其計(jì)算結(jié)果的可靠性一直受到爭(zhēng)議，這也一直是該領(lǐng)域研究者們所關(guān)注的焦點(diǎn)[34]。

1.5 功能核磁共振成像技術(shù)

MRI發(fā)展于上世紀(jì)70年代，其基本原理是通過(guò)在強(qiáng)梯度磁場(chǎng)下疊加一個(gè)高頻激發(fā)磁場(chǎng)，使得特定原子（通常為氫原子或氧原子）能級(jí)狀態(tài)發(fā)生變化，通過(guò)檢測(cè)原子狀態(tài)轉(zhuǎn)換時(shí)以電磁波形式逸出的能量來(lái)獲得該種類原子的空間密度分布，從而區(qū)分不同組織或活動(dòng)狀態(tài)。fMRI是基于MRI的腦功能定位技術(shù)，其主要觀測(cè)指標(biāo)血氧水平依賴（Blood-Oxygen-Level Dependent，BOLD）信號(hào)，與PET類似，都是利用了局部神經(jīng)活動(dòng)強(qiáng)度與代謝原料的需求關(guān)系。

隨著fMRI在認(rèn)知神經(jīng)科學(xué)領(lǐng)域的普及，大量的研究也開(kāi)始關(guān)注其在皮層功能定位中的應(yīng)用。早期若干研究初步確認(rèn)了fMRI在皮層運(yùn)動(dòng)及體感功能定位上的可行性[35-40]。隨后有研究開(kāi)始系統(tǒng)評(píng)估fMRI在臨床應(yīng)用效果，如Lee等[41]在其神經(jīng)外科中心的病例回顧報(bào)告中指出，fMRI運(yùn)動(dòng)功能定位的結(jié)果對(duì)89%的腫瘤病人和91%的癲癇病人手術(shù)過(guò)程有貢獻(xiàn)； Krishanan等[42]發(fā)現(xiàn)，手術(shù)切除部位如果在fMRI功能激活點(diǎn)10 mm范圍以外則基本不會(huì)造成運(yùn)動(dòng)功能損傷，而在5 mm以內(nèi)則有很可能造成術(shù)后運(yùn)動(dòng)功能損傷。fMRI在語(yǔ)言功能定位中得到結(jié)果則并不盡如人意，如 Giussani等[43]在一份文獻(xiàn)總結(jié)中報(bào)道稱，如果以術(shù)中皮層電刺激為標(biāo)準(zhǔn)的話，fMRI的語(yǔ)言功能定位結(jié)果敏感性為59%～100%，而特異性為0%～97%。造成這種現(xiàn)象的主要原因是語(yǔ)言功能本身的復(fù)雜性，但其也常受到病人病理狀態(tài)[44]、任務(wù)設(shè)計(jì)[45]、磁場(chǎng)強(qiáng)度[46-47]以及采集參數(shù)的影響。

大家都承認(rèn)科學(xué)普及出版社于2006年翻譯出版的英國(guó)惠特菲爾德所著《彩圖世界科技史》(原書名：History of Science；2003年出版于英國(guó))是一本很好的科普著作.然而不管該書的作者是否具有“科普”的潛在追求，但該書的性質(zhì)卻明白無(wú)誤的是“科學(xué)史”——正如其原書名所示：History of Science；其編寫方式也是歷史性的(時(shí)間順序).科學(xué)史是一個(gè)學(xué)科、專業(yè)，但絕對(duì)不是“科普”專業(yè).那么我們何以會(huì)將其視為一本很好的科普著作呢？

fMRI在時(shí)空分辨率和信噪比上都優(yōu)于PET，幾乎不會(huì)對(duì)人體造成損傷，其信號(hào)采集基本亦不需要額外的成本，而且隨著技術(shù)的推廣，部署成本也顯著降低。fMRI的空間分辨率可隨著外部梯度磁場(chǎng)強(qiáng)度的提高而提高，但也受限于其信號(hào)本身的屬性，因?yàn)楫a(chǎn)生BOLD信號(hào)的微動(dòng)脈和微靜脈與活動(dòng)的神經(jīng)元之間約有1 mm的誤差。類似的，由于神經(jīng)活動(dòng)與血氧信號(hào)之間的延遲關(guān)系，其時(shí)間分辨率最短也只能以秒計(jì)。

fMRI在應(yīng)用中最大的挑戰(zhàn)是其信號(hào)極易受到運(yùn)動(dòng)干擾，有研究表明受試者頭部不到1 mm的位移就會(huì)對(duì)成像結(jié)果產(chǎn)生顯著影響[48]，而病人又常常比正常人更易出現(xiàn)不自主的運(yùn)動(dòng)，為此很多研究者著力于發(fā)展新的固定或監(jiān)測(cè)設(shè)備[49]和頭動(dòng)矯正算法[50]。此外，也有很多研究者致力于將fMRI納入標(biāo)準(zhǔn)化的操作流程，為此他們提出針對(duì)整套的多種皮層功能定位的任務(wù)方案，這些整套任務(wù)可以迅速完成包括語(yǔ)言、運(yùn)動(dòng)、視覺(jué)甚至情感等功能的皮層定位[51-53]。另外值得一提的是，與功能定位密切相關(guān)的白質(zhì)纖維追蹤也只能靠以MRI為基礎(chǔ)的彌散張量成像技術(shù)（Diffusion Tensor Imaging，DTI）來(lái)實(shí)現(xiàn)，鑒于此，fMRI和DTI的聯(lián)合應(yīng)用有望被納入神經(jīng)外科手術(shù)的標(biāo)準(zhǔn)規(guī)程[54]。

fMRI在臨床皮層功能定位方面近來(lái)有兩個(gè)方面的發(fā)展值得關(guān)注，實(shí)時(shí)功能核磁成像（Real-time fMRI，Rt-fMRI）和靜息態(tài)功能核磁成像（Resting-state fMRI，Rs-fMRI）。自Cox等[55]最早實(shí)現(xiàn)了Rt-fMRI以來(lái)，隨著圖像采集技術(shù)，計(jì)算機(jī)計(jì)算能力以及算法的提高和改進(jìn)，其可靠性和實(shí)用性都大大提高。目前Rt-fMRI主要基于回波平面成像，它能夠最大限度的提高圖像采集速率。Rt-fMRI的數(shù)據(jù)處理可以在一個(gè)滑動(dòng)時(shí)間窗里進(jìn)行，也可以是對(duì)之前全部數(shù)據(jù)進(jìn)行計(jì)算形成積累統(tǒng)計(jì)量。Rt-fMRI已經(jīng)被成功應(yīng)用于包括運(yùn)動(dòng)、軀體感覺(jué)和語(yǔ)言等多種功能的皮層定位[56-58]。盡管其相對(duì)于傳統(tǒng)方法在噪聲去除和分辨率上有所欠缺，有效性也缺少大樣本數(shù)據(jù)支持，但其時(shí)效性在臨床環(huán)境下無(wú)疑具有很大的優(yōu)越性。

Biswal等[59]首次發(fā)現(xiàn)低于0.1 Hz的自發(fā)fMRI信號(hào)中也有重要信息，即低頻皮層活動(dòng)信號(hào)在互相關(guān)聯(lián)的區(qū)域呈現(xiàn)出很高的相關(guān)性，這構(gòu)成了Rs-fMRI技術(shù)的理論基礎(chǔ)[60]。在方法上，Rs-fMRI可以用解剖位置較為明確的種子點(diǎn)感興趣區(qū)來(lái)定位相關(guān)聯(lián)的其他功能區(qū)，如被腫瘤影響的運(yùn)動(dòng)區(qū)可以通過(guò)計(jì)算與對(duì)側(cè)未受影響的運(yùn)動(dòng)區(qū)的相關(guān)性而得到定位[61]；還可以通過(guò)獨(dú)立成分分析（Independent Component Analysis，ICA）自動(dòng)提取各功能網(wǎng)絡(luò)[62]。相較而言，種子點(diǎn)分析得到的結(jié)果較為準(zhǔn)確，但長(zhǎng)距離功能連接尤其是兩半球之間的連接很容易受到影響，因此有得出錯(cuò)誤結(jié)論的風(fēng)險(xiǎn)；ICA不需要確定種子點(diǎn)，也較少受連接缺失影響，因?yàn)槠淇梢詫⒈桓糸_(kāi)的功能網(wǎng)絡(luò)呈現(xiàn)為兩個(gè)獨(dú)立部分，但I(xiàn)CA的缺點(diǎn)在于得到的結(jié)果很多是無(wú)意義或噪音成分，其需要經(jīng)過(guò)人為挑選來(lái)確定重要功能。

總體而言，Rs-fMRI的優(yōu)點(diǎn)在于其適用于很多不能配合認(rèn)知任務(wù)的病人群體，如運(yùn)動(dòng)或認(rèn)知功能受損的患者和低齡兒童等，其也能夠在睡眠甚至麻醉狀態(tài)下進(jìn)行，此外其利用同一批數(shù)據(jù)即可定位所有功能網(wǎng)絡(luò)，這大大提高了效率。

1.6 經(jīng)顱磁刺激技術(shù)

1985年，Barker等[63]首次實(shí)現(xiàn)了用磁脈沖對(duì)人腦運(yùn)動(dòng)皮層的非侵入性刺激，即TMS。TMS的基本原理是通過(guò)放置在頭部上方的電磁線圈快速充放電，在線圈下方空間產(chǎn)生聚焦于某一點(diǎn)并快速變化的磁場(chǎng)，進(jìn)而在目標(biāo)區(qū)域產(chǎn)生電場(chǎng)刺激神經(jīng)組織。近來(lái)，隨著依據(jù)個(gè)體核磁成像數(shù)據(jù)的導(dǎo)航系統(tǒng)被引入TMS系統(tǒng)[64]以及刺激線圈及參數(shù)的優(yōu)化，TMS的空間分辨率大大提高，其在實(shí)質(zhì)上已經(jīng)成為最接近皮層電刺激的技術(shù)，而其本身具有的無(wú)創(chuàng)性更使得其在臨床上得到迅速普及[65-66]。很多研究者[67-70]都論證了TMS在運(yùn)動(dòng)功能和語(yǔ)言功能定位中的有效性。TMS在臨床應(yīng)用的安全性也得到了大樣本數(shù)據(jù)的支持[71]。最近有一些回顧性報(bào)道指出，TMS應(yīng)用于術(shù)前功能評(píng)估可以減小開(kāi)顱面積，縮短手術(shù)時(shí)間，以及更好地避免術(shù)后功能損傷[72-74]。

1.7 皮層光學(xué)成像技術(shù)

神經(jīng)元活動(dòng)同樣可以改變大腦皮層的光學(xué)特性，如對(duì)特定波長(zhǎng)光線的吸收率和散射率等等，以此作為基礎(chǔ)的光學(xué)成像技術(shù)也可以用來(lái)進(jìn)行皮層功能定位[75]。目前臨床研究較多的OPI都是以血紅蛋白相關(guān)信號(hào)為基礎(chǔ)，因此其與BOLD信號(hào)的機(jī)制類似，但在時(shí)空分辨率上能高一到兩個(gè)數(shù)量級(jí)[76]。OPI應(yīng)用于外科手術(shù)皮層功能成像已有若干報(bào)道[77-85]，包括軀體感覺(jué)、運(yùn)動(dòng)和語(yǔ)言等，其可靠性也得到了較為系統(tǒng)的驗(yàn)證。光學(xué)信號(hào)的采集也需要在開(kāi)顱條件下進(jìn)行，而且其需要額外的數(shù)據(jù)采集分析設(shè)備，因此臨床推廣程度并不高。

但OPI幾乎是目前神經(jīng)科學(xué)領(lǐng)域發(fā)展最快的技術(shù)[86]，多光子顯微成像已經(jīng)可以實(shí)現(xiàn)以單細(xì)胞甚至亞細(xì)胞級(jí)的空間分辨率和10 kHz的時(shí)間分辨率對(duì)腦皮層進(jìn)行在體記錄[87]。由于目前在神經(jīng)科學(xué)領(lǐng)域應(yīng)用的OPI多依賴于轉(zhuǎn)基因熒光蛋白或外部熒光標(biāo)記物質(zhì)，且成像的視野范圍受限于鏡頭尺寸而十分有限，因此較少在臨床應(yīng)用。但筆者認(rèn)為安全有效的熒光活性物質(zhì)的開(kāi)發(fā)和成像范圍的擴(kuò)大都是可以逐步解決的問(wèn)題，因而將高分辨率光學(xué)成像用于OPI研究具有很好的發(fā)展應(yīng)用前景。

2 皮層功能定位技術(shù)間的比較和聯(lián)合應(yīng)用

實(shí)際上,每一種單獨(dú)的技術(shù)方案都有其自身的諸多限制，無(wú)法實(shí)現(xiàn)對(duì)大腦皮層功能的充分精確定位。因此，應(yīng)用多種技術(shù)聯(lián)合施測(cè)將有助于直接比較不同方法間的差異，進(jìn)而得到更為準(zhǔn)確的結(jié)果。皮層功能定位技術(shù)間的比較結(jié)果，見(jiàn)表1。

表1 皮層功能定位技術(shù)比較

早在1995年，Morioka等[88]就聯(lián)合使用MEG、fMRI、運(yùn)動(dòng)誘發(fā)電位和TMS來(lái)定位一名癲癇病人的運(yùn)動(dòng)皮層，并獲得一致性較好的結(jié)果。Shinoura等[89]經(jīng)過(guò)比較指出定位軀體感覺(jué)皮層時(shí)，fMRI比體感誘發(fā)電位更為可靠。Roberts等[90]比較了fMRI和TMS在運(yùn)動(dòng)皮層定位上的結(jié)果，發(fā)現(xiàn)兩者誤差在5 mm以內(nèi)，但Lotze等[91]發(fā)現(xiàn)兩者在3D空間里誤差達(dá)13.9 mm，并認(rèn)為其與兩種技術(shù)原理的差異有關(guān)。Forster等[92]發(fā)現(xiàn)，以皮層電刺激為標(biāo)準(zhǔn)的話，TMS的誤差為（10.5±5.67）mm，而fMRI的誤差為（15.0±7.61）mm，Coburger等[93]也得到類似的結(jié)論。

但同樣以皮層電刺激為標(biāo)準(zhǔn)， Babajani-Feremi等[94]于最近的一項(xiàng)研究中指出fMRI的定位準(zhǔn)確度雖然不及ECoG，但優(yōu)于TMS。造成這種差異的原因可能是多方面的，這也從另外一個(gè)角度說(shuō)明fMRI于TMS在準(zhǔn)確度上基本相當(dāng)。為了彌補(bǔ)fMRI時(shí)間分辨率低的問(wèn)題， Dale等[95]開(kāi)發(fā)了一種將fMRI和MEG結(jié)合應(yīng)用的方法，并將其應(yīng)用于語(yǔ)言功能定位，得到高時(shí)空分辨率的結(jié)果，這一技術(shù)隨后得到了ECoG的驗(yàn)證[96]。這表明聯(lián)合應(yīng)用無(wú)創(chuàng)技術(shù)可以達(dá)到與顱內(nèi)皮層直接檢測(cè)技術(shù)相當(dāng)?shù)慕Y(jié)果。

3 總結(jié)與展望

綜合而言，fMRI和TMS在目前的無(wú)創(chuàng)功能定位技術(shù)中最適用于臨床環(huán)境。fMRI設(shè)備近來(lái)在國(guó)內(nèi)的普及程度大幅提高，技術(shù)和理論的發(fā)展也已經(jīng)相對(duì)成熟，而其與DTI技術(shù)結(jié)合能夠?yàn)樯窠?jīng)外科手術(shù)提供非常有價(jià)值的信息。TMS操作簡(jiǎn)單，且其能夠解決fMRI不能確定的必要性的問(wèn)題，但TMS的效率不高，因此其適合在fMRI的定位結(jié)果的基礎(chǔ)上進(jìn)行驗(yàn)證性施測(cè)，以節(jié)省時(shí)間。術(shù)前無(wú)創(chuàng)功能定位技術(shù)目前尚無(wú)法取代術(shù)中直接皮層定位，因此皮層電刺激仍然是神經(jīng)外科手術(shù)功能定位的標(biāo)準(zhǔn)流程操作，但術(shù)中ECoG具有諸多方面的優(yōu)勢(shì)，也正在受到越來(lái)越多的重視。然而，筆者認(rèn)為在未來(lái)10～20年的時(shí)間內(nèi)，光學(xué)成像將發(fā)展成為臨床術(shù)中皮層活動(dòng)記錄的主要技術(shù)。

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本文編輯 劉峰

Application and Development of Functional Cortical Mapping in Clinical Research

WEN Jian-bin, LI Xiao-li

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China

Electrical cortical stimulation (ECS) was considered as the “gold standard” of functional cortical mapping, which played an important role in the effect of neurosurgery surgery. With the development of neuroimaging technology and theory, more and more new methods were used in functional cortical mapping of neurosurgery, for example electrocorticography (ECoG), positron emission tomography (PET), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and optical cortical imaging (OCI). The principle of these technologies were brief l y introduced in this paper, and we compared the present situation of the application of these technologies from clinical reliability, security, detection efficiency, cost and application status respectively. Finally, we made the outlook for the future development of clinical functional cortical mapping technology.

functional cortical mapping; neurosurgery; functional magnetic resonance imaging; transcranial magnetic stimulation; electrocorticography

R44

A

10.3969/j.issn.1674-1633.2017.05.031

1674-1633(2017)05-0116-07

2017-03-16

2017-03-30

國(guó)家自然科學(xué)基金面上項(xiàng)目“經(jīng)顱磁刺激誘導(dǎo)的腦節(jié)律挖掘和分析”（61273063）。

李小俚，教授，主要研究方向?yàn)樯窠?jīng)工程。

通訊作者郵箱：xiaoli@bnu.edu.cn