吸煙對反應(yīng)抑制的影響：證據(jù)、原因和爭論*

趙 鑫 劉曉婷 昝香怡 周愛保

(1西北師范大學(xué)心理學(xué)院,行為康復(fù)訓(xùn)練研究中心,蘭州 730070)(2蘭州大學(xué)第二醫(yī)院VIP呼吸科,蘭州 730070)

1 引言

近期的研究發(fā)現(xiàn),吸煙會對個體的認(rèn)知功能造成一定程度的影響(Billieux et al.,2010;Buzzell,Fedota,Roberts,&McDonald,2014;Gray et al.,2014;Impey,Chique-Alfonzo,Shah,Fisher,&Knott,2013;Luijten et al.,2011a;Spinella,2002)。研究者認(rèn)為,這是由于煙草中的尼古丁會影響大腦的執(zhí)行功能(executive function,EF)(Ashare,Falcone,&Lerman,2014;Dawkins,Powell,West,Powell,&Pickering,2007;Heishman,Kleykamp,&Singleton,2010;Livingstone et al.,2009)。執(zhí)行功能作為大腦的高級認(rèn)知功能,對一系列的認(rèn)知與行為起到了關(guān)鍵的作用。反應(yīng)抑制是一種重要的執(zhí)行功能(Clark,1996),指抑制已經(jīng)形成的動作反應(yīng),是對行動的抑制(抑制優(yōu)勢反應(yīng)或反應(yīng)傾向)過程,是執(zhí)行控制的一個關(guān)鍵組成部分(Johnstone,Barry,Markovska,Dimoska,&Clarke,2009)。更具體的說,反應(yīng)抑制就是抑制不再需要或不恰當(dāng)?shù)男袨?以便個體可以對外界環(huán)境進(jìn)行各種靈活的和有目的的行為反應(yīng)(Verbruggen&Logan,2009)。另外,這一能力對于結(jié)束不再相關(guān)任務(wù)、改正錯誤、依據(jù)變化改變原有任務(wù)等具有重要意義(Aron&Poldrack,2006)。一些研究表明,與不吸煙者相比,吸煙者的反應(yīng)抑制功能會受到所攝入的尼古丁的影響(Charles-Walsh,Furlong,Munro,&Hester,2014;Luijten et al.,2011a;Monterosso,Aron,Cordova,Xu,&London,2005)。研究者大多采用Go/NoGo任務(wù)(Buzzell et al.,2014;Dinn,Aycicegi,&Harris,2004;Evans,Park,Maxfield,&Drobes,2009;Impey et al.,2013;Longo,Fried,Cameron,&Smith,2013;Luijten et al.,2011a;Rass,Fridberg,&O’Donnell,2014;Spinella,2002)和停止信號任務(wù)(Stop-Signal tasks,SST)(Billieux et al.,2010;de Ruiter,Oosterlaan,Veltman,vanden Brink,& Goudriaan,2012;Logemann, B?cker, Deschamps, Kemner, &Kenemans,2014;Monterosso et al.,2005;Rass et al.,2014;Reynolds et al.,2007)對吸煙者的反應(yīng)抑制能力進(jìn)行評估。吸煙者反應(yīng)抑制能力的研究對于探明煙草成癮者以及尼古丁依賴者執(zhí)行功能受影響的深層原因及機(jī)制有一定的價值。臨床上,對于煙草成癮者的干預(yù)與治療也具有重要的實踐意義。本文在總結(jié)相關(guān)研究的基礎(chǔ)上,闡述吸煙對反應(yīng)抑制能力影響的證據(jù)、原因以及所存在的爭議,以期對該領(lǐng)域的研究提供新的視角。

2 吸煙對反應(yīng)抑制能力的影響——來自行為、ERPs、腦成像的研究

目前,許多研究者采用行為實驗(Billieux et al.,2010;Powell,Pickering,Dawkins,West,&Powell,2004;Reynolds et al.,2007)、事件相關(guān)電位(event-related potentials,ERPs)技術(shù)(Buzzell et al.,2014;Impey et al.,2013;Luijten et al.,2011a,b)以及功能磁共振成像(functional magenetic resonance imaging,fMRI)技術(shù)(de Ruiter et al.,2012;Ettinger et al.,2009;Gray et al.,2014;Hartwell et al.,2011;Longo et al.,2013;Luijten et al.,2013)研究發(fā)現(xiàn),吸煙會對個體的反應(yīng)抑制能力產(chǎn)生影響。

2.1 行為研究

在行為層面上,研究者采用Go/NoGo任務(wù)和Stop-Signal任務(wù)發(fā)現(xiàn),吸煙者的虛報率(Commission error)和反應(yīng)時兩個指標(biāo)都顯著高于正常健康對照組被試(Billieux et al.,2010;de Ruiter et al.,2012;Nestor,McCabe,Jones,Clancy,&Garavan,2011;Reynolds et al.,2007)。虛報率是對不需要做出反應(yīng)的非目標(biāo)刺激做出的反應(yīng),是衡量反應(yīng)抑制能力的一個重要的行為指標(biāo)(Thorell,Lindqvist,Bergman Nutley,Bohlin,&Klingberg,2009),研究者認(rèn)為吸煙者在Go/NoGo任務(wù)和Stop-Signal任務(wù)中虛報率較高的原因在于吸煙者的大腦執(zhí)行功能受到所攝入的尼古丁的影響(Bekker,B?cker,van Hunsel,van Den Berg,&Kenemans,2005;Billieux et al.,2010;Luijten et al.,2011a)。目前,大量的研究者對吸煙者與不吸煙者的反應(yīng)抑制能力進(jìn)行比較研究時采用線索反應(yīng)模式(Brody,Mandelkern,&Jarvik,et al.,2004;Luijten et al.,2011a,b;Mogg,Bradley,Field,&De Houwer,2003;Munafò,Mogg,Roberts,Bradley,& Murphy,2003;Sayette&Hufford,1994;Waters&Feyerabend,2000),線索反應(yīng)模式通過向個體呈現(xiàn)物理刺激來誘發(fā)其渴求,其中又分為真實刺激(Sayette&Hufford,1994)、視頻刺激(Baumann&Sayette,2006;Brody et al.,2002;Monterosso et al.,2005;Tong,Bovbjerg,&Erblich,2007)、圖片刺激(Hitsman et al.,2008;Luijten et al.,2011b)、聽覺刺激和腳本/想象刺激(Epstein,Temple,Roemmich,&Bouton,2009;Soetens,Braet,Dejonckheere,& Roets,2006;Wegner,1992)。有關(guān)吸煙者反應(yīng)抑制的研究通過呈現(xiàn)經(jīng)過評定后的標(biāo)準(zhǔn)化圖片,采用最明顯的視覺刺激的方式來誘發(fā)吸煙者的渴求。Luijten等人(2011a)采用Go/NoGo任務(wù)對吸煙者與正常健康被試的對照研究表明,吸煙者在NoGo刺激上的虛報率顯著高于正常對照組。另外,有研究采用Stop-Signal任務(wù)對輕度吸煙者和中度吸煙者的對照研究表明,中度吸煙者(吸煙量平均每天11～20支)對Stop信號的抑制反應(yīng)時間更長,成功抑制比例更低(Bekker et al.,2005;Billieux et al.,2010)。另外,Rass等人(2014)通過對連續(xù)吸煙者、間斷吸煙者和不吸煙者的反應(yīng)抑制能力進(jìn)行比較發(fā)現(xiàn),連續(xù)吸煙者的反應(yīng)抑制潛伏期顯著小于間斷吸煙者和正常健康被試。有研究者采用Stop-Signal任務(wù)對戒煙時間不同的吸煙者和正常被試的反應(yīng)抑制對比研究發(fā)現(xiàn),吸煙者在戒煙時間較長(10小時)情況下其反應(yīng)抑制能力受到一定程度的影響,正常健康對照組被試的停止任務(wù)績效顯著高于吸煙群體,即正常群體的抑制成功率高,停止信號反應(yīng)時(SSRT)短(Charles-Walsh et al.,2014;Logemann et al.,2014;Monterosso et al.,2005)。

2.2 ERPs研究

研究者從行為層面上發(fā)現(xiàn),與不吸煙者相比,吸煙者的反應(yīng)抑制能力受到所攝入的尼古丁的影響(Bekker et al.,2005;Billieux et al.,2010;Charles-Walsh etal.,2014;Dawkins,Powell,Pickering,Powell,&West,2009;Logemann et al.,2014;Rass et al.,2014)。研究者們還采用事件相關(guān)電位技術(shù)揭示了吸煙對反應(yīng)抑制加工過程的影響(Buzzell et al.,2014;Impey et al.,2013;Logemann et al.,2014;Luijten et al.,2011a)。Luijten等人(2011a)比較了19名吸煙者和20名不吸煙的健康被試在Go/NoGo任務(wù)中的ERPs成分,結(jié)果顯示,吸煙者的NoGo-N2波幅顯著低于正常健康被試,而吸煙組和不吸煙組在NoGo-P3成分上未表現(xiàn)出顯著差異。Buzzell等人(2014)的研究支持了上述結(jié)果,該研究以大學(xué)本科生為被試,檢測了15名輕度吸煙者和15名不吸煙者的ERPs成分,研究發(fā)現(xiàn),輕度吸煙組的NoGo-N2波幅明顯小于正常對照組,而兩組被試的NoGo-P3成分無顯著差異。一般認(rèn)為,NoGo-N2主要定位于前扣帶回(Bekker,Kenemans,&Verbaten,2005;Dimoska,Johnstone,&Barry,2006;Nieuwenhuis,Yeung,van Den Wildenberg,&Ridderinkhof,2003;Yeung,Botvinick,&Cohen,2004)和右側(cè)眶額葉(Strik,Fallgatter,Brandeis,& Pascual-Marqui,1998);NoGo-P3定位于眶額葉(Bokura,Yamaguchi,&Kobayashi,2001)。盡管兩者的心理過程沒有最終確定,但是可以認(rèn)為,NoGo-N2和NoGo-P3可能分別代表了與抑制控制有關(guān)的兩個加工過程,反應(yīng)抑制和沖突監(jiān)控(Ruchsow et al.,2008)。有觀點(diǎn)認(rèn)為NoGo-N2反映了一種自上而下的抑制機(jī)制(Falkenstein,Hoormann,&Hohnsbein,1999),即在運(yùn)動執(zhí)行前抑制不適當(dāng)?shù)姆磻?yīng)傾向(Kok,Ramautar,De Ruiter,Band,&Ridderinkhof,2004),這種早期加工的異常很可能反應(yīng)了吸煙者在運(yùn)動執(zhí)行前抑制不適當(dāng)?shù)姆磻?yīng)傾向上受到所攝入的尼古丁的影響(Luijten et al.,2011a)。

2.3 腦成像研究

近期,對吸煙者反應(yīng)抑制能力的腦成像研究發(fā)現(xiàn),與不吸煙者相比,吸煙者丘腦(Thalamic)、額中回(Middle frontal gyrus)和前扣帶回(Anterior cingulate cortex)灰質(zhì)體積減小(Brody,Mandelkern,&Lee et al.,2004;Gallinat et al.,2006)。另外, 腦成像研究還發(fā)現(xiàn),吸煙者額葉(諸如ACC、PFC和OFC)、枕葉和顳葉,包括海馬旁回腦區(qū)的灰質(zhì)體積明顯減小、密度明顯降低。丘腦、小腦和黑質(zhì)的灰質(zhì)體積或密度也發(fā)生了變化(Gallinat et al.,2006)。吸煙者的丘腦灰質(zhì)體積減少可能與尼古丁對吸煙者認(rèn)知功能的影響有關(guān)(Sharma&Brody,2009)。有研究發(fā)現(xiàn),吸煙者在對與吸煙有關(guān)的刺激進(jìn)行反應(yīng)抑制時,與不吸煙者相比,吸煙者眶額葉皮層(Orbitofrontal cortex OFC)、前額皮層(Prefrontal cortex PFC)和前扣帶回皮層(ACC)的激活增強(qiáng)(Hartwell et al.,2011;McBride,Barrett,Kelly,Aw,& Dagher,2006;Wilson,Sayette,Delgado,&Fiez,2005)。Brody 等(2002)采用正電子發(fā)射斷層掃描(Positron Emission Tomography PET)技術(shù)對重度吸煙者和非吸煙者呈現(xiàn)與香煙相關(guān)線索的錄像作為香煙渴求誘發(fā)刺激,間隔10天對被試進(jìn)行香煙相關(guān)線索和中性線索作用下的兩次掃描,結(jié)果發(fā)現(xiàn)嚴(yán)重吸煙者比非吸煙者在扣帶回前部、顳葉和眶額皮層的葡萄糖代謝增加更多。

綜上所述,研究者借用行為、ERPs和腦成像研究手段,發(fā)現(xiàn)了吸煙可能會對反應(yīng)抑制能力產(chǎn)生影響的證據(jù)。但是,一些ERPs和腦成像研究的結(jié)果只能說明吸煙者與不吸煙者在反應(yīng)抑制導(dǎo)致的腦激活上存在差異,這僅能作為吸煙影響反應(yīng)抑制能力的間接證據(jù),還不能完全揭示二者之間的因果關(guān)系。之后的研究應(yīng)關(guān)注腦激活數(shù)據(jù)與行為數(shù)據(jù)的聯(lián)合分析,以進(jìn)一步探討吸煙與反應(yīng)抑制能力損傷之間的因果關(guān)系。

3 吸煙對反應(yīng)抑制能力影響的原因

3.1 吸煙對前額葉系統(tǒng)的影響

吸煙者表現(xiàn)出較差的反應(yīng)抑制能力,可能是因為吸煙者在尼古丁的長期作用下,認(rèn)知控制網(wǎng)絡(luò)等相關(guān)腦區(qū)受到影響,導(dǎo)致吸煙個體不能使用情景預(yù)期來指導(dǎo)選擇,最終導(dǎo)致反應(yīng)抑制能力下降(Cole et al.,2010)。由于額葉是執(zhí)行和控制行為的主要腦區(qū)(Fowler,Volkow,Kassed,&Chang,2007),而成癮者最大的特征是不能控制自己反復(fù)使用成癮物質(zhì)的行為(Volkow,Fowler,&Wang,2003)。因此,吸煙對抑制控制能力的影響可能與額葉某個或某些腦區(qū)活動改變有關(guān)。而腦成像研究表明,尼古丁依賴者的前額腦區(qū)異常(Brody,Mandelkern,&Jarvik,et al.,2004;Carroll,Sutherland,Salmeron,Ross,&Stein,2014;Gallinat et al.,2006;Luijten et al.,2013)。前額葉(Prefrontal cortex,PFC)系統(tǒng)主要由眶額葉皮層(Orbital frontal cortex,OFC)、前扣帶回皮層(Anterior cingulate cortex,ACC)、背外側(cè)前額葉皮層(Dorsolateral prefrontal cortex,DLPFC)、腹外側(cè)前額葉皮層(Ventrolateral prefrontal cortex,VLPFC)、額下回(Inferior frontal gyrus,IFG)等部分組成,對個體的抑制控制功能發(fā)揮著重要作用(Egner,2011)。與不吸煙者相比,吸煙者反應(yīng)抑制能力的減弱與前額葉系統(tǒng)的失調(diào)息息相關(guān)(Ettinger et al.,2009;Fregni et al.,2008;Gallinat et al.,2006;Spinella,2002)。有研究者發(fā)現(xiàn),與正常健康被試相比,吸煙者前額葉與前扣帶回皮層、前額葉與眶額葉皮層的功能連接下降(Luijten et al.,2013);背外側(cè)前額皮質(zhì)(DLPFC)和腹外側(cè)前額葉皮質(zhì)(VLPFC)的皮層灰質(zhì)體積和密度明顯減小,而且吸煙者左半球背側(cè)前扣帶回(Dorsal anterior cingulate cortex D-ACC)的灰質(zhì)體積和右半球小腦的灰質(zhì)密度降低(Brody,Mandelkern,&Jarvik,et al.,2004);前額葉(PFC)和前扣帶回皮層(ACC)的神經(jīng)反應(yīng)性活動也減弱了(Riggs et al.,2007)。背外側(cè)前額葉皮質(zhì)與前扣帶回皮層、眶額葉皮層及其前額葉腦區(qū)的功能連接受損,導(dǎo)致吸煙者大腦功能出現(xiàn)異常,從而表現(xiàn)出反應(yīng)抑制能力下降。

3.2 吸煙對中腦邊緣多巴胺系統(tǒng)的影響

中腦邊緣多巴胺系統(tǒng)(mesolimbic dopamine system MLDS)是腦內(nèi)獎賞或強(qiáng)化系統(tǒng)的主要結(jié)構(gòu),其獎賞回路由腹側(cè)被蓋區(qū)(Ventral Tegmental Area,VTA)、伏隔核(Nucleus Accumbens,NAc)和杏仁核(Amygdala)等構(gòu)成(王惠玲,趙晏,2003),它是包括尼古丁在內(nèi)的很多成癮物質(zhì)的中介系統(tǒng)(鄧林園,方曉義,2005)。有研究發(fā)現(xiàn),在藥物依賴者服藥期間,從中腦腹側(cè)被蓋區(qū)神經(jīng)元末稍釋放的多巴胺增加,而且,這些藥物通過不同的靶位激活中腦邊緣多巴胺系統(tǒng),這種激活增加了中腦腹側(cè)被蓋區(qū)的多巴胺神經(jīng)元的放電,隨后增加多巴胺遞質(zhì)釋放到伏隔核和前額葉皮層等邊緣前腦的其他腦區(qū)(張開鎬,2002)。

fMRI研究表明,當(dāng)給被試靜脈注射尼古丁后發(fā)現(xiàn),尼古丁引起伏隔核、杏仁核、扣帶回以及額葉等腦區(qū)神經(jīng)活動的增強(qiáng)(Stein et al.,1998)。另外,有研究采用fMRI技術(shù)探測發(fā)現(xiàn),被試暴露于香煙相關(guān)線索時,尼古丁依賴者中腦邊緣多巴胺系統(tǒng)和前額葉皮層均得到激活,并且報告渴求感增強(qiáng)(Due,Huettel,Hall,&Rubin,2002;Hitsman et al.,2008)。

在動物成癮方面,研究者用老鼠進(jìn)行的活體內(nèi)微透析實驗結(jié)果發(fā)現(xiàn)尼古丁使用可以導(dǎo)致中腦腹側(cè)被蓋區(qū)(VTA)的多巴胺釋放明顯增多(Rahman,Zhang,&Corrigall,2003)。Yin和 French等(2000)的研究也發(fā)現(xiàn)尼古丁顯著增加了多巴胺神經(jīng)元的神經(jīng)脈沖放電。上述研究表明中腦邊緣多巴胺系統(tǒng)和尼古丁依賴息息相關(guān),在尼古丁直接刺激或者尼古丁渴求誘發(fā)線索刺激作用下,所激活的腦區(qū)基本上都是中腦邊緣多巴胺系統(tǒng)以及相關(guān)的腦區(qū)。Mansvelder,Keath和McGehee(2002)研究發(fā)現(xiàn)尼古丁引起腹側(cè)被蓋區(qū)內(nèi)γ－氨基丁酸(γ-aminobutyric acid,GABA)傳遞的抑制。

γ-氨基丁酸主要作用是抑制多巴胺細(xì)胞并且對其它結(jié)構(gòu)產(chǎn)生影響,比如腳橋被蓋核、谷氨酸能的神經(jīng)元等。尼古丁通過直接誘導(dǎo)多巴胺的釋放或抑制GABA能神經(jīng)元,最終導(dǎo)致腹側(cè)被蓋區(qū)的多巴胺輸入端向伏隔核釋放多巴胺的持續(xù)增強(qiáng)(Picciotto&Corrigall,2002)。正常情況下,多巴胺神經(jīng)元還受到通過腹側(cè)被蓋區(qū)的GABA中間神經(jīng)元以及包括伏隔核和蒼白球在內(nèi)的其他腦區(qū)投射來的GABA纖維的抑制性控制。但是,它們在接觸尼古丁后很快就會出現(xiàn)去敏化,結(jié)果將導(dǎo)致向DA神經(jīng)元的抑制性輸入減弱,這樣一來,對多巴胺神經(jīng)元的抑制就解除了,使釋放到伏隔核區(qū)的多巴胺量增加。有研究發(fā)現(xiàn),吸煙者的快感體驗與多巴胺水平的增加有關(guān)(Brody et al.,2006)。這表明尼古丁的攝入使個體產(chǎn)生陶醉感和愉悅感,就算是短時間地偶爾吸煙也足以使人產(chǎn)生尼古丁或香煙依賴。

4 吸煙對反應(yīng)抑制能力影響的爭議

如前所述,雖然有大量的研究發(fā)現(xiàn)吸煙對反應(yīng)抑制能力有影響(Glass et al.,2009;Billieux et al.,2010;de Ruiter et al.,2012;Luijten et al.,2011a,b;Spinella,2002),但是,另外一些研究卻并未發(fā)現(xiàn)這一現(xiàn)象(Dinn et al.,2004;Galván,Poldrack,Baker,McGlennen,&London,2011;Rass et al.,2014;Luijten et al.,2013;Monterosso et al.,2005;Rass et al.,2014;Reynolds et al.,2007)。例如,Buzzell等人(2014)選取吸煙者與不吸煙者作為被試,比較兩組被試在Go/NoGo任務(wù)中Go試次的漏報率和NoGo試次的虛報率,研究結(jié)果發(fā)現(xiàn),吸煙者與不吸煙者在行為結(jié)果上未表現(xiàn)出差異;Evans等人(2009)的研究也發(fā)現(xiàn),吸煙者在NoGo試次的正確率以及Go試次的反應(yīng)時兩個指標(biāo)上與不吸煙者相比沒有差異。可見,目前對吸煙是否影響個體的反應(yīng)抑制能力還存在爭議。研究結(jié)果產(chǎn)生爭議的原因可能主要有以下三點(diǎn)：

第一,研究者采用的實驗范式不同所得出的結(jié)論可能會有差異。在已有研究中,研究者通常使用Stop-Signal任務(wù)和Go/NoGo任務(wù)對吸煙者反應(yīng)抑制進(jìn)行研究。例如,Buzzell等(2014)使用Go/NoGo任務(wù)對吸煙者和非吸煙者的反應(yīng)抑制能力進(jìn)行研究發(fā)現(xiàn),兩組被試在行為反應(yīng)上無明顯差異。Logemann等人(2014)利用Stop-Signal任務(wù)對吸煙者的行為抑制能力進(jìn)行了評估,他們發(fā)現(xiàn)吸煙者對Go刺激的反應(yīng)速度與正常對照組相比沒有明顯差別,但吸煙者的SSRT卻明顯延長。Stop-Signal和Go/NoGo兩種任務(wù)所依賴的加工機(jī)制不完全相同,在Stop-Signal任務(wù)中,要停止的反應(yīng)已經(jīng)處于加工過程之中,加工已經(jīng)到達(dá)相當(dāng)水平,遠(yuǎn)遠(yuǎn)高出了對NoGo刺激的加工。對此有研究發(fā)現(xiàn),基底神經(jīng)節(jié)(basal ganglia)在Stop-Signal任務(wù)中對動作反應(yīng)的發(fā)起和抑制有重要作用(Eagle&Robbins,2003),基底神經(jīng)節(jié)是前腦中的一組皮質(zhì)下神經(jīng)核,包括尾狀核、殼核、蒼白球、丘腦底核(subthalamic nucleus STN)和中腦黑質(zhì)(Alexander&Crutcher,1990)。在基底神經(jīng)節(jié)的神經(jīng)核中,丘腦底核可能是參與反應(yīng)抑制加工的關(guān)鍵結(jié)構(gòu)(Cohen&Frank,2009;Ray et al.,2012;Wiecki&Frank,2013)。Aron和 Poldrack(2006)研究了丘腦底核和SSRT之間的關(guān)系,研究發(fā)現(xiàn)丘腦底核激活越強(qiáng),被試的SSRT越短。即：SSRT較短的被試丘腦底核激活強(qiáng)于SSRT較長的被試。對吸煙者與不吸煙者的腦機(jī)制結(jié)構(gòu)進(jìn)行對比發(fā)現(xiàn),與不吸煙者相比,吸煙者的丘腦、小腦和黑質(zhì)的灰質(zhì)體積或密度減小,既然反應(yīng)和不反應(yīng)之間的競爭主要在基底神經(jīng)節(jié)的神經(jīng)核中進(jìn)行,刺激或損傷這些神經(jīng)核將會對反應(yīng)抑制產(chǎn)生明顯影響(Chambers et al,2006;2007)。此外,有研究發(fā)現(xiàn)Go/NoGo任務(wù)所激活左側(cè)大腦的其它一些區(qū)域,如前扣帶回、前運(yùn)動輔助區(qū)等都與高水平的運(yùn)動計劃及行為選擇相關(guān),而在Stop-Signal任務(wù)中,前額葉皮層、基底神經(jīng)節(jié)、額下回等都參與了反應(yīng)停止操作(Rubia et al.,2001)。這表明,較之Stop-Signal任務(wù),Go/NoGo任務(wù)中的抑制更多涉及行為的選擇和行為的準(zhǔn)備。

第二,實驗任務(wù)的難度不同也可能影響實驗結(jié)果。研究發(fā)現(xiàn),Go/NoGo任務(wù)的難度取決于Go刺激和NoGo刺激的呈現(xiàn)時間以及NoGo刺激所占的比率(Evans et al.,2009;Luijten et al.,2011a)。例如,Evans等人(2009)采用的Go/NoGo任務(wù)中刺激呈現(xiàn)時間為800 ms,整個實驗共包括900個trial,其中83個NoGo trial,在此研究中發(fā)現(xiàn)吸煙者在NoGo試次的正確率以及Go試次的反應(yīng)時兩個指標(biāo)上與不吸煙者相比沒有差異。而Luijten等人(2011a)采用的Go/NoGo任務(wù)中刺激呈現(xiàn)時間為200ms,整個實驗共包括 400個trial,其中NoGo試次占所有試次的25%,該研究得出了相反的結(jié)論,即吸煙者在NoGo試次的正確率上顯著低于不吸煙者。因此我們認(rèn)為,采取相同的Go/NoGo任務(wù),刺激呈現(xiàn)的時間和NoGo試次所占的比例不同影響了上述實驗結(jié)果的不一致。對這一實驗結(jié)果有研究發(fā)現(xiàn),背外側(cè)前額葉與前扣帶回在反應(yīng)抑制中的激活隨工作記憶負(fù)荷增加而增強(qiáng),Simmonds,Pekar和 Mostofsky(2008)對 10項使用Go/NoGo范式研究反應(yīng)抑制能力的fMRI研究的元分析發(fā)現(xiàn),與簡單的抑制任務(wù)相比,工作記憶負(fù)荷較高的復(fù)雜抑制任務(wù)更多的激活了額中回(middle frontal gyrus),額下回(inferior frontal gyrus),頂下小葉(inferior parietal lobule)和顳-頂交界處(temporoparietal junction TPJ),頂下小葉和前額皮質(zhì)有密切的雙向纖維聯(lián)系,對執(zhí)行控制至關(guān)重要。但是,這些腦區(qū)只在復(fù)雜任務(wù)條件下同時激活。與這種解釋一致,有研究發(fā)現(xiàn)在增加工作記憶負(fù)荷的Go/NoGo任務(wù)中背外側(cè)前額皮層激活增強(qiáng),而簡單Go/NoGo任務(wù)中該區(qū)并無激活增強(qiáng)(Rowe,Friston,Frackowiak,&Passingham,2002)。但是,與不吸煙者相比,吸煙者背外側(cè)前額皮質(zhì)(DLPFC)和腹外側(cè)前額葉皮質(zhì)(VLPFC)的皮層灰質(zhì)體積和密度明顯減小(Brody,Mandelkern,&Jarvik,et al.,2004),因此,吸煙者與不吸煙者相比,在難度較大的Go/NoGo任務(wù)中吸煙者在NoGo刺激上的正確率顯著小于正常對照組。

第三,所選取的吸煙被試的吸煙成癮程度也可能是影響實驗結(jié)果的一個重要因素。例如,有研究者選取輕度吸煙和不吸煙的大學(xué)生作為被試,采用Go/NoGo任務(wù)對正常健康被試和輕度吸煙被試的反應(yīng)抑制能力進(jìn)行比較研究發(fā)現(xiàn),輕度吸煙組被試和正常健康組被試在Go的反應(yīng)時和NoGo的正確率兩個指標(biāo)上均未表現(xiàn)出差異(Buzzell et al.,2014;Evans et al.,2009);但是,Luijten等人(2011a)選取19名中度吸煙和20名不吸煙的大學(xué)本科生作為被試,采用Go/NoGo任務(wù)對兩組被試的反應(yīng)抑制能力進(jìn)行比較,研究結(jié)果發(fā)現(xiàn),中度吸煙者在NoGo試次的正確率上顯著低于不吸煙者,而且與不吸煙者相比,中度吸煙者的NoGo-N2波幅顯著低于正常健康被試。這說明,吸煙組的成癮程度可能會影響到實驗結(jié)果。當(dāng)前,有些研究已證明吸煙的成癮程度與個體的反應(yīng)抑制能力有關(guān)。如,Spinella(2002)采用Go/NoGo任務(wù)研究發(fā)現(xiàn),被試在實驗中犯錯誤的概率與每天吸煙的數(shù)量呈正相關(guān);Billieux等人(2010)的研究也發(fā)現(xiàn)吸煙者反應(yīng)抑制的個體差異與每天抽煙的數(shù)量有關(guān)。研究認(rèn)為,對優(yōu)勢反應(yīng)的抑制能力越差,吸煙成癮程度越重,相反,對優(yōu)勢反應(yīng)的抑制能力越好其吸煙成癮程度越輕。Robinson,Pritchard和Davis(1992)比較了吸低尼古丁含量(0.06 mg)和高尼古丁含量(0.6 mg)的香煙前后EEG的變化,發(fā)現(xiàn)在控制了吸煙量和吸煙強(qiáng)度的條件下,尼古丁含量為 0.6mg的香煙引起EEG的激活,但0.06mg的沒有。

5 展望

雖然許多研究者從行為到神經(jīng)機(jī)制對吸煙成癮人群的反應(yīng)抑制能力展開了大量研究,但還存在眾多疑問,今后可以著重從以下幾個方面進(jìn)行研究。

第一,盡管不同研究者都對尼古丁激活大腦前額葉系統(tǒng)和中腦邊緣多巴胺系統(tǒng)這一事實達(dá)成一致,但刺激方式局限于視覺或視聽覺,且對具體激活腦區(qū)及核團(tuán)的定位尚存在較大爭議,這可能是因為在進(jìn)行掃描時選擇的被試吸煙成癮程度以及所處的渴求狀態(tài)不同所致。因此,將來的研究可以對處于不同的香煙剝奪狀態(tài)(如剛吸完一支煙與吸煙后2小時這兩種不同狀態(tài))下的吸煙者的反應(yīng)抑制能力進(jìn)行對比研究,同時,還可以比較不同類型的人群,包括香煙成癮者、香煙成癮戒斷者以及不吸煙者之間在香煙或者香煙相關(guān)線索刺激下反應(yīng)抑制能力及其大腦活動的變化情況,從而使香煙成癮機(jī)制的研究更精確也更全面。

第二,尼古丁依賴同其他依賴性藥物機(jī)制之間的差異至今沒有太多研究者有所涉及;因而,用同樣的研究模式和手段,對毒品、酒精和香煙等常見依賴性藥物在藥物直接刺激或相關(guān)的環(huán)境線索作用下大腦活動狀況的異同進(jìn)行分析,找出吸煙者反應(yīng)抑制能力受損的特異性,從而為香煙成癮的戒斷發(fā)展出更有針對性的干預(yù)方案。

第三,到目前為止,對反應(yīng)抑制能力的研究主要采用Go/NoGo任務(wù)和Stop-Signal任務(wù)。但是,由于Go/NoGo任務(wù)要求只對Go刺激反應(yīng),對NoGo刺激并不反應(yīng),這樣可能導(dǎo)致在Go/NoGo范式中觀察到的抑制控制效應(yīng)已被反應(yīng)相關(guān)加工污染,并且難以提取反應(yīng)時間,常常不能為反應(yīng)抑制提供有效的行為指標(biāo)(Yuan,He,Qinglin,Chen,&Li,2008);Stop-Signal任務(wù)雖然能提供行為指標(biāo),但行為抑制信號在時間上的不確定性容易混淆抑制信號和任務(wù)信號誘發(fā)的腦活動。近年來有研究者將雙選擇oddball范式用來進(jìn)行反應(yīng)抑制能力的研究(Yuan et al.,2008;Yuan et al.,2012)。雙選擇oddball范式是對傳統(tǒng)oddball范式的改編,該范式要求被試既快又準(zhǔn)的對大概率的標(biāo)準(zhǔn)刺激和小概率的偏差刺激做兩類不同的按鍵反應(yīng)。由于標(biāo)準(zhǔn)刺激的呈現(xiàn)概率遠(yuǎn)大于偏差刺激,因此,被試對標(biāo)準(zhǔn)刺激的反應(yīng)將成為優(yōu)勢反應(yīng),當(dāng)偏差刺激出現(xiàn)時,被試需要抑制對標(biāo)準(zhǔn)刺激的優(yōu)勢反應(yīng),從而確保對偏差刺激做出正確的行為反應(yīng)。而偏差刺激反應(yīng)時與標(biāo)準(zhǔn)刺激反應(yīng)時之差則為反應(yīng)抑制的行為學(xué)指標(biāo)(辛勇,李紅,袁加錦,2010)。因此,在以后的研究中可以使用雙選擇oddball范式對吸煙者的反應(yīng)抑制能力與不吸煙者進(jìn)行對比研究,并且比較Go/NoGo范式、Stop-Signal范式以及雙選擇oddball范式在行為、ERPs和腦成像上所得結(jié)果的異同,為以后進(jìn)行反應(yīng)抑制能力的研究提供更有效的研究范式。

最后,開發(fā)改善吸煙人群反應(yīng)抑制缺陷的干預(yù)方法與技術(shù)。對吸煙成癮人群反應(yīng)抑制缺陷的認(rèn)知與神經(jīng)機(jī)制的研究,最終是為了改善和治療吸煙成癮人群的反應(yīng)抑制缺陷。然而,對于這方面的干預(yù)方法與技術(shù)的研究才剛剛起步。研究表明,預(yù)期想象訓(xùn)練和金錢管理指導(dǎo)能夠在一定程度上降低吸煙成癮人群的反應(yīng)抑制缺陷(Martin-Soelch et al.,2001;Powell et al.,2004)。但是,目前這些方法與技術(shù)都還處于研究階段,離真正的臨床治療階段還較遠(yuǎn)。因此,需要不斷細(xì)化、完整這些方法和技術(shù),使其有更好的操作性、規(guī)范性和臨床效果。

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