吸煙對反應抑制的影響：證據、原因和爭論*

趙 鑫 劉曉婷 昝香怡 周愛保

(1西北師范大學心理學院,行為康復訓練研究中心,蘭州 730070)(2蘭州大學第二醫院VIP呼吸科,蘭州 730070)

1 引言

近期的研究發現,吸煙會對個體的認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)。研究者認為,這是由于煙草中的尼古丁會影響大腦的執行功能(executive function,EF)(Ashare,Falcone,&Lerman,2014;Dawkins,Powell,West,Powell,&Pickering,2007;Heishman,Kleykamp,&Singleton,2010;Livingstone et al.,2009)。執行功能作為大腦的高級認知功能,對一系列的認知與行為起到了關鍵的作用。反應抑制是一種重要的執行功能(Clark,1996),指抑制已經形成的動作反應,是對行動的抑制(抑制優勢反應或反應傾向)過程,是執行控制的一個關鍵組成部分(Johnstone,Barry,Markovska,Dimoska,&Clarke,2009)。更具體的說,反應抑制就是抑制不再需要或不恰當的行為,以便個體可以對外界環境進行各種靈活的和有目的的行為反應(Verbruggen&Logan,2009)。另外,這一能力對于結束不再相關任務、改正錯誤、依據變化改變原有任務等具有重要意義(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(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(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)對吸煙者的反應抑制能力進行評估。吸煙者反應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行功能受影響的深層原因及機制有一定的價值。臨床上,對于煙草成癮者的干預與治療也具有重要的實踐意義。本文在總結相關研究的基礎上,闡述吸煙對反應抑制能力影響的證據、原因以及所存在的爭議,以期對該領域的研究提供新的視角。

2 吸煙對反應抑制能力的影響——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)、事件相關電位(event-related potentials,ERPs)技術(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(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)研究發現,吸煙會對個體的反應抑制能力產生影響。

2.1 行為研究

在行為層面上,研究者采用Go/NoGo任務和Stop-Signal任務發現,吸煙者的虛報率(Commission error)和反應時兩個指標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的非目標刺激做出的反應,是衡量反應抑制能力的一個重要的行為指標(Thorell,Lindqvist,Bergman Nutley,Bohlin,&Klingberg,2009),研究者認為吸煙者在Go/NoGo任務和Stop-Signal任務中虛報率較高的原因在于吸煙者的大腦執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抑制能力進行比較研究時采用線索反應模式(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),線索反應模式通過向個體呈現物理刺激來誘發其渴求,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)。有關吸煙者反應抑制的研究通過呈現經過評定后的標準化圖片,采用最明顯的視覺刺激的方式來誘發吸煙者的渴求。Luijten等人(2011a)采用Go/NoGo任務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)通過對連續吸煙者、間斷吸煙者和不吸煙者的反應抑制能力進行比較發現,連續吸煙者的反應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任務對戒煙時間不同的吸煙者和正常被試的反應抑制對比研究發現,吸煙者在戒煙時間較長(10小時)情況下其反應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現,與不吸煙者相比,吸煙者的反應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電位技術揭示了吸煙對反應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任務中的ERPs成分,結果顯示,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成分上未表現出顯著差異。Buzzell等人(2014)的研究支持了上述結果,該研究以大學本科生為被試,檢測了15名輕度吸煙者和15名不吸煙者的ERPs成分,研究發現,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,但是可以認為,NoGo-N2和NoGo-P3可能分別代表了與抑制控制有關的兩個加工過程,反應抑制和沖突監控(Ruchsow et al.,2008)。有觀點認為NoGo-N2反映了一種自上而下的抑制機制(Falkenstein,Hoormann,&Hohnsbein,1999),即在運動執行前抑制不適當的反應傾向(Kok,Ramautar,De Ruiter,Band,&Ridderinkhof,2004),這種早期加工的異常很可能反應了吸煙者在運動執行前抑制不適當的反應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,對吸煙者反應抑制能力的腦成像研究發現,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)灰質體積減小(Brody,Mandelkern,&Lee et al.,2004;Gallinat et al.,2006)。另外, 腦成像研究還發現,吸煙者額葉(諸如ACC、PFC和OFC)、枕葉和顳葉,包括海馬旁回腦區的灰質體積明顯減小、密度明顯降低。丘腦、小腦和黑質的灰質體積或密度也發生了變化(Gallinat et al.,2006)。吸煙者的丘腦灰質體積減少可能與尼古丁對吸煙者認知功能的影響有關(Sharma&Brody,2009)。有研究發現,吸煙者在對與吸煙有關的刺激進行反應抑制時,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(Hartwell et al.,2011;McBride,Barrett,Kelly,Aw,& Dagher,2006;Wilson,Sayette,Delgado,&Fiez,2005)。Brody 等(2002)采用正電子發射斷層掃描(Positron Emission Tomography PET)技術對重度吸煙者和非吸煙者呈現與香煙相關線索的錄像作為香煙渴求誘發刺激,間隔10天對被試進行香煙相關線索和中性線索作用下的兩次掃描,結果發現嚴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,發現了吸煙可能會對反應抑制能力產生影響的證據。但是,一些ERPs和腦成像研究的結果只能說明吸煙者與不吸煙者在反應抑制導致的腦激活上存在差異,這僅能作為吸煙影響反應抑制能力的間接證據,還不能完全揭示二者之間的因果關系。之后的研究應關注腦激活數據與行為數據的聯合分析,以進一步探討吸煙與反應抑制能力損傷之間的因果關系。

3 吸煙對反應抑制能力影響的原因

3.1 吸煙對前額葉系統的影響

吸煙者表現出較差的反應抑制能力,可能是因為吸煙者在尼古丁的長期作用下,認知控制網絡等相關腦區受到影響,導致吸煙個體不能使用情景預期來指導選擇,最終導致反應抑制能力下降(Cole et al.,2010)。由于額葉是執行和控制行為的主要腦區(Fowler,Volkow,Kassed,&Chang,2007),而成癮者最大的特征是不能控制自己反復使用成癮物質的行為(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活動改變有關。而腦成像研究表明,尼古丁依賴者的前額腦區異常(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)、背外側前額葉皮層(Dorsolateral prefrontal cortex,DLPFC)、腹外側前額葉皮層(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揮著重要作用(Egner,2011)。與不吸煙者相比,吸煙者反應抑制能力的減弱與前額葉系統的失調息息相關(Ettinger et al.,2009;Fregni et al.,2008;Gallinat et al.,2006;Spinella,2002)。有研究者發現,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);背外側前額皮質(DLPFC)和腹外側前額葉皮質(VLPFC)的皮層灰質體積和密度明顯減小,而且吸煙者左半球背側前扣帶回(Dorsal anterior cingulate cortex D-ACC)的灰質體積和右半球小腦的灰質密度降低(Brody,Mandelkern,&Jarvik,et al.,2004);前額葉(PFC)和前扣帶回皮層(ACC)的神經反應性活動也減弱了(Riggs et al.,2007)。背外側前額葉皮質與前扣帶回皮層、眶額葉皮層及其前額葉腦區的功能連接受損,導致吸煙者大腦功能出現異常,從而表現出反應抑制能力下降。

3.2 吸煙對中腦邊緣多巴胺系統的影響

中腦邊緣多巴胺系統(mesolimbic dopamine system MLDS)是腦內獎賞或強化系統的主要結構,其獎賞回路由腹側被蓋區(Ventral Tegmental Area,VTA)、伏隔核(Nucleus Accumbens,NAc)和杏仁核(Amygdala)等構成(王惠玲,趙晏,2003),它是包括尼古丁在內的很多成癮物質的中介系統(鄧林園,方曉義,2005)。有研究發現,在藥物依賴者服藥期間,從中腦腹側被蓋區神經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,這種激活增加了中腦腹側被蓋區的多巴胺神經元的放電,隨后增加多巴胺遞質釋放到伏隔核和前額葉皮層等邊緣前腦的其他腦區(張開鎬,2002)。

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

在動物成癮方面,研究者用老鼠進行的活體內微透析實驗結果發現尼古丁使用可以導致中腦腹側被蓋區(VTA)的多巴胺釋放明顯增多(Rahman,Zhang,&Corrigall,2003)。Yin和 French等(2000)的研究也發現尼古丁顯著增加了多巴胺神經元的神經脈沖放電。上述研究表明中腦邊緣多巴胺系統和尼古丁依賴息息相關,在尼古丁直接刺激或者尼古丁渴求誘發線索刺激作用下,所激活的腦區基本上都是中腦邊緣多巴胺系統以及相關的腦區。Mansvelder,Keath和McGehee(2002)研究發現尼古丁引起腹側被蓋區內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胞并且對其它結構產生影響,比如腳橋被蓋核、谷氨酸能的神經元等。尼古丁通過直接誘導多巴胺的釋放或抑制GABA能神經元,最終導致腹側被蓋區的多巴胺輸入端向伏隔核釋放多巴胺的持續增強(Picciotto&Corrigall,2002)。正常情況下,多巴胺神經元還受到通過腹側被蓋區的GABA中間神經元以及包括伏隔核和蒼白球在內的其他腦區投射來的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去敏化,結果將導致向DA神經元的抑制性輸入減弱,這樣一來,對多巴胺神經元的抑制就解除了,使釋放到伏隔核區的多巴胺量增加。有研究發現,吸煙者的快感體驗與多巴胺水平的增加有關(Brody et al.,2006)。這表明尼古丁的攝入使個體產生陶醉感和愉悅感,就算是短時間地偶爾吸煙也足以使人產生尼古丁或香煙依賴。

4 吸煙對反應抑制能力影響的爭議

如前所述,雖然有大量的研究發現吸煙對反應抑制能力有影響(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現這一現象(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任務中Go試次的漏報率和NoGo試次的虛報率,研究結果發現,吸煙者與不吸煙者在行為結果上未表現出差異;Evans等人(2009)的研究也發現,吸煙者在NoGo試次的正確率以及Go試次的反應時兩個指標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抑制能力還存在爭議。研究結果產生爭議的原因可能主要有以下三點：

第一,研究者采用的實驗范式不同所得出的結論可能會有差異。在已有研究中,研究者通常使用Stop-Signal任務和Go/NoGo任務對吸煙者反應抑制進行研究。例如,Buzzell等(2014)使用Go/NoGo任務對吸煙者和非吸煙者的反應抑制能力進行研究發現,兩組被試在行為反應上無明顯差異。Logemann等人(2014)利用Stop-Signal任務對吸煙者的行為抑制能力進行了評估,他們發現吸煙者對Go刺激的反應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兩種任務所依賴的加工機制不完全相同,在Stop-Signal任務中,要停止的反應已經處于加工過程之中,加工已經到達相當水平,遠遠高出了對NoGo刺激的加工。對此有研究發現,基底神經節(basal ganglia)在Stop-Signal任務中對動作反應的發起和抑制有重要作用(Eagle&Robbins,2003),基底神經節是前腦中的一組皮質下神經核,包括尾狀核、殼核、蒼白球、丘腦底核(subthalamic nucleus STN)和中腦黑質(Alexander&Crutcher,1990)。在基底神經節的神經核中,丘腦底核可能是參與反應抑制加工的關鍵結構(Cohen&Frank,2009;Ray et al.,2012;Wiecki&Frank,2013)。Aron和 Poldrack(2006)研究了丘腦底核和SSRT之間的關系,研究發現丘腦底核激活越強,被試的SSRT越短。即：SSRT較短的被試丘腦底核激活強于SSRT較長的被試。對吸煙者與不吸煙者的腦機制結構進行對比發現,與不吸煙者相比,吸煙者的丘腦、小腦和黑質的灰質體積或密度減小,既然反應和不反應之間的競爭主要在基底神經節的神經核中進行,刺激或損傷這些神經核將會對反應抑制產生明顯影響(Chambers et al,2006;2007)。此外,有研究發現Go/NoGo任務所激活左側大腦的其它一些區域,如前扣帶回、前運動輔助區等都與高水平的運動計劃及行為選擇相關,而在Stop-Signal任務中,前額葉皮層、基底神經節、額下回等都參與了反應停止操作(Rubia et al.,2001)。這表明,較之Stop-Signal任務,Go/NoGo任務中的抑制更多涉及行為的選擇和行為的準備。

第二,實驗任務的難度不同也可能影響實驗結果。研究發現,Go/NoGo任務的難度取決于Go刺激和NoGo刺激的呈現時間以及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任務中刺激呈現時間為800 ms,整個實驗共包括900個trial,其中83個NoGo trial,在此研究中發現吸煙者在NoGo試次的正確率以及Go試次的反應時兩個指標上與不吸煙者相比沒有差異。而Luijten等人(2011a)采用的Go/NoGo任務中刺激呈現時間為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。因此我們認為,采取相同的Go/NoGo任務,刺激呈現的時間和NoGo試次所占的比例不同影響了上述實驗結果的不一致。對這一實驗結果有研究發現,背外側前額葉與前扣帶回在反應抑制中的激活隨工作記憶負荷增加而增強,Simmonds,Pekar和 Mostofsky(2008)對 10項使用Go/NoGo范式研究反應抑制能力的fMRI研究的元分析發現,與簡單的抑制任務相比,工作記憶負荷較高的復雜抑制任務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有密切的雙向纖維聯系,對執行控制至關重要。但是,這些腦區只在復雜任務條件下同時激活。與這種解釋一致,有研究發現在增加工作記憶負荷的Go/NoGo任務中背外側前額皮層激活增強,而簡單Go/NoGo任務中該區并無激活增強(Rowe,Friston,Frackowiak,&Passingham,2002)。但是,與不吸煙者相比,吸煙者背外側前額皮質(DLPFC)和腹外側前額葉皮質(VLPFC)的皮層灰質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生作為被試,采用Go/NoGo任務對正常健康被試和輕度吸煙被試的反應抑制能力進行比較研究發現,輕度吸煙組被試和正常健康組被試在Go的反應時和NoGo的正確率兩個指標上均未表現出差異(Buzzell et al.,2014;Evans et al.,2009);但是,Luijten等人(2011a)選取19名中度吸煙和20名不吸煙的大學本科生作為被試,采用Go/NoGo任務對兩組被試的反應抑制能力進行比較,研究結果發現,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果。當前,有些研究已證明吸煙的成癮程度與個體的反應抑制能力有關。如,Spinella(2002)采用Go/NoGo任務研究發現,被試在實驗中犯錯誤的概率與每天吸煙的數量呈正相關;Billieux等人(2010)的研究也發現吸煙者反應抑制的個體差異與每天抽煙的數量有關。研究認為,對優勢反應的抑制能力越差,吸煙成癮程度越重,相反,對優勢反應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,發現在控制了吸煙量和吸煙強度的條件下,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機制對吸煙成癮人群的反應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和中腦邊緣多巴胺系統這一事實達成一致,但刺激方式局限于視覺或視聽覺,且對具體激活腦區及核團的定位尚存在較大爭議,這可能是因為在進行掃描時選擇的被試吸煙成癮程度以及所處的渴求狀態不同所致。因此,將來的研究可以對處于不同的香煙剝奪狀態(如剛吸完一支煙與吸煙后2小時這兩種不同狀態)下的吸煙者的反應抑制能力進行對比研究,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線索刺激下反應抑制能力及其大腦活動的變化情況,從而使香煙成癮機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的環境線索作用下大腦活動狀況的異同進行分析,找出吸煙者反應抑制能力受損的特異性,從而為香煙成癮的戒斷發展出更有針對性的干預方案。

第三,到目前為止,對反應抑制能力的研究主要采用Go/NoGo任務和Stop-Signal任務。但是,由于Go/NoGo任務要求只對Go刺激反應,對NoGo刺激并不反應,這樣可能導致在Go/NoGo范式中觀察到的抑制控制效應已被反應相關加工污染,并且難以提取反應時間,常常不能為反應抑制提供有效的行為指標(Yuan,He,Qinglin,Chen,&Li,2008);Stop-Signal任務雖然能提供行為指標,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信號誘發的腦活動。近年來有研究者將雙選擇oddball范式用來進行反應抑制能力的研究(Yuan et al.,2008;Yuan et al.,2012)。雙選擇oddball范式是對傳統oddball范式的改編,該范式要求被試既快又準的對大概率的標準刺激和小概率的偏差刺激做兩類不同的按鍵反應。由于標準刺激的呈現概率遠大于偏差刺激,因此,被試對標準刺激的反應將成為優勢反應,當偏差刺激出現時,被試需要抑制對標準刺激的優勢反應,從而確保對偏差刺激做出正確的行為反應。而偏差刺激反應時與標準刺激反應時之差則為反應抑制的行為學指標(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抑制能力與不吸煙者進行對比研究,并且比較Go/NoGo范式、Stop-Signal范式以及雙選擇oddball范式在行為、ERPs和腦成像上所得結果的異同,為以后進行反應抑制能力的研究提供更有效的研究范式。

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

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