吸烟对反应抑制的影响：证据、原因和争论*

赵 鑫 刘晓婷 昝香怡 周爱保

(1西北师范大学心理学院,行为康复训练研究中心,兰州 730070)(2兰州大学第二医院VIP呼吸科,兰州 730070)

1 引言

近期的研究发现,吸烟会对个体的认知功能造成一定程度的影响(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)。研究者认为,这是由于烟草中的尼古丁会影响大脑的执行功能(executive function,EF)(Ashare,Falcone,&Lerman,2014;Dawkins,Powell,West,Powell,&Pickering,2007;Heishman,Kleykamp,&Singleton,2010;Livingstone et al.,2009)。执行功能作为大脑的高级认知功能,对一系列的认知与行为起到了关键的作用。反应抑制是一种重要的执行功能(Clark,1996),指抑制已经形成的动作反应,是对行动的抑制(抑制优势反应或反应倾向)过程,是执行控制的一个关键组成部分(Johnstone,Barry,Markovska,Dimoska,&Clarke,2009)。更具体的说,反应抑制就是抑制不再需要或不恰当的行为,以便个体可以对外界环境进行各种灵活的和有目的的行为反应(Verbruggen&Logan,2009)。另外,这一能力对于结束不再相关任务、改正错误、依据变化改变原有任务等具有重要意义(Aron&Poldrack,2006)。一些研究表明,与不吸烟者相比,吸烟者的反应抑制功能会受到所摄入的尼古丁的影响(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任务(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)和停止信号任务(Stop-Signal tasks,SST)(Billieux et al.,2010;de Ruiter,Oosterlaan,Veltman,vanden Brink,& Goudriaan,2012;Logemann, Böcker, Deschamps, Kemner, &Kenemans,2014;Monterosso et al.,2005;Rass et al.,2014;Reynolds et al.,2007)对吸烟者的反应抑制能力进行评估。吸烟者反应抑制能力的研究对于探明烟草成瘾者以及尼古丁依赖者执行功能受影响的深层原因及机制有一定的价值。临床上,对于烟草成瘾者的干预与治疗也具有重要的实践意义。本文在总结相关研究的基础上,阐述吸烟对反应抑制能力影响的证据、原因以及所存在的争议,以期对该领域的研究提供新的视角。

2 吸烟对反应抑制能力的影响——来自行为、ERPs、脑成像的研究

目前,许多研究者采用行为实验(Billieux et al.,2010;Powell,Pickering,Dawkins,West,&Powell,2004;Reynolds et al.,2007)、事件相关电位(event-related potentials,ERPs)技术(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)技术(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)研究发现,吸烟会对个体的反应抑制能力产生影响。

2.1 行为研究

在行为层面上,研究者采用Go/NoGo任务和Stop-Signal任务发现,吸烟者的虚报率(Commission error)和反应时两个指标都显著高于正常健康对照组被试(Billieux et al.,2010;de Ruiter et al.,2012;Nestor,McCabe,Jones,Clancy,&Garavan,2011;Reynolds et al.,2007)。虚报率是对不需要做出反应的非目标刺激做出的反应,是衡量反应抑制能力的一个重要的行为指标(Thorell,Lindqvist,Bergman Nutley,Bohlin,&Klingberg,2009),研究者认为吸烟者在Go/NoGo任务和Stop-Signal任务中虚报率较高的原因在于吸烟者的大脑执行功能受到所摄入的尼古丁的影响(Bekker,Böcker,van Hunsel,van Den Berg,&Kenemans,2005;Billieux et al.,2010;Luijten et al.,2011a)。目前,大量的研究者对吸烟者与不吸烟者的反应抑制能力进行比较研究时采用线索反应模式(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),线索反应模式通过向个体呈现物理刺激来诱发其渴求,其中又分为真实刺激(Sayette&Hufford,1994)、视频刺激(Baumann&Sayette,2006;Brody et al.,2002;Monterosso et al.,2005;Tong,Bovbjerg,&Erblich,2007)、图片刺激(Hitsman et al.,2008;Luijten et al.,2011b)、听觉刺激和脚本/想象刺激(Epstein,Temple,Roemmich,&Bouton,2009;Soetens,Braet,Dejonckheere,& Roets,2006;Wegner,1992)。有关吸烟者反应抑制的研究通过呈现经过评定后的标准化图片,采用最明显的视觉刺激的方式来诱发吸烟者的渴求。Luijten等人(2011a)采用Go/NoGo任务对吸烟者与正常健康被试的对照研究表明,吸烟者在NoGo刺激上的虚报率显著高于正常对照组。另外,有研究采用Stop-Signal任务对轻度吸烟者和中度吸烟者的对照研究表明,中度吸烟者(吸烟量平均每天11～20支)对Stop信号的抑制反应时间更长,成功抑制比例更低(Bekker et al.,2005;Billieux et al.,2010)。另外,Rass等人(2014)通过对连续吸烟者、间断吸烟者和不吸烟者的反应抑制能力进行比较发现,连续吸烟者的反应抑制潜伏期显著小于间断吸烟者和正常健康被试。有研究者采用Stop-Signal任务对戒烟时间不同的吸烟者和正常被试的反应抑制对比研究发现,吸烟者在戒烟时间较长(10小时)情况下其反应抑制能力受到一定程度的影响,正常健康对照组被试的停止任务绩效显著高于吸烟群体,即正常群体的抑制成功率高,停止信号反应时(SSRT)短(Charles-Walsh et al.,2014;Logemann et al.,2014;Monterosso et al.,2005)。

2.2 ERPs研究

研究者从行为层面上发现,与不吸烟者相比,吸烟者的反应抑制能力受到所摄入的尼古丁的影响(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)。研究者们还采用事件相关电位技术揭示了吸烟对反应抑制加工过程的影响(Buzzell et al.,2014;Impey et al.,2013;Logemann et al.,2014;Luijten et al.,2011a)。Luijten等人(2011a)比较了19名吸烟者和20名不吸烟的健康被试在Go/NoGo任务中的ERPs成分,结果显示,吸烟者的NoGo-N2波幅显著低于正常健康被试,而吸烟组和不吸烟组在NoGo-P3成分上未表现出显著差异。Buzzell等人(2014)的研究支持了上述结果,该研究以大学本科生为被试,检测了15名轻度吸烟者和15名不吸烟者的ERPs成分,研究发现,轻度吸烟组的NoGo-N2波幅明显小于正常对照组,而两组被试的NoGo-P3成分无显著差异。一般认为,NoGo-N2主要定位于前扣带回(Bekker,Kenemans,&Verbaten,2005;Dimoska,Johnstone,&Barry,2006;Nieuwenhuis,Yeung,van Den Wildenberg,&Ridderinkhof,2003;Yeung,Botvinick,&Cohen,2004)和右侧眶额叶(Strik,Fallgatter,Brandeis,& Pascual-Marqui,1998);NoGo-P3定位于眶额叶(Bokura,Yamaguchi,&Kobayashi,2001)。尽管两者的心理过程没有最终确定,但是可以认为,NoGo-N2和NoGo-P3可能分别代表了与抑制控制有关的两个加工过程,反应抑制和冲突监控(Ruchsow et al.,2008)。有观点认为NoGo-N2反映了一种自上而下的抑制机制(Falkenstein,Hoormann,&Hohnsbein,1999),即在运动执行前抑制不适当的反应倾向(Kok,Ramautar,De Ruiter,Band,&Ridderinkhof,2004),这种早期加工的异常很可能反应了吸烟者在运动执行前抑制不适当的反应倾向上受到所摄入的尼古丁的影响(Luijten et al.,2011a)。

2.3 脑成像研究

近期,对吸烟者反应抑制能力的脑成像研究发现,与不吸烟者相比,吸烟者丘脑(Thalamic)、额中回(Middle frontal gyrus)和前扣带回(Anterior cingulate cortex)灰质体积减小(Brody,Mandelkern,&Lee et al.,2004;Gallinat et al.,2006)。另外, 脑成像研究还发现,吸烟者额叶(诸如ACC、PFC和OFC)、枕叶和颞叶,包括海马旁回脑区的灰质体积明显减小、密度明显降低。丘脑、小脑和黑质的灰质体积或密度也发生了变化(Gallinat et al.,2006)。吸烟者的丘脑灰质体积减少可能与尼古丁对吸烟者认知功能的影响有关(Sharma&Brody,2009)。有研究发现,吸烟者在对与吸烟有关的刺激进行反应抑制时,与不吸烟者相比,吸烟者眶额叶皮层(Orbitofrontal cortex OFC)、前额皮层(Prefrontal cortex PFC)和前扣带回皮层(ACC)的激活增强(Hartwell et al.,2011;McBride,Barrett,Kelly,Aw,& Dagher,2006;Wilson,Sayette,Delgado,&Fiez,2005)。Brody 等(2002)采用正电子发射断层扫描(Positron Emission Tomography PET)技术对重度吸烟者和非吸烟者呈现与香烟相关线索的录像作为香烟渴求诱发刺激,间隔10天对被试进行香烟相关线索和中性线索作用下的两次扫描,结果发现严重吸烟者比非吸烟者在扣带回前部、颞叶和眶额皮层的葡萄糖代谢增加更多。

综上所述,研究者借用行为、ERPs和脑成像研究手段,发现了吸烟可能会对反应抑制能力产生影响的证据。但是,一些ERPs和脑成像研究的结果只能说明吸烟者与不吸烟者在反应抑制导致的脑激活上存在差异,这仅能作为吸烟影响反应抑制能力的间接证据,还不能完全揭示二者之间的因果关系。之后的研究应关注脑激活数据与行为数据的联合分析,以进一步探讨吸烟与反应抑制能力损伤之间的因果关系。

3 吸烟对反应抑制能力影响的原因

3.1 吸烟对前额叶系统的影响

吸烟者表现出较差的反应抑制能力,可能是因为吸烟者在尼古丁的长期作用下,认知控制网络等相关脑区受到影响,导致吸烟个体不能使用情景预期来指导选择,最终导致反应抑制能力下降(Cole et al.,2010)。由于额叶是执行和控制行为的主要脑区(Fowler,Volkow,Kassed,&Chang,2007),而成瘾者最大的特征是不能控制自己反复使用成瘾物质的行为(Volkow,Fowler,&Wang,2003)。因此,吸烟对抑制控制能力的影响可能与额叶某个或某些脑区活动改变有关。而脑成像研究表明,尼古丁依赖者的前额脑区异常(Brody,Mandelkern,&Jarvik,et al.,2004;Carroll,Sutherland,Salmeron,Ross,&Stein,2014;Gallinat et al.,2006;Luijten et al.,2013)。前额叶(Prefrontal cortex,PFC)系统主要由眶额叶皮层(Orbital frontal cortex,OFC)、前扣带回皮层(Anterior cingulate cortex,ACC)、背外侧前额叶皮层(Dorsolateral prefrontal cortex,DLPFC)、腹外侧前额叶皮层(Ventrolateral prefrontal cortex,VLPFC)、额下回(Inferior frontal gyrus,IFG)等部分组成,对个体的抑制控制功能发挥着重要作用(Egner,2011)。与不吸烟者相比,吸烟者反应抑制能力的减弱与前额叶系统的失调息息相关(Ettinger et al.,2009;Fregni et al.,2008;Gallinat et al.,2006;Spinella,2002)。有研究者发现,与正常健康被试相比,吸烟者前额叶与前扣带回皮层、前额叶与眶额叶皮层的功能连接下降(Luijten et al.,2013);背外侧前额皮质(DLPFC)和腹外侧前额叶皮质(VLPFC)的皮层灰质体积和密度明显减小,而且吸烟者左半球背侧前扣带回(Dorsal anterior cingulate cortex D-ACC)的灰质体积和右半球小脑的灰质密度降低(Brody,Mandelkern,&Jarvik,et al.,2004);前额叶(PFC)和前扣带回皮层(ACC)的神经反应性活动也减弱了(Riggs et al.,2007)。背外侧前额叶皮质与前扣带回皮层、眶额叶皮层及其前额叶脑区的功能连接受损,导致吸烟者大脑功能出现异常,从而表现出反应抑制能力下降。

3.2 吸烟对中脑边缘多巴胺系统的影响

中脑边缘多巴胺系统(mesolimbic dopamine system MLDS)是脑内奖赏或强化系统的主要结构,其奖赏回路由腹侧被盖区(Ventral Tegmental Area,VTA)、伏隔核(Nucleus Accumbens,NAc)和杏仁核(Amygdala)等构成(王惠玲,赵晏,2003),它是包括尼古丁在内的很多成瘾物质的中介系统(邓林园,方晓义,2005)。有研究发现,在药物依赖者服药期间,从中脑腹侧被盖区神经元末稍释放的多巴胺增加,而且,这些药物通过不同的靶位激活中脑边缘多巴胺系统,这种激活增加了中脑腹侧被盖区的多巴胺神经元的放电,随后增加多巴胺递质释放到伏隔核和前额叶皮层等边缘前脑的其他脑区(张开镐,2002)。

fMRI研究表明,当给被试静脉注射尼古丁后发现,尼古丁引起伏隔核、杏仁核、扣带回以及额叶等脑区神经活动的增强(Stein et al.,1998)。另外,有研究采用fMRI技术探测发现,被试暴露于香烟相关线索时,尼古丁依赖者中脑边缘多巴胺系统和前额叶皮层均得到激活,并且报告渴求感增强(Due,Huettel,Hall,&Rubin,2002;Hitsman et al.,2008)。

在动物成瘾方面,研究者用老鼠进行的活体内微透析实验结果发现尼古丁使用可以导致中脑腹侧被盖区(VTA)的多巴胺释放明显增多(Rahman,Zhang,&Corrigall,2003)。Yin和 French等(2000)的研究也发现尼古丁显著增加了多巴胺神经元的神经脉冲放电。上述研究表明中脑边缘多巴胺系统和尼古丁依赖息息相关,在尼古丁直接刺激或者尼古丁渴求诱发线索刺激作用下,所激活的脑区基本上都是中脑边缘多巴胺系统以及相关的脑区。Mansvelder,Keath和McGehee(2002)研究发现尼古丁引起腹侧被盖区内γ－氨基丁酸(γ-aminobutyric acid,GABA)传递的抑制。

γ-氨基丁酸主要作用是抑制多巴胺细胞并且对其它结构产生影响,比如脚桥被盖核、谷氨酸能的神经元等。尼古丁通过直接诱导多巴胺的释放或抑制GABA能神经元,最终导致腹侧被盖区的多巴胺输入端向伏隔核释放多巴胺的持续增强(Picciotto&Corrigall,2002)。正常情况下,多巴胺神经元还受到通过腹侧被盖区的GABA中间神经元以及包括伏隔核和苍白球在内的其他脑区投射来的GABA纤维的抑制性控制。但是,它们在接触尼古丁后很快就会出现去敏化,结果将导致向DA神经元的抑制性输入减弱,这样一来,对多巴胺神经元的抑制就解除了,使释放到伏隔核区的多巴胺量增加。有研究发现,吸烟者的快感体验与多巴胺水平的增加有关(Brody et al.,2006)。这表明尼古丁的摄入使个体产生陶醉感和愉悦感,就算是短时间地偶尔吸烟也足以使人产生尼古丁或香烟依赖。

4 吸烟对反应抑制能力影响的争议

如前所述,虽然有大量的研究发现吸烟对反应抑制能力有影响(Glass et al.,2009;Billieux et al.,2010;de Ruiter et al.,2012;Luijten et al.,2011a,b;Spinella,2002),但是,另外一些研究却并未发现这一现象(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)选取吸烟者与不吸烟者作为被试,比较两组被试在Go/NoGo任务中Go试次的漏报率和NoGo试次的虚报率,研究结果发现,吸烟者与不吸烟者在行为结果上未表现出差异;Evans等人(2009)的研究也发现,吸烟者在NoGo试次的正确率以及Go试次的反应时两个指标上与不吸烟者相比没有差异。可见,目前对吸烟是否影响个体的反应抑制能力还存在争议。研究结果产生争议的原因可能主要有以下三点：

第一,研究者采用的实验范式不同所得出的结论可能会有差异。在已有研究中,研究者通常使用Stop-Signal任务和Go/NoGo任务对吸烟者反应抑制进行研究。例如,Buzzell等(2014)使用Go/NoGo任务对吸烟者和非吸烟者的反应抑制能力进行研究发现,两组被试在行为反应上无明显差异。Logemann等人(2014)利用Stop-Signal任务对吸烟者的行为抑制能力进行了评估,他们发现吸烟者对Go刺激的反应速度与正常对照组相比没有明显差别,但吸烟者的SSRT却明显延长。Stop-Signal和Go/NoGo两种任务所依赖的加工机制不完全相同,在Stop-Signal任务中,要停止的反应已经处于加工过程之中,加工已经到达相当水平,远远高出了对NoGo刺激的加工。对此有研究发现,基底神经节(basal ganglia)在Stop-Signal任务中对动作反应的发起和抑制有重要作用(Eagle&Robbins,2003),基底神经节是前脑中的一组皮质下神经核,包括尾状核、壳核、苍白球、丘脑底核(subthalamic nucleus STN)和中脑黑质(Alexander&Crutcher,1990)。在基底神经节的神经核中,丘脑底核可能是参与反应抑制加工的关键结构(Cohen&Frank,2009;Ray et al.,2012;Wiecki&Frank,2013)。Aron和 Poldrack(2006)研究了丘脑底核和SSRT之间的关系,研究发现丘脑底核激活越强,被试的SSRT越短。即：SSRT较短的被试丘脑底核激活强于SSRT较长的被试。对吸烟者与不吸烟者的脑机制结构进行对比发现,与不吸烟者相比,吸烟者的丘脑、小脑和黑质的灰质体积或密度减小,既然反应和不反应之间的竞争主要在基底神经节的神经核中进行,刺激或损伤这些神经核将会对反应抑制产生明显影响(Chambers et al,2006;2007)。此外,有研究发现Go/NoGo任务所激活左侧大脑的其它一些区域,如前扣带回、前运动辅助区等都与高水平的运动计划及行为选择相关,而在Stop-Signal任务中,前额叶皮层、基底神经节、额下回等都参与了反应停止操作(Rubia et al.,2001)。这表明,较之Stop-Signal任务,Go/NoGo任务中的抑制更多涉及行为的选择和行为的准备。

第二,实验任务的难度不同也可能影响实验结果。研究发现,Go/NoGo任务的难度取决于Go刺激和NoGo刺激的呈现时间以及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任务中刺激呈现时间为800 ms,整个实验共包括900个trial,其中83个NoGo trial,在此研究中发现吸烟者在NoGo试次的正确率以及Go试次的反应时两个指标上与不吸烟者相比没有差异。而Luijten等人(2011a)采用的Go/NoGo任务中刺激呈现时间为200ms,整个实验共包括 400个trial,其中NoGo试次占所有试次的25%,该研究得出了相反的结论,即吸烟者在NoGo试次的正确率上显著低于不吸烟者。因此我们认为,采取相同的Go/NoGo任务,刺激呈现的时间和NoGo试次所占的比例不同影响了上述实验结果的不一致。对这一实验结果有研究发现,背外侧前额叶与前扣带回在反应抑制中的激活随工作记忆负荷增加而增强,Simmonds,Pekar和 Mostofsky(2008)对 10项使用Go/NoGo范式研究反应抑制能力的fMRI研究的元分析发现,与简单的抑制任务相比,工作记忆负荷较高的复杂抑制任务更多的激活了额中回(middle frontal gyrus),额下回(inferior frontal gyrus),顶下小叶(inferior parietal lobule)和颞-顶交界处(temporoparietal junction TPJ),顶下小叶和前额皮质有密切的双向纤维联系,对执行控制至关重要。但是,这些脑区只在复杂任务条件下同时激活。与这种解释一致,有研究发现在增加工作记忆负荷的Go/NoGo任务中背外侧前额皮层激活增强,而简单Go/NoGo任务中该区并无激活增强(Rowe,Friston,Frackowiak,&Passingham,2002)。但是,与不吸烟者相比,吸烟者背外侧前额皮质(DLPFC)和腹外侧前额叶皮质(VLPFC)的皮层灰质体积和密度明显减小(Brody,Mandelkern,&Jarvik,et al.,2004),因此,吸烟者与不吸烟者相比,在难度较大的Go/NoGo任务中吸烟者在NoGo刺激上的正确率显著小于正常对照组。

第三,所选取的吸烟被试的吸烟成瘾程度也可能是影响实验结果的一个重要因素。例如,有研究者选取轻度吸烟和不吸烟的大学生作为被试,采用Go/NoGo任务对正常健康被试和轻度吸烟被试的反应抑制能力进行比较研究发现,轻度吸烟组被试和正常健康组被试在Go的反应时和NoGo的正确率两个指标上均未表现出差异(Buzzell et al.,2014;Evans et al.,2009);但是,Luijten等人(2011a)选取19名中度吸烟和20名不吸烟的大学本科生作为被试,采用Go/NoGo任务对两组被试的反应抑制能力进行比较,研究结果发现,中度吸烟者在NoGo试次的正确率上显著低于不吸烟者,而且与不吸烟者相比,中度吸烟者的NoGo-N2波幅显著低于正常健康被试。这说明,吸烟组的成瘾程度可能会影响到实验结果。当前,有些研究已证明吸烟的成瘾程度与个体的反应抑制能力有关。如,Spinella(2002)采用Go/NoGo任务研究发现,被试在实验中犯错误的概率与每天吸烟的数量呈正相关;Billieux等人(2010)的研究也发现吸烟者反应抑制的个体差异与每天抽烟的数量有关。研究认为,对优势反应的抑制能力越差,吸烟成瘾程度越重,相反,对优势反应的抑制能力越好其吸烟成瘾程度越轻。Robinson,Pritchard和Davis(1992)比较了吸低尼古丁含量(0.06 mg)和高尼古丁含量(0.6 mg)的香烟前后EEG的变化,发现在控制了吸烟量和吸烟强度的条件下,尼古丁含量为 0.6mg的香烟引起EEG的激活,但0.06mg的没有。

5 展望

虽然许多研究者从行为到神经机制对吸烟成瘾人群的反应抑制能力展开了大量研究,但还存在众多疑问,今后可以着重从以下几个方面进行研究。

第一,尽管不同研究者都对尼古丁激活大脑前额叶系统和中脑边缘多巴胺系统这一事实达成一致,但刺激方式局限于视觉或视听觉,且对具体激活脑区及核团的定位尚存在较大争议,这可能是因为在进行扫描时选择的被试吸烟成瘾程度以及所处的渴求状态不同所致。因此,将来的研究可以对处于不同的香烟剥夺状态(如刚吸完一支烟与吸烟后2小时这两种不同状态)下的吸烟者的反应抑制能力进行对比研究,同时,还可以比较不同类型的人群,包括香烟成瘾者、香烟成瘾戒断者以及不吸烟者之间在香烟或者香烟相关线索刺激下反应抑制能力及其大脑活动的变化情况,从而使香烟成瘾机制的研究更精确也更全面。

第二,尼古丁依赖同其他依赖性药物机制之间的差异至今没有太多研究者有所涉及;因而,用同样的研究模式和手段,对毒品、酒精和香烟等常见依赖性药物在药物直接刺激或相关的环境线索作用下大脑活动状况的异同进行分析,找出吸烟者反应抑制能力受损的特异性,从而为香烟成瘾的戒断发展出更有针对性的干预方案。

第三,到目前为止,对反应抑制能力的研究主要采用Go/NoGo任务和Stop-Signal任务。但是,由于Go/NoGo任务要求只对Go刺激反应,对NoGo刺激并不反应,这样可能导致在Go/NoGo范式中观察到的抑制控制效应已被反应相关加工污染,并且难以提取反应时间,常常不能为反应抑制提供有效的行为指标(Yuan,He,Qinglin,Chen,&Li,2008);Stop-Signal任务虽然能提供行为指标,但行为抑制信号在时间上的不确定性容易混淆抑制信号和任务信号诱发的脑活动。近年来有研究者将双选择oddball范式用来进行反应抑制能力的研究(Yuan et al.,2008;Yuan et al.,2012)。双选择oddball范式是对传统oddball范式的改编,该范式要求被试既快又准的对大概率的标准刺激和小概率的偏差刺激做两类不同的按键反应。由于标准刺激的呈现概率远大于偏差刺激,因此,被试对标准刺激的反应将成为优势反应,当偏差刺激出现时,被试需要抑制对标准刺激的优势反应,从而确保对偏差刺激做出正确的行为反应。而偏差刺激反应时与标准刺激反应时之差则为反应抑制的行为学指标(辛勇,李红,袁加锦,2010)。因此,在以后的研究中可以使用双选择oddball范式对吸烟者的反应抑制能力与不吸烟者进行对比研究,并且比较Go/NoGo范式、Stop-Signal范式以及双选择oddball范式在行为、ERPs和脑成像上所得结果的异同,为以后进行反应抑制能力的研究提供更有效的研究范式。

最后,开发改善吸烟人群反应抑制缺陷的干预方法与技术。对吸烟成瘾人群反应抑制缺陷的认知与神经机制的研究,最终是为了改善和治疗吸烟成瘾人群的反应抑制缺陷。然而,对于这方面的干预方法与技术的研究才刚刚起步。研究表明,预期想象训练和金钱管理指导能够在一定程度上降低吸烟成瘾人群的反应抑制缺陷(Martin-Soelch et al.,2001;Powell et al.,2004)。但是,目前这些方法与技术都还处于研究阶段,离真正的临床治疗阶段还较远。因此,需要不断细化、完整这些方法和技术,使其有更好的操作性、规范性和临床效果。

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