探討神經性相關之抑制能力與提取-消除程序對於重度菸癮患者的影響

吸菸是一種慢性成癮的疾病，容易誘導大腦產生病變，甚至對成癮物質失去控制能力。在成癮研究中發現，提取－消除程序（retrieval-extinction procedure, R-E procedure）可以應用於動物和人類成癮者，有效地減弱他們對於藥物線索的記憶、減少動機效應（motivational effects）。我們的目標是探討記憶的提取－消除程序是否能減少重度菸成癮者在現實生活中使用尼古丁的渴望以及使用狀況，同時探討大腦抑制相關腦區的活化狀態（抑制能力好壞）是否會調節提取－消除程序的效果，並使用階層線性模型預測追蹤期間對時間點i的菸渴求與時間點i+1的抽菸根數。研究對象為33名預計參加尼古丁替代療法（nicotine replacement therapy, NRT）的重度菸癮者，被隨機分配到兩組：提取消除組和主動控制組。在實驗操弄前後利用問卷以及基本生理測量檢測參與者對菸的認知態度、行為與成癮程度。使用停止信號作業（stop-signal task）和fMRI測量抑制控制能力（inhibitory control ability）相關的大腦區域。追蹤期採用經驗取樣紀錄參與者在真實生活中使用香菸的情形（追蹤21天，一天寄送8封簡訊）。結果顯示，提取－消除程序無法減少重度菸癮者對菸的外顯態度與行為。腦造影結果顯示，在反應抑制基礎線，右側前運動輔助區與右側殼核區域的活化增加與時間點i的菸渴求以及時間點i+1的吸菸根數減少有顯著相關。參與者具有更好的抑制控制能力，可能具有更好的治療結果，例如對於物質有較少渴望或較少使用香菸。大多數使用R-E程序的研究都以動物為受試者，少有研究採用人類作為研究對象。故本研究將提供關於提取－消除程序、成癮相關認知與行為以及大腦抑制腦區更多不同的觀點，在臨床應用層面上也提供物質成癮者非侵入性與非藥物治療的可能性，並提供實驗室神經認知任務作為日常生活抑制控制指標的可能性。

Smoking is a chronic addictive disease that easily induces brain damage and even loses control of addictive substance. The retrieval-extinction procedure (R-E procedure) can be applied to animal and human addicts, effectively reducing their memory of drug cues and reducing motivational effects. We asked whether the R-E procedure can reduce the heavy smokers’ craving for smoking and predict the smoking status in real life. We also asked whether the inhibition-related brain regions can moderate the effect of R-E procedure. Finally, we asked whether the craving at time point i can predict the smoking behavior at time point i + 1 by using hierarchical multilevel linear modeling (HLM). Thirty-three heavy smokers who planned to participate the nicotine replacement therapy (NRT) were randomly assigned to two groups: the R-E group and active control group. Participants’ explicit cognitions, behaviors and craving toward smoking were measured before and after experimental manipulation. Their preparatory control of motor inhibition was measured by employing stop-signal task during brain scanning. Smoking behaviors were monitored for 21 days. Result showed the R-E procedure didn’t reduce the explicit attitudes and behaviors of heavy smokers. Resulted of fMRI, participants with higher right pre-supplementary motor area and right putamen activation during response inhibition were significantly and negatively moderated by the link between craving at time i and subsequent smoking at time i+1. That is, better inhibitory control may have better outcomes. Very few studies using the R-E procedure adopted the human participants. Our study provides important insight about the R-E procedure in human participants. Also, we provide the possibility of non-invasive and non-pharmacological treatment of substance addiction patients at the clinical application, and the possibility of laboratory neurocognitive tasks as indicators of daily life inhibition control.