Kosten Thomas R, Scanley Barbara Ellen, Tucker Karen A, Oliveto Alison, Prince Chekema, Sinha Rajita, Potenza Marc N, Skudlarski Pawel, Wexler Bruce E
Department of Psychiatry, Yale University School of Medicine, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
Neuropsychopharmacology. 2006 Mar;31(3):644-50. doi: 10.1038/sj.npp.1300851.
This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R>0.65; P<0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.
本研究采用功能磁共振成像(fMRI)来检测可卡因依赖(CD)患者在接触可卡因相关线索期间大脑激活与药物复吸之间的关联。我们对17名CD受试者进行了为期2周的住院成像。受试者随后进入一项为期10周的门诊安慰剂对照、双盲随机临床试验,在此期间每周三次评估尿毒理学以计算治疗效果评分(TES)。较差的TES与左侧中央前回、颞上回和后扣带回皮质(PCC)以及右侧颞中回和舌回的血氧水平依赖(BOLD)激活相关(R>0.65;P<0.005)。左侧PCC激活也区分出了8名未复吸者(TES高于平均值且完成治疗)和9名复吸者。未复吸者的可卡因阴性尿液比例(92%)显著高于复吸者(66%),而复吸者平均仅接受了3.2周的治疗。fMRI期间的渴求自我报告在未复吸者和复吸者之间没有差异,且与TES无关。在观看可卡因相关线索图像时,可卡因滥用复吸与感觉联合皮质、运动皮质和PCC的激活增加有关。这些结果表明,可卡因滥用复吸与感觉、运动和认知 - 情感加工区域中对可卡因线索的大脑激活增加有关。这种生理激活比渴求的主观报告更能预测复吸,可能是治疗开发的一个有用靶点。