强制和自愿戒毒者线索诱发海洛因渴求反应的差异

目的 比较环境线索诱发强制和自愿戒毒者海洛因渴求反应的差异。方法 208名强制戒毒被试者和172名自愿戒毒被试者暴露于海洛因相关环境线索,根据被试者的自我报告,采用Likert分级法评价线索诱发的渴求程度,填写主观戒断反应问卷、毒品使用情况和一般社会学资料,并测量暴露前后血压、心率及瞳孔。采用独立样本t检验,比较线索暴露诱发强制和自愿戒毒被试者渴求及生理指标的差异。结果 暴露后,自愿戒毒被试者的渴求分值明显高于强制戒毒被试者（P〈0．01）,强制戒毒被试者暴露前的收缩压和舒张压均明显高于自愿戒毒被试者（P〈0．01）,但暴露后两组血压未见显著性差异（P〉0．05）。结论 环境线索诱发强制和自愿戒毒被试者渴求反应存在差异,可能与实验地点、调查者和测量方法的不同有关。     

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates cue-induced craving for heroin

BackgroundTranscranial direct current stimulation (tDCS) is an effective approach to modulate brain region functions. We assessed if a single tDCS session over the bilateral frontal-parietal-temporal (FPT) areas would reduce cue induced craving in heroin addicts.MethodsTwenty non-treated, long-term heroin-addicted subjects were randomly assigned to receive either real tDCS (1.5 mA, cathodal over bilateral FPT for 20 min) or control tDCS stimulation (turning off the stimulation after 30 s). The participants received heroin cue exposure (containing both injection and inhalation procedures) before and after stimulation and rated their craving after each block of cue presentation.ResultsStimulation of the bilateral FPT with real tDCS for 20 min reduced craving scores significantly (68 ± 8.4 pre-stimulation vs. 43 ± 7.6 post-stimulation, p = 0.003), while the control stimulation group showed no significant changes. No side effects of tDCS were reported.ConclusionsOne session of tDCS over bilateral FPT area significantly reduced subjective craving score induced by heroin cues in heroin addicted subjects.     

线索诱发海洛因依赖者心理渴求及相关因素分析

目的　了解环境线索对海洛因依赖者心理渴求的影响及其相关因素。方法　380名戒断 期海洛因依赖者暴露于海洛因相关环境线索,测量暴露前后血压、心率、瞳孔,Likert分级法记录暴露前 后的渴求程度,完成自编诱发后戒断反应问卷及自编毒品使用情况和一般社会学资料。采用配对t检 验,比较暴露前后渴求程度及心率、血压等生理指标的变化,运用逐步回归分析与线索诱发渴求相关的 指标。结果　暴露后渴求、心率、血压及瞳孔均明显高于暴露前,差别有极显著意义(分别为t= -15.02,-14.23,-8.12,-5.03,-14.65,P<0.01)。诱发渴求与毒品依赖自评分值、诱发后心率及 主观戒断反应呈正相关,与成瘾时间呈成负相关。结论　环境线索可以使戒断期海洛因依赖者心理渴 求明显增加,依赖自评分值、诱发后心率、主观戒断反应及成瘾时间均与诱发渴求程度相关。     

Neural substrates of resisting craving during cigarette cue exposure.

BACKGROUND: In cigarette smokers, the most commonly reported areas of brain activation during visual cigarette cue exposure are the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving. METHODS: Forty-two tobacco-dependent smokers underwent functional magnetic resonance imaging, during which they were presented with videotaped cues. Three cue presentation conditions were tested: cigarette cues with subjects allowing themselves to crave (cigarette cue crave), cigarette cues with the instruction to resist craving (cigarette cue resist), and matched neutral cues. RESULTS: Activation was found in the cigarette cue resist (compared with the cigarette cue crave) condition in the left dorsal anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus. Lower magnetic resonance signal for the cigarette cue resist condition was found in the cuneus bilaterally, left lateral occipital gyrus, and right postcentral gyrus. These relative activations and deactivations were more robust when the cigarette cue resist condition was compared with the neutral cue condition. CONCLUSIONS: Suppressing craving during cigarette cue exposure involves activation of limbic (and related) brain regions and deactivation of primary sensory and motor cortices.     

线索诱发海洛因依赖者戒断期心理渴求的功能磁共振成像研究

目的　探讨线索诱发海洛因依赖者戒断期心理渴求的特异神经结构,为寻找干预复吸的有效策略提供理论依据。方法　采用3 0T磁共振成像系统,对30例戒断期海洛因依赖者和17名健康对照者在观看自然风光和吸毒图片时行全脑扫描,识别线索诱发海洛因渴求的特异脑区。结果(1)与观看自然风光相比,观看吸毒图片可以诱导戒断期海洛因依赖者产生明显心理渴求(t=-6 535,P<0 001),且渴求程度与吸毒量呈正相关(r=0 464,P=0 01)。(2)共发现17个参与线索诱发海洛因渴求的特异脑区,主要集中在前额叶皮质和边缘系统,以左侧为主。自我报告渴求与激活脑区数目及左侧额下回、额中回、扣带回前部、额内测回,右侧眶额皮质、杏仁核和岛叶等7个脑区的激活体积呈正相关(P<0 05)。结论　多个脑区参与线索诱发海洛因渴求,既包括认知过程又涉及情感加工,不同渴求程度激活脑区数目与某些脑区的激活体积不同。     

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers

BackgroundCue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers.MethodsNicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided.ResultsForty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group.LimitationsAs participants were not seeking treatment, clinical outcomes are lacking.ConclusionNicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue–elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.     

Prelimbic cortex is a common brain area activated during cue‐induced reinstatement of cocaine and heroin seeking in a polydrug self‐administration rat model

Many preclinical studies examined cue‐induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self‐administration relapse model in rats to determine similarities and differences in brain areas activated during cue‐induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg per infusion, 3‐hr/day, 18 day) or heroin (0.03 mg/kg per infusion) on alternating days (9 day for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue‐induced reinstatement where they were exposed to either heroin‐ or cocaine‐associated cues. We observed cue‐selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue‐induced neuronal activation in different subregions of the medial prefrontal cortex, dorsal striatum, nucleus accumbens, and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue‐induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos‐expressing cells was similar for the heroin and cocaine cue‐activated neurons. Overall, the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use.     

基于独立成分分析方法的海洛因成瘾者功能磁共振成像研究

目的 使用独立成分分析(ICA)法分析功能磁共振(fMRI)数据研究线索诱导因素导致海洛因成瘾者复吸的神经网络. 方法 安徽医科大学附属省立医院神经外科自2010年2月至2010年12月对海洛因成瘾组(n=15,来自安徽省戒毒康复中心)和正常对照组(n=15,来自招募的志愿者)在接受吸毒相关场景视频刺激的同时进行fMRI扫描,然后使用ICA方法对数据进行分析和比较2组受试者脑区的激活情况. 结果 与正常对照组相比,海洛因成瘾组患者双侧前额叶、左前扣带回、双侧后扣带回、左侧顶叶、左侧颞下回的激活降低;双侧伏核、右侧海马以及部分枕叶的激活增强,差异有统计学意义(P＜0.05). 结论 ICA方法是一种有效的任务相关fMRI数据分析方法,海洛因成瘾者学习记忆和奖赏系统相关脑区功能改变是线索诱发复吸的重要原因,主要涉及左前额叶、左顶叶、前后扣带回、海马、伏核等脑区.     

Common biology of craving across legal and illegal drugs - a quantitative meta-analysis of cue-reactivity brain response

The present quantitative meta-analysis set out to test whether cue-reactivity responses in humans differ across drugs of abuse and whether these responses constitute the biological basis of drug craving as a core psychopathology of addiction. By means of activation likelihood estimation, we investigated the concurrence of brain regions activated by cue-induced craving paradigms across studies on nicotine, alcohol and cocaine addicts. Furthermore, we analysed the concurrence of brain regions positively correlated with self-reported craving in nicotine and alcohol studies. We found direct overlap between nicotine, alcohol and cocaine cue reactivity in the ventral striatum. In addition, regions of close proximity were observed in the anterior cingulate cortex (ACC; nicotine and cocaine) and amygdala (alcohol, nicotine and cocaine). Brain regions of concurrence in drug cue-reactivity paradigms that overlapped with brain regions of concurrence in self-reported craving correlations were found in the ACC, ventral striatum and right pallidum (for alcohol). This first quantitative meta-analysis on drug cue reactivity identifies brain regions underlying nicotine, alcohol and cocaine dependency, i.e. the ventral striatum. The ACC, right pallidum and ventral striatum were related to drug cue reactivity as well as self-reported craving, suggesting that this set of brain regions constitutes the core circuit of drug craving in nicotine and alcohol addiction.     

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues

BACKGROUND: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. METHODS: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. RESULTS: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. CONCLUSIONS: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.     

Novel cues reinstate cocaine-seeking behavior and induce Fos protein expression as effectively as conditioned cues

Cue reinstatement of extinguished cocaine-seeking behavior is a widely used model of cue-elicited craving in abstinent human addicts. This study examined Fos protein expression in response to cocaine cues or to novel cues as a control for activation produced by test novelty. Rats were trained to self-administer cocaine paired with either a light or a tone cue, or received yoked saline and cue presentations, and then underwent daily extinction training. They were then tested for reinstatement of extinguished cocaine-seeking behavior elicited by response-contingent presentations of either the cocaine-paired cue or a novel cue (that is, tone for those trained with a light or vice versa). Surprisingly, conditioned and novel cues both reinstated responding and increased Fos similarly in most brain regions. Exceptions included the anterior cingulate, which was sensitive to test cue modality in saline controls and the dorsomedial caudate-putamen, where Fos was correlated with responding in the novel, but not conditioned, cue groups. In subsequent experiments, we observed a similar pattern of reinstatement in rats trained and tested for sucrose-seeking behavior, whereas rats trained and tested with the cues only reinstated to a novel, and not a familiar, light or tone. The results suggest that novel cues reinstate responding to a similar extent as conditioned cues regardless of whether animals have a reinforcement history with cocaine or sucrose, and that both types of cues activate similar brain circuits. Several explanations as to why converging processes may drive drug and novel cue reinforcement and seeking behavior are discussed.     

Individual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study

Measures of cue reactivity provide a means of studying and understanding addictive behavior. We wanted to examine the relationship between different cue reactivity measures, such as attentional bias and subjective craving, and functional brain responses toward smoking-related cues in smokers. We used eye-tracking measurements, a questionnaire for smoking urges-brief and functional magnetic resonance imaging to assess the responses to smoking-related and neutral visual cues from 25 male smokers after 36 h of smoking abstinence. Regression analyses were conducted to determine the correlation between cue-evoked brain responses and the attentional bias to smoking-related cues. The eye gaze dwell time percentage was longer in response to smoking-related cues than neutral cues, indicating significant differences in attentional bias towards smoking-related cues. The attentional bias to smoking-related cues correlated with subjective craving ratings (r=0.660, p<0.001). The dorsolateral prefrontal cortex, the putamen, the posterior cingulate cortex and the primary motor cortex were associated with the attentional bias to smoking-related cues, whereas the orbitofrontal cortex, the insula and the superior temporal gyrus were associated with smoking-related cue-induced craving and smoking urges. These results suggest that attentional mechanisms in combination with motivational and reward-related mechanisms play a role in smoking-related cue reactivity. We confirmed a positive correlation between different smoking-related cue reactivities, such as attentional bias and subjective craving, and functional brain responses in various individuals. Further studies in this field might contribute to a better individualized understanding of addictive behavior.     

Functional neuroimaging studies in addiction: multisensory drug stimuli and neural cue reactivity

Neuroimaging studies on cue reactivity have substantially contributed to the understanding of addiction. In the majority of studies drug cues were presented in the visual modality. However, exposure to conditioned cues in real life occurs often simultaneously in more than one sensory modality. Therefore, multisensory cues should elicit cue reactivity more consistently than unisensory stimuli and increase the ecological validity and the reliability of brain activation measurements. This review includes the data from 44 whole-brain functional neuroimaging studies with a total of 1168 subjects (812 patients and 356 controls). Correlations between neural cue reactivity and clinical covariates such as craving have been reported significantly more often for multisensory than unisensory cues in the motor cortex, insula and posterior cingulate cortex. Thus, multisensory drug cues are particularly effective in revealing brain-behavior relationships in neurocircuits of addiction responsible for motivation, craving awareness and self-related processing.     

The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue‐induced craving of smokers

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty‐five young male smokers and 26 age‐ and gender‐matched nonsmokers participated in the smoking cue‐reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC‐efferent pathways contributed to smoking cue‐induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue‐induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC‐caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC‐caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC‐caudate pathway in smoking cue‐induced craving in smokers, which may reflect top‐down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644–4656, 2017. © 2017 Wiley Periodicals, Inc.     

Mindful attention reduces neural and self-reported cue-induced craving in smokers

An emerging body of research suggests that mindfulness-based interventions may be beneficial for smoking cessation and the treatment of other addictive disorders. One way that mindfulness may facilitate smoking cessation is through the reduction of craving to smoking cues. The present work considers whether mindful attention can reduce self-reported and neural markers of cue-induced craving in treatment seeking smokers. Forty-seven (n = 47) meditation-naïve treatment-seeking smokers (12-h abstinent from smoking) viewed and made ratings of smoking and neutral images while undergoing functional magnetic resonance imaging (fMRI). Participants were trained and instructed to view these images passively or with mindful attention. Results indicated that mindful attention reduced self-reported craving to smoking images, and reduced neural activity in a craving-related region of subgenual anterior cingulate cortex (sgACC). Moreover, a psychophysiological interaction analysis revealed that mindful attention reduced functional connectivity between sgACC and other craving-related regions compared to passively viewing smoking images, suggesting that mindfulness may decouple craving neurocircuitry when viewing smoking cues. These results provide an initial indication that mindful attention may describe a ‘bottom-up’ attention to one’s present moment experience in ways that can help reduce subjective and neural reactivity to smoking cues in smokers.     

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two ¹⁸F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order—one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.     

环境线索对戒断期海洛因依赖者神经电生理的影响

目的 了解戒断期海洛因依赖者暴露在吸毒相关环境线索下神经电生理指标的变化特点.方法 采用自身配对设计,指导382例戒断康复期的海洛因依赖者进行放松训练后,观看吸毒相关视频及展示的海洛因模拟物及吸毒用具,同时采用多导联生物反馈仪记录环境线索暴露前后神经电生理指标,评估暴露前后的心理渴求程度,分析心理渴求程度及神经电生理各指标的变化特点.结果 (1)海洛因相关环境线索暴露后,心理渴求程度较暴露前增加[暴露前:(18±22)mm;暴露后:(29±29)mm],肌电[暴露前:(12±7)μV;暴露后:(14±10)μV]及皮肤导电性[暴露前:(6.8±4.3)μS;暴露后:(7.4±4.3)μS]均增加(P<0.01).(2)线索暴露中的脑电各项指标[δ波、θ波、α波、感觉运动节律(SMR)、低β波和高β波的百分率]均低于诱发前(P<0.01～0.05).(3)心理渴求变化与脑电θ波、α波和SMR呈负相关(相关系数为-0.13、-0.12和-0.12);除肌电、δ波外,上述各电生理指标与皮肤导电性之间呈负相关(Pearson相关系数为-0.18～-0.22);余各项指标间呈正相关.结论 海洛因依赖者暴露在吸毒相关环境时,诱发心理渴求反应增强,并引起多项神经电生理指标的变化.     

Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study

In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two (18)F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order--one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.