强迫性特征在药物成瘾行为中的易感性及其前额叶-反奖赏系统神经基础

强迫性是一种与不顾严重后果的固着行为密切相关的神经心理结构, 大脑神经系统对强迫性行为的调控机制崩溃是导致药物成瘾的直接原因。以往研究对于奖赏系统(中脑-皮层-边缘神经环路)在成瘾行为中的作用及机制已经具有丰富的了解, 但针对药物成瘾的强迫性特征本身以及前额叶-反奖赏系统神经环路在成瘾行为中的作用机制了解有限, 尤其是缺乏对药物成瘾强迫性特征的系统考察、缺少遗传学研究以及非兴奋剂类药物的汇聚证据。项目拟结合人类成瘾行为的遗传学视角(海洛因成瘾者与其无药物使用的兄弟姐妹对照), 结合神经认知、脑电生理、神经影像等不同层面的方法和技术, 对药物成瘾强迫性的外在表征、神经生物学基础以及与个体差异有关的遗传易感性进行探索, 期在进一步识别药物成瘾的神经生物标记, 为探寻潜在的药物或非药物干预靶点提供更多证据。     

基于“相关线索-自动化用药行为”联结的成瘾记忆消退

成瘾记忆消退致力于消除成瘾者相关线索与药物奖赏效应的联结,以达到消除心理渴求、戒断成瘾行为的目的,但其效果还十分有限。最近,大量的动物和人类实验研究发现:在相关线索下,成瘾者的激活脑区不仅包括中脑边缘皮层-背内侧纹状体,还延伸到感觉运动脑区-背外侧纹状体。这意味着成瘾记忆中存在相关线索与自动化(习惯性)用药行为的联结。所以,与成瘾相关的记忆可能包含两种不同的成分:一是与药物奖赏效应相关的情绪记忆,另一种是与用药动作、技能有关的动作记忆(程序记忆)。由于在成瘾阶段,药物奖赏效应对药物使用和复发的作用已经相对减少,因此,针对成瘾记忆的消退训练,以相关线索与自动化用药行为的联结为标靶,可能可以取得更好的效果,值得做进一步的深入探索。     

成瘾人群的决策障碍：研究范式与神经机制

药物成瘾者和赌博成瘾者常常偏好即刻的奖赏而忽视将来的消极结果。在进行决策任务时, 他们倾向于做出不利的选择, 偏好短时的获益而不顾长期的损失, 这是一种决策障碍的表现。延迟折扣任务(DDT)、爱荷华赌博任务(IGT)和剑桥赌博任务(CGT)是研究决策障碍的三种常用方法和范式, 分别考察成瘾人群的冲动性决策、决策短视和决策时的冒险行为。近十几年来的研究表明, 前额叶皮层(PFC)在人类的决策活动中起重要作用。其中, 腹内侧前额叶(VMPFC)、眶额叶(OFC)、背外侧前额叶(DLPFC)等皮层的功能变化与成瘾人群的决策障碍有密切关系。     

强迫症的脑功能障碍

近期,对强迫症(OCD)的现象学解释强调了病人在特定情境下错误识别和情绪与动机功能的异常加工。来自神经解剖、神经生理以及近期神经心理和功能成像等的相关研究证据显示：OCD病人眶额皮层（OFC）、前扣带回皮层（ACC）的过度激活可能会导致错误识别功能和对行为结果预期的情绪与动机评价增高;背外侧前额皮层(DLPC)的活动减弱损害了对信息加工的认知整合能力。以上这些皮层信号在控制行为活动程序的尾状核进行整合。OCD病人的强迫性观念和行为可能由这些结构相关的神经网络中一个或多个环节的功能障碍所致     

努力控制及其神经基础

本文对努力控制的概念、发展及其神经基础进行了归纳和总结。我们发现努力控制涉及的脑区主要包括背外侧和腹外侧前额叶,前扣带回,顶上和顶下小叶以及辅助运动皮层等。此外,通过分析对比后发现努力控制与执行功能之间在行为表现和神经基础上有密切关系：两者都与个体的学业成绩、情绪状态和攻击行为等有关;努力控制涉及的脑区有很大部分处于具有执行功能的突显网络和额顶控制网络。这些证据表明两者之间可能有共同的脑结构基础。     

物质成瘾及其戒除:基于反转学习的视角

物质成瘾与反转学习损伤密切相关,成瘾者往往不能灵活地适应变化的刺激—结果的联结,这可能进一步加剧成瘾者的物质使用。近年来研究发现,物质成瘾者的反转学习相关的腹外侧前额和背外侧前额等脑区激活异常,这些异常与成瘾者的冲动性和强迫性有关。此外,个体的反转学习能力对其成瘾行为具有一定预测性。今后应增加对不同类型物质成瘾者的反转学习脑机制及物质相关线索对成瘾者反转学习影响的研究,并且进一步探讨成瘾者的冲动性和强迫性对其反转学习的调节及个体反转学习能力对其成瘾行为的预测。     

药物成瘾的易感性生物标记：从神经认知到分子遗传的证据

药物成瘾作为一种慢性复发性的脑疾病,具有从偶然性用药、规律性用药到强迫性用药的渐进式发展特征。研究提示,药物成瘾存在潜在的个体易感性机制,即在成瘾发生过程中不同个体接触药物后的成瘾风险并不相同,探索药物成瘾的神经生物标记是揭示成瘾易感性机制的重要途径。近十多年来,关于成瘾易感性标记的研究不断积聚。文章从神经认知、神经影像及脑电生理、分子遗传等层面梳理与药物成瘾生物标记有关的证据,试图在基因-大脑-心理-行为的理论框架下,对成瘾的发生发展机制进行综合阐释,期望为未来研究在探索药物成瘾的候选神经生物标记、寻找临床干预试验的精准靶点等方面提供更多理论参考。     

经颅直流电刺激在抑郁症治疗中的应用

已有的神经影像学研究成果揭示, 抑郁症发作的重要原因之一是大脑前额叶皮层结构和功能受损。经颅直流电刺激(tDCS)作为一种无创脑刺激, 选取前额叶皮层作为刺激区域, 通过调节皮层兴奋性来治疗抑郁症, 能够有效缓解抑郁症状和改善受损的认知功能, 疗效明显且持久稳定。针对tDCS在抑郁症治疗研究中的问题, 未来可从有效性、个体差异以及预防干预等六个方面进一步研究, 以期tDCS作为一种具有潜力的治疗手段, 在临床上有更为广泛地应用。     

右侧背外侧前额叶在视觉工作记忆中的因果性作用

以往的影像学研究表明右侧背外侧前额叶皮层(DLPFC)在视觉工作记忆中发挥重要作用, 然而缺乏因果性的证据。本研究旨在考察右侧DLPFC的激活与视觉工作记忆容量的因果关系, 并探讨这一关系受到记忆负荷的调节及其神经机制。被试接受经颅直流电刺激之后完成视觉工作记忆变化检测任务, 根据被试在虚假刺激情况下从负荷4到负荷6任务记忆容量的增量将被试分为低记忆增长潜力组(简称低潜力组)和高记忆增长潜力组(简称高潜力组), 结果发现正性电刺激右侧DLPFC相对于虚假电刺激显著提升了高潜力组被试在低记忆负荷(负荷4)下的记忆容量及其对应的提取阶段的脑电指标SPCN成分。表明右侧DLPFC在视觉工作记忆的提取阶段发挥重要的因果性作用; 正性经颅直流电刺激右侧DLPFC可使工作记忆容量高潜力被试获得更多的脑活动增益, 并导致更好的行为提升效果。     

经颅直流电刺激在注意缺陷多动障碍治疗中的应用

经颅直流电刺激(tDCS)治疗注意缺陷多动障碍(ADHD)主要是选取患者的背外侧前额叶(DLPFC)作为刺激区域, 通过调节其皮层兴奋性, 从而缓解其ADHD的症状和改善其受损的认知功能。针对tDCS在ADHD治疗研究中的问题, 未来可从有效性、确定最佳刺激参数、个体差异、不同亚型及与其他疗法联合使用等五个方面来进一步研究。     

Making and breaking habits: Revisiting the definitions and behavioral factors that influence habits in animals

Habits have garnered significant interest in studies of associative learning and maladaptive behavior. However, habit research has faced scrutiny and challenges related to the definitions and methods. Differences in the conceptualizations of habits between animal and human studies create difficulties for translational research. Here, we review the definitions and commonly used methods for studying habits in animals and humans and discuss potential alternative ways to assess habits, such as automaticity. To better understand habits, we then focus on the behavioral factors that have been shown to make or break habits in animals, as well as potential mechanisms underlying the influence of these factors. We discuss the evidence that habitual and goal-directed systems learn in parallel and that they seem to interact in competitive and cooperative manners. Finally, we draw parallels between habitual responding and compulsive drug seeking in animals to delineate the similarities and differences in these behaviors.     

Curiosity adapted the cat: the role of trait curiosity in newcomer adaptation

Using longitudinal data from 123 newcomers across 12 telemarketing organizations, we examined the role of 2 forms of trait curiosity (specific and diversive) as antecedents of proximal adaptation behaviors (information seeking and positive framing) and more distal, in-role and extra-role behaviors (job performance and taking charge). Results suggest that specific curiosity predicts information seeking behaviors, whereas diversive curiosity promotes positive framing. Results also support the relationship between positive framing and performance and the extra-role behavior of taking charge. Overall, the study validates the role of curiosity as a multifaceted individual difference that serves as an antecedent to newcomer adaptation.     

Limbic-striatal memory systems and drug addiction

Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits. Such habits evolve through a cascade of complex associative processes with Pavlovian and instrumental components that may depend on the integration and coordination of output from several somewhat independent neural systems of learning and memory, each contributing to behavioral performance. Data are reviewed that help to define the influences of conditioned Pavlovian stimuli on goal-directed behavior via sign-tracking, motivational arousal, and conditioned reinforcement. Such influences are mediated via defined corticolimbic-striatal systems converging on the ventral striatum and driving habit-based learning that may depend on the dorsal striatum. These systems include separate and overlapping influences from the amygdala, hippocampus, and cingulate and medial prefrontal cortex on drug-seeking as well as drug-taking behavior, including the propensity to relapse.     

Does adolescent risk taking imply weak executive function? A prospective study of relations between working memory performance,impulsivity, and risk taking in early adolescence

Studies of brain development suggest that the increase in risk taking observed during adolescence may be due to insufficient prefrontal executive function compared to a more rapidly developing subcortical motivation system. We examined executive function as assessed by working memory ability in a community sample of youth (n = 387, ages 10 to 12 at baseline) in three annual assessments to determine its relation to two forms of impulsivity (sensation seeking and acting without thinking) and a wide range of risk and externalizing behavior. Using structural equation modeling, we tested a model in which differential activation of the dorsal and ventral striatum produces imbalance in the function of these brain regions. For youth high in sensation seeking, both regions were predicted to develop with age. However, for youth high in the tendency to act without thinking, the ventral striatum was expected to dominate. The model predicted that working memory ability would exhibit (1) early weakness in youth high in acting without thinking but (2) growing strength in those high in sensation seeking. In addition, it predicted that (3) acting without thinking would be more strongly related to risk and externalizing behavior than sensation seeking. Finally, it predicted that (4) controlling for acting without thinking, sensation seeking would predict later increases in risky and externalizing behavior. All four of these predictions were confirmed. The results indicate that the rise in sensation seeking that occurs during adolescence is not accompanied by a deficit in executive function and therefore requires different intervention strategies from those for youth whose impulsivity is characterized by early signs of acting without thinking.     

Behavior change after context disruption: Opportunities and pitfalls

Many behaviors are performed automatically in response to contextual cues rather than conscious intentions, which can make behavior change challenging. The combined discontinuity and self-activation hypotheses predict that disruption to a context that cues behaviors can provide opportunity for behavior change guided by intentions rather than contextual cues. In this study, we asked an online sample of participants (N = 452) to report on desired change in the frequency of new, unwanted, or potentially habitual behaviors following a contextual disruption due to the COVID-19 pandemic. We find a distinction between new ‘start’ behaviors and unwanted ‘stop’ behaviors where new behaviors appear more personally meaningful (i.e. higher in autonomous motivation and positive affective attitude) than unwanted or potentially habitual behaviors. Our results suggest that behavior change theory and interventions that acknowledge differential processes between starting new behaviors and stopping old unwanted behaviors would provide greater insights for behavior science.     

基于驱动与控制相互作用的成瘾冲动性结构与机制

物质成瘾者具有明显的冲动性特征, 表现为难以戒断的成瘾物质使用。这种行为的产生除了抑制控制的问题外, 源于多个维度的驱动力也是重要的原因。低弱的抑制力无法抵挡驱力的作用, 出现不平衡状态, 形成难以控制的渴求下的强迫性用药或习惯性用药行为倾向。驱动力来源于多方面, 奖赏效应, 通过条件作用形成的S-R式相关线索反应以及感觉寻求等人格特质; 控制成分则包括了反应抑制与无法延迟满足的执行控制功能。     

潜在冲突情境下7岁儿童的资源获得行为

采用实验室观察, 对7岁儿童(中国160人, 加拿大133人)在潜在冲突情境下的资源获得行为进行考察, 旨在比较中西文化背景下, 儿童资源获得行为上的差异及其背后的文化意义。结果表明：中国儿童的求助成人和给予行为显著多于加拿大儿童; 加拿大儿童的资源获得失败和为自己获得资源的频率显著高于中国儿童。果敢行为和轮流规则都是有效的资源获得方式; 请求行为则是无效的。求助成人是中国男孩获得资源的一种有效方式; 对加拿大儿童来说, 则是无效的。     

Immediate early gene activation in hippocampus and dorsal striatum: effects of explicit place and response training

Evidence from lesion, electrophysiological, and neuroimaging studies support the hypothesis that the hippocampus and dorsal striatum process afferent inputs in such a way that each structure regulates expression of different behaviors in learning and memory. The present study sought to determine whether rats explicitly trained to perform one of two different learning strategies, spatial or response, would display disparate immediate early gene activation in hippocampus and striatum. c-Fos and Zif268 immunoreactivity (IR) was measured in both hippocampus and striatum 30 or 90 min following criterial performance on a standard plus-maze task (place learners) or a modified T-maze task (response learners). Place and response learning differentially affected c-Fos-IR in striatum but not hippocampus. Specifically, explicit response learning induced greater c-Fos-IR activation in two subregions of the dorsal striatum. This increased c-Fos-IR was dependent upon the number of trials performed prior to reaching behavioral criterion and accuracy of performance during post-testing probe trials. Quantification of Zif268-IR in both hippocampus and striatum failed to distinguish between place and response learners. The changes in c-Fos-IR occurred 30 min, but not 90 min, post-testing. The synthesis of c-Fos early in testing could reflect the recruitment of key structures in learning. Consequently, animals that were able to learn the response task efficiently displayed greater amounts of c-Fos-IR in dorsal striatum.     

Cognitive Restructuring-Assistance in the Clinical Extinction of Fear and Avoidance

Abstract

Two case studies are presented in which the attempted extinction of negative reinforcement-maintained behavior was unsuccessful because clients were unable to completely stop avoiding the target situations. Clinical treatment was based on the hypothesis that a self-control deficit caused the problem behavior to be maintained because of partial negative reinforcement. In the first case, a male college student experienced considerable anxiety while urinating in public restrooms. He frequently avoided or escaped restrooms with people in them, thus causing a number of secondary problems. The second case was a college female who engaged in an obsessive-compulsive chain in which a catastro-phizing thought set the occasion for engaging in compulsive behavior. The compulsive behavior was taking up a large amount of her time. After unsuccessfully using therapeutic instructions designed to preclude avoidance, systematic cognitive restructuring was used as a way to increase the likelihood clients would follow instructions and discontinue avoidance behavior by decreasing the mediational control of negative and irrational verbal behaviors. Both cases showed that compliance with the extinction instructions was enhanced by combining cognitive restructuring with the treatment program.