个体冲动性对物质滥用与成瘾的影响及脑机制

冲动性是一多维的概念,一般指个体缺乏足够预见性或对自身的行为结果缺乏考虑和判断。个体冲动性和物质滥用与成瘾之间存在双重关系,即个体特质冲动性是物质滥用与成瘾的重要危险因素,而滥用成瘾性物质又会进一步损害个体的冲动控制功能。本文将论述个体冲动性和物质滥用与成瘾之间的相关性及冲动性增加潜在的神经机制。了解个体的冲动特质和物质滥用与成瘾者冲动性的改变,研究物质滥用与成瘾者冲动障碍的神经生物学机制,不仅有助于我们揭示物质滥用与成瘾的发生、发展,以及脱毒后复发的脑机制,而且有助于我们探索药物疗法以外的行为干预手段。     

药物成瘾者决策缺陷的特征、机制及干预

药物成瘾者存在决策缺陷, 并表现出冲动性、风险寻求、奖赏失调、躯体内感信号缺失等特征。神经影像学研究表明药物滥用导致成瘾者背外侧前额皮层、前扣带回、眶额叶皮层、腹内侧前额皮层、杏仁核、脑岛等脑区受损, 这些损伤是引发其决策缺陷的主要原因。认知训练有利于提高个体的决策能力, 如目标管理训练和正念冥想等可以增强个体工作记忆、促进自我觉察和以目标为导向的行为; 而非侵入性脑刺激则可以直接改变与成瘾者决策相关脑区的激活状态, 从而提升与决策相关的认知功能。总体而言, 未来认知训练和非侵入性脑刺激在成瘾干预方面仍有广阔的拓展空间。     

冲动性对不同成瘾行为发展的调控及其神经机制

近年来越来越多的研究证据提示, 个体冲动性在成瘾疾患发生发展机制中具有关键作用, 可能成为成瘾行为的潜在易感标记以及早期识别和干预的重要靶点, 但冲动性对不同成瘾行为变化发展的调控机制尚不明确。项目拟综合跨成瘾谱系比较、纵向追踪设计、冲动行为干预等研究途径, 采用人格测量、神经认知、神经影像等技术, 首先比较尼古丁依赖者与网络游戏成瘾者的冲动性结构及其在前额叶–纹状体环路的结构功能改变; 然后采用混合分组设计筛选出具有高低冲动性的非成瘾青少年进行连续追踪研究, 考察冲动性对尼古丁依赖与网络游戏成瘾的预测效力; 并采用认知行为训练, 对吸烟成瘾者与网络游戏成瘾者进行冲动干预, 考察行为干预对冲动性水平及前额叶–纹状体环路功能的改变, 以及对不同成瘾行为发展的抑制后效。旨在探索冲动性作为成瘾的潜在易感标记及干预靶点的效力。     

长期戒断海洛因成瘾者冲动性相关脑区的结构及功能特征

冲动性是药物成瘾者的典型特征, 它既包含了抑制控制成瘾者药物使用的力量, 也包含驱动成瘾者使用药物的成分, 两者不平衡导致冲动性用药行为。海洛因成瘾者本身具有冲动性人格特质, 长时间的海洛因使用又会造成成瘾者冲动性相关的大脑结构与功能的异常。目前难以确定戒断后, 冲动性及相关的大脑结构与功能是否还呈异常状态。本研究采用基于体素的形态学分析、低频振幅、局部一致性和功能连接方法, 以35例海洛因成瘾戒断者和无任何成瘾史的健康个体26人为研究对象, 探索在长期戒断后, 海洛因成瘾者与其冲动性相关的驱动、控制系统脑网络的结构和功能情况。结果显示, 相比对照组, 戒断组灰质总体积及右内侧额上回的灰质体积显著减小, 右侧颞中回和左内侧旁扣带回的灰质体积随用药总量的增加而降低; 右侧眶部额下回与尾状核功能连接显著增强, 右侧颞中回和左侧中央前回功能连接显著降低; 右眶额中回的ReHo值、右眶额下回和左海马体的ALFF值比对照组显著更低, 而右中央后回的ReHo值显著更高。这些脑区的状况与冲动性的神经基础相吻合, 说明海洛因成瘾戒断者在戒断44个月, 奖赏、凸显、习惯性行为等网络系统仍然呈现异常状态, 且与成瘾药物使用总量有关。这些异常可能是成瘾冲动性的驱动力的神经基础, 可以作为解释成瘾者戒断后容易复吸的因素之一。     

冲动还是习惯?成瘾不同阶段中冲动性的性质与机制

冲动性是一种缺乏充分思考、不顾后果的冒险行为或行为倾向, 它既表现在人格特质中, 也会表现为各类环境中的行为。成瘾者具有典型的冲动性特征, 但成瘾者的冲动性是如何影响和促进成瘾行为的发生、发展, 目前还并不明朗。从成瘾形成的不同阶段, 也许可以对此有更进一步的了解。在药物使用的开始阶段, 冲动性人格特质作为动机原因, 促进成瘾物质的首次使用; 接着操作性条件学习导致用药者进入“目标-导向”阶段, 呈现出选择冲动性。第三阶段, 经典条件学习又使相关线索和药物效应不断匹配, 形成条件反射性药物使用行为。成瘾者进入习惯性用药阶段, 表现出显著的停止冲动性。     

时间洞察力对成瘾行为的影响及其机制

成瘾行为给个体和社会带来了严重的危害。对成瘾人群时间洞察力的研究成为探讨成瘾行为产生和发展的一个新的视角。过去消极、现在享乐和现在宿命时间洞察力取向的个体更可能出现成瘾行为, 而未来时间洞察力取向则是成瘾行为的一个保护性因素, 它不仅可以减少成瘾行为的发生, 也有利于成瘾行为的康复。从自我调节, 冲动性决策等行为机制和前额叶的神经机制方面可以帮助我们深入理解时间洞察力对成瘾行为的影响。未来研究可以进一步探讨不同成瘾行为者时间洞察力的一致性与特异性; 采用纵向研究方法探讨成瘾者时间洞察力的动态变化过程; 对成瘾者的洞察力进行干预, 增加成瘾者的未来时间洞察力, 减少其过去消极和现在时间洞察力取向来帮助成瘾者实现时间洞察力的平衡, 从而提高其戒断效果。     

大脑皮层-背侧纹状体通路在吗啡强迫性觅药和用药行为中的作用

药物成瘾是以强迫性觅药和用药行为为核心特征的慢性脑疾病。从初始用药到强迫性用药是成瘾者的觅药行为从目标导向性向习惯化发展的过程。强迫性觅药和用药行为是依赖于背外侧纹状体的习惯化行为, 同时前额叶皮层-背内侧纹状体通路对行为的控制减弱, 导致感觉运动皮层-背外侧纹状体通路对行为的控制持续占主导地位, 是成瘾行为具有强迫性特征的重要神经基础。本项目围绕这一重要问题展开研究, 在建立具有成瘾特征的动物模型的基础上, 采用行为学、行为药理学和组织形态学等方法揭示皮层-纹状体通路在强迫性觅药和用药行为中的作用。研究结果有望为进一步寻找该神经网络参与成瘾行为的分子机制提供重要线索。     

反馈相关负波与成瘾

反馈相关负波(feedback-related negativity, FRN)是反馈加工诱发的脑电成分, 体现了个体对奖赏的敏感性。成瘾分为物质成瘾和行为成瘾, 两类个体的反馈加工都呈现病理性模式。相对于普通反馈物(如金钱), 物质成瘾个体在加工成瘾物质时诱发的FRN波幅显著增大; 在与非成瘾被试的对照研究中, 物质成瘾者加工金钱反馈时的FRN也表现出与成瘾相关的异常模式; 在行为成瘾个体中亦观察到与物质成瘾个体类似的FRN失调现象。但以往多数研究中对成瘾类型的区分还不够详细, 未来研究应进一步考虑成瘾不同亚型的特点; 且成瘾个体往往伴随其他精神障碍(如抑郁、焦虑), 将来的研究要区分共病因素的影响, 揭示成瘾独特的奖赏加工机制问题。     

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。     

毒品成瘾者情绪加工及应对方式的特点:基于负性情绪的视角

负性情绪是导致个体毒品成瘾及复吸的主要心理因素。毒品成瘾者在情绪加工过程中会夸大负性刺激,产生负性化偏向,提高负性情绪的唤醒度,最终导致其产生更多负性情绪体验。而当毒品成瘾者体验到诸如焦虑、抑郁、压力等负性情绪时,他们却更倾向于使用毒品来缓解或逃避负性情绪带来的不愉快体验。研究表明,毒品成瘾者这种负性情绪加工异常的根本原因在于长期毒品滥用所导致的个体大脑情绪回路相关脑区的受损,如杏仁核、海马、额叶等。未来研究应更进一步探讨成瘾者负性情绪加工与毒品成瘾之间的关系;并对戒断者在负性情绪加工能力的恢复方面做进一步探索,开展更多的关于如何改善成瘾者及戒断者对负性情绪应对方式的研究,从而更为有效抑制个体对毒品形成的心理依赖及强迫的药物渴求行为。     

Valence specific response reversal deficits and risk for mania

Response reversal deficits are well documented in bipolar disorder (BD). Although frequently construed as an index of reward processing abnormalities, these response reversal deficits might simply result from more general cognitive inflexibility. Given that both are implicated in BD, our goal was to more carefully test whether reversal learning deficits are specific to reward processing or reflect more general cognitive inflexibility. To more carefully assess deficits, a novel variant of the response reversal task was used to separate responses to in reward versus punishment feedback. In addition, while response reversal deficits are well documented in BD, it is still unknown if these deficits are observable in people at risk for the disorder, whose performance would be unconfounded by medication use and illness course. To assess the presence of premorbid response reversal deficits, we tested students at risk for developing BD, as defined by the well-validated Hypomanic Personality Scale. Undergraduates (n?=?99) were randomly assigned to complete either a reward only or a punishment only version of a response reversal task. Mania risk was related to difficulty reversing responses following reward, but not punishment feedback. Findings suggest that a deficit in response reversal may be an index of reward dysregulation in BD, and that this deficit can be observed even in those at high risk for the development of BD.     

Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats

Drug addicts make poor decisions. These decision-making deficits have been modeled in addicts and laboratory animals using reversal-learning tasks. However, persistent reversal-learning impairments have been shown in rats and monkeys only after noncontingent cocaine injections. Current thinking holds that to represent the human condition effectively, animal models of addiction must utilize self-administration procedures in which drug is earned contingently; thus, it remains unclear whether reversal-learning deficits caused by noncontingent cocaine exposure are relevant to addiction. To test whether reversal learning deficits are caused by contingent cocaine exposure, we trained rats to self-administer cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30 d of withdrawal, and then tested for reversal learning more than a month later. We found robust time-dependent increases in cue-induced cocaine seeking in the two extinction tests (incubation of craving) and severe reversal-learning impairments.     

Aging affects acquisition and reversal of reward-based associative learning

Reward-based associative learning is mediated by a distributed network of brain regions that are dependent on the dopaminergic system. Age-related changes in key regions of this system, the striatum and the prefrontal cortex, may adversely affect the ability to use reward information for the guidance of behavior. The present study investigated the effects of healthy aging on different components of reward learning, such as acquisition, reversal, effects of reward magnitude, and transfer of learning. A group of 30 young (mean age = 24.2 yr) and a group of 30 older subjects (mean age = 64.1 yr) completed two probabilistic reward-based stimulus association learning tasks. Older subjects showed poorer overall acquisition and impaired reversal learning, as well as deficits in transfer learning. When only those subjects who showed evidence of significant learning were considered, younger subjects showed equivalently fast learning irrespective of reward magnitude, while learning curves in older subjects were steeper for high compared to low reward magnitudes. Acquired equivalence learning, which requires generalization across stimuli and transfer of learned contingencies to new stimuli, was mildly impaired in older subjects.     

网络成瘾者的行为冲动性——来自爱荷华赌博任务的证据

以84名大学生为被试(网络成瘾和对照组被试各42名),采用感觉寻求量表和爱荷华赌博任务(Iowa Gambling Task)范式比较两组被试在感觉寻求水平和决策行为反应模式方面的差异.结果发现,与对照组被试相比,网络成瘾者的感觉寻求总分和去抑制、厌恶单调及寻求激动和惊险三个分量表得分显著增加,在IGT任务中优先选择收益和惩罚频率高的不利扑克牌,其冒险的决策策略并没有随着决策次数的增加而改变.这表明网络成瘾者的决策功能受损并表现出“即时收益优先”的决策模式和对强化物潜在风险的高耐受性.     

The application of mindfulness-based cognitive interventions in the treatment of co-occurring addictive and mood disorders

This article reviews the theory, clinical application, and empirical findings on mindfulness-based cognitive therapy (MBCT) for mental health and addictive disorders. Expanding upon the research demonstrating the efficacy of cognitive-behavioral therapy (CBT) for addiction, this article develops and explores the rationale for combining mindfulness-based interventions with evidence-based CBTs in treating addictive disorders, with an emphasis on substance use disorders with co-occurring mood disorders. This article proposes that deficits in affect--regulation related to the behavioral and emotional effects of neurobiological changes that occur with long-term substance abuse--pose a unique set of challenges in early recovery. Prolonged use of addictive substances impairs the brain pathways that mediate certain affect regulation functions. These functions involve attention and inhibitory control, the saliency of and response to addictive versus natural reward stimuli, and the ability to detach or maintain perspective in response to strong emotional states. In treating this affective dysregulation, which can contribute to the vulnerability to relapse in the early stages of recovery, the affect-regulation-specific focus of MBCT adds a valuable element to augment CBT for addiction. Summarizing magnetic resonance imaging and positron emission tomography findings on the effects of MBCT and the neurobiology of drug addiction, this article outlines directions for further research on potential benefits of MBCT for the recovering individual. Finally, this article describes a structured protocol, developed at the Mount Sinai School of Medicine in New York City, which combines CBT with mindfulness-based intervention, for the treatment of affect-regulation issues specific to co-occurring addictive and mood disorders.     

Touch screen assays of behavioural flexibility and error characteristics in Eastern grey squirrels (<Emphasis Type="Italic">Sciurus carolinensis</Emphasis>)

Behavioural flexibility allows animals to adjust their behaviours according to changing environmental demands. Such flexibility is frequently assessed by the discrimination–reversal learning task. We examined grey squirrels’ behavioural flexibility, using a simultaneous colour discrimination–reversal learning task on a touch screen. Squirrels were trained to select their non-preferred colour in the discrimination phase, and their preferred colour was rewarded in a subsequent reversal phase. We used error rates to divide learning in each phase into three stages (perseveration, chance level and ‘learned’) and examined response inhibition and head-switching during each stage. We found consistent behavioural patterns were associated with each learning stage: in the perseveration stage, at the beginning of each training phase, squirrels showed comparable response latencies to correct and incorrect stimuli, along with a low level of head-switching. They quickly overcame perseveration, typically in one to three training blocks. In the chance-level stage, response latencies to both stimuli were low, but during initial discrimination squirrels showed more head-switches than in the previous stage. This suggests that squirrels were learning the current reward contingency by responding rapidly to a stimulus, but with increased attention to both stimuli. In the learned stage, response latencies to the correct stimulus and the number of head-switches were at their highest, whereas incorrect response latencies were at their lowest, and differed significantly from correct response latencies. These results suggest increased response inhibition and attention allowed the squirrels to minimise errors. They also suggest that errors in the ‘learned’ stage were related to impulsive emission of the pre-potent or previously learned responses.     

物质成瘾领域延迟折扣研究中的外部效度问题

物质成瘾者的跨期决策缺陷已被大量使用金钱延迟折扣任务的研究所证实。然而近年来, 来自金钱延迟折扣任务变式(成瘾物质延迟折扣任务、性延迟折扣任务和跨类别延迟折扣任务)的发现表明, 在物质成瘾领域的延迟折扣研究中单一使用金钱延迟折扣任务存在一定的局限性。首先, 物质成瘾者对金钱的延迟折扣水平可能并不能完全代表其对成瘾物质、性和其它自然奖赏的延迟折扣水平; 其次, 仅使用单一延迟折扣任务可能存在对物质成瘾者跨期决策过程的过度简化; 最后, 金钱延迟折扣任务较其变式对物质成瘾者的一些临床特征不够敏感。未来研究应进一步丰富、拓展物质成瘾领域的跨类别延迟折扣研究, 并对可能影响跨期决策的时间因素进行深入探索。