Brain Imaging Studies of Negative Reinforcement in Humans

治疗毒瘾的一个主要挑战是了解获得性关联如何与厌恶的强化剂 促进回避行为，并引发药物使用的开始和复发。对非人类动物的研究 开始阐明回避学习的神经行为机制，但很少有人努力 将这些发现转化为人类群体。支持长期的神经再生脑机制 记忆的形成被认为是为了改变刺激的表征并加强语境 关联作为其激励属性的函数。建议的研究采用了认知神经科学。 描述人类动机脑系统如何调节陈述性记忆形成的观点 并导致行为回避。尽管人类的陈述性记忆传统上是使用列表- 学习范式、计算机图形界面和沉浸式虚拟现实(VR)的最新进展 技术允许开发新的导航回避任务，提供与 动物文献和更接近真实世界的模型吸毒者的逃避行为作为回应 对环境压力的影响。健康的参与者将接受一系列的功能性磁共振 在传统的列表学习和新颖的背景下呈现强化刺激的成像研究 基于VR的导航学习和记忆任务。第一系列实验比较了 陈述性记忆系统上的食欲和厌恶的工具性强化。第二个系列 实验确定了负面情绪状态如何放大激励属性的助记效应 作为情绪修复的一种形式，工具性的增强剂和激励寻求奖励(“解脱”)。第三个系列 实验开发了一种多感官、身临其境的VR范例，模拟压力诱导的回避和 逃避一项结合了导航和列表学习方法的自然记忆任务。功能性 连通性建模与多重回归和独立分量分析相结合，将 描述动机和记忆系统的相互作用及其与个体的关系 行为表现指数和回避特质指标的差异。因此，拟议的研究 代表了一种系统和创新的人类回避学习方法，结合了尖端的VR 技术和功能神经成像方法。这项研究结果将弥补在翻译方面的差距 了解积极的增强剂、情绪状态和压力源如何改变厌恶行为的影响 对学习和记忆系统的影响，帮助建立显著特征的内部地图 环境。

A major challenge to treating drug addiction is understanding how learned associations to aversive reinforcers promote avoidant behavior and trigger the onset and relapse of drug use. Studies in non-human animals have begun to elucidate the neurobehavioral mechanisms of avoidance learning, but there have been few efforts to translate these findings to human populations. Neuroplastic brain mechanisms that support long-term memory formation are hypothesized to alter the representations of stimuli and strengthen contextual associations as a function of their incentive properties. The proposed research adopts a cognitive neuroscience perspective to characterize how motivational brain systems modulate declarative memory formation in humans and lead to behavioral avoidance. Although human declarative memory is traditionally probed using list- learning paradigms, recent advances in computer graphics interfaces and immersive virtual reality (VR) technology permit the development of novel navigational avoidance tasks that provide a tighter link with the animal literature and more closely model real-world avoidant behaviors exhibited by drug addicts in response to environmental stressors. Healthy participants will undergo a series of functional magnetic resonance imaging studies that present reinforcing stimuli within the context of both traditional list-learning and novel VR-based navigational learning and memory tasks. The first series of experiments compares the influence of appetitive versus aversive instrumental reinforcers on declarative memory systems. The second series of experiments determines how negative mood states amplify the mnemonic effects of the incentive properties of instrumental reinforcers and motivate reward-seeking ("relief") as a form of mood repair. The third series of experiments develops a multisensory, immersive VR paradigm that simulates stress-induced avoidance and escape on a naturalistic memory task that combines navigational and list-learning approaches. Functional connectivity modeling, in combination with multiple regression and independent components analyses, will characterize the interactions of motivational and memory systems and their relationship to individual differences in behavioral performance indices and trait markers of avoidance. The proposed studies thus represent a systematic and innovative approach to human avoidance learning that combines cutting-edge VR technology and functional neuroimaging methods. The research findings will bridge a translational gap in understanding how positive reinforcers, mood states, and stressors modify the impact of aversive behavioral consequences on learning and memory systems that help establish internal maps of salient features of the environment.