Neurocomputational mechanisms of explore-exploit decision making in prefrontal and motivational neural circuits

前额叶和动机神经回路探索利用决策的神经计算机制

• 批准号: 10442437
• 负责人: VINCENT D COSTA
• 金额: $ 75.77万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442437
• 关键词: Amygdaloid structure; Animals; Anterior; Attenuated; Behavior; Behavioral; Brain; Brain region; Code; Computer Models; Conditioned Reflex; Data; Decision Making; Desire for food; Disease; Equilibrium; Feedback; Goals; Grant; Human; Lead; Learning; Lesion; Location; Macaca mulatta; Mental disorders; Modeling; Monkeys; Motivation; Neurons; Nucleus Accumbens; Outcome; Pathway interactions; Pattern; Personal Satisfaction; Population; Prefrontal Cortex; Primates; Process; Psychiatry; Quality of life; Research; Rewards; Signal Transduction; Testing; Time; Training; Uncertainty; arm; base; cognitive control; experience; flexibility; neural circuit; neuromechanism; novel; relating to nervous system; willingness

Project Summary The explore-exploit dilemma refers to the challenge of deciding when to forego choices with known consequences to explore new opportunities and learn more about them. Managing this trade-off is a fundamental component of behavioral flexibility. Excessive exploration or exploitation impedes learning and results in poor choices leading to undesired outcomes. Explore-exploit decision making is understudied in psychiatry despite its ecological validity and relevance in understanding disorders characterized by inflexible behaviors. One reason for this is we have not identified if the brain encodes information relevant for managing explore-exploit tradeoffs differently when exploration is motivated by either appetitive or aversive consequences. Another reason is that while there is evidence in humans that frontopolar cortex—the most anterior part of prefrontal cortex which is unique to primates—implements decisions to explore new opportunities, the neural mechanisms underlying changes in frontopolar activity that prompt exploration are unclear. Neurons in the orbitofrontal cortex, basolateral amygdala, and nucleus accumbens encode value signals that inform explore-exploit decisions. This suggests a more dynamic interplay between frontopolar cortex and motivational brain regions during explore- exploit decision making than is currently hypothesized. This proposal tests the hypothesis that frontopolar cortex implements decisions to explore, but is reliant on appetitive and aversive value signals computed in motivational neural circuits to balance exploration and exploitation. We predict that bottom-up feedback to frontopolar cortex from brain regions classically associated with signaling reward value is critical for balancing exploration and exploitation. In Aim 1 we will test if monkeys explore more often when choices in a multi-arm bandit task are associated with gains or losses, and use computational modeling of choices to define valence dependent differences in their willingness to explore. In Aim 2 we will simultaneously record neural activity in frontopolar and orbitofrontal cortex, basolateral amygdala, and nucleus accumbens to determine if bottom-up information flow from motivational brain regions to frontopolar cortex predicts decisions to explore or exploit, and if exploratory choices are encoded differently when exploration is motivated by gains versus losses. In Aim 3 will use pathway-specific chemogenetics to excite or inhibit basolateral amygdala neurons that project to the nucleus accumbens, while recording neural activity in the nucleus accumbens and frontopolar cortex. We will to test the prediction that excitation of this pathway increases exploitation due to heightened encoding of exploitative signals in nucleus accumbens and decreased encoding of exploration signals in frontopolar cortex. Upon completion of these aims, we will understand how imbalances in explore-exploit decision making emerge in different psychiatric disorders based on the integrity of prefrontal cortex and motivational circuits.

项目摘要 探索-利用困境指的是在已知的情况下决定何时放弃选择的挑战 探索新的机会，并了解更多关于他们的后果。管理这种权衡是一个基本的 行为灵活性的一部分。过度的探索或开发会阻碍学习，导致学习效果不佳。 选择导致不希望的结果。探索-利用决策在精神病学中研究不足， 它在理解以僵化行为为特征的疾病方面的生态有效性和相关性。一个原因 因为我们还没有确定大脑是否编码了与管理探索-利用权衡相关的信息 当探索的动机是欲望或厌恶的结果时，情况就不同了。另一个原因是 虽然有证据表明，人类的额极皮层-前额叶皮层的最前部， 这是灵长类动物所独有的--执行探索新机会的决定， 促使探索的额极活动的变化尚不清楚。眶额皮层的神经元， 基底外侧杏仁核和脑桥核编码告知探索-利用决策的价值信号。这 表明在探索过程中，额极皮层和动机脑区域之间存在更动态的相互作用， 利用决策比目前假设的。这个提议验证了额极皮层 实施决策探索，但依赖于在动机计算的欲望和厌恶的价值信号 平衡探索和开发的神经回路我们预测，自下而上的反馈到额极皮层 从大脑区域典型地与信号奖励价值是至关重要的平衡探索， 剥削在目标1中，我们将测试当多臂强盗任务中的选择是 与收益或损失相关，并使用选择的计算建模来定义效价依赖 他们探索的意愿不同。在目标2中，我们将同时记录额极神经活动， 和眶额皮质、基底外侧杏仁核和脑桥核来确定自下而上的信息 从动机脑区到额极皮层的流动预测了探索或利用的决定，如果 当探索的动机是收益与损失时，探索性选择的编码不同。目标3将 使用通路特异性化学遗传学来刺激或抑制投射到核的基底外侧杏仁核神经元 同时记录下丘脑核和额极皮质的神经活动。我们将测试 预测该途径的激发由于剥削信号的增强编码而增加剥削 额极皮质探测信号编码减少。完成后 这些目标，我们将了解探索-利用决策的不平衡如何出现在不同的精神病患者中， 基于前额叶皮层和动机回路完整性的疾病。