LC-ACC interactions supporting adaptive, feedback-driven decisions

项目总结/摘要 我们的长期目标是了解大脑如何在一个灵活的、依赖于上下文的环境中处理信息。 支持有效决策的方式。许多以前的决策研究集中在如何 大脑积累用于选择特定动作的证据，这表明涉及对 个体感觉运动神经元的持续活动，为适当的动作做准备。然而，大脑 还必须经常以灵活的方式在各种行动中积累证据，对此知之甚少。我们 建议要求灵活积累跨行动反馈相关证据的决策 取决于前扣带皮层（ACC），内侧上的皮质结构之间的相互作用 每个大脑半球的表面与大脑的其他部分有广泛的连接， 脑干蓝斑核（LC），是神经调质去甲肾上腺素的主要来源 (NE)大脑的其他部分。ACC和LC有很强的相互联系，并被认为是相互作用的 支持认知的关键特征，包括自适应信息处理，但 这些相互作用还没有被很好地理解。我们的主要假设是，这些相互作用调节活动 ACC神经元群体的模式实现了跨试验证据积累的过程， 使用奖励和错误反馈来管理改变行为选择的决定。我们特别 有兴趣了解这些调节如何与ACC中协调变异的变化相关， 对神经群体如何处理信息有重大影响。为了验证这个假设，我们使用 同时，互补测量来自单个神经元和神经元群体的神经元活动， 在两个任务的背景下，这两个大脑区域需要不同形式的跨试验积累， 反馈信息以指导扫视决策。我们有三个具体目标。目标1是了解如何 LC中单个神经元的活动模式与这些任务的表现有关。目标2：了解 LC和ACC中神经元活动模式之间的关系如何与这些任务的表现相关。 目的3是使用操作的组合来识别时间上精确的因果贡献， 从LC到ACC的特定活动模式对任务绩效的影响。这些目标将提供新的 机械和计算的见解如何LC相关的调节ACC人口活动的支持 ACC在灵活连接多项试验的性能监测和控制方面的作用。我们的调查结果 与研究领域标准（RDoC）框架中的许多结构直接相关，因此具有 广泛的意义领域，旨在了解复杂行为的神经基板及其 某些精神障碍的功能障碍。

PROJECT SUMMARY/ABSTRACT Our long-term goal is to understand how the brain processes information in a flexible, context-dependent manner to support effective decision-making. Many previous studies of decision-making focused on how the brain accumulates evidence used to select a particular action, which was shown to involve modulations of persistent activity of individual sensory-motor neurons that prepare the appropriate action. However, the brain must also often accumulate evidence in a flexible manner across actions, about which little is known. We propose that decisions requiring the flexible accumulation of feedback-related evidence across actions depends on interactions between the Anterior Cingulate Cortex (ACC), a cortical structure on the medial surface of each cerebral hemisphere that has widespread connectivity with other parts of the brain, and the brainstem nucleus locus coeruleus (LC), which is the primary source of the neuromodulator norepinephrine (NE) to the rest of the brain. The ACC and LC have strong, reciprocal connections and are thought to interact in ways that support key features of cognition, including adaptive information processing, but the details of these interactions are not well understood. Our primary hypothesis is that these interactions modulate activity patterns of populations of ACC neurons that implement a process of across-trial evidence accumulation that uses reward and error feedback to govern decisions to switch behavioral choices. We are particularly interested in understanding how these modulations relate to changes in coordinated variability in ACC that can have major effects on how neural populations process information. To test this hypothesis, we use simultaneous, complementary measurements of neuronal activity from single and populations of neurons from the two brain areasin the context of two tasks that require different forms of across-trial accumulation of feedback information to guide saccadic decisions. We have three Specific Aims. Aim 1 is to understand how activity patterns of individual neurons in the LC relate to performance on these tasks. Aim 2 is to understand how relationships between neuronal activity patterns in the LC and ACC relate to performance on these tasks. Aim 3 is to use a combination of manipulations to identify causal contributions of temporally precise, pathway specific activity patterns from LC to ACC on task performance. Together these Aims will provide new mechanistic and computational insights into how LC-related modulations of ACC population activity support ACC's role in flexibly linking performance monitoring and control across multiple trials. Our findings will have direct relevance to numerous constructs in the Research Domain Criteria (RDoC) framework and thus have broad significance to fields that aim to understand the neural substrates of complex behaviors and their dysfunction in certain mental disorders.