Multi-scale Orbitofrontal Networks Underlying Reward Processing

 描述(申请人提供)：在物质滥用障碍，渴望和复发可能会发生，即使在长期戒断，对成功的长期治疗构成了一个关键的挑战。当支持基于奖励的学习和决策的大脑回路将任意提示与药物的行为强化效果联系起来时，这些现象就会出现。眼眶前额叶皮质是做出基于奖励的决策的关键区域，与成瘾有很大关系。到目前为止，我们已经知道，眼眶额叶皮质编码了预测的奖励的主观价值，但眼眶额叶网络使用价值信息来通知学习和选择的确切机制仍不清楚。一种理论认为，眼眶前额叶神经元将多个输入结合在一起，包括计算抽象值的感觉信息，因此刺激信息以自下而上的方式对眼眶前额叶值进行编码。另一种观点认为，眼眶前额叶皮质做出与价值相关的预测，以自上而下的方式影响下游的刺激表示。至关重要的是，这两种说法都预测到，眶前叶神经元编码的是价值信息；区别在于这些信息在网络层面上是如何使用的。在这里，我们将研究刺激值是如何在局部眼眶前额网络和更广泛的功能电路中处理的。为了评估局部网络属性，我们将在清醒的猴子执行奖励偏好任务时使用急性神经生理学方法。我们将同时记录单个神经元和局部场电位，它们被认为是反映潜在网络水平功能的信号，并专注于局部场电位的时空动态，以及它们与值编码神经元的关系。为了评估大规模的功能网络，我们将记录接受颅内监测的人类患者的大脑皮质电(ECoG)信号，为癫痫手术做准备。患者将接受强化学习任务的测试，同时我们从处理学习任务中使用的刺激的眼眶额叶皮质和解剖连接的感觉区域进行记录。在学习过程中，我们将确定眼眶额值表征如何与感觉刺激表征相互作用。总体而言，这项工作将使用翻译方法来确定眼眶前额叶价值编码如何与多个尺度上的网络水平活动相关，这可能会导致针对异常奖赏加工条件的新治疗方法，如成瘾障碍。此外，这项提议还提供了突出的培训潜力。我将受益于两位老牌导师的专业知识：沃利斯博士专门研究非人类灵长类神经生理学，张博士是神经外科医生和研究员，专门研究人类患者的脑功能图和皮层脑电图。他们的培训将帮助我建立一个独立的研究项目，将多种方法结合起来，了解奖励处理如何影响学习、记忆和决策等高级认知能力。

 DESCRIPTION (provided by applicant): In substance abuse disorders, cravings and relapses can occur even after long periods of abstinence, posing a key challenge for successful long-term treatment. These phenomena arise when brain circuits that support reward-based learning and decision-making associate arbitrary cues with behaviorally reinforcing effects of drugs. The orbitofrontal cortex is a region crucial to reward-based decision-making, and has been strongly implicated in addiction. To date, it is known that the orbitofrontal cortex encodes the subjective value of predicted rewards, but the precise mechanism by which orbitofrontal networks use value information to inform learning and choice remains unclear. One theory suggests that orbitofrontal neurons combine multiple inputs, including sensory information to compute an abstract value, so that stimulus information contributes to orbitofrontal value coding in a bottom-up fashion. Another view holds that orbitofrontal cortex makes value-related predictions that influences downstream stimulus representations in a top-down fashion. Crucially, both accounts predict that orbitofrontal neurons encode value information; the distinction lies in how that information is used at a network level. Here, we will investigate how stimulus values are processed in both local orbitofrontal networks and broader functional circuits. To assess local network properties, we will use acute neurophysiology approaches in awake, behaving monkeys as they perform a reward preference task. We will record both single neurons and local field potentials, signals believed to reflect underlying network-level function, and focus on spatiotemporal dynamics in local field potentials, and their relationship to value-encoding neurons. To assess large-scale functional networks, we will record electrocorticography (ECoG) signals from the brains of human patients undergoing intracranial monitoring in preparation for epilepsy surgery. Patients will be tested in a reinforcement-learning task, while we simultaneously record from orbitofrontal cortex and anatomically linked sensory areas that process the stimuli used in the learning task. Over the course of learning, we will determine how orbitofrontal value representations interact with sensory stimulus representations. Overall, this work will use translational approaches to determine how orbitofrontal value coding relates to network-level activity at multiple scales, which could lead to novel therapeutic approaches for conditions of aberrant reward processing, such as addiction disorders. In addition, this proposal offers outstanding training potential. I will benefit from the expertise of two established mentors Dr. Wallis who specializes in non-human primate neurophysiology, and Dr. Chang, a neurosurgeon and researcher specializing in functional brain mapping and ECoG in human patients. Their training will help me build an independent research program that combines multiple approaches to understand how reward processing impacts higher cognitive abilities such as learning, memory and decision-making.