Neural representation of reward in frontal cortex

描述（由申请人提供）：选择行为背后的神经机制对于理解成瘾很重要，成瘾的一个特征是无法控制选择。额叶对选择行为至关重要，因为对这一区域的损伤会导致决策的特定障碍。额叶的两个区域特别令人感兴趣：前扣带皮层（ACC）和眶额皮层（OFC）。需要决策和选择行为的任务始终激活这两个区域，这两个区域都包含编码与选择方案价值相关的各个方面的神经元。此外，ACC和OFC都参与成瘾：成瘾者在这两个领域表现出结构和功能的变化。然而，我们对每个区域独立地对选择行为过程做出的贡献知之甚少。为了确定这一点，我们将使用神经生理学技术，同时记录从两个领域，而受试者从事的任务，旨在涉及ACC或OFC。我们将比较和对比ACC和OFC神经元的功能特性。我们的目的是通过提供对这两个区域在成瘾中所起作用的更深入的理解，来分离这两个区域的功能。选择行为的理论框架强调了两个必须发生的过程。首先，个体必须预测选择任一选项的可能结果。其次，个人必须评估预测的结果，以确定哪个更有价值。ACC和OFC的解剖结构表明这两个区域对这些过程的贡献不同。ACC和OFC都与负责处理与奖励相关信息的领域相联系。然而，ACC与运动区的联系很强，而与感觉区的联系很弱，而OFC则表现出相反的模式。因此，我们将检验的第一个假设是，ACC神经元预测与不同行为反应相关的结果，而OFC神经元预测与环境刺激相关的结果。我们将通过记录任务期间ACC和OFC神经元的活动来测试这一假设，其中受试者必须基于反应-结果或刺激-结果关联来进行选择。我们要检验的第二个假设是，ACC而不是OFC评估了获得回报所需的努力量。我们将通过对比ACC和OFC神经元在一项任务中的编码来测试这一假设，该任务要求我们的受试者将结果的价值（我们通过改变果汁奖励的大小来操纵）与获得结果所需的努力（我们使用受试者必须按下的扭矩可调节杠杆来操纵以获得奖励）进行整合。概括起来，我们的具体目标如下：1.确定ACC和OFC的预测结果与反应或刺激分别2的过程中的贡献。确定行政协调会和竞争事务办公室对评估基于努力的选择的贡献 公共卫生相关性：该项目的重点是前扣带皮层（ACC）和眶额皮层（OFC），这两个大脑区域显示了吸毒成瘾者的结构和功能变化。我们将在两个任务中记录这两个区域的神经元的电活动，这两个任务旨在对选择行为的不同方面进行征税。成瘾的特点是难以控制选择行为，因此了解这一过程的生理基础可以让我们开发治疗成瘾行为的新治疗策略。

DESCRIPTION (provided by applicant): The neural mechanisms underlying choice behavior are important for understanding addiction, a characteristic of which is a failure to exert control over choices. The frontal lobe is critical to choice behavior since damage to this region produces specific impairments in decision-making. Two areas of the frontal lobe are of particular interest: anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC). Tasks that require decision-making and choice behavior consistently activate both areas, and both areas contain neurons that encode various aspects related to the value of choice alternatives. In addition, both ACC and OFC are involved in addiction: addicts show structural and functional changes in the two areas. However, we have little understanding about what each area independently contributes to the process of choice behavior. To determine this, we will use neurophysiological techniques to record simultaneously from both areas while subjects are engaged in tasks designed to involve either ACC or OFC. We will compare and contrast the functional properties of ACC and OFC neurons. Our aim is to dissociate the functions of the two areas based on their neurophysiological properties there by providing a deeper understanding of the role that they play in addiction. Theoretical frameworks of choice behavior highlight two processes that must occur. First, the individual must predict the likely outcome of selecting either alternative. Second, the individual must evaluate the predicted outcomes in order to determine which is more valuable. The anatomy of ACC and OFC suggests the differential contribution that the two areas may make to these processes. ACC and OFC both connect with areas responsible for processing reward-related information. However, ACC strongly connects with motor areas and only weakly with sensory areas, while OFC shows the opposite pattern. Thus, the first hypothesis we will test is that ACC neurons predict outcomes associated with different behavioral responses whereas OFC neurons predict outcomes associated with environmental stimuli. We will test this hypothesis by recording the activity of ACC and OFC neurons during tasks where the subject has to base choices on response- outcome or stimulus-outcome associations. The second hypothesis we will test is that ACC, but not OFC, evaluates the amount of effort necessary to earn a payoff. We will test this hypothesis by contrasting the encoding of ACC and OFC neurons during a task that requires our subject to integrate an outcome's value (which we manipulate by varying the magnitude of a juice reward) with the effort required to obtain the outcome (which we manipulate using a torque adjustable lever that the subject must press to earn the reward). To summarize, our specific aims are as follows: 1. Determine the contribution of ACC and OFC to the process of predicting outcomes associated with responses or stimuli respectively 2. Determine the contribution of ACC and OFC to the evaluation of effort-based choices PUBLIC HEALTH RELEVANCE: This project focuses on the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), two areas of the brain that show structural and functional changes in people addicted to drugs. We will record the electrical activity from neurons in both areas during two tasks designed to tax different aspects of choice behavior. Addiction is characterized by a difficulty in exerting control over choice behavior, and so understanding the physiological underpinnings of this process could allow us to develop novel therapeutic strategies for the treatment of addictive behavior.