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，因为该区域的损伤会对决策产生特定的损害。额叶的两个区域特别值得关注：前扣带皮层（ACC）和眶额皮质（OFC）。需要决策和选择行为的任务始终激活这两个区域，这两个区域都包含神经元，它们编码与选择选项价值相关的各个方面。此外，ACC和OFC都与成瘾有关：成瘾者在这两个区域表现出结构和功能上的变化。然而，我们对每个区域对选择行为过程的独立贡献知之甚少。为了确定这一点，我们将使用神经生理学技术，在受试者从事涉及ACC或OFC的任务时，同时记录两个区域的活动。我们将比较和对比ACC和OFC神经元的功能特性。我们的目标是根据这两个区域的神经生理特性来分离它们的功能，从而更深入地了解它们在成瘾中所扮演的角色。选择行为的理论框架强调了两个必须发生的过程。首先，个人必须预测选择任何一个选项的可能结果。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的解剖表明这两个区域可能对这些过程有不同的贡献。ACC和OFC都与负责处理奖励相关信息的区域相连。然而，ACC与运动区有很强的联系，与感觉区只有微弱的联系，而OFC则表现出相反的模式。因此，我们将验证的第一个假设是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ACC和OFC神经元在受试者必须根据反应-结果或刺激-结果关联做出选择的任务中的活动来验证这一假设。我们要测试的第二个假设是，ACC（而不是OFC）评估获得回报所需的努力量。我们将通过对比ACC和OFC神经元在任务中的编码来检验这一假设，该任务要求我们的受试者将结果的值（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（我们使用一个扭矩可调杠杆来操纵，受试者必须按下才能获得奖励）整合起来。综上所述，我们的具体目标如下：分别确定ACC和OFC在预测与反应或刺激相关的结果过程中的作用确定ACC和OFC对基于努力的选择评估的贡献

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.