Neural representation of reward in frontal cortex

描述(由申请者提供)：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对选择施加控制。额叶对选择行为至关重要，因为对该区域的损害会在决策过程中产生特定的损害。额叶的两个区域特别受关注：前扣带回皮质(ACC)和眶前叶皮质(OFC)。需要决策和选择行为的任务会持续激活这两个区域，这两个区域都包含编码与选择选择价值相关的各个方面的神经元。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的变化。然而，我们对每个领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，同时从两个区域进行记录。我们将比较和对比ACC和OFC神经元的功能特性。我们的目的是通过更深入地了解这两个区域在成瘾中所起的作用，根据它们的神经生理特性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，个人必须预测选择其中一种选择的可能结果。其次，个人必须评估预测的结果，以确定哪个更有价值。对ACC和OFC的解剖表明，这两个区域可能对这些过程做出了不同的贡献。ACC和OFC都与负责处理与奖励有关的信息的区域相连。但ACC与运动区的联系较强，与感觉区的联系较弱，而OFC则表现出相反的模式。因此，我们要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中ACC和OFC神经元的活动来检验这一假设，在这些任务中，受试者必须根据反应-结果或刺激-结果关联做出选择。我们将检验的第二个假设是，ACC，而不是OFC，评估赚取回报所需的努力程度。我们将通过对比Acc和OFC神经元的编码来检验这一假设，该任务要求受试者将结果的值(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(我们使用受试者必须按下以获得奖励的扭矩可调杠杆来操纵)进行积分。总而言之，我们的具体目标如下：1.确定ACC和OFC在预测与反应或刺激相关的结果的过程中的贡献2.确定ACC和OFC对基于努力的选择的评估的贡献 公共卫生相关性：该项目关注前扣带回皮质(ACC)和眼眶额叶皮质(OFC)，这两个区域显示了吸毒者大脑结构和功能的变化。我们将记录两个任务期间两个区域神经元的电活动，这两个任务旨在对选择行为的不同方面进行征税。成瘾的特点是难以对选择行为进行控制，因此了解这一过程的生理基础可以帮助我们开发治疗成瘾行为的新的治疗策略。

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.