Decision Making and Orbitofrontal Cortex

决策和眶额皮质

基本信息

批准号：
8261937
负责人：
DAEYEOL LEE
金额：
$ 37.24万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8261937
关键词：
Address Animals Anxiety Disorders Behavior Therapy Behavioral Characteristics Choice Behavior Clinical Code Computers Costs and Benefits Decision Making Diagnosis Dimensions Drug Addiction Economics Environment Evaluation Excision Expectancy Failure Frequencies Functional disorder Gambling Goals Individual Iowa Knowledge Lead Learning Lesion Macaca mulatta Mental disorders Metric Mood Disorders Nature Neurons Outcome Paper Patients Play Prevention Primates Probability Psychological reinforcement Public Health Punishment Reversal Learning Rewards Role Series Signal Transduction Simulate Source Stimulus Substance abuse problem Symptoms Testing Uncertainty Update base behavioral impairment design drug addict economic value improved information processing multitask neuroimaging neurophysiology novel preference public health relevance reinforcer relating to nervous system research study treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Patients with lesions in the orbitofrontal cortex display characteristic behavioral deficits in various decision- making tasks. They are impaired in revising their behavioral strategies when the previously advantageous actions no longer produce desirable outcomes and integrating multiple dimensions of the decision outcomes to make optimal choices. These behavioral changes resemble the symptoms of drug addicts who are unable to discontinue the use of abused substance that are no longer pleasurable and lead to negative consequences. Dysfunctions of the orbitofrontal cortex are also implicated in many mood and anxiety disorders. In addition, patients with orbitofrontal lesions are unable to take into consideration hypothetical outcomes from unchosen actions to improve their decision-making strategies. Despite this wide clinical implication of the orbitofrontal dysfunctions, the nature of specific computational steps embodied in the orbitofrontal cortex and disrupted in many mental disorders is unknown. Studies proposed in this application will investigate how multiple reward- related parameters and various decision variables are encoded and integrated by individual neurons of the primate orbitofrontal cortex. First, we will test whether the neurons in the orbitofrontal cortex will integrate multiple reward parameters during an inter-temporal gambling task in which the magnitude, delay, and uncertainty of reward available from each option is systematically manipulated. Second, we will investigate whether neurons in different subdivisions of the orbitofrontal cortex tend to specialize in propagating the signals related to positive and negative outcomes. This will be tested in a token-based decision-making task in which the animal's choice behaviors are reinforced and punished by the delivery and removal of conditioned reinforcers, respectively. Finally, we will also test whether the information about the hypothetical outcomes from unchosen actions are reflected and integrated with the signals related to the animal's choices in the activity of orbitofrontal neurons. The results from these experiments will elucidate how the signals originating from different sources are integrated and transformed in the orbitofrontal cortex so that they can be used directly to guide the animal's choices. Accordingly, the proposed studies will contribute to prevention and more efficient treatment strategies for substance abuse and other mental disorders that involve the orbitofrontal cortex. PUBLIC HEALTH RELEVANCE: Lesions and abnormal activity in the orbitofrontal cortex produces a variety of behavioral impairments, often highlighted by the failures in adaptively learning the optimal decision-making strategies. Accordingly, orbitofrontal dysfunctions are implicated in drug addiction and other psychiatric disorders, including anxiety and mood disorders. Combining a series of novel behavioral tasks and multi-channel neurophysiological recordings, the proposed studies will elucidate the cellular basis for information processing in the orbitofrontal cortex and contribute to improving diagnosis and treatment strategies for many mental illnesses.

描述（由申请人提供）：眶额皮质病变的患者在各种决策任务中表现出特征性的行为缺陷。当以前有利的行为不再产生理想的结果时，他们在修改行为策略和整合决策结果的多个维度以做出最佳选择时会受到损害。这些行为变化类似于吸毒者的症状，他们无法停止使用不再令人愉悦并导致负面后果的滥用物质。眶额皮质功能障碍也与许多情绪和焦虑障碍有关。此外，患有眶额病变的患者无法考虑未选择的行动的假设结果来改善他们的决策策略。尽管眶额功能障碍具有广泛的临床意义，但在许多精神疾病中，眶额皮层所体现的特定计算步骤的性质尚不清楚。本申请提出的研究将调查灵长类动物眶额皮层的单个神经元如何编码和整合多个奖励相关参数和各种决策变量。首先，我们将测试眶额皮层中的神经元是否会在跨期赌博任务中整合多个奖励参数，其中系统地操纵每个选项的奖励的大小、延迟和不确定性。其次，我们将研究眶额皮层不同分区的神经元是否倾向于专门传播与积极和消极结果相关的信号。这将在基于令牌的决策任务中进行测试，其中动物的选择行为分别通过条件强化物的传递和去除来强化和惩罚。最后，我们还将测试有关未选择行为的假设结果的信息是否与动物在眶额神经元活动中的选择相关的信号得到反映和整合。这些实验的结果将阐明来自不同来源的信号如何在眶额皮层中整合和转化，以便它们可以直接用于指导动物的选择。因此，拟议的研究将有助于预防和更有效地治疗涉及眶额皮质的药物滥用和其他精神障碍。公共健康相关性：眶额皮层的病变和异常活动会产生各种行为障碍，通常表现为适应性学习最佳决策策略的失败。因此，眶额功能障碍与药物成瘾和其他精神疾病有关，包括焦虑和情绪障碍。结合一系列新颖的行为任务和多通道神经生理学记录，拟议的研究将阐明眶额皮层信息处理的细胞基础，并有助于改善许多精神疾病的诊断和治疗策略。