Decision Making and Orbitofrontal Cortex

决策和眶额皮质

• 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
• 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

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）：眶额皮质中有病变的患者在各种决策任务中显示出特征性的行为缺陷。当先前有利的行动不再产生理想的结果并整合决策结果以做出最佳选择的多个维度时，它们会受到修改行为策略的损害。这些行为变化类似于无法停止使用不再令人愉悦并导致负面后果的滥用物质的吸毒者的症状。轨道额皮层的功能障碍也与许多情绪和焦虑症有关。此外，轨道额叶病变的患者无法考虑未选择的行动以改善其决策策略的假设结果。尽管眶额功能障碍具有广泛的临床意义，但尚不清楚眶额皮层体现并破坏的特定计算步骤的性质还是未知的。本应用程序中提出的研究将研究如何由灵长类眶额皮质的单个神经元编码和整合多个相关的参数和各种决策变量。首先，我们将测试轨道皮层中的神经元是否会在阶段间赌博任务中整合多个奖励参数，在这种赌博赌博任务中，从每个选项中可获得的幅度，延迟和不确定性是系统地操纵的。其次，我们将研究轨道额皮层不同细分中的神经元是否专门传播与正面和负面结果相关的信号。这将在基于令牌的决策任务中进行测试，在该任务中，动物的选择行为分别通过提供和去除条件增强剂来加强和惩罚。最后，我们还将测试是否反映了关于未选择的作用的假设结果的信息，并与与动物在眶额神经元活动中选择相关的信号进行了整合。这些实验的结果将阐明源自不同来源的信号如何在轨道额皮层中进行整合和转换，从而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的治疗策略，以实现涉及轨道额皮质的其他精神疾病。 公共卫生相关性：眶额皮质中的病变和异常活动会产生各种行为障碍，通常是由于自适应学习最佳决策策略的失败而突出的。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。拟议的研究结合了一系列新型的行为任务和多通道神经生理记录，将阐明轨道额皮质中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。