Decision Making and Orbitofrontal Cortex

决策和眶额皮质

• 批准号: 8043667
• 负责人: DAEYEOL LEE
• 金额: $ 36.87万
• 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/8043667
• 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）：眶额皮质病变患者在各种决策任务中表现出特征性行为缺陷。当先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受到损害。这些行为变化类似于吸毒成瘾者的症状，他们无法停止使用不再令人愉快并导致负面后果的滥用物质。眶额皮质的功能障碍也与许多情绪和焦虑症有关。此外，眶额病变的患者无法考虑未选择的行为的假设结果，以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，但眶额皮质中具体的计算步骤的性质以及许多精神障碍中的破坏是未知的。本申请中提出的研究将调查多个奖励相关参数和各种决策变量如何被灵长类动物眶额皮层的单个神经元编码和整合。首先，我们将测试眶额皮层中的神经元是否会在跨时间赌博任务中整合多个奖励参数，其中每个选项的奖励的大小，延迟和不确定性被系统地操纵。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。这将在一个基于标记的决策任务中进行测试，其中动物的选择行为分别通过传递和移除条件反射器来加强和惩罚。最后，我们还将测试是否从未选择的行动的假设结果的信息反映和整合与动物的选择在眶额神经元的活动的信号。这些实验的结果将阐明来自不同来源的信号是如何在眶额皮层中整合和转换的，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的治疗策略，药物滥用和其他精神疾病，涉及眶额皮质。 公共卫生关系：眶额皮层的病变和异常活动会产生各种行为障碍，通常表现为自适应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障碍，包括焦虑和情绪障碍有关。结合一系列新的行为任务和多通道神经生理记录，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。