Decision Making and Orbitofrontal Cortex

描述(申请人提供)：眼眶前额叶皮质损伤的患者在各种决策任务中表现出特征性的行为缺陷。当以前有利的行动不再产生理想的结果时，他们在修改自己的行为策略以及整合决策结果的多个维度以做出最优选择方面受到损害。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快并导致负面后果的滥用物质。眼眶前额叶皮质功能障碍也与许多情绪和焦虑症有关。此外，眼眶额部病变的患者无法考虑未选择的行动的假设结果，以改善他们的决策策略。尽管眼眶额叶功能障碍具有广泛的临床意义，但在许多精神障碍中，包含在眼眶额叶皮质并被破坏的特定计算步骤的性质尚不清楚。在这项申请中提出的研究将调查多个与奖励相关的参数和各种决策变量是如何由灵长类眼眶前皮质的单个神经元编码和整合的。首先，我们将测试在跨期赌博任务中，眼眶前额叶皮质中的神经元是否会整合多个奖励参数，在该任务中，每个选项可用的奖励的大小、延迟和不确定性都被系统地操纵。其次，我们将调查眼眶前额叶皮质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。这将在一项基于代币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移除条件增强剂来强化和惩罚。最后，我们还将测试关于未选择动作的假设结果的信息是否被反映并与动物在眶前叶神经元活动中的选择相关的信号相结合。这些实验的结果将阐明来自不同来源的信号是如何在眼眶额叶皮质中整合和转换的，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地治疗药物滥用和其他涉及眼眶额叶皮质的精神障碍。

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.