The role of the orbitofrontal cortex in goal-directed behavior

眶额皮质在目标导向行为中的作用

• 批准号: 8063317
• 负责人: Elizabeth A West
• 金额: $ 4.18万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063317
• 关键词: Ablation; Accounting; Agonist; Amygdaloid structure; Animals; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Brain; Corpus striatum structure; Craniocerebral Trauma; Cues; Decision Making; Disease; Drug Addiction; Environment; Expectancy; Food; Goals; Impairment; Individual; Knowledge; Laboratories; Learning; Lesion; Link; Macaca; Measures; Methods; Monkeys; Muscimol; Operative Surgical Procedures; Outcome; Patients; Performance; Phase; Primates; Procedures; Process; Rattus; Reporting; Rewards; Rodent; Role; Satiation; Secondary to; Staging; Stimulus; Stroke; Structure; System; Taste Perception; Testing; Therapeutic Intervention; Training; Update; Work; addiction; base; behavior change; feeding; flexibility; neural circuit; neuropsychiatry; nonhuman primate; reinforcer; relating to nervous system; research study; response; reward processing; species difference; tumor

DESCRIPTION (provided by applicant): The ability of an animal to alter behavior in response to changes in their environment is known as flexible goal-directed behavior. Patients with neuropsychiatric disorders (e.g., addiction, ADHD, and autism) often have difficulty with this type of behavior. In the laboratory one type of task used to measure flexible goal directed behavior is a conditioned reinforcer devaluation task. In this task, animals form associations between stimuli (e.g. objects) and specific reinforcer(s) (e.g. various food rewards). The reinforcer is subsequently "devalued" by selective satiation (feeding one of the foods ad libitum). Following devaluation, normal subjects adjust their responding which reflects the new "value" of the reinforcer. The orbitofrontal cortex (OFC) in conjunction with several other brain structures (e.g., amygdala, striatum) is an important neural substrate involved in the conditioned reinforcer devaluation task. However, it is unknown if OFC is necessary for linking the decreased value of the food to the stimuli that predicts it, or guiding choices during testing. The goal of this proposal is to elucidate the neural circuitry involved in different stages of reinforcer devaluation. Specifically, the proposed experiments plan to determine the role of the OFC in reinforcer devaluation and compare and contrast the roles in rodents and non human primates. I propose to use reversible pharmacological manipulations in macaque monkeys to study the role of OFC during different stages of reinforcer devaluation (forming associations, registering a change in reinforcer value, updating reinforcer value to the stimuli, guiding choices to reflect the change in value). Reversible pharmacological manipulations provide an opportunity to delineate the role of OFC involved in individual phases of the task. In addition I plan to compare the role of the OFC in conditioned reinforcer devaluation across species. To achieve this, I developed a new rodent (rat) reinforcer- devaluation task that further reconciles the differences between the monkey and the rat tasks used to date. I also propose to study the effects of lesion in rats in the new rat reinforcer devaluation task to compare directly with previous work using various forms of reinforcer devaluation tasks in rats. Further understanding of the neural circuitry underlying flexible goal- directed behavior will help elucidate mechanisms for impairments in patients with neuropsychiatric disorders. This will provide new and more selective target systems for therapeutic intervention for individuals with maladaptive reward processing. The following aims will be used to reach my goals: specific aim 1-Determine the role of OFC in different phases of reinforcer devaluation in macaque monkeys. Specific aim 2- Determine the role of OFC in reinforcer devaluation in rats. A direct comparison OFC across species in a specific reinforcer devaluation task will enhance our understanding of the neural circuitry involved in flexible goal directed behavior. PUBLIC HEALTH RELEVANCE: Patients with addiction, autism, or attention deficit hyperactivity disorder are impaired in adjusting responding based on consequences. These types of deficits are studied by measuring the ability of a subject to alter behavior based on changing outcomes. The goal of this proposal is to further understand the role of a specific brain structure (orbitofrontal cortex) using a task which measures changing behavior.

描述（由申请人提供）：动物根据环境变化而改变行为的能力被称为灵活的目标导向行为。患有神经精神疾病（例如成瘾、多动症和自闭症）的患者通常难以做出此类行为。在实验室中，用于测量灵活的目标导向行为的一类任务是条件强化物贬值任务。在此任务中，动物在刺激（例如物体）和特定强化物（例如各种食物奖励）之间形成关联。随后，强化剂会因选择性饱足（随意喂食其中一种食物）而“贬值”。贬值后，正常受试者会调整他们的反应，这反映了强化物的新“价值”。眶额皮质（OFC）与其他几个大脑结构（例如杏仁核、纹状体）结合是参与条件强化物贬值任务的重要神经基质。然而，目前尚不清楚 OFC 是否有必要将食物的价值下降与预测它的刺激联系起来，或在测试过程中指导选择。该提案的目的是阐明参与强化物贬值不同阶段的神经回路。具体来说，拟议的实验计划确定 OFC 在强化物贬值中的作用，并比较和对比啮齿动物和非人类灵长类动物的作用。我建议在猕猴中使用可逆药理学操作来研究 OFC 在强化物贬值的不同阶段（形成关联、记录强化物价值的变化、更新刺激物的强化物价值、指导选择以反映价值变化）期间的作用。可逆药理学操作提供了一个机会来描述 OFC 在任务各个阶段中的作用。此外，我计划比较 OFC 在不同物种条件强化物贬值中的作用。为了实现这一目标，我开发了一种新的啮齿动物（大鼠）强化物贬值任务，进一步调和了迄今为止使用的猴子和大鼠任务之间的差异。我还建议在新的大鼠强化物贬值任务中研究病变对大鼠的影响，以直接与之前在大鼠中使用各种形式的强化物贬值任务的工作进行比较。进一步了解灵活的目标导向行为背后的神经回路将有助于阐明神经精神疾病患者的损伤机制。这将为具有适应不良奖励处理的个体的治疗干预提供新的、更具选择性的目标系统。以下目标将用于实现我的目标： 具体目标 1-确定 OFC 在猕猴强化物贬值的不同阶段中的作用。具体目标 2-确定 OFC 在大鼠强化物贬值中的作用。在特定强化物贬值任务中直接比较不同物种的 OFC 将增强我们对灵活目标导向行为所涉及的神经回路的理解。 公共卫生相关性：患有成瘾症、自闭症或注意力缺陷多动障碍的患者根据后果调整反应的能力受到损害。这些类型的缺陷是通过测量受试者根据变化的结果改变行为的能力来研究的。该提案的目标是通过测量行为变化的任务进一步了解特定大脑结构（眶额皮质）的作用。