The Role of Orbitofrontal Cortex in Risky Decision-Making

眶额皮质在风险决策中的作用

• 批准号: 10226054
• 负责人: Daniel Gabriel
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226054
• 关键词: Action Potentials; Acute; Animal Model; Area; Attenuated; Automobile Driving; Behavior; Biological; Biological Markers; Brain; Chronic; Data; Data Analyses; Decision Making; Disease; Educational Status; Electrophysiology (science); Event; Goals; Implant; Individual; Individual Differences; Intervention; Lead; Lesion; Measures; Mentorship; Microinjections; Modality; Modeling; Neurobiology; Neurons; Optics; Outcome; Pathologic; Pharmaceutical Preparations; Play; Process; Publications; Punishment; Rattus; Research Personnel; Rewards; Risk; Risk-Taking; Role; Shock; Substance Use Disorder; Technical Expertise; Techniques; Therapeutic; Time; Training; Viral Vector; addiction; base; biomarker development; biomarker identification; career; complex data; design; experimental study; extracellular; foot; high risk; in vivo; novel; novel marker; optogenetics; preference; risky driving; signal processing; substance abuser; substance use; therapy development

(7) Project Summary/Abstract Substance use disorder is a chronic, intractable disease characterized by pathological risk-taking behavior, which engenders ongoing drug seeking despite the risk of consequences. This proposal harnesses a rat model to understand the neuronal activity that contributes to risky decision-making. The Risky Decision-Making Task (RDT) offers choice between a small, safe reward and a large reward accompanied by an escalating risk of mild foot shock. While risk-taking on average decreases with increasing risk of punishment, the RDT reveals wide variability in risk preference, including a subpopulation of rats that consistently prefer the large reward despite high risk of punishment. Understanding the neuronal mechanisms of this natural variability in risky decision-making may contribute to development of treatments that target aberrant decision-making processes in substance abusers. A likely locus of the functional activity driving risky decision-making is the orbitofrontal cortex (OFC), an area implicated in several modalities of risk-based decision-making as well as vulnerability to substance use. Experiments in this proposal will assess how differences in OFC processing drive individual differences in risk-taking by measuring and manipulating OFC activity during risky decision-making. Aim one will utilize in vivo single-unit electrophysiology to measure functional neuronal activity in OFC during risky decision-making. Activity will be measured during a specially designed version of RDT that parses apart distinct epochs within the decision-making process: pre-decision deliberation, and post-decision outcome anticipation. To determine how OFC predicts individual biases in risk-taking, event-evoked OFC activity will be compared between rats with different levels of risk preference. Aim two will utilize optogenetic inhibition to suppress OFC activity during different epochs within risky decision-making. This will identify the causal role of OFC in driving risk-taking, and determine if OFC modulation of risk-taking diverges as a function of risk- preference. The experiments outlined above will both measure and manipulate OFC activity during an understudied form of addiction-relevant risky decision-making, which may lead to novel biomarkers and/or precise treatments for the chronic insensitivity to risk of punishment observed in addiction. In addition, this proposal will offer a strong training component including critical technical skills, complex data analysis and signal processing, the opportunity for multiple high impact publications, and strong mentorship from a team of investigators at various career stages.

(7)项目总结/摘要 物质使用障碍是一种慢性、难治性疾病，其特征是病理性冒险行为， 这导致了持续的毒品寻求，尽管有后果的风险。这项提议利用了一个老鼠模型 来了解神经元活动对风险决策的影响。风险决策任务 (RDT)提供了一个小的，安全的奖励和一个大的奖励伴随着不断上升的风险之间的选择， 轻度足部电击尽管平均而言，冒险行为会随着惩罚风险的增加而减少，但RDT显示， 风险偏好的广泛变异性，包括一个始终喜欢大回报的大鼠亚群 尽管有很高的惩罚风险。了解这种自然变异的神经机制， 决策可能有助于开发针对异常决策过程的治疗方法 药物滥用者一个可能的功能活动的轨迹驱动风险决策是眶额 皮层（OFC），一个涉及几种基于风险的决策方式以及易受 物质使用。在这个提议中的实验将评估OFC加工的差异如何驱动个体 在风险决策过程中，通过测量和操纵OFC活动来衡量风险承担的差异。瞄准一号 将利用体内单单位电生理学来测量在有风险的过程中OFC中的功能性神经元活动。 决策的活动将在专门设计的RDT版本中进行测量， 决策过程中的不同时期：决策前的审议和决策后的结果 期待为了确定眶额皮层如何预测个体在冒险中的偏差，事件诱发的眶额皮层活动将被 在不同风险偏好水平的大鼠之间进行比较。目的二将利用光遗传学抑制， 在风险决策的不同时期抑制OFC活动。这将确定的因果作用， OFC在驱动风险承担中的作用，并确定OFC对风险承担的调节是否作为风险的函数而发散- 偏好上面概述的实验将测量和操纵OFC活动， 未充分研究的成瘾相关风险决策形式，这可能导致新的生物标志物和/或 针对成瘾中观察到的对惩罚风险长期不敏感的精确治疗。另外这款 提案将提供强有力的培训内容，包括关键技术技能、复杂的数据分析和 信号处理，多个高影响力出版物的机会，以及来自 不同职业阶段的调查员。

项目成果

Effects of the psychoactive compounds in green tea on risky decision-making.

绿茶中精神活性化合物对风险决策的影响。

• DOI: 10.1097/fbp.0000000000000664
• 发表时间: 2022-02-01
• 期刊: Behavioural pharmacology
• 影响因子: 1.6
• 作者: Liley AE;Joyner HN;Gabriel DBK;Simon NW
• 通讯作者: Simon NW

Lateral Orbitofrontal Cortex and Basolateral Amygdala Regulate Sensitivity to Delayed Punishment during Decision-making.

外侧眶额皮层和基底外侧杏仁核在决策过程中调节对延迟惩罚的敏感性。

• DOI: 10.1523/eneuro.0170-22.2022
• 发表时间: 2022
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Liley,AnnaE;Gabriel,DanielBK;Simon,NicholasW
• 通讯作者: Simon,NicholasW

Divergent risky decision-making and impulsivity behaviors in Lewis rat substrains with low genetic difference.

遗传差异较小的 Lewis 大鼠亚系存在不同的风险决策和冲动行为。

• DOI: 10.1037/bne0000557
• 发表时间: 2023
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Gabriel,DanielBK;Liley,AnnaE;Franks,HunterT;Minnes,GraceL;Tutaj,Monika;Dwinell,MelindaR;deJong,TristanV;Williams,RobertW;Mulligan,MeganK;Chen,Hao;Simon,NicholasW
• 通讯作者: Simon,NicholasW