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The Neuronal Mechanisms Underlying Choice Behavior in the Frontal Lobe

额叶选择行为背后的神经机制

基本信息

批准号：
7682960
负责人：
Steve Wayne Kennerley
金额：
$ 3.34万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2010-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Many of our everyday choices require a cost-benefit analysis across a range of decision variables (e.g. likelihood of success, size or quality of the payoff, amount of work required to achieve outcome). A recent model of decision-making has proposed that the orbitofrontal cortex (OFC) contributes to choice behavior by integrating all of the variables necessary to make a decision. Damage to the frontal lobe, including the OFC and the anterior cingulate cortex (ACC), impairs the ability to make optimal choices in our everyday lives. Dysfunction of these regions has also been associated with many neuropsychiatric illnesses where choice behavior is impaired, particularly disorders involving impulsive or compulsive choice behavior. This includes disorders such as obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), pathological aggression, phobic and anxiety disorder, addiction and compulsive gambling. In severe cases, removal of the ACC has even been used as a treatment for pathological aggression, anxiety disorders and OCD. Yet it remains unclear how these distinct cortical areas contribute to choice behavior. We will test the hypothesis that OFC neurons encode all the parameters necessary to make a decision, by deriving an abstract value signal. We will simultaneously record the activity of single neurons in four different frontal areas (ACC, OFC, ventrolateral prefrontal cortex and dorsolateral prefrontal cortex) in awake, behaving monkeys while they choose between two pictures associated with different values varied along three physically different valuation scales. Specifically, monkeys will choose between one group of pictures that differ in their association with reward magnitude, one group in their association with the amount of effort required to earn a fixed reward, and a third group in the probability that a reward would be delivered. Additional experiments will manipulate the parameters underlying the choice, to determine precisely on what the value signal is based. Finally, we will investigate the functional interaction of the frontal lobe with the midbrain dopaminergic system, known to at least partially underlie ADHD. We will test the hypothesis that dopamine serves as a teaching signal, training neurons in the frontal lobe as to which choices are more optimal. The experiments in this project will help elucidate the anatomy, neurophysiology and neuropharmacology that underpin choice behavior, and in doing so, determine avenues of research directed towards the development of improved interventions and treatments for these disorders.

描述（由申请人提供）：我们的许多日常选择都需要对一系列决策变量（例如成功的可能性、回报的规模或质量、实现结果所需的工作量）进行成本效益分析。最近的决策模型提出，眶额皮层（OFC）通过整合决策所需的所有变量来促进选择行为。额叶（包括 OFC 和前扣带皮层 (ACC)）受损会削弱我们在日常生活中做出最佳选择的能力。这些区域的功能障碍也与许多选择行为受损的神经精神疾病有关，特别是涉及冲动或强迫性选择行为的疾病。这包括强迫症（OCD）、注意力缺陷多动症（ADHD）、病理性攻击、恐惧症和焦虑症、成瘾和强迫性赌博等疾病。在严重的情况下，去除 ACC 甚至被用来治疗病理性攻击、焦虑症和强迫症。然而，目前尚不清楚这些不同的皮质区域如何影响选择行为。我们将通过导出抽象值信号来测试 OFC 神经元对做出决策所需的所有参数进行编码的假设。我们将同时记录清醒、行为猴子的四个不同额叶区域（ACC、OFC、腹外侧前额叶皮层和背外侧前额叶皮层）中单个神经元的活动，同时它们在与沿着三个物理不同的评估尺度变化的不同值相关的两张图片之间进行选择。具体来说，猴子会在一组与奖励大小的关联不同的图片、一组与获得固定奖励所需的努力量的关联、以及第三组与获得奖励的概率的关联之间进行选择。额外的实验将操纵选择背后的参数，以精确确定价值信号的基础。最后，我们将研究额叶与中脑多巴胺能系统的功能相互作用，已知该系统至少部分是多动症的基础。我们将测试多巴胺作为教学信号的假设，训练额叶中的神经元以确定哪些选择更佳。该项目中的实验将有助于阐明支撑选择行为的解剖学、神经生理学和神经药理学，并在此过程中确定针对这些疾病开发改进的干预措施和治疗方法的研究途径。