The Neuronal Mechanisms Underlying Choice Behavior in the Frontal Lobe

描述（由申请人提供）：我们的许多日常选择需要对一系列决策变量进行成本效益分析（例如成功的可能性，回报的大小或质量，实现结果所需的工作量）。最近的一个决策模型提出，眶额皮层（OFC）通过整合做出决策所需的所有变量来促进选择行为。额叶的损伤，包括眶额皮层和前扣带皮层（ACC），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。这包括诸如强迫症（OCD）、注意力缺陷多动障碍（ADHD）、病理性攻击性、恐怖症和焦虑症、成瘾和强迫性赌博等疾病。在严重的情况下，切除ACC甚至被用作病理性攻击，焦虑症和强迫症的治疗。然而，这些不同的皮层区域如何影响选择行为仍不清楚。我们将测试的假设，即OFC神经元编码的所有必要的参数作出决定，通过推导出一个抽象的价值信号。我们将同时记录清醒的、行为正常的猴子在两张图片之间选择时四个不同额叶区域（ACC、OFC、腹外侧前额叶皮层和背外侧前额叶皮层）单个神经元的活动，这两张图片与沿着三个不同的生理评价尺度变化的不同价值相关。具体来说，猴子会在一组与奖励大小相关性不同的图片中进行选择，一组与获得固定奖励所需的努力量相关，第三组与奖励获得的概率相关。其他实验将操纵选择背后的参数，以精确地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，已知至少部分是ADHD的基础。我们将检验这样一个假设，即多巴胺是一种教学信号，它训练额叶中的神经元，让它们知道哪些选择更理想。该项目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的改进干预和治疗方法的研究途径。

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.