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都需要对一系列决策变量(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)进行成本效益分析。最近的一个决策模型提出，眼眶前额叶皮质(OFC)通过整合做出决定所需的所有变量来影响选择行为。额叶受损，包括OFC和前扣带回(ACC)，损害了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神经精神疾病有关，这些疾病的选择行为受到损害，特别是涉及冲动或强迫选择行为的障碍。这包括强迫症(OCD)、注意力缺陷多动障碍(ADHD)、病理性攻击性、恐惧症和焦虑症、成瘾和强迫性赌博等障碍。在严重的情况下，切除ACC甚至被用来治疗病理性攻击、焦虑症和强迫症。然而，目前还不清楚这些不同的大脑皮层区域如何影响选择行为。我们将通过推导抽象的值信号来测试OFC神经元编码做出决定所需的所有参数的假设。我们将同时记录清醒行为猴四个不同额区(ACC、OFC、腹外侧额叶皮质和背外侧前额叶皮质)的单个神经元的活动，同时让它们在三个物理上不同的评估尺度上选择与不同值相关联的两张图片。具体地说，猴子会在三组图片之间做出选择：一组图片与奖励大小的关联不同，一组图片与获得固定奖励所需的努力程度相关联，第三组图片与奖励发放的概率不同。其他实验将操纵选择背后的参数，以准确地确定价值信号是基于什么。最后，我们将研究额叶和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。我们将测试多巴胺作为教学信号的假设，训练额叶中的神经元选择哪种选择更优。这个项目中的实验将有助于阐明支持选择行为的解剖学、神经生理学和神经药理学，并在这样做的过程中，确定针对这些疾病的改进干预和治疗的研究途径。

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.