THE ROLE OF PREFRONTAL REGIONS IN ECONOMIC CHOICE AND CHOICE-GUIDED BEHAVIOR

描述(由申请人提供)：许多精神和神经障碍--包括额颞型痴呆症、强迫症、严重抑郁症和药物成瘾--可以广泛地描述为患者做出了“糟糕的选择”。虽然这些障碍扰乱了各种领域的选择行为--包括食物、金钱、跨期选择、社会选择等--但缺陷可以统一地描述为影响基于主观偏好的选择，在那里不存在本质上正确的选择。这种行为被称为“经济选择”(EC)。作为一个心理过程，EC需要为可用选项赋值--然后通过比较值来做出决定。这项研究提案的首要目标是在神经元水平上了解在EC过程中如何计算和比较价值，以及如何将选择结果转化为适当的行动。近年来的许多工作研究了主观价值的神经编码，主观价值是由多个决定因素(商品、其数量、动机状态、时间延迟等)整合而成的。基于神经生理学、影像和损伤研究的逐渐形成的共识是，选择可能基于在眼眶额叶皮质(OFC)和腹内侧额叶皮质(VmPFC)计算的值。然而，关键问题仍然悬而未决。值得注意的是，OFC中的神经元编码的值独立于所选择的视觉运动偶发事件(在“商品空间”中)。然而，大多数选择最终都会导致行动。此外，不同的选择往往与承担不同成本的行动相关联。因此，一个广泛的问题是，OFC中价值的抽象表示如何与潜在的行动计划的神经活动相关。利用一个将经济选择与行动计划分离的任务，我们将解决两个具体问题。首先，我们将考察神经机制，通过这些机制，选择结果所选择的好东西将指导行动计划。解剖学方面的考虑和初步结果表明，这种“良好的行为转换”涉及外侧前额叶皮质(LPFC)和前扣带回皮质(ACC)。其次，我们将研究行动成本是否以及如何与其他价值决定因素相结合。此外，我们将解决猴子神经生理学研究(通常在OFC中发现细胞编码主观价值，但在vmPFC中没有)和人类成像研究(其中大多数强调vmPFC中的价值信号)之间的文献差异。我们推测，这种差异可能部分是由于vmPFC活动与自主神经反应高度相关，自主神经反应在决策过程中很强，但在训练后减弱。这些问题将通过单细胞记录和执行经济选择的猴子的可逆失活来解决。近年来，我们发展了一种新的方法来研究估值和EC的神经生物学，并被证明是卓有成效和有影响力的。通过解决一些最紧迫和最开放的问题，这项研究可能会塑造我们对EC背后的神经机制和精神疾病中的功能障碍的理解。

DESCRIPTION (provided by applicant): Many mental and neurological disorders - including frontotemporal dementia, obsessive-compulsive disorder, major depression and drug addiction - can be broadly characterized as patients making "poor choices". While these disorders disrupt choice behavior in a variety of domains - including food, money, intertemporal choices, social choices, etc. - deficits can be unitarily described as affecting choices based on subjective preferences, where no intrinsically correct option exists. This behavior is referred to as "economic choice" (EC). As a mental process, EC entails assigning values to the available options - a decision is then made by comparing values. The overarching goal of this research proposal is to understand at the neuronal level how values are computed and compared during EC, and how choice outcomes are transformed into suitable actions. Much work in recent years examined the neural encoding of subjective value, defined by the integration of multiple "determinants" (a commodity, its quantity, the motivational state, time delays, etc.). The emerging consensus based on neurophysiology, imaging and lesion studies is that choices might be based on values computed in the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (vmPFC). Key questions remain, however, open. Notably, neurons in the OFC encode value independently of the visuomotor contingencies of choice (in "goods space"). However, most choices eventually lead to an action. Moreover, different options are often associated with actions bearing different costs. Thus a broad issue is how the abstract representation of value in OFC relates to neural activity underlying action planning. Using a task that dissociates economic choice from action planning, we will address two specific questions. First, we will examine the neuronal mechanisms through which the choice outcome the chosen good guides an action plan. Anatomical considerations and preliminary results suggest that this "good-to-action transformation" involve the lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC). Second, we will examine whether and how action costs are integrated with other determinants of value. In addition, we will address a discrepancy in the literature between monkey neurophysiology studies (which generally found cells encoding subjective values in OFC but not in vmPFC) and human imaging studies (most of which emphasized value signals in vmPFC). We hypothesize that this discrepancy might be partly due to the fact that vmPFC activity is highly correlated with autonomic responses, which are strong during decision making but subside after training. These issues will be addressed using single cell recordings and reversible inactivation in monkeys performing economic choices. In recent years, we developed a new approach to study the neurobiology of valuation and EC that has proven both fruitful and influential. By addressing some of the most pressing and open questions, this research may shape our understanding of the neural mechanisms that underlie EC and that malfunction in mental illness.