Neural mechanisms of decision making in frontal cortex

额叶皮层决策的神经机制

• 批准号: 372305-2010
• 负责人: Euston, David
• 金额: $ 2.04万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528528
• 关键词: Neural; mechanisms; decision; making; frontal

To make adaptive decisions in a ever-changing world, information about the past must be brought to bear on the present decision. Actions that lead to reward are likely to be repeated, while those leading to punishment are not. A specific frontal brain region, the medial prefrontal cortex (mPFC), appears critical to this process. For example, humans with mPFC damage show poor judgement in decisions involving risk. In rats, the homologous region plays a critical role in retrieval of memories. I hypothesize that the role of the mPFC in both humans and rats is to guide decisions by predicting the emotional consequences of contemplated actions, using past experience as a guide. To test this hypothesis, I will use multi-electrode recording (in which tiny wires are used to record spiking activity from dozens of neurons simultaneously) and temporary inactivation (involving local injections of anesthetics) to study decision making in rats. The first group of experiments seek to uncover how reward and fear are represented by neurons in mPFC. Are the same set of neurons used to code both positive and negative experiences? Experiments will also look at the influence of mitigating factors, such as control over noxious stimuli or effort needed to achieve reward, on the neural coding of noxious or rewarding stimuli. A second group of experiments explores the role of mPFC in memory retrieval. They seek to clarify whether mPFC mediates short-term memory in addition to its well documented role in long-term memory. A final group of experiments seeks direct evidence that mPFC guides decisions by predicting emotional responses to planned actions. One experiment involves switching the stimuli which lead to reward from one dimension to another. A second uses a gambling task involving a choice between a high-risk, high reward option and a safer, lower reward option. In both cases, I expect to see neural activity directly related to the anticipated emotional outcome of individual choices. This research seeks a mechanistic understanding of the role of mPFC in decision making in both rats and humans and will further our understanding of the many mental disorders tied to mPFC dysfunction including addiction, schizophrenia and depression.

为了在不断变化的世界中做出适应性决策，必须将过去的信息应用于当前的决策。 导致奖励的行为可能会重复，而导致惩罚的行为则不会重复。 一个特定的额叶脑区域，即内侧前额叶皮层（mPFC），似乎对该过程至关重要。 例如，mPFC 受损的人在涉及风险的决策中表现出较差的判断力。 在大鼠中，同源区域在记忆检索中起着至关重要的作用。 我假设 mPFC 在人类和大鼠中的作用是通过以过去的经验为指导来预测预期行为的情绪后果来指导决策。 为了检验这个假设，我将使用多电极记录（其中使用细电线同时记录数十个神经元的尖峰活动）和暂时失活（涉及局部注射麻醉剂）来研究大鼠的决策。 第一组实验试图揭示 mPFC 中的神经元如何代表奖励和恐惧。 是否使用同一组神经元来编码积极和消极的经历？ 实验还将研究缓解因素对有害或奖励刺激的神经编码的影响，例如对有害刺激的控制或获得奖励所需的努力。 第二组实验探讨了 mPFC 在记忆检索中的作用。 他们试图澄清 mPFC 除了在长期记忆中的作用之外，是否还介导短期记忆。 最后一组实验寻求直接证据，证明 mPFC 通过预测对计划行动的情绪反应来指导决策。 一项实验涉及将导致奖励的刺激从一个维度切换到另一个维度。 第二个使用赌博任务，涉及在高风险、高回报选项和更安全、低回报选项之间进行选择。 在这两种情况下，我期望看到神经活动与个人选择的预期情感结果直接相关。 这项研究旨在从机制上理解 mPFC 在大鼠和人类决策中的作用，并将进一步加深我们对与 mPFC 功能障碍相关的许多精神疾病的理解，包括成瘾、精神分裂症和抑郁症。