Neural mechanisms of decision making in frontal cortex

为了在一个不断变化的世界中做出适应性的决定，必须将过去的信息用于当前的决定。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。一个特定的大脑额叶区域，内侧前额叶皮层（mPFC），似乎对这一过程至关重要。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关键作用。我假设，无论是人类还是老鼠，中前额叶皮层的作用都是利用过去的经验，通过预测预期行为的情感后果来指导决策。为了验证这一假设，我将使用多电极记录（用细导线同时记录几十个神经元的峰值活动）和暂时失活（包括局部注射麻醉剂）来研究大鼠的决策能力。第一组实验试图揭示奖励和恐惧是如何由中前额皮质神经元表示的。是同一组神经元用来编码积极和消极的体验吗？实验还将研究减轻因素的影响，如对有害刺激的控制或获得奖励所需的努力，对有害或有益刺激的神经编码的影响。第二组实验探讨了中前额叶皮层在记忆提取中的作用。他们试图澄清，除了在长期记忆中有充分记载的作用外，mPFC是否还调节短期记忆。最后一组实验寻求mPFC通过预测对计划行动的情绪反应来指导决策的直接证据。其中一个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。第二种是赌博任务，包括在高风险、高回报的选择和更安全、低回报的选择之间做出选择。在这两种情况下，我都希望看到与个人选择的预期情感结果直接相关的神经活动。本研究寻求对大鼠和人类中mPFC在决策中的作用的机制理解，并将进一步加深我们对与mPFC功能障碍相关的许多精神障碍的理解，包括成瘾、精神分裂症和抑郁症。

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.