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，过去的信息必须适用于现在的决定。导致奖励的行为很可能会重复，而导致惩罚的行为则不会重复。一个特定的额叶大脑区域，内侧前额叶皮质(MPFC)，似乎对这一过程至关重要。例如，mPFC受损的人类在涉及风险的决策中表现出糟糕的判断力。在大鼠中，同源区域在记忆提取中起着关键作用。我假设，在人类和大鼠身上，mPFC的作用都是通过预测预期行为的情感后果来指导决策，并以过去的经验为指导。为了验证这一假设，我将使用多电极记录(使用微小的导线同时记录数十个神经元的放电活动)和暂时失活(包括局部注射麻醉剂)来研究大鼠的决策过程。第一组实验试图揭示mPFC中神经元是如何代表奖励和恐惧的。用来编码积极和消极体验的神经元是相同的吗？实验还将考察缓解因素的影响，例如对有害刺激的控制或实现奖励所需的努力，对有害或奖励刺激的神经编码的影响。第二组实验探索了mPFC在记忆提取中的作用。他们试图澄清mPFC除了在长期记忆中的已知作用外，是否还调节短期记忆。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。第二个实验使用一个赌博任务，其中包括在高风险、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，我希望看到神经活动与个人选择的预期情感结果直接相关。这项研究试图从机制上理解mPFC在大鼠和人类决策中的作用，并将进一步了解与mPFC功能障碍有关的许多精神障碍，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.