Thalamic regulation of prefrontal dynamics in decision making under uncertainty

不确定性下决策中前额叶动态的丘脑调节

• 批准号: 10429542
• 负责人: Arghya Mukherjee
• 金额: $ 10.92万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429542
• 关键词: Address; Animal Behavior; Animals; Attention; Auditory; Behavior; Behavioral; Belief; Belief System; Biological Models; Brain; Communication; Communities; Complex; Conflict (Psychology); Cues; Data; Decision Making; Development Plans; Dissection; Dorsal; Economics; Electrophysiology (science); Environment; Failure; Foundations; Future; Genetic; Human; Learning; Mental disorders; Mentors; Modeling; Modernization; Molecular; Mus; Neurons; Noise; Outcome; Phase; Play; Population; Prefrontal Cortex; Primates; Probability; Process; Psychiatry; Psychological reinforcement; Psychoses; Psychotic Disorders; Regulation; Research; Research Proposals; Rewards; Rodent; Role; Schizophrenia; Sensory; Signal Transduction; Source; Specific qualifier value; Stimulus; Structure; System; Techniques; Testing; Thalamic structure; Therapeutic; Training; Tupaia; Tupaiidae; Uncertainty; Update; Visual; attentional control; base; behavioral outcome; career; career development; cell type; cognitive control; cognitive neuroscience; cognitive process; experimental study; frontal lobe; in vivo; neural circuit; optogenetics; public health relevance; relating to nervous system; sensory input; statistics; targeted treatment; tool; translational study

Abstract: Research Plan: Decision making is a process through which actions are selected based on sensory cues or value of desired outcome. Critical to their function decision making systems, like the prefrontal cortex (PFC), need to capture the causal structure of its environment (an internal model or belief system) and update its internal beliefs when underlying associations change. While a lot of effort has gone into understanding neural circuit mechanisms within the PFC recent findings suggest that interactions with the medio dorsal thalamus (MD) is crucial for its function and are especially important when decisions must be made using information that is noisy. Moreover, failure to resolve noise in updating internal beliefs is thought to underlie schizophrenia and related psychotic illnesses. Thus, determining the circuit mechanisms of MD-PFC interactions is relevant to not only cognitive neuroscience but also to psychiatry. This K99/R00 research proposal will address the role of MD in regulating PFC dynamics during decision making under uncertainty through the following three Aims. Aim 1, will explore if genetically identifiable populations within the MD, due to their unique connectivity with the PFC, are selectively geared towards resolving sensory input uncertainty arising from high noise versus low signal. Aim 2 will explore the role of MD in a multi-step decision making paradigm to study human-like reasoning using treeshrews (Tupaia), which are akin to basal primates. The first two Aims 2 will be carried out in the K99 training phase. In Aim 3, performed in the independent R00 phase the findings from Aim 1 and 2 will be extended to economic decision making where uncertainty exists at the level of expected rewards. These Aims collectively, will elucidate the circuit mechanisms through which the MD-PFC interactions play a role in resolving uncertainty in decisions and will further provide precise targets through which deficits in decision making can be therapeutically ameliorated. Career Development Plan: The K99 training will provide the tools and training necessary to study the activity of neurons in the brain to decipher underlying circuit mechanisms. The R00 phase will build the foundations of an independent research career driven by experiments that deconstructs complex decision making into a combination of simpler cognitive processes sub served by specified circuitry.

摘要： 研究计划：决策是一个过程，通过这个过程，根据感官线索选择行动， 期望结果的价值。对他们的功能决策系统至关重要，如前额叶皮层（PFC）， 需要捕捉其环境的因果结构（内部模型或信念系统），并更新其 当潜在的关联发生变化时的内部信念。 虽然很多努力都是为了了解PFC内的神经回路机制， 表明与背内侧丘脑（MD）的相互作用对其功能至关重要， 当必须使用噪声信息做出决策时，这很重要。此外，未能解决噪音， 更新内在信念被认为是精神分裂症和相关精神病的基础。因此，在本发明中， 确定MD-PFC相互作用的电路机制不仅与认知神经科学有关， 精神病学也是如此。本K99/R 00研究提案将讨论MD在调节PFC动态中的作用 在不确定性下的决策过程中，通过以下三个目标。目标1，将探索基因 MD内可识别的人群，由于他们与PFC的独特连接，选择性地适应 致力于解决由高噪音与低信号引起的感官输入不确定性。目标2将探讨 MD在多步决策范式中的作用，以研究使用treeshrews（Tupaia）的类人推理， 它们类似于灵长类动物。前两个目标2将在K99训练阶段进行。在目标3中， 在独立的R 00阶段，目标1和2的结果将扩展到经济决策 在预期回报水平存在不确定性的情况下进行决策。这些目标将共同阐明 一种电路机制，通过这种机制，MD-PFC相互作用在解决决策中的不确定性方面发挥作用 并将进一步提供精确的靶点，通过这些靶点， 改善。 职业发展计划：K99培训将提供学习该活动所需的工具和培训 来破译潜在的电路机制。R 00阶段将建立基础 一个独立的研究生涯，由实验驱动，将复杂的决策分解为一个 由特定回路辅助的简单认知过程的组合。