Neural circuits underlying flexible control of evidence evaluation timescales in decision making

项目摘要 几乎在所有精神障碍中都可以观察到决策能力受损。神经回路机制 因此，负责灵活控制决策的人特别有希望成为 治疗以改善决策障碍。在阐明 支持影响决策过程的认知灵活性的许多方面的神经机制， 但相关的是，人们对控制证据形式和时间尺度的机制知之甚少。 评估决策。与用于研究的主导范式相反， 感知决策，侧重于涉及重复样本的线性整合的情况， 相反，许多决策受益于根据时间对证据进行不同的加权。 拟议中的实验将使用大鼠模型系统来探测柔性神经元的神经回路。 在这种情况下的证据评估控制。第一个目标是开发一种新的听觉 改变检测范式，以研究神经对涉及非整合形式的决策的贡献 证据评估。具体地说，我们将研究一个已知的大脑区域网络如何编码 在涉及证据线性整合的任务中，决策变量在这里编码决策变量 基于时间动态加权的证据评价方法。第二个目标将测试如何改变 判决界限影响变化检测范例中的这种编码。决策界限确定 选择承诺所需的证据数量，因此它们在控制选择承诺方面发挥着关键作用。 证据评估的时间表。我们将同时记录三个大脑区域之前 分别涉及决策界限的控制，以检查相关的神经变化 在区域之间协调。第三个目标将测试改变的决策内核如何引起变化 在同一个大脑区域网络中。决策核确定如何将证据加权为 时间的功能，因此它们在控制证据评价的形式上起着关键作用。我们将首先 检查每个被研究的大脑区域改变其对外部环境的反应动力学的程度。 基于改变的决策核的证据。接下来，我们将探讨那些直接参与 电路中负责改变反应动力学的区域与遗传改变的 来自上游神经处理的反应动力学。这项工作的目的是揭露目标 在特定的神经回路机制水平上进行原则性治疗，以改善决策 与精神障碍相关的损伤，包括我们实验室正在进行的工作。从长远来看，我们 我希望这项研究能够利用人类、非人类灵长类动物和啮齿类动物模型的组合 系统产生的神经回路机制的详细了解，基础灵活 控制决策的证据评估，为治疗开发铺平道路。

Project Summary Impaired decision making is observed in almost all mental disorders. Neural circuits mechanisms responsible for the flexible control of decision making therefore hold particular promise as targets for treatments to improve decision making impairments. Much progress has been made in elucidating the neural mechanisms supporting many aspects of cognitive flexibility that influence decision processes, but relevantly little is known about the mechanisms that control the form and timescale of evidence evaluation for decision making. In contrast to the dominant paradigms used for the study of perceptual decisions that focus on situations involving linear integration of repeated samples of evidence, many decisions instead benefit from weighting evidence differentially as a function of time. The proposed experiments will use a rat model system to probe the neural circuits underlying flexible control of evidence evaluation in these circumstances. The first aim will develop a new auditory change detection paradigm to study neural contributions to decisions involving non-integrative forms of evidence evaluation. Specifically, we will examine how a network of brain regions known to encode decision variables in tasks involving linear integration of evidence here encodes decision variables based on dynamic weighting with time in evidence evaluation. The second aim will test how altered decision bounds affect this encoding in the change detection paradigm. Decision bounds determine the amount of evidence needed for choice commitment, so they play a key role in control over the timescale of evidence evaluation. We will simultaneously record from three brain regions previously implicated separately in the control of decision bounds to examine how associated neural changes are coordinated between regions. The third aim will test how altered decision kernels induce changes in the same network of brain regions. Decision kernels determine how evidence is weighted as a function of time, so they play a key role in control over the form of evidence evaluation. We will first examine the degree to which each of the studied brain regions alters it response dynamics to external evidence based on altered decision kernels. Next, we will probe the direct involvement of those regions in circuits responsible for the altered response dynamics versus the inheriting of altered response dynamics from upstream neural processing. The objective of this work is to expose targets for principled treatments at the level of specific neural circuit mechanisms to improve decision making impairments associated with mental disorders, including ongoing work in our lab. In the long term, we expect this research to harness a combination of human, non-human primate, and rodent model systems to produce a detailed understanding of the neural circuit mechanisms that underlie flexible control over evidence evaluation for decision making, paving the way for treatment development.