Functions and thalamocortical interactions of macaque higher order thalamus in cognitive control

项目2总结 项目2(P2)将通过研究认知控制对中心假设1和3做出具体贡献 丘脑的两个高级核团，内侧后枕核(mdPUL；灵长类动物特有的部分) 枕骨)和MD及其皮质网络。人类和非人类灵长类动物的损伤研究 (NHP)表明，特别是这些原子核，它们主要与极大扩张的 联想皮层在包括执行功能在内的认知控制功能中发挥着重要作用， 注意力和工作记忆。具体地说，我们将目标是mdPul-额顶(额眼视野，FEF；外侧 顶内区域(LIP)在中心的“知觉下注意不确定”(APU)任务中的网络和MD- PFC-ACC(背外侧前额叶皮质，dlPFC；前扣带回皮质，ACC)在中枢的 “分层决策”(HDM)任务。前一项研究将允许直接比较与感官相关的 枕骨的部分在同一任务中被探测，在P1中，在大范围，在P3中，在电路水平，在P4中，在 网络级别与灵长类特定的mdpul。后一项研究将补充电路级(P3)和网络 相同HDM任务的水平(P4)调查。所有三个动物项目的结果预计都将提供一个 健康人P4和P4神经影像间接神经测量的机制模型 如何在疾病中改变它们(第5页)。计算结果将为所采取的计算建模方法提供依据 在核心B中。鉴于国家方案项目(P1、P2)的数据结构相似，项目领导人将密切合作 与Core C合作，建立通用的前处理程序和分析策略，以及探测 并开发创新的新战略，以表征同时获得的人口记录。在P2P中， 我们建议对丘脑和相互连接的皮质区域进行同步记录，以测试KEY 关于高级丘脑在认知中的作用的假说。在目标1中，我们将研究 在我们的APU任务中训练猴子的mdPul-lip-FEF网络。我们的假设是枕骨计算信号 反映了在注意过程中控制大脑皮层区域功能连接的决策不确定性 分配。在目标2中，我们将针对我们的HDM训练的猴子的MD中的dlPFC、ACC及其投影区 任务。我们的假设是，MD代表规则映射的不确定性，并将调节ACC-dlPFC的相互作用 基于这样的表述。在目标3中，我们将描述丘脑的不同和共性 AIMS 1和2中研究的电路的计算和丘脑皮质相互作用以确定可能的 出现的一般功能组织原则，而不考虑特定的丘脑皮质回路 核团是核团的一部分或由其支持的认知活动。总体而言，P2的预期成果将 为人类丘脑的机制和生物学上可信的模型提供必要的信息 功能。

PROJECT 2 SUMMARY Project 2 (P2) will specifically contribute to Center hypothesis 1 and 3 by investigating cognitive control functions of two higher order thalamic nuclei, the medio-dorsal pulvinar (mdPUL; a primate-specific part of the pulvinar) and the MD along with their cortical networks. Lesion studies in humans and non-human primates (NHP) indicate that particularly these nuclei, which are primarily interconnected with the vastly expanded association cortices, play an important role in cognitive control functions including executive functioning, attention, and working memory. Specifically, we will target a mdPul-fronto-parietal (frontal eye field, FEF; lateral intraparietal area, LIP) network in the Center’s “Attention-under-perceptual-uncertainty” (APU) task and an MD- PFC-ACC (dorsolateral prefrontal cortex, dlPFC; anterior cingulate cortex, ACC) network in the Center’s “Hierarchical Decision Making” (HDM) task. The former study will permit a direct comparison of sensory-related parts of pulvinar probed in the same task in P1 at the large-scale, in P3 at the circuit level, and in P4 at the network level with the primate-specific mdPul. The latter study will complement the circuit level (P3) and network level (P4) investigation of the same HDM task. The results of all three animal projects are expected to provide a mechanistic model for the indirect neural measures obtained with neuroimaging in healthy humans in P4 and how they may be altered in disease (P5). The outcomes will inform the computational modeling approach taken in Core B. Given the similar data structure of the NHP projects (P1, P2), the project leaders will closely collaborate with Core C to establish common preprocessing routines and analytical strategies, as well as probe and develop innovative novel strategies to characterize simultaneously acquired population recordings. In P2, we propose to perform simultaneous recordings from thalamus and interconnected cortical areas to test key hypotheses about the role of higher order thalamus in cognition. In Aim 1, we will investigate interactions of a mdPul-LIP-FEF network in monkeys trained on our APU task. Our hypothesis is that pulvinar computes signals that reflect decision uncertainty to control functional connectivity across cortical areas during attentional allocation. In Aim 2, we will target dlPFC, ACC and their projection zones in MD in monkeys trained on our HDM task. Our hypothesis is that MD represents rule mapping uncertainty and will modulate ACC-dlPFC interactions based on such representation. In Aim 3, we will characterize differences and commonalities in thalamic computations and thalamocortical interactions of the circuits investigated in aims 1 and 2 to identify possible general functional organization principles that emerge regardless of the specific thalamocortical circuit that a nucleus is part of or the cognitive operations supported by it. Collectively, the expected outcomes for P2 will provide essential information towards a mechanistic and biologically plausible model for human thalamus function.