Mechanistic dissection of cognitive thalamocortical engagement in attention and hierarchical reasoning.

认知丘脑皮质参与注意力和层次推理的机制剖析。

• 批准号: 10633808
• 负责人: Michael M Halassa
• 金额: $ 49.25万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-03 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633808
• 关键词: Address; Animals; Area; Attention; Behavior; Behavior Control; Brain; Chronic; Cognition; Cognitive; Collaborations; Color; Complement; Cues; Data; Data Analytics; Decision Making; Diagnosis; Disease; Dissection; Dorsal; Environment; Esthesia; Functional disorder; Glean; Human; Individual; Learning; Link; Macaca; Maps; Methamphetamine; Modeling; Motion; Optics; Pattern; Perception; Play; Primates; Pulvinar structure; Regulation; Resistance; Rodent; Role; Schizophrenia; Signal Transduction; Stimulus; Stream; Structure; Symptoms; System; Task Performances; Testing; Thalamic structure; Training; Tupaia; Tupaiidae; Uncertainty; Viral; Vision; Visual; Visual Cortex; Visual System; Work; area striata; brain behavior; brain size; cognitive task; experimental study; frontal lobe; functional restoration; insight; model organism; pharmacologic; response; statistics; synergism; theories; therapeutic evaluation; tool

Abstract Higher order thalamic regions play critical roles in cognitive processing by regulating their cortical targets. Data from both such regions, the pulvinar and mediodorsal thalamus, indicate that their engagement in decision making increases in challenging conditions, including perceptual uncertainty. Schizophrenia is a disorder characterized by heightened susceptibitly to uncertainty on one end and perturbed connectivity between higher order thalamus and associative cortical targets, on another. Therefore, identifying the mechanistic links between higher order thalamic engagement and cognitive processing is translationally- relevant; higher order thalamic regions may be viable targets for neurostimulation in treatment-resistant schizophrenia. This project will utilize Tupaia Bellangeri (Tree shrews) as a model organism to contribute to the overall Aims of this Center. Tupaia is a basal primate with a brain size amenable for optical perturbations that can be readily observed at the level of behavior, tightening the casual inferences that can be made about brain-behavior relationships. In Aim I of this project, we will build upon our extensive preliminary data on MD thalamic function. This will be in close collaboration with P3, which will perform analogous experiments in macaque collectively identifying the mechanisms by which the MD regulates interactions between frontal cortical areas in the context of hierarchical reasoning. In Aim II, we will use the visual system of Tupaia to ask analogous questions on pulvinar regulation of dorsal versus ventral visual stream engagement in a motion vs. color switching task; this will be coordinated closely with P1, which will target the pulvinar in the macaque. Lastly, Aim III will leverage a pharmacological model relevant to the pathophysiology of schizophrenia (chronic methamphetamine) to examine brain-behavior relationships in the context of task performance. This will be done in close coordination with P5, which will interrogate higher order thalamic structure in humans with schizophrenia and healthy controls. In all Aims, there will be close collaboration with P4, Cores B and C, to ensure that the data contributes general insights for building a biologically-plausible model of the human thalamus. Altogether, successful completion of our Aims promises to contribute to the overall vision of this Center in propelling the basic understanding of thalamocortical processing and cognition forward, as well as deriving translational insights for treatment of schizophrenia.

抽象的 高阶丘脑区域通过调节其皮质靶标在认知过程中起关键作用。 来自这两个区域的数据，Pulvinar和中型丘脑，表明它们参与 决策在具有挑战性的条件下增加，包括感知不确定性。精神分裂症是 疾病的特征是一端的敏感性增强至不确定性和连通性的障碍 在高阶丘脑和同性皮质靶标之间，另一个。因此，确定 高阶丘脑参与与认知处理之间的机械联系是翻译 相关的;高阶丘脑区域可能是可行的耐药性神经刺激的靶标 精神分裂症。该项目将利用tupaia bellangeri（树sh）作为模型有机体 这个中心的总体目标。图帕亚是一种基础灵长类动物，可用于光学扰动 这可以在行为层面上很容易观察到，从而收紧了可以做出的休闲推论 脑行为关系。在该项目的目标中，我们将基于有关MD的广泛初步数据 丘脑功能。这将与P3密切合作，该P3将在 猕猴集体识别MD调节额叶之间相互作用的机制 在层次推理的背景下的皮质区域。在AIM II中，我们将使用Tupaia的视觉系统询问 关于运动中背侧与腹侧视觉流的脉冲调节的类似问题 vs.颜色切换任务；这将与P1紧密协调，该P1将针对猕猴的脉冲。 最后，AIM III将利用与精神分裂症的病理生理学相关的药理学模型（慢性 甲基苯丙胺）在任务绩效的背景下检查脑行为关系。这将是 与P5密切协调，这将询问人类的高阶丘脑结构 精神分裂症和健康对照。总的来说，将与P4，核心B和C进行密切合作与 确保数据有助于建立人类生物学上的模型的一般见解 丘脑。总的来说，成功完成我们的目标有望为这一总体愿景做出贡献 中心是推动对丘脑皮质加工和认知向前的基本理解以及 得出用于治疗精神分裂症的翻译见解。