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目标在认知处理中发挥关键作用。 来自丘脑枕丘和内侧丘脑这两个区域的数据表明，它们参与 在具有挑战性的条件下做出决策会增加，包括感知不确定性。精神分裂症是一种 一种疾病，其特征是一端对不确定性高度敏感且连通性受到干扰 另一方面，在高阶丘脑和关联皮质目标之间。因此，识别 高阶丘脑参与和认知处理之间的机械联系是平移的- 相关的;高阶丘脑区域可能是治疗抵抗性神经刺激的可行目标 精神分裂症。该项目将利用 Tupaia Bellangeri（树鼩）作为模式生物，以促进 本中心的总体目标。图帕亚是一种基础灵长类动物，其大脑大小适合光学扰动 在行为层面上很容易观察到，从而加强了可以做出的随意推论 大脑与行为的关系。在该项目的目标 I 中，我们将基于 MD 的广泛初步数据 丘脑功能。这将与 P3 密切合作，P3 将在 猕猴共同确定了 MD 调节额叶之间相互作用的机制 层次推理背景下的皮质区域。在Aim II中，我们将使用Tupaia的视觉系统来询问 关于运动中背侧和腹侧视觉流参与的枕调节的类似问题 与颜色切换任务；这将与 P1 密切协调，P1 将针对猕猴的 pulvinar。 最后，Aim III 将利用与精神分裂症（慢性）病理生理学相关的药理学模型 甲基苯丙胺）来检查任务执行背景下的大脑行为关系。这将是 与 P5 密切配合完成，它将询问人类的高阶丘脑结构 精神分裂症和健康对照。在所有目标中，将与 P4、核心 B 和 C 密切合作，以 确保数据为构建生物学上合理的人类模型提供一般见解 丘脑。总而言之，成功完成我们的目标有望为实现这一目标的总体愿景做出贡献 中心致力于推动丘脑皮质处理和认知的基本理解，以及 得出治疗精神分裂症的转化见解。