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.

摘要 丘脑高阶区域通过调节其皮质靶点在认知过程中起着关键作用。 来自这两个区域的数据，枕丘脑和中背丘脑，表明他们参与 在具有挑战性的条件下，包括感知的不确定性，决策能力会增加。精神分裂症是一种 以一端的不确定性和扰动的连接性为特征的高度不确定性的无序 在另一个实验中，高级丘脑和关联皮层的目标之间存在联系。因此，识别 高级丘脑参与和认知过程之间的机械联系是间接的- 相关;高阶丘脑区域可能是治疗抵抗性神经刺激的可行靶点 精神分裂症本项目将利用树鼩作为模式生物， 本中心的总体目标。树鼩是一种基础灵长类动物，其大脑大小适合光学扰动 这可以很容易地在行为层面上观察到，收紧了可以做出的关于 脑行为关系在本项目的目标一，我们将建立在我们广泛的初步数据MD 丘脑功能这将与P3密切合作，P3将在 猕猴共同确定机制，其中MD调节额叶之间的相互作用， 皮层区域在层次推理的背景下。在Aim II中，我们将使用Tupaia的视觉系统来询问 运动中枕对背侧与腹侧视觉流参与调节的类似问题 vs.颜色切换任务;这将与P1密切协调，P1将靶向猕猴的枕。 最后，目标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），以检查在任务执行的背景下，大脑行为的关系。这将是 与P5密切协调，这将询问人类的高级丘脑结构， 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， 确保数据有助于建立一个生物学上合理的人类模型的一般见解 丘脑总之，成功完成我们的目标，将有助于实现这一总体愿景。 中心在推动丘脑皮层处理和认知的基本理解前进，以及 获得精神分裂症治疗的转化见解。