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

摘要 高阶丘脑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，枕叶和背内侧丘脑的数据表明，它们参与了 决策在具有挑战性的条件下增加，包括感知上的不确定性。精神分裂症是一种 一端易受不确定性和连通性干扰的紊乱 在高级丘脑和联合皮质靶点之间，在另一种情况下。因此，确定 高级丘脑参与和认知处理之间的机械联系在翻译上是- 相关；高阶丘脑区域可能是治疗耐药患者神经刺激的有效靶点 精神分裂症。该项目将利用Tupaia Bellangeri(树鼠)作为模式生物，为 该中心的总体目标。图帕亚是一种基本的灵长类动物，其大脑大小不受光学干扰的影响 这很容易在行为层面上观察到，强化了可以做出的随意推断 大脑-行为关系。在这个项目的目标I中，我们将建立在我们关于MD的广泛初步数据的基础上 丘脑功能。这将与P3密切合作，P3将在 猕猴共同识别MD调节额叶之间相互作用的机制 分层推理背景下的大脑皮层区域。在AIM II中，我们将使用图帕亚的视觉系统来询问 关于运动中背侧和腹侧视流参与的枕部调节的类似问题 与颜色切换任务；这将与P1密切协调，P1将瞄准猕猴的枕骨。 最后，AIM III将利用与精神分裂症(慢性)的病理生理学相关的药理学模型 甲基苯丙胺)，在任务表现的背景下检查大脑-行为关系。这将是 与P5密切协调完成，P5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AIMS中，将与P4、核心B和C密切合作，以 确保这些数据有助于建立一个生物学上可信的人类模型 丘脑。总而言之，成功完成我们的目标将有助于实现这一总体愿景 中心推动对丘脑皮质处理和认知的基本理解，以及 获得治疗精神分裂症的翻译性见解。

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.