Cognitive Control Functions of the Human Thalamus

项目摘要 认知控制是一个总括性术语，描述了调节认知、感知和 进行适应性目标导向行为所需的运动功能。患有神经和精神疾病的患者 疾病，例如精神分裂症、注意力缺陷多动障碍（ADHD）、创伤性脑损伤和 中风，患有认知控制障碍。虽然额顶叶和纹状体回路的功能在 认知控制已经被广泛研究，越来越多的证据表明丘脑的作用。丘脑 核团与多个皮层区域有相互和非相互联系，整合调节性输入 从其他皮层下结构，并支配兴奋性和抑制性皮层神经元。尽管如此 突出的连接概况，人类丘脑在认知控制中的作用及其功能障碍的影响 并没有得到很好的理解。本研究的目的是确定认知控制功能 丘脑的一部分。我们的中心假设，基于我们广泛的初步数据和解剖 在动物模型中，丘脑皮层回路的特性是丘脑核支持认知控制， 调节皮质活动，包括诱发反应、皮质网络相互作用和神经振荡。 这些皮层活动体现了选择或维持任务相关信息的神经认知过程， 并且它们可以通过有针对性地增加丘脑皮质的相互作用而被选择性地放大。因此，委员会认为， 丘脑皮质功能障碍可导致认知僵化、注意力分散增加和计划不良。来测试我们 假设，我们提出了一种新的方法，整合认知行为任务，具体操纵 选择和维护任务相关信息的过程（例如，工作记忆和设置切换）， 多模式神经成像（fMRI和EEG）和人类丘脑病变研究。我们将首先确定 功能组织（地形）的丘脑皮层功能连接的认知控制（目的1），其中 尚未在人类中系统地绘制出来。然后我们将确定丘脑皮质的相互作用 通过检查任务相关信息与任务的关系以及对任务的调节作用来选择和保持任务相关信息， 相关皮质活动（目标2和3）。对于所有研究，我们将招募健康个体， 丘脑病变和来自病变对照组的对照患者。通过收集多模式神经成像 数据从患者的局灶性丘脑病变，我们将确定如何破坏丘脑皮质的相互作用， 影响与任务相关的皮层神经活动和行为。我们的研究结果将确定如何 丘脑皮质连接的分布使丘脑核团参与多种认知控制 功能，并详细说明在患者中观察到的丘脑皮质功能障碍的认知和神经影响 丘脑中风，以及其他疾病，如多动症和精神分裂症。

PROJECT SUMMARY Cognitive control is an umbrella term that describes processes that regulate cognitive, perceptual, and motor functions needed to perform adaptive, goal-directed behaviors. Patients with neurological and psychiatric disorders, for example schizophrenia, attention-deficit hyperactivity disorder (ADHD), traumatic brain injury and stroke, suffer from impairments in cognitive control. Although the function of frontoparietal and striatal circuits in cognitive control have been extensively studied, increasing evidence suggests a role for the thalamus. Thalamic nuclei have reciprocal and non-reciprocal connections with multiple cortical regions, integrate modulatory inputs from other subcortical structures, and innervate both excitatory and inhibitory cortical neurons. Despite this prominent connectivity profile, the role of the human thalamus in cognitive control and effects of its dysfunction are not well understood. The objective of the proposed research is to determine the cognitive control functions of the human thalamus. Our central hypothesis, based on our extensive preliminary data and anatomical properties of thalamocortical circuits in animal models, is that thalamic nuclei support cognitive control by modulating cortical activities that include evoked responses, cortical network interactions, and neural oscillations. These cortical activities instantiate neurocognitive processes that select or maintain task-relevant information, and they can be selectively amplified through targeted increases in thalamocortical interactions. Consequently, thalamocortical dysfunction can lead to cognitive rigidity, increased distraction, and poor planning. To test our hypothesis, we propose a novel approach that integrates cognitive behavioral tasks that specifically manipulate processes that select and maintain task-relevant information (for example, working memory and set switching), multimodal neuroimaging (fMRI and EEG), and human thalamic lesions studies. We will first determine the functional organization (topography) of thalamocortical functional connectivity for cognitive control (Aim 1), which has not yet been systematically mapped in humans. We will then determine how thalamocortical interactions select and maintain task-relevant information by examining its relationship with, and modulatory effects on, task- related cortical activities (Aims 2 and 3). For all studies, we will recruit healthy individuals, patients with focal thalamic lesions, and control patients from a lesion comparison group. By collecting multimodal neuroimaging data from patients with focal thalamic lesions, we will determine how the disruption of thalamocortical interactions affects task-related cortical neural activities and behavior. Results from our proposed research will establish how the distribution of thalamocortical connectivity enables thalamic nuclei to participate in multiple cognitive control functions, and specify the cognitive and neural repercussions of thalamocortical dysfunction observed in patients with thalamic stroke, as well as other disorders such as ADHD and schizophrenia.