Thalamic Mechanisms of Cognitive Control

描述（由申请人提供）：认知控制是一种认知能力，它允许我们适应性地调节感官、知觉、运动和其他心理过程，以实现目标导向的行为。一个著名的认知控制理论认为，额叶皮层是自上而下的控制信号的来源，这些信号使低级大脑过程产生偏见，从而产生自愿行为。然而，控制信号是如何传递到大脑皮层区域，以增强任务相关和抑制任务无关的过程仍然存在很大的争议。这个建议的目的是测试一个假设，丘脑作为一个“枢纽”，以调解自上而下的偏置信号从额叶皮层内的感觉运动网络的目标皮层网站。这一假设来自解剖学证据，表明存在经丘脑的皮质-丘脑-皮质通路，其在分布的皮质区域之间提供广泛和弥漫的联系，并且丘脑-皮质通路支配皮质GABA能抑制性神经元，其对于调节新皮质过程至关重要。为了验证我的假设，我们将通过系统地检查丘脑与皮层的功能相互作用来评估丘脑在认知控制中的作用。在目标1中，我将使用静息态泛函 连接性磁共振成像和图论测量，如网络中心性和参与系数，以量化丘脑对功能的贡献。 大脑网络通讯研究丘脑局灶性病变的患者将进一步增强我的推理能力，我将评估丘脑病变如何对网络互动产生负面影响。完成目标1将证明丘脑作为一个关键节点，支持认知控制和感觉运动网络之间的网络通信，允许任务特定的偏置信号到达适当的皮层目标。在目标2中，我们将采用 一项尖端的同步经颅磁刺激（TMS）和功能性MRI（fMRI）研究，旨在绘制额丘脑皮层通路内的信息流方向，该通路参与抑制分散注意力的感觉信息。结合行为任务，fMRI可以检测本地和远程TMS效应以及这些效应如何随任务条件而变化。这种新颖的方法将使我能够绘制与任务相关的网络动态。我们假设在分心抑制期间在额叶皮层上施加TMS脉冲将增加丘脑活动，并增强丘脑-皮层连接以抑制与任务无关的表征相关的皮层活动。完成目标2将证明，额叶-丘脑-皮层通路介导认知抑制的自上而下的偏置信号。许多神经和精神疾病如创伤性脑损伤、痴呆、精神分裂症、抑郁症和注意力缺陷障碍的特征在于认知控制缺陷。关于丘脑和认知控制的基本知识可以提供大量疾病的本质的实质性见解，这些疾病越来越多地被认为受到异常丘脑-皮质连接的影响。

DESCRIPTION (provided by applicant): Cognitive control is a cognitive capacity that allows us to adaptively regulate sensory, perceptual, motor, and other mental processes for goal-directed behaviors. A prominent theory of cognitive control suggests that the frontal cortex is the source of top-down control signals that bias lower-order brain processes to generate voluntary behaviors. However, how control signals are communicated to distribute cortical regions to enhance task-relevant and inhibit task-irrelevant processes remains much debated. The goal of this proposal is to test a hypothesis that the thalamus serves as a "hub" to mediate top-down biasing signals transmitted from the frontal cortex to targeted cortical sites within sensorimotor networks. This hypothesis is drawn from anatomical evidence indicating that there are transthalamic, cortico-thalamo-cortical pathways that provide widespread and diffuse linkages between distributed cortical regions, and that thalamo-cortical pathways innervate cortical GABAergic inhibitory neurons that are critical for modulating neocortical processes. To test my hypothesis, the role of thalamus in cognitive control will be assessed by systematically examining its functional interaction with the cortex. In Aim 1, I will use resting-state functional connectivity magnetic resonance imaging and graph theoretic measures such as network centrality and participation coefficient to quantify the contribution of the thalamus to functional brain network communications. Studying patients with focal thalamic lesions will further enhance my inferential power, and I will evaluate how thalamic lesions negatively affect network interactions. Completing Aim 1 will demonstrate that the thalamus serves as a pivotal node to support network communication between cognitive control and sensorimotor networks, allowing task-specific biasing signals to reach their appropriate cortical targets. In Aim 2, we will employ a cutting-edge simultaneous transcranial magnetic stimulation (TMS) and functional MRI (fMRI) study to map the direction of information flow within fronto-thalamo-cortical pathways involved in suppressing distracting sensory information. Coupled with a behavioral task, fMRI can detect local and remote TMS effects and how these vary with task conditions. This novel approach will enable me to map task-related network dynamics. We hypothesized that applying TMS pulse over the frontal cortex during distracter suppression will increase thalamic activity, and enhance thalamo- cortical connectivity to suppress cortical activities associated with task-irrelevant representations. Completing Aim 2 will demonstrate that a fronto-thalamo-cortical pathway mediates top-down biasing signals for cognitive inhibition. Many neurologic and psychiatric disorders such as traumatic brain injury, dementia, schizophrenia, depression, and attention-deficit disorders are characterized by deficient cognitive control. Basic knowledge about the thalamus and cognitive control can provide substantial insights into the nature of a large number of disorders that are increasingly acknowledged to be affected by aberrant thalamo-cortical connectivity.