Thalamic Mechanisms of Cognitive Control

描述(申请人提供)：认知控制是一种认知能力，允许我们对目标导向行为的感觉、知觉、运动和其他心理过程进行适应性调节。一个著名的认知控制理论表明，额叶皮质是自上而下控制信号的来源，这些信号使较低级别的大脑过程偏向于产生自愿行为。然而，控制信号如何传递到大脑皮质区域，以增强任务相关和抑制任务无关的过程仍有很大争议。这项提议的目的是检验一种假设，即丘脑作为一个“中枢”，将自上而下的偏向信号从额叶皮质传递到感觉运动网络中的目标皮质部位。这一假说来自于解剖学证据，表明存在跨丘脑、皮质-丘脑-皮质通路，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能抑制神经元，而皮质GABA能抑制神经元是调节新皮质过程的关键。为了验证我的假设，丘脑在认知控制中的作用将通过系统地检查其与皮质的功能相互作用来评估。在目标1中，我将使用静止状态泛函 连通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 大脑网络通信。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将证明丘脑是支持认知控制和感觉运动网络之间的网络通信的关键节点，允许特定任务的偏向信号到达其适当的皮质目标。在目标2中，我们将使用 一项同时进行经颅磁刺激(TMS)和功能磁共振成像(FMRI)的尖端研究，旨在绘制涉及抑制分心感觉信息的额叶-丘脑-皮质通路中的信息流方向。与行为任务相结合，fMRI可以检测本地和远程TMS影响，以及这些影响如何随着任务条件的变化而变化。这种新颖的方法将使我能够绘制与任务相关的网络动态图。我们假设，在分心干扰抑制期间，在额叶皮质上施加TMS脉冲将增加丘脑活动，并增强丘脑-皮质连接，以抑制与任务无关表征相关的皮质活动。完成目标2将证明额叶-丘脑-皮质通路为认知抑制调节自上而下的偏向信号。许多神经和精神疾病，如创伤性脑损伤、痴呆症、精神分裂症、抑郁症和注意力缺陷障碍，都以认知控制不足为特征。关于丘脑和认知控制的基础知识可以为大量疾病的性质提供实质性的见解，这些疾病越来越多地被认为受到丘脑-皮质连接异常的影响。

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.