Thalamic Mechanisms of Cognitive Control

描述（由申请人提供）：认知控制是一种认知能力，使我们能够自适应地调节感官、知觉、运动和其他目标导向行为的心理过程。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，这些信号会影响较低层次的大脑过程，从而产生自愿行为。然而，控制信号如何传递到皮层的各个区域以增强任务相关和抑制任务无关的过程仍然存在很多争论。这一提议的目的是验证一种假设，即丘脑作为一个“枢纽”，调解从额叶皮层传递到感觉运动网络中目标皮质部位的自上而下的偏置信号。这一假说来自解剖学证据，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散的联系，并且丘脑-皮质通路支配皮质gaba能抑制神经元，这些神经元对调节新皮质过程至关重要。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层的功能相互作用来评估。在Aim 1中，我将使用静息状态函数

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.