Thalamic Mechanisms of Cognitive Control

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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.