Project Summary Cognitive control refers to the general ability that allows one to complete relevant everyday tasks and pursue demanding goals in the face of distraction. This flexible control of information processing is linked to the prefrontal cortex (PFC), which is found to modulate brain activity by enhancing task-relevant processes and down-regulating processes in task-irrelevant regions. Different regions of the PFC form critical elements of brain networks that have been related to cognitive control: the cingulo-opercular (CO) network, linked to maintaining alertness, and the fronto-parietal (FP) network, linked to moment-to-moment adjustments of behavior. While the distinction between these networks is well-studied, it is unclear how these networks interact to support performance in the midst of changing task demands. Using a task-switching paradigm and converging brain imaging methods, this proposal aims to investigate the dynamic mechanisms of cognitive control by analyzing brain network interactions and its specific effects on behavior. Specifically, Aim 1 will examine large-scale whole-brain reorganization and changing fronto-parietal (FP) and cingulo-opercular (CO) network interactions as mechanisms for dynamic implementation of cognitive control. Greater network interactions driven by greater connectivity between cognitive control networks in response to cognitively demanding situations (i.e. switch trials) is hypothesized to facilitate transfer and processing of information to achieve relevant goals. This first aim will probe whether such reconfiguration occurs rapidly as task demands change from trial to trial in a switching paradigm that requires rapid redirection of attentional control from one task to another. Functional magnetic resonance imaging (fMRI), a method that estimates neural activity using associated changes in blood flow, will be used to extract measures of correlated activity between brain regions and networks. Aim 2 will involve perturbing activity in the CO & FP cognitive control networks to determine the differential effects of specific network disruption on cognitive control, simulating neurological disorders that involve changes in connected, but undamaged brain regions. Transcranial magnetic stimulation (TMS) will be used to for this second aim; TMS is a non-invasive technique that can temporarily suppress brain activity over a targeted region without long-term consequences on brain function or behavior. Gaining insight into the dynamics of cognitive control?both at the adaptive task level and following network disruption, can shed light on the broad effects of PFC disruption in patients with traumatic brain injury, stroke, and depression. Identifying the brain mechanisms important for performance, and the ways in which acute damage modifies these mechanisms will inform biomarkers that can aid in developing diagnostic tools and avenues for treatment.