PROJECT SUMMARY. The ability to integrate sensory information over time to guide adaptive behavior is a critical component of healthy cognition that is disrupted in psychiatric illnesses and neurological disorders. Motivational salience is known to bias sensory processing and lead to systematic errors in perceptual decisions. Past work has shown that errors can be driven by the enhancement of neural responses to motivationally desirable perceptual features, but the neural mechanisms that underlie this enhancement are underspecified. The locus coeruleus norepinephrine (LC-NE) system modulates neural responsivity to sensory stimuli, and is well-positioned to mediate motivational effects on perceptual decisions. The proposed research will use novel LC imaging methods and causal manipulation of neural activity using transcranial magnetic stimulation (TMS) to investigate the role of the LC-NE system in mediating motivational biases in perceptual decision-making. Participants will perform a visual categorization task where they are motivated to see one percept over another while undergoing functional magnetic resonance imaging (fMRI). Prior work has faced significant challenges in reliably measuring LC signal using fMRI due to its small size and individual variability in its location. Aim 1 will thus use recently developed neuromelanin-sensitive imaging sequences to localize the LC in individual participants and assess how LC activity tracks the enhancement or suppression of sensory representations decoded using multivoxel pattern analysis (MVPA). The proposed study will test two hypothesized mechanisms that allow the LC-NE system to selectively enhance the neural representation of desirable percepts: 1) amplifying neural responses to desirable features via changes in neural gain and 2) suppressing neural responses to less desirable features by increasing inhibition to sensory cortices via the dorsolateral prefrontal cortex (DLPFC). Aim 2 will then use TMS to disrupt DLPFC function prior to participants performing the task in the MRI scanner. If motivational effects on sensory representations are causally dependent on the DLPFC, exogenously perturbing DLPFC will reduce or even eliminate these effects. These results will thus provide causal evidence that the DLPFC modulates motivational biases in perceptual decision-making. The proposed research will address a fundamental gap in our understanding of how motivation shapes sensory processing and perceptual decision-making. The knowledge gained from these studies will lay the foundation for future work investigating the motivational bases of deficits in perceptual decision-making in diseased brain states. The proposed research also affords training in LC imaging and TMS, innovative tools that will allow the characterization and manipulation of neural circuits that underlie various motivation-cognition interactions. Future work will use these methods to probe motivational biases in other cognitive domains...