PROJECT SUMMARY. To find an object in a complex scene, we use feature-based attention to guide our search, typically in conjunction with spatial attention and targeting eye movements. When searching for our keys on a table, for example, the features of the keys are used as an attentional template that guides the eyes to the various objects sharing features with keys until the keys are found. Work from our own and other labs has found that objects with attended features or attended locations are processed more efficiently in visual cortex, while the processing of unattended, distracting objects is suppressed. To design an effective neural prosthesis or to treat people with sensory or attentional impairments, we need a better mechanistic understanding of these attentional mechanisms at the systems level. The interconnected structures important for the control of attention have many common features. At the surface level, these common features suggest there may be little difference in their functions. However, our results show surprising specificity instead. We find that the ventral pre-arcuate area (VPA) and the frontal eye fields (FEF) in prefrontal cortex (PFC) have different functions in visual search. Specifically, VPA appears to mediate the selection of likely targets based on their features, and FEF directs spatial attention and gaze to those possible targets until the object of the search, the target, is found. We hypothesize that VPA and FEF work together as an interconnected system for guiding gaze to objects we are searching for, and that they also provide attentional feedback to the occipital and temporal cortex, including the mid-superior temporal sulcus (mid-STS) region. This feedback biases visual processing in favor of attended target features. In Aim 1, we will test whether feedback from FEF to visual cortex and VPA is specific for attended locations, as we propose, or whether the feedback conveys priority values computed from both attended features and locations. In Aim 2, we will use electrical stimulation coupled with functional magnetic resonance imaging (fMRI) to finely map the connectome of the mid-STS region, which receives projections from VPA and has been recently proposed as an important component of the system for the top-down control of attention. The published connectome will provide a test of anatomical mapping principles that we recently discovered in PFC, and it will be a valuable resource for the neuroscience community. In Aim 3, we will use neurophysiological recordings in VPA, FEF, the mid-STS, and other structures proposed to be important for attention, coupled with causal methods such as optogenetics and muscimol injections to test our hypotheses about the roles of the different components. One of the key innovations of this project is that we will map the connectivity of the recorded sites with electrical stimulation and fMRI so that we can target our recordings to the specific neuronal groups in different struc...