PROJECT SUMMARY A crucial function of the central nervous system is to bias behavior toward events and outcomes that hold relevance for survival. It is well recognized that odors have a strong effect on animal behavior, as they guide food search, maternal bonding, and mate selection. Even though humans do not consider olfaction to be a dominant sense, humans are similarly swayed by the rewarding properties of odors. With recent developments in the pattern-based analysis of functional magnetic resonance imaging (fMRI) data and non-invasive brain stimulation techniques, we are now in a position to explore the neural mechanisms of olfactory reward in humans. During the previous funding cycle, we gained key insights into how odor rewards are represented in orbitofrontal cortex (OFC), and how the dopaminergic midbrain may support these representations. The objective of the current renewal application is to capitalize on these novel methods in order to address new questions arising from these initial findings about the neural mechanisms of odor-guided behavior in humans. Specifically, we will use OFC-targeted transcranial magnetic stimulation (TMS) and novel behavioral tasks that involve food odors as rewards to reveal the specific contribution of different OFC networks to decision making. Moreover, the proposed studies will combine network-based TMS with pattern-based fMRI to elucidate the neural mechanisms that drive learning about the identity of future odor rewards. Complementary studies will examine how one’s motivational state modulates perceptional and neural responses to food odors, such that they can aid the detection of biologically relevant rewards in the environment. Together the experiments proposed in this project will fundamentally extend our understanding of olfactory reward processing in the human brain at the functional and mechanistic level, with implications for neuroscientific research on learning, memory, and behavior in general. Moreover, the findings from this work can lead to a better understanding of the behavioral deficits described in a variety of neuropsychiatric disorders, including Schizophrenia, eating disorders, and addiction, and may ultimately provide insights into the development of novel diagnostic and therapeutic approaches.