PT - JOURNAL ARTICLE AU - James D. Howard AU - Rachel Reynolds AU - Devyn E. Smith AU - Joel L. Voss AU - Geoffrey Schoenbaum AU - Thorsten Kahnt TI - Targeted stimulation of human orbitofrontal networks disrupts outcome-guided behavior AID - 10.1101/740399 DP - 2019 Jan 01 TA - bioRxiv PG - 740399 4099 - http://biorxiv.org/content/early/2019/08/20/740399.short 4100 - http://biorxiv.org/content/early/2019/08/20/740399.full AB - Outcome-guided behavior requires knowledge about the current value of expected outcomes. Such behavior can be isolated in the reinforcer devaluation task, which assesses the ability to infer the current value of rewards after devaluation. Animal lesion studies demonstrate that orbitofrontal cortex (OFC) is necessary for normal behavior in this task, but a causal role for human OFC in outcome-guided behavior has not been established. Here we used sham-controlled non-invasive continuous theta-burst stimulation (cTBS) to temporarily disrupt human OFC network activity prior to devaluation of food odor rewards in a between-subjects design. Subjects in the sham group appropriately avoided Pavlovian cues associated with devalued food odors. However, subjects in the stimulation group persistently chose those cues, even though devaluation of food odors themselves was unaffected by cTBS. This behavioral impairment was mirrored in changes in resting-stated functional magnetic resonance imaging (rs-fMRI) activity, such that subjects in the stimulation group exhibited reduced global OFC network connectivity after cTBS, and the magnitude of this reduction was correlated with choices after devaluation. These findings demonstrate the feasibility of indirectly targeting the human OFC with non-invasive cTBS, and indicate that OFC is specifically required for inferring the value of expected outcomes.