Targeted Stimulation of Human Orbitofrontal Networks Disrupts Outcome-Guided Behavior

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 specific 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 by stimulating a site in the lateral prefrontal cortex that is strongly connected to OFC prior to devaluation of food odor rewards. 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-state functional magnetic resonance imaging (rs-fMRI) activity such that subjects in the stimulation group exhibited reduced 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. •Animal orbitofrontal cortex (OFC) is critical for responding in the devaluation task•Connectivity-guided TMS of human OFC impairs choices for devalued outcomes•OFC-targeted TMS disrupts orbitofrontal network connectivity, predicting behavior•OFC-targeted TMS does not impair value-based choices in general Howard et al. show that indirectly targeting orbitofrontal cortex (OFC) with TMS disrupts choices that require inference without affecting value-based choices in general. Moreover, TMS reduces OFC network connectivity, and the magnitude of this effect predicts individual differences in the behavioral impairment.