Targeted Stimulation of Human Orbitofrontal Networks Disrupts Outcome-Guided Behavior.

James D Howard,Thorsten Kahnt,Devyn E Smith,Joel L Voss,Rachel Reynolds,Geoffrey Schoenbaum

doi:10.1016/j.cub.2019.12.007

James D Howard, Thorsten Kahnt + Show 4 more

Open Access

https://doi.org/10.1016/j.cub.2019.12.007

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Abstract

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.

Highlights

To make adaptive choices, organisms must anticipate the value of expected outcomes
Experiments in rodents and nonhuman primates demonstrate that inactivation of the orbitofrontal cortex (OFC) results in continued responding to Pavlovian cues predicting a devalued outcome, indicating an inability to infer its new value [6,7,8,9,10,11,12,13]
(D) Using the Neurosynth database of resting-state functional magnetic resonance imaging (rs-fMRI) data, we identified a coordinate in central/lateral OFC (x = 28, y = 38, z = À16) that has high functional connectivity (r > 0.2) with a region of lateral prefrontal cortex (LPFC) that is accessible to transcranial magnetic stimulation (TMS)

Summary

Introduction

Organisms must anticipate the value of expected outcomes. In the face of continually changing motivational states and external contingencies, this requires the ability to infer the current value of specific outcomes on the fly, without the need for new learning [1, 2]. When perusing the menu at a new restaurant, we can readily infer how much we will like each option and make a choice without having to try each one first. Such inference, or mental simulation, is a hallmark of outcome-guided behavior, distinguishing it from behavior that can be based on first-hand experience [3, 4]. Experiments in rodents and nonhuman primates demonstrate that inactivation of the orbitofrontal cortex (OFC) results in continued responding to Pavlovian cues predicting a devalued outcome, indicating an inability to infer its new value [6,7,8,9,10,11,12,13]. Neuroimaging studies show a correlation between human OFC activity and updated reward expectations in devaluation tasks [14,15,16], definitive evidence in support of a causal role for human OFC in outcome-guided behavior is lacking

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