Processing in Lateral Orbitofrontal Cortex Is Required to Estimate Subjective Preference during Initial, but Not Established, Economic Choice.

The orbitofrontal cortex (OFC) is proposed to be critical to economic decision making. Yet one can inactivate OFC without affecting well-practiced choices. One possible explanation of this lack of effect is that well-practiced decisions are codified into habits or configural-based policies not normally thought to require OFC. Here, we tested this idea by training rats to choose between different pellet pairs across a set of standard offers and then inactivating OFC subregions during choices between novel offers of previously experienced pairs or between novel pairs of previously experienced pellets. Contrary to expectations, controls performed as well on novel as experienced offers yet had difficulty initially estimating their subjective preference on novel pairs, difficulty exacerbated by lateral OFC inactivation. This pattern of results indicates that established economic choice reflects the use of an underlying model or goods space and that lateral OFC is only required for normal behavior when the established framework must incorporate new information.

Real-Time Value Integration during Economic Choice Is Regulated by Orbitofrontal Cortex.

Neural correlates implicate the orbitofrontal cortex (OFC) in value-based or economic decision making [1-3]. Yet inactivation of OFC in rats performing a rodent version of the standard economic choice task is without effect [4, 5], a finding more in accord with ideas that the OFC is primarily necessary for behavior when new information must be taken into account [6-9]. Neural activity in the OFC spontaneously updates to reflect new information, particularly about outcomes [10-16], and the OFC is necessary for adjustments to learned behavior only under these conditions [4, 16-26]. Here, we merge these two independent lines of research by inactivating lateral OFC during an economic choice that requires new information about the value of the predicted outcomes to be incorporated into an already established choice. Outcome value was changed by pre-feeding the rats one of two food options before testing. In control rats, this pre-feeding resulted in divergent changes in choice behavior that depended on the rats' prior preference for the pre-fed food. Optogenetic inactivation of the OFC disrupted this bi-directional effect of pre-feeding without affecting other measures that describe the underlying choice behavior. This finding unifies the role of the OFC in economic choice with its role in a host of other behaviors, causally demonstrating that the OFC is not necessary for economic choice per se-unless that choice incorporates new information about the outcomes.

Medial orbitofrontal inactivation does not affect economic choice.

How are decisions made between different goods? One theory spanning several fields of neuroscience proposes that their values are distilled to a single common neural currency, the calculation of which allows for rational decisions. The orbitofrontal cortex (OFC) is thought to play a critical role in this process, based on the presence of neural correlates of economic value in lateral OFC in monkeys and medial OFC in humans. We previously inactivated lateral OFC in rats without affecting economic choice behavior. Here we inactivated medial OFC in the same task, again without effect. Behavior in the same rats was disrupted by inactivation during progressive ratio responding previously shown to depend on medial OFC, demonstrating the efficacy of the inactivation. These results indicate that medial OFC is not necessary for economic choice, bolstering the proposal that classic economic choice is likely mediated by multiple, overlapping neural circuits.

Brief, But Not Prolonged, Pauses in the Firing of Midbrain Dopamine Neurons Are Sufficient to Produce a Conditioned Inhibitor.

Prediction errors are critical for associative learning. In the brain, these errors are thought to be signaled, in part, by midbrain dopamine neurons. However, although there is substantial direct evidence that brief increases in the firing of these neurons can mimic positive prediction errors, there is less evidence that brief pauses mimic negative errors. Whereas pauses in the firing of midbrain dopamine neurons can substitute for missing negative prediction errors to drive extinction, it has been suggested that this effect might be attributable to changes in salience rather than the operation of this signal as a negative prediction error. Here we address this concern by showing that the same pattern of inhibition will create a cue able to meet the classic definition of a conditioned inhibitor by showing suppression of responding in a summation test and slower learning in a retardation test. Importantly, these classic criteria were designed to rule out explanations founded on attention or salience; thus the results cannot be explained in this manner. We also show that this pattern of behavior is not produced by a single, prolonged, ramped period of inhibition, suggesting that it is precisely timed, sudden change and not duration that conveys the teaching signal.SIGNIFICANCE STATEMENT Here we show that brief pauses in the firing of midbrain dopamine neurons are sufficient to produce a cue that meets the classic criteria defining a conditioned inhibitor, or a cue that predicts the omission of a reward. These criteria were developed to distinguish actual learning from salience or attentional effects; thus these results formally show that brief pauses in the firing of dopamine neurons can serve as key teaching signals in the brain. Interestingly, this was not true for gradual prolonged pauses, suggesting it is the dynamic change in firing that serves as the teaching signal.