Dissociable roles of medial orbitofrontal cortex in human operant extinction learning

Abstract

Operant extinction, which features modification of instrumental responses to stimuli following a change in associated reinforcement, is an important form of learning for organisms in dynamic environments. Animal studies have highlighted orbital and medial prefrontal cortex and amygdala as mediators of operant extinction. Yet little is known about the neural mediators of operant extinction learning in humans. Using a novel fMRI paradigm, we report dissociable functional responses in distinct regions of medial orbitofrontal cortex (mOFC) during successful appetitive and aversive based operant extinction. During successful operant extinction, increased activity was observed in frontopolar OFC, while decreased activity was observed in caudal mOFC and rostral anterior cingulate cortex (rACC) relative to both (i) successful control trials where the reinforcement associated with the stimulus does not change; and (ii) successful acquisition trials during initial learning of the stimulus- reinforcement associations. Functional connectivity analysis demonstrated inverse connectivity between frontopolar OFC and both rACC and the amygdala. These data support animal models suggesting the importance of mOFC - amygdala interaction during operant extinction and expand our knowledge of the neural systems in humans. These findings suggest that in humans, frontopolar OFC modulates activity in caudal mOFC, rACC and amygdala during successful operant extinction learning.

vlPFC–vmPFC–Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion

“…The first is that in older individuals, vlPFC engages vmPFC, which in turn exerts a modulatory influence on the amygdala. This possibility is appealing given vmPFC's role in regulatory processes including fear extinction and reversal learning (Milad et al 2007;Finger et al 2008;Schiller et al 2008;Sehlmeyer et al 2009;Schiller and Delgado 2010), yet the fact that vlPFC recruitment and vmPFC-amygdala connectivity were uncorrelated makes it seem less plausible. The second possibility is that increasingly negative vmPFC-amygdala coupling indexes the degree to which the amygdala is receptive to prefrontal modulation across development (Gee et al 2013), but that vlPFC and vmPFC exert independent influences on the amygdala during reappraisal.…”

Structure–function relationships in the processing of regret in the orbitofrontal cortex

“…Instrumental conditioning is based on two different processes computed in distinct brain areas, i.e., goal-directed learning of associations between responses and outcomes and habit learning of associations between stimuli and responses. Devaluation of outcomes in instrumental conditioning showed that the medial OFC is critical involved in the first process, associating a response with its incentive value of the outcome (Valentin et al 2007;Finger et al 2008).…”

Hippocampal activation during extinction learning predicts occurrence of the renewal effect in extinction recall

“…In appetitive Pavlovian extinction, NA efflux in mPFC of rats was increased (Mingote et al, 2004). During successful operant extinction learning, activity in frontopolar OFC in humans increased while activity in mOFC decreased (Finger et al, 2008), compared to acquisition of the stimulus-reinforcement association. Hippocampal neurons respond to a conditioned stimulus whether it signals food or a shock, thus they are involved in both aversive and appetitive conditioning (Segal et al, 1972).…”