The Neural Correlates of Cued Reward Omission

Abstract

Compared to our understanding of positive prediction error signals occurring due to unexpected reward outcomes, less is known about the neural circuitry in humans that drives negative prediction errors during omission of expected rewards. While classical learning theories such as Rescorla–Wagner or temporal difference learning suggest that both types of prediction errors result from a simple subtraction, there has been recent evidence suggesting that different brain regions provide input to dopamine neurons which contributes to specific components of this prediction error computation. Here, we focus on the brain regions responding to negative prediction error signals, which has been well-established in animal studies to involve a distinct pathway through the lateral habenula. We examine the activity of this pathway in humans, using a conditioned inhibition paradigm with high-resolution functional MRI. First, participants learned to associate a sensory stimulus with reward delivery. Then, reward delivery was omitted whenever this stimulus was presented simultaneously with a different sensory stimulus, the conditioned inhibitor (CI). Both reward presentation and the reward-predictive cue activated midbrain dopamine regions, insula and orbitofrontal cortex. While we found significant activity at an uncorrected threshold for the CI in the habenula, consistent with our predictions, it did not survive correction for multiple comparisons and awaits further replication. Additionally, the pallidum and putamen regions of the basal ganglia showed modulations of activity for the inhibitor that did not survive the corrected threshold.

Cortico-Striatal Activity Characterizes Human Safety Learning via Pavlovian Conditioned Inhibition

“…Although few, if any, existing fMRI studies have translated the Pavlovian conditioned inhibition model to human fear conditioning, it has recently been reported in a study of appetitive conditioning, where the inhibitor predicted reward-omission, and evoked dorsalstriatal responses similar to those observed here (Mollick et al, 2021). Consistent with associative learning theory (Roesch et al, 2012), these overlapping findings suggest that USomission can function as a potent reinforcer when it contradicts expectation (Tobler et al, 2003), rather than being a meaningless or neutral event.…”

The Role of the Lateral Habenula in Inhibitory Learning from Reward Omission

“…In short, the omission of reward should not cause substantial disturbance to a sated individual. This could be another possibility for explaining the failure ofMollick et al (2021) to replicate Tobbler et al's findings.…”

“…Similarly, the study by Mollick et al (2021) failed to capture decreased activity in midbrain dopamine regions during reward omissions. The authors argued that their fMRI spatial resolution may have also precluded the distinction between these regions and the adjacent GABAergic RTMg (which was presumably active as well during reward omissions).…”

“…While an earlier human fMRI study (Salas et al, 2010) already documented that the habenula is activated when an expected reward is omitted (i.e., negative reward prediction error), evidence for the backpropagation of this effect remains elusive. A possible explanation for the null result reported by Mollick et al (2021) is that the human LHb is quite small and cannot be differentiated from the medial habenula with standard fMRI resolutions (cf. Salas et al, 2010).…”

“…Therefore, bothTobler et al and Chang et al's findings are relevant to elucidate the function of LHb physiology in learning from experiences involving reward omission. In another recent study,Mollick et al (2021) intended to test this notion with humans in an fMRI study. The aim of this study was to replicateTobler et al's (2003) behavioral protocol but including the measurement of the activity in different regions across the whole brain (not only in midbrain dopamine cells).Mollick et al indeed captured…”