Amygdala and nucleus accumbens involvement in appetitive extinction

Abstract

Extinction of appetitive conditioning is regarded as an important model for the treatment of psychiatric disorders like addiction. However, very few studies have investigated its neural correlates. Therefore, we investigated neural correlates of appetitive extinction in a large human sample including all genders (N = 76, 40 females) to replicate and extend results from a previous study. During differential appetitive conditioning, one stimulus (CS+) was paired with the chance to win a monetary reward, whereas another stimulus (CS−) was not. During appetitive extinction on the next day, neither the CS+ nor the CS− were reinforced. After successful acquisition of appetitive conditioning, the extinction phase elicited significant reductions of valence and arousal ratings toward the CS+ and a significant reduction in skin conductance responses to the CS+ from early to late extinction. On a neural level, early extinction showed significant differential (CS+ − CS−) activation in dACC and hippocampus, whereas involvement of the vACC and caudate nucleus did not replicate. The differential activation of amygdala and nucleus accumbens during late extinction was replicated, with the amygdala displaying significantly higher differential activation during the late phase of extinction as compared to the early phase of extinction. We show discernible signals for reward learning and extinction in subregions of amygdala and nucleus accumbens after extinction learning. This successful replication underlines the role of nucleus accumbens and amygdala in neural models of appetitive extinction in humans that was previously only based on animal findings.

The role of intolerance of uncertainty in the acquisition and extinction of reward

“…Firstly, to be comparable with previous research on IU and uninstructed Pavlovian conditioned threat (Morriss et al, 2015, Morriss, Christakou, et al, 2016, Morriss, Macdonald, et al, 2016), the current study used an uninstructed Pavlovian conditioned reward (i.e., to receive the reward no action is required). However, as far as we are aware only one study to date has used monetary reward with an uninstructed Pavlovian design (Tapia Leon et al., 2018), and the majority of research has used uninstructed instrumental designs (Kruse et al., 2018, 2020; Kruse et al., 2017; i.e., to receive the reward an action needs to be made). Thus, the current study provides important information on Pavlovian conditioned reward generally and in relation to IU but there is limited research to directly compare against.…”

“…We hypothesized that during reward acquisition training, skin conductance responding and liking ratings would be higher, and corrugator supercilii activity would be lower, to the learned reward (CS+) versus neutral (CS−) cues, indicative of conditioned responding (Andreatta & Pauli, 2015; Ebrahimi et al., 2019; Kruse et al., 2017; Kruse et al., 2018; Kruse et al., 2020; Tapia León et al., 2018; Tapia León et al., 2019; van den Akker et al., 2017; Wardle et al., 2018). Given the lack of IU‐related findings for the acquisition training phase in past research, we did not have any specific IU hypotheses for the acquisition training phase.…”

“…We measured skin conductance response, corrugator supercilii activity (i.e., brow muscle indicative of negative or positive affect) and liking ratings of the CS+ and CS− during the acquisition and extinction training phases. We used secondary rewards (i.e., money) as unconditioned stimuli and visual shape stimuli as conditioned stimuli, in line with previous conditioning research (Andreatta & Pauli, 2015, 2019; Ebrahimi et al., 2019; Kruse et al., 2020; Kruse et al., 2018; Kruse et al., 2017; Tapia León et al., 2018; Tapia León et al., 2019; van den Akker et al., 2017). We used a 50% reinforcement rate during acquisition training to prolong the effect of conditioning (Bouton, 2002) and induce greater uncertainty during extinction similar to our previous work (Morriss, 2019; Wake et al., 2020).…”

Instrumental and Pavlovian Mechanisms in Alcohol Use Disorder

“…Human neuroimaging studies have repeatedly identified activity within dopaminergic midbrain, VS (including NAcc), OFC, dorsal ACC, and amygdala during appetitive Pavlovian conditioning [120,[155][156][157][158][159][160][161][162]; for a meta-analysis, see 163]. In line with preclinical evidence showing that the infralimbic PFC promotes extinction recall, regulating Pavlovian relapse phenomena [141,164], the vmPFC is considered particularly relevant for the recall of extinction memory, in concert with striatum and amygdala [165][166][167][168], and the inhibition of appetitive responses [117,169].…”

“…Human studies often employ differential conditioning protocols in which one stimulus (CS+) is paired with the US while a second (CS−) is not. Both appetitive and aversive CRs have been quantified on various response systems, including subjective ratings, psychophysiological measures, and neuroimaging [116][117][118][119][120]. Recent research has found evidence of behaviors similar to sign-and goal-tracking in healthy participants.…”