Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression

Abstract

Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497) has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction.

Preparing for (valenced) action: The role of differential effort in the orthogonalized go/no‐go task

“…The contribution of effort‐related processes aside, a direct coupling between action and valence could of course still exist (in which dopamine might be involved; see also Frank, Moustafa, Haughey, Curran, & Hutchison, ; Frank et al, ). This has also been suggested by other previous studies investigating instrumental learning, where it was shown that subjects were more successful in learning to withhold a response (no‐go) when anticipating punishment and to actively respond (go) when anticipating reward (Cavanagh et al, ; Chowdhury, Guitart‐Masip, Lambert, Dolan, & Düzel, ; Guitart‐Masip, Huy et al, ; Guitart‐Masip et al, ; Richter et al, ). Nevertheless, in the current study action and effort are clearly intertwined, and anticipation of no‐go does not necessarily induce (preparation for) active inhibition or withdrawal, but rather altogether diminished (preparatory) cognitive resources devoted to the task.…”

“…One group of studies (Cavanagh, Eisenberg, Guitart‐Masip, Huys, & Frank, ; Guitart‐Masip et al, ; Guitart‐Masip, Chowdhury et al, ; Guitart‐Masip, Huys et al, ; Richter et al, ) that has elegantly investigated the effects of action requirements and reward value and their interaction has crossed both factors in a cue‐based paradigm (the so‐called orthogonalized go/no‐go task). This led to four conditions indicated by different cues: go to win, go to avoid losing, no‐go to win, and no‐go to avoid losing, which were used to compare differential anticipatory neural activity related to action and valence (Guitart‐Masip et al, ; Guitart‐Masip, Chowdhury et al, ).…”

Learning in anticipation of reward and punishment: Perspectives across the human lifespan

“…Performance as defined by percentage of correct (optimal) choices was assessed using a 4-way analysis of covariance (ANCOVA) with action (go/no-go), valence (win/lose) and time (1 st /2 nd half) as within-subject factors, age group (children and adolescents/young adults/midlife/older adults) as a between-subject factor and gender as a covariate. As in previous studies (Guitart-Masip et al , 2012 b , 2014; Richter et al , 2014) we observed main effects of time (F 1,243 = 17.18, p < 0.0001) and action (F 1,243 = 38.67, p < 0.0001) as well as an action x time interaction (F 1,243 = 8.27, p =0.004), and an action x valence interaction (F 1,243 = 14.21, p < 0.0005). Subjects demonstrated an increase in performance from the first to the second half of the experiment ( t 246 = -14.90, p < 0.0001) and performed better in conditions requiring a go choice than in trials requiring a no-go choice ( t 246 = 15.22, p < 0.0001).…”

“…Using a go/no-go task that independently dissociates, i.e. orthogonalizes, action and valence, young adults demonstrate striking asymmetry in instrumental learning by being better at learning to emit a behavioral response in anticipation of reward and better at withholding a response in anticipation of punishment (Guitart-Masip et al , 2012 b ; Cavanagh et al , 2013, Chowdhury et al , 2013 b ; Guitart-Masip et al , 2014; Richter et al , 2014). Computational modeling approaches in young adults have shown this asymmetry in instrumental action learning is due to a Pavlovian coupling between action and valence expectation where the strength of this bias relates to failure in learning the conflicting conditions: withholding a response in anticipation of reward and emitting a response in anticipation of punishment (Guitart-Masip et al , 2012 b ; Cavanagh et al , 2013; Guitart-Masip et al , 2013).…”

“Watch out!”: Effects of instructed threat and avoidance on human free‐operant approach–avoidance behavior

“…Currently, it remains unclear what variable(s) contributed to the between-subject variability observed. Further research addressing the interplay among individual differences variables in AA, such as anxiety (Aupperle et al, 2011), depression (Trew, 2011) and genetic factors (Richter et al, 2014), may provide new insights.…”