Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience

Item does not contain fulltextRATIONALE: We have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition. OBJECTIVES: We sought to examine the role of serotonin in punishment-induced inhibition. We also examined the impact of induced mood on this effect to assess whether effects of tryptophan depletion on affective inhibition are moderated by mood. METHODS: Healthy females consumed a balanced amino acid mixture with (N = 20) or without (N = 21) the serotonin precursor tryptophan. Each subject completed either negative or neutral mood induction. All subjects completed the reward and punishment reversal learning task adopted in the previous study. RESULTS: We demonstrate a punishment prediction impairment in individuals who consumed tryptophan which was absent in individuals who were depleted of tryptophan. This effect was impervious to mood state. CONCLUSIONS: Our results suggest that serotonin promotes the inhibition of responses to punishing outcomes. This may lead to reduced punishment prediction accuracy in the presence of tryptophan and may contribute to resilience to affective disorders. Reduction of serotonin via tryptophan depletion then removes this inhibition. As such, we highlight a mechanism by which reduced serotonin can contribute to disorders of impulsivity and compulsivity as well as disorders of emotion.1 januari 201

Assessing animal affect: an automated and self-initiated judgement bias task based on natural investigative behaviour

Scientific methods for assessing animal affect, especially affective valence (positivity or negativity), allow us to evaluate animal welfare and the effectiveness of 3Rs Refinements designed to improve wellbeing. Judgement bias tasks measure valence; however, task-training may be lengthy and/or require significant time from researchers. Here we develop an automated and self-initiated judgement bias task for rats which capitalises on their natural investigative behaviour. Rats insert their noses into a food trough to start trials. They then hear a tone and learn either to stay for 2 s to receive a food reward or to withdraw promptly to avoid an air-puff. Which contingency applies is signalled by two different tones. Judgement bias is measured by responses to intermediate ambiguous tones. In two experiments we show that rats learn the task in fewer sessions than other automated variants, generalise responses across ambiguous tones as expected, self-initiate 4-5 trials/min, and can be tested repeatedly. Affect manipulations generate main effect trends in the predicted directions, although not localised to ambiguous tones, so further construct validation is required. We also find that tone-reinforcer pairings and reinforcement or non-reinforcement of ambiguous trials can affect responses to ambiguity. This translatable task should facilitate more widespread uptake of judgement bias testing

Valence-dependent influence of serotonin depletion on model-based choice strategy.

Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the reward condition, but promoted it under punishment. This effect on appetitive and aversive goal-directed behaviour is likely mediated by alteration of the average reward representation produced by TD, which is consistent with previous studies. Overall, the major implication of this study is that serotonin differentially affects goal-directed learning as a function of affective valence. These findings are relevant for a further understanding of psychiatric disorders associated with breakdown of goal-directed behavioural control such as obsessive-compulsive disorders or addictions.This research was funded by Wellcome Trust Grants awarded to VV (Intermediate WT Fellowship) and Programme Grant (089589/Z/09/Z) awarded to TWR, BJE, ACR, JWD and BJS. It was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). YW was supported by the Fyssen Foundation. SP is supported by Marie Curie Intra-European Fellowship (FP7-People-2012-IEF).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/mp.2015.4

Neural processes mediating contextual influences on human choice behaviour

Contextual influences on choice are ubiquitous in ecological settings. Current evidence suggests that subjective values are normalized with respect to the distribution of potentially available rewards. However, how this context-sensitivity is realised in the brain remains unknown. To address this, here we examine functional magnetic resonance imaging (fMRI) data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts. At the beginning of each block (when information about context is provided), hippocampus is activated and this response is enhanced when contextual influence on choice increases. In addition, response to value in ventral tegmental area/substantia nigra (VTA/SN) shows context-sensitivity, an effect enhanced with an increased contextual influence on choice. Finally, greater response in hippocampus at block start is associated with enhanced context sensitivity in VTA/SN. These findings suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain

An effect of serotonergic stimulation on learning rates for rewards apparent after long intertrial intervals

Serotonin has widespread, but computationally obscure, modulatory effects on learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven decision-making task. Animals showed two distinct choice strategies. Choices after short inter-trial-intervals (ITIs) depended only on the last trial outcome and followed a win-stay-lose-switch pattern. In contrast, choices after long ITIs reflected outcome history over multiple trials, as described by reinforcement learning models. We found that optogenetic stimulation during a trial significantly boosted the rate of learning that occurred due to the outcome of that trial, but these effects were only exhibited on choices after long ITIs. This suggests that serotonin neurons modulate reinforcement learning rates, and that this influence is masked by alternate, unaffected, decision mechanisms. These results provide insight into the role of serotonin in treating psychiatric disorders, particularly its modulation of neural plasticity and learning.info:eu-repo/semantics/publishedVersio

Bonsai Trees in Your Head: How the Pavlovian System Sculpts Goal-Directed Choices by Pruning Decision Trees

When planning a series of actions, it is usually infeasible to consider all potential future sequences; instead, one must prune the decision tree. Provably optimal pruning is, however, still computationally ruinous and the specific approximations humans employ remain unknown. We designed a new sequential reinforcement-based task and showed that human subjects adopted a simple pruning strategy: during mental evaluation of a sequence of choices, they curtailed any further evaluation of a sequence as soon as they encountered a large loss. This pruning strategy was Pavlovian: it was reflexively evoked by large losses and persisted even when overwhelmingly counterproductive. It was also evident above and beyond loss aversion. We found that the tendency towards Pavlovian pruning was selectively predicted by the degree to which subjects exhibited sub-clinical mood disturbance, in accordance with theories that ascribe Pavlovian behavioural inhibition, via serotonin, a role in mood disorders. We conclude that Pavlovian behavioural inhibition shapes highly flexible, goal-directed choices in a manner that may be important for theories of decision-making in mood disorders

The Role of Serotonin in the Regulation of Patience and Impulsivity

Classic theories suggest that central serotonergic neurons are involved in the behavioral inhibition that is associated with the prediction of negative rewards or punishment. Failed behavioral inhibition can cause impulsive behaviors. However, the behavioral inhibition that results from predicting punishment is not sufficient to explain some forms of impulsive behavior. In this article, we propose that the forebrain serotonergic system is involved in “waiting to avoid punishment” for future punishments and “waiting to obtain reward” for future rewards. Recently, we have found that serotonergic neurons increase their tonic firing rate when rats await food and water rewards and conditioned reinforcer tones. The rate of tonic firing during the delay period was significantly higher when rats were waiting for rewards than for tones, and rats were unable to wait as long for tones as for rewards. These results suggest that increased serotonergic neuronal firing facilitates waiting behavior when there is the prospect of a forthcoming reward and that serotonergic activation contributes to the patience that allows rats to wait longer. We propose a working hypothesis to explain how the serotonergic system regulates patience while waiting for future rewards