Papers by Sebastien Bouret
PLOS Biology, 2021
The brain stem noradrenergic nucleus locus coeruleus (LC) is involved in various costly processes... more The brain stem noradrenergic nucleus locus coeruleus (LC) is involved in various costly processes: arousal, stress, and attention. Recent work has pointed toward an implication in physical effort, and indirect evidence suggests that the LC could be also involved in cognitive effort. To assess the dynamic relation between LC activity, effort production, and difficulty, we recorded the activity of 193 LC single units in 5 monkeys performing 2 discounting tasks (a delay discounting task and a force discounting task), as well as a simpler target detection task where conditions were matched for difficulty and only differed in terms of sensory-motor processes. First, LC neurons displayed a transient activation both when monkeys initiated an action and when exerting force. Second, the magnitude of the activation scaled with the associated difficulty, and, potentially, the corresponding amount of effort produced, both for decision and force production. Indeed, at action initiation in both d...
The trade-off between effort and reward is one of the main determinants of behavior and its alter... more The trade-off between effort and reward is one of the main determinants of behavior and its alteration is at the heart of major disorders such as depression or Parkinson’s disease. Monoaminergic neuromodulators are thought to play a key role in this trade-off, but their relative contribution remains unclear. Rhesus monkeys (Macaca mulatta) performed a choice-task requiring a trade-off between the volume of fluid reward and the amount of force to be exerted on a grip. In line with a causal role of noradrenaline in effort, decreasing noradrenaline levels with systemic clonidine injections (0.01mg/kg) decreased exerted force and enhanced the weight of upcoming force on choices, without any effect on reward sensitivity. Computational modeling demonstrated that NA acted on a single hidden variable, which affected both choices (as a variable of decision) and force production (as a driving force). Thus, our data strongly support noradrenaline’s implication in effort processing.
The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in b... more The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behaviour. Both noradrenergic and dopaminergic neurons respond to salient cues predicting reward availability and to stimulus novelty, and shape action selection strategies. However, their roles in motivation have seldom been directly compared. We therefore examined the activity of noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with the likelihood of engaging with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) sensitive to the task state change, the discovery of the new task condition in unrepeated trials. This indicates that while dopamine is primarily important for the promotion of actions directed towards currently available rewards, nora...
Trends in Neurosciences, 2018
Psychopharmacology, Jan 11, 2018
While several theories have highlighted the importance of the noradrenergic system for behavioral... more While several theories have highlighted the importance of the noradrenergic system for behavioral flexibility, a number of recent studies have also shown a role for noradrenaline in motivation, particularly in effort processing. Here, we designed a novel sequential cost/benefit decision task to test the causal influence of noradrenaline on these two functions in rhesus monkeys. We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels and examined how this manipulation influenced performance on the task. Clonidine had two specific and distinct effects: first, it decreased choice variability, without affecting the cost/benefit trade-off; and second, it reduced force production, without modulating the willingness to work. Together, these results support an overarching role for noradrenaline in facing challenging situations in two complementary ways: by modulating behavioral volatility, which would facilitate ada...
Psychopharmacology, Jan 11, 2018
The article Dual contributions of noradrenaline to behavioural flexibility and motivation written... more The article Dual contributions of noradrenaline to behavioural flexibility and motivation written by Caroline I. Jahn, Sophie Gilardeau, Chiara Varazzani, Bastien Blain, Jerome Sallet, Mark E. Walton, Sebastien Bouret was originally published electronically on the publisher's internet portal.
Frontiers in neuroscience, 2018
The ability to learn and follow abstract rules relies on intact prefrontal regions including the ... more The ability to learn and follow abstract rules relies on intact prefrontal regions including the lateral prefrontal cortex (LPFC) and the orbitofrontal cortex (OFC). Here, we investigate the specific roles of these brain regions in learning rules that depend critically on the formation of abstract concepts as opposed to simpler input-output associations. To this aim, we tested monkeys with bilateral removals of either LPFC or OFC on a rapidly learned task requiring the formation of the abstract concept of same vs. different. While monkeys with OFC removals were significantly slower than controls at both acquiring and reversing the concept-based rule, monkeys with LPFC removals were not impaired in acquiring the task, but were significantly slower at rule reversal. Neither group was impaired in the acquisition or reversal of a delayed visual cue-outcome association task without a concept-based rule. These results suggest that OFC is essential for the implementation of a concept-based...
PLoS computational biology, 2017
Theory of Mind (ToM), i.e. the ability to understand others' mental states, endows humans wit... more Theory of Mind (ToM), i.e. the ability to understand others' mental states, endows humans with highly adaptive social skills such as teaching or deceiving. Candidate evolutionary explanations have been proposed for the unique sophistication of human ToM among primates. For example, the Machiavellian intelligence hypothesis states that the increasing complexity of social networks may have induced a demand for sophisticated ToM. This type of scenario ignores neurocognitive constraints that may eventually be crucial limiting factors for ToM evolution. In contradistinction, the cognitive scaffolding hypothesis asserts that a species' opportunity to develop sophisticated ToM is mostly determined by its general cognitive capacity (on which ToM is scaffolded). However, the actual relationships between ToM sophistication and either brain volume (a proxy for general cognitive capacity) or social group size (a proxy for social network complexity) are unclear. Here, we let 39 individua...
Brain : a journal of neurology, Jan 29, 2017
Motivation deficits, such as apathy, are pervasive in both neurological and psychiatric diseases.... more Motivation deficits, such as apathy, are pervasive in both neurological and psychiatric diseases. Even when they are not the core symptom, they reduce quality of life, compromise functional outcome and increase the burden for caregivers. They are currently assessed with clinical scales that do not give any mechanistic insight susceptible to guide therapeutic intervention. Here, we present another approach that consists of phenotyping the behaviour of patients in motivation tests, using computational models. These formal models impose a precise and operational definition of motivation that is embedded in decision theory. Motivation can be defined as the function that orients and activates the behaviour according to two attributes: a content (the goal) and a quantity (the goal value). Decision theory offers a way to quantify motivation, as the cost that patients would accept to endure in order to get the benefit of achieving their goal. We then review basic and clinical studies that h...
The ability to learn and follow abstract rules relies on intact prefrontal regions including the ... more The ability to learn and follow abstract rules relies on intact prefrontal regions including the lateral prefrontal cortex (LPFC) and the orbitofrontal cortex (OFC). Here, we investigate the specific roles of these brain regions in learning rules that depend critically on the formation of abstract concepts as opposed to simpler input-output associations. To this aim, we tested monkeys with bilateral removals of either LPFC or OFC on a rapidly learned task requiring the formation of the abstract concept of same vs. different. While monkeys with OFC removals were significantly slower than controls at both acquiring and reversing the concept-based rule, monkeys with LPFC removals were not impaired in acquiring the task, but were significantly slower at rule reversal. Neither group was impaired in the acquisition or reversal of a delayed visual cue-outcome association task without a concept-based rule. These results suggest that OFC is essential for the implementation of a concept-based...
To survive in their complex environment, primates must integrate information over time and adjust... more To survive in their complex environment, primates must integrate information over time and adjust their actions beyond immediate events. The underlying neurobiological processes, however, remain unclear. Here, we assessed the contribution of the ventromedial prefrontal cortex (VMPFC), a brain region important for value-based decision making. We recorded single VMPFC neurons in monkeys performing a task where obtaining fluid rewards required squeezing a grip. The willingness to perform the action was modulated not only by visual information about Effort and Reward levels, but also by contextual factors such as Trial Number (i.e fatigue and/or satiety) or behavior in recent trials. A greater fraction of VMPFC neurons encoded contextual information, compared to visual stimuli. Moreover, the dynamics of VMPFC firing was more closely related to slow changes in motivational states driven by these contextual factors rather than rapid responses to individual task events. Thus, the firing of...
Revue de primatologie, 2015
La motivation regroupe l’ensemble des processus qui sous-tendent le comportement, en bref, pourqu... more La motivation regroupe l’ensemble des processus qui sous-tendent le comportement, en bref, pourquoi on fait ce que l’on fait ? Que ce soit en termes de choix entre plusieurs actions ou de quantite d’energie depensee pour une action donnee, les comportements du rapport entre les benefices attendus et les couts escomptes. Au niveau cerebral, la motivation implique un certain nombre de structures clefs, comme les systemes neuromodulateurs et le cortex prefrontal. En effet, ces structures sont atteintes dans de nombreuses maladies neurologiques (Parkinson) ou psychiatriques (depression). Mais la contribution specifique de ces structures aux processus motivationnels precis reste mal comprise. Par ailleurs, la regulation des comportements en fonction du rapport entre les apports et les depenses energetiques est essentielle pour apprehender le comportement des primates dans leur milieu naturel. Mieux comprendre les bases cerebrales de la motivation devrait donc nous aider a mieux comprendre le comportement de l’ensemble des primates. Notre travail de recherche vise a identifier les processus cerebraux impliques dans la gestion du compromis entre la recompense (le but de l’action) et l’effort physique necessaire a son obtention. Nous entrainons des singes (Macaca mulatta) dans des tâches simples ou ils doivent produire un effort physique (serrer une pince) pour obtenir une recompense hydrique. Nous mesurons plusieurs variables comportementales (choix, temps de reaction, force exercee, expressions faciales) et vegetatives (diametre pupillaire). Une fois les singes entraines, nous mesurons l’activite des neurones du cortex prefrontal, ainsi que celle des neurones a dopamine (DA) de la substance noire (SN) et des neurones a noradrenaline (NA) du locus coeruleus (LC). Nous evaluons par ailleurs le role des systemes dopaminergiques (DA) et noradrenergiques (NA) en utilisant des traitements pharmacologiques (L-DOPA et Atomoxetine). Nous avons ainsi identifie les roles specifiques de plusieurs elements clefs dans le controle de la motivation en fonction du compromis effort/recompense. Tout d’abord, nous montrons que les deux systemes neuromodulateurs regulent l’engagement des singes en fonction d’informations sur la recompense et la difficulte. Nous confirmons le role de la DA dans les processus incitatifs, c’est-a-dire l’energisation en fonction de la valeur du but. La NA aurait un role complementaire, en favorisant la production d’effort en fonction de la difficulte attendue. Par ailleurs, nous montrons que le cortex prefrontal ventro-median joue un role specifique dans les processus d’evaluation en fonction de parametres internes. Nos experiences futures viseront a comprendre les interactions fonctionnelles entre ces differentes structures cerebrales, et ainsi a mieux comprendre le comportement des primates.
Revue de primatologie, 2015
The ability to anticipate how another individual will behave is a critical skill in the animal ki... more The ability to anticipate how another individual will behave is a critical skill in the animal kingdom. Humans typically deal with this problem using their Theory of Mind (ToM), i.e. the ability to decipher beliefs and intentions of others. Although non-human primates (apes in particular) exhibit elaborate social behavior, there is no established consensus on whether this mirrors some form of sophisticated ToM. We suggest that ToM sophistication can be operationally defined in terms of the depth of recursive beliefs, as in "I think that you think that I think...". Importantly, mutual social interactions may call for highly recursive beliefs: not only do I think that you think, but I also think that you think that I think... This study aims at comparing how primate species (including humans) differ with respect to this form of ToM sophistication. The main novelty of our experimental approach is to estimate each primate’s ToM sophistication from its performance in repeated interactive games that are calibrated using information theoretic models of (artificial) recursive ToM. We first validated our model in human subjects and then tested 6 species of captive non-human primates (3 species of great apes: orangutans, gorillas, chimpanzees, and 3 species of old-world monkeys: lion-tailed macaques, rhesus macaques and collared mangabeys) in an adaptation of the task used in the human study. Our paradigm consisted in a “hide and seek” game in which individuals played against a human opponent (a familiar zoo keeper). In each trial, the individual had to infer where food had been hidden by the experimenter opponent (either in his right or left hand). In fact, the location of the food was chosen by learning algorithms, some of which endowed with artificial ToM. Critically, we varied the sophistication of these algorithms, yielding three conditions, ranging from a control (a simple random biased sequence) to a mildly sophisticated ToM agent (1-ToM). The profile of primates’ performances against the different algorithms was then used to infer their ToM sophistication. Preliminary results show that the pattern of performance of nonhuman primates differ from those of humans. Although most nonhuman primates tended to win in the control condition, they lost against the 1-ToM agent, in contrast to the human group (that won). Surprisingly, comparing the performances between the non-human primates' species did not reveal any significant inter-species difference. Therefore, great apes did not perform better than monkeys in our task. Interestingly, variability in the performances actually seems more to rely on inter-individual differences rather than on inter-species differences. Moreover, in every species, at least one individual exhibited mild (but statistically significant) ToM sophistication. Taken together, these data indicate that the distribution of ToM sophistication within each of these non-human primate species is quite heterogeneous. Further analyses are in progress to identify predictive factors (e.g. familiarity with humans, age, motivation and frustration during the game) that could explain away inter-individual differences, thus eventually revealing (or not) inter‑species differences [Authors Aurore San‑Galli and Marie Devaine contributed equally to this work].
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 20, 2015
Motivation determines multiple aspects of behavior, including action selection and energization o... more Motivation determines multiple aspects of behavior, including action selection and energization of behavior. Several components of the underlying neural systems have been examined closely, but the specific role of the different neuromodulatory systems in motivation remains unclear. Here, we compare directly the activity of dopaminergic neurons from the substantia nigra pars compacta and noradrenergic neurons from the locus coeruleus in monkeys performing a task manipulating the reward/effort trade-off. Consistent with previous reports, dopaminergic neurons encoded the expected reward, but we found that they also anticipated the upcoming effort cost in connection with its negative influence on action selection. Conversely, the firing of noradrenergic neurons increased with both pupil dilation and effort production in relation to the energization of behavior. Therefore, this work underlines the contribution of dopamine to effort-based decision making and uncovers a specific role of no...
The Journal of Neuroscience, 2015
The noradrenergic nucleus locus ceruleus (LC) is associated classically with arousal and attentio... more The noradrenergic nucleus locus ceruleus (LC) is associated classically with arousal and attention. Recent data suggest that it might also play a role in motivation. To study how LC neuronal responses are related to motivational intensity, we recorded 121 single neurons from two monkeys while reward size (one, two, or four drops) and the manner of obtaining reward (passive vs active) were both manipulated. The monkeys received reward under three conditions: (1) releasing a bar when a visual target changed color; (2) passively holding a bar; or (3) touching and releasing a bar. In the first two conditions, a visual cue indicated the size of the upcoming reward, and, in the third, the reward was constant through each block of 25 trials. Performance levels and lipping intensity (an appetitive behavior) both showed that the monkeys' motivation in the task was related to the predicted reward size. In conditions 1 and 2, LC neurons were activated phasically in relation to cue onset, a...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 4, 2015
A major challenge for decision theory is to account for the instability of expressed preferences ... more A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between the VMPFC and the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus acti...
Frontiers in Behavioral Neuroscience, 2012
Rewards have many influences on learning, decision-making, and performance. All seem to rely on c... more Rewards have many influences on learning, decision-making, and performance. All seem to rely on complementary actions of two closely related catecholaminergic neuromodulators, dopamine (DA), and noradrenaline (NA). We compared single unit activity of dopaminergic neurons of the substantia nigra pars compacta (SNc) and noradrenergic neurons of the locus coeruleus (LC) in monkeys performing a reward schedule task. Their motivation, indexed using operant performance, increased as they progressed through schedules ending in reward delivery. The responses of dopaminergic and noradrenergic neurons around the time of major task events, visual cues predicting trial outcome and operant action to complete a trial were similar in that they occurred at the same time. They were also similar in that they both responded most strongly to the first cues in schedules, which are the most informative cues. The neuronal responses around the time of the monkeys' actions were different, in that the response intensity profiles changed in opposite directions. Dopaminergic responses were stronger around predictably rewarded correct actions whereas noradrenergic responses were greater around predictably unrewarded correct actions. The complementary response profiles related to the monkeys operant actions suggest that DA neurons might relate to the value of the current action whereas the noradrenergic neurons relate to the psychological cost of that action.
Journal of Physiology-Paris, 2015
Among all factors modulating our motivation to perform a given action, the ability to represent i... more Among all factors modulating our motivation to perform a given action, the ability to represent its outcome is clearly the most determining. Representation of outcomes, rewards in particular, and how they guide behavior, have sparked much research. Both practically and theoretically, understanding the relationship between the representation of outcome value and the organization of goal directed behavior implies that these two processes can be assessed independently. Most of animal studies essentially used instrumental actions as a proxy for the expected goal-value. The purpose of this article is to consider alternative measures of expected outcome value in animals, which are critical to understand the behavioral and neurobiological mechanisms relating the representation of the expected outcome to the organization of the behavior oriented towards its obtention. This would be critical in the field of decision making or social interactions, where the value of multiple items must often be compared and/or shared among individuals to determine the course of actions.
The Journal of Neuroscience, 2013
Predicting and valuing potential rewards requires integrating sensory, associative, and contextua... more Predicting and valuing potential rewards requires integrating sensory, associative, and contextual information with subjective reward preferences. Previous work has identified regions in the prefrontal cortex and medial temporal lobe believed to be important for each of these functions. For example, activity in the orbital prefrontal cortex (PFo) encodes the specific sensory properties of and preferences for rewards, while activity in the rhinal cortex (Rh) encodes stimulus-stimulus and stimulus–reward associations. Lesions of either structure impair the ability to use visual cues or the history of previous reinforcement to value expected rewards. These areas are linked via reciprocal connections, suggesting it might be their interaction that is critical for estimating expected value. To test this hypothesis, we interrupted direct, intra-hemispheric PFo-Rh interaction in monkeys by performing crossed unilateral ablations of these regions (functional disconnection). We asked whether ...
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Papers by Sebastien Bouret