Sebastien Bouret

The noradrenergic nucleus locus coeruleus (LC) is involved in numerous cognitive functions. Its activation often enhances sensory and motor performance and its activity correlates with arousal, which altogether suggest a general role in the mobilization of resources for cognition and action. We recently showed its strong and specific implication in physical effort and indirect evidence suggest that it might also be involved in cognitive effort. To address this question directly, we used a pharmacogenetic approach in rhesus macaques to selectively and reversibly inhibit LC neurons in a cognitively challenging task. Two monkeys were injected with viral vectors expressing inhibitory DREADDs (hM4Di) specifically in noradrenergic LC neurons, allowing reversible suppression of LC activity via systemic administration of deschloroclozapine (DCZ, 0.1 mg/kg). A third monkey served as a control and only received DCZ injections. Monkeys performed a simple hole-board task in which they searched for food rewards (raisins) hidden in a 5×5 grid of wells. In the transparent condition, rewards were visible, requiring minimal cognitive effort. In the opaque condition, rewards were hidden, such that monkey had to rely upon working memory to avoid revisiting empty wells. Thus, performance in opaque condition required more cognitive effort. Behavioral analysis showed that LC inhibition had no effect on performance in the transparent condition. However, in the opaque condition, it significantly impaired performance by increasing errors (revisits), without affecting the total number of rewards obtained, response times, or overall motivation. Monkeys compensated the decrease in success rate by performing more trials, indicating reduced efficiency rather than disengagement. These findings demonstrate that the LC plays a critical causal role in mobilizing cognitive resources for a demanding task. This is in line with the idea that the noradrenergic system contributes broadly to cognitive control and effort, extending previous findings on its involvement in physical effort. Overall, the study provides strong evidence linking LC activity to cognitive effort regulation, thereby complementing non-invasive studies in humans.

Making the best choice in one situation is critical, but it relies on limited cognitive capacities. Numerous animal species adjust the amount of cognitive resources allocated to a decision using a trade-off between speed and accuracy, where decision time corresponds to an investment of cognitive control, which scales with the expected increase in reward. In humans, recent studies indicate that control allocation is regulated not only based upon its potential benefits, but also upon its potential cost, through a metacognitive monitoring process. Is it the case in other primates? We addressed this issue in rhesus monkeys with a detailed analysis of the relation among choice accuracy, choice difficulty and response time in a two-choice task. In contrast to typical demonstrations of speed-accuracy trade-off, we found higher choice accuracy in trials with faster response time, above and beyond choice difficulty. This relationship can be explained by a model of metacognitive decision monitoring where the cost of cognitive control is traded against confidence benefits. Thus, rhesus monkeys also seem to rely upon supervisory monitoring to modulate the amount of control exerted over their decision efficacy. This might drive future research on the evolution of cognitive and neurophysiological processes underlying decision making.

The noradrenergic nucleus locus coeruleus (LC) is involved in numerous cognitive functions. Its activation often enhances sensory and motor performance and its activity correlates with arousal, which altogether suggest a general role in the mobilization of resources for cognition and action. We recently showed its strong and specific implication in physical effort and indirect evidence suggest that it might also be involved in cognitive effort. To address this question directly, we used a pharmacogenetic approach in rhesus macaques to selectively and reversibly inhibit LC neurons in a cognitively challenging task. Two monkeys were injected with viral vectors expressing inhibitory DREADDs (hM4Di) specifically in noradrenergic LC neurons, allowing reversible suppression of LC activity via systemic administration of deschloroclozapine (DCZ, 0.1 mg/kg). A third monkey served as a control and only received DCZ injections. Monkeys performed a simple hole-board task in which they searched for food rewards (raisins) hidden in a 5×5 grid of wells. In the transparent condition, rewards were visible, requiring minimal cognitive effort. In the opaque condition, rewards were hidden, such that monkey had to rely upon working memory to avoid revisiting empty wells. Thus, performance in opaque condition required more cognitive effort. Behavioral analysis showed that LC inhibition had no effect on performance in the transparent condition. However, in the opaque condition, it significantly impaired performance by increasing errors (revisits), without affecting the total number of rewards obtained, response times, or overall motivation. Monkeys compensated the decrease in success rate by performing more trials, indicating reduced efficiency rather than disengagement. These findings demonstrate that the LC plays a critical causal role in mobilizing cognitive resources for a demanding task. This is in line with the idea that the noradrenergic system contributes broadly to cognitive control and effort, extending previous findings on its involvement in physical effort. Overall, the study provides strong evidence linking LC activity to cognitive effort regulation, thereby complementing non-invasive studies in humans.

Pour comprendre la diversité des processus cognitifs chez les primates, il est essentiel de tenir compte des contraintes socio-écologiques auxquelles ils doivent faire face dans leur milieu naturel. Par ailleurs, les études en laboratoire ont permis de caractériser avec précision une palette de processus neuro-cognitifs chez quelques espèces, notamment l’humain et le macaque rhésus, mais la façon dont ces processus neuro-cognitifs pourraient être mis en jeu en conditions naturelles, ainsi que la variabilité de ces processus à travers les espèces, justement en fonction de leur socialité et de leur écologie, reste essentiellement inconnue. Depuis plusieurs années, nous avons mis en place une approche interdisciplinaire pour aborder cette question difficile. Cette approche vise à caractériser un lien potentiel entre 1) les processus neuro-cognitifs utilisés en conditions contrôlées de laboratoire par les neurosciences cognitives et 2) les facteurs socio-écologiques qui caractérisent la diversité des contraintes que rencontrent les différentes espèces de primates dans leur milieu naturel. Pour ce faire, nous avons utilisé le volume de trois régions spécifiques du cortex préfrontal comme proxy de l’importance de l’opération cognitive dans laquelle chaque structure est impliquée : le cortex préfrontal ventromédian, impliqué dans la prise de décision et l’évaluation, le cortex préfrontal dorso-latéral, impliqué dans la mémoire de travail et le pôle frontal, impliqué dans la métacognition. Globalement, nous montrons que la variation de volume de chacune de ces régions est liée à un jeu de variables socio-écologiques spécifiques, au-delà des effets attendus par la phylogénie. Nous montrerons en quoi ces relations spécifiques permettent non seulement de mieux comprendre l’évolution des processus neuro-cognitifs classiques, mais surtout de combiner les concepts de neurosciences cognitives et d’écologie comportementale pour mieux comprendre le comportement et la cognition des primates dans leur milieu naturel.

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively, involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints), and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints) and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily travelled distance (an index of ecological constraints) and population density (an index of social constraint). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data clarifies the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

Difficult decisions typically involve mental effort, which scales with the deployment of cognitive (e.g., mnesic, attentional) resources engaged in processing decision-relevant information. But how does the brain regulate mental effort? A possibility is that the brain optimizes a resource allocation problem, whereby the amount of invested resources balances its expected cost (i.e. effort) and benefit. Our working assumption is that subjective decision confidence serves as the benefit term of the resource allocation problem, hence the “metacognitive” nature of decision control. Here, we present a computational model for the online metacognitive control of decisions or oMCD. Formally, oMCD is a Markov Decision Process that optimally solves the ensuing resource allocation problem under agnostic assumptions about the inner workings of the underlying decision system. We demonstrate how this makes oMCD a quasi-optimal control policy for a broad class of decision processes, including -but not limited to- progressive attribute integration . We disclose oMCD’s main properties (in terms of choice, confidence and response time), and show that they reproduce most established empirical results in the field of value-based decision making. Finally, we discuss the possible connections between oMCD and most prominent neurocognitive theories about decision control and mental effort regulation.

Humans have been shown to strategically explore. They can identify situations in which gathering information about distant and uncertain options is beneficial for the future. Because primates rely on scare resources when they forage, they are also thought to strategically explore, but whether they use the same strategies as humans and the neural bases of strategic exploration in monkeys are largely unknown. We designed a sequential choice task to investigate whether monkeys mobilize strategic exploration based on whether that information can improve subsequent choice, but also to ask the novel question about whether monkeys adjust their exploratory choices based on the contingency between choice and information, by sometimes providing the counterfactual feedback, about the option not chosen. We show that monkeys decreased their reliance on expected value when exploration could be beneficial, but this was not mediated by changes in the effect of uncertainty on choices. We found strategic exploratory signals in anterior and mid-cingulate cortex (ACC/MCC) and dorsolateral prefrontal cortex (dlPFC). This network was most active when a low value option was chosen which suggests a role in counteracting expected value signals, when exploration away from value should to be considered. Such strategic exploration was abolished when the counterfactual feedback was available. Learning from counterfactual outcome was associated with the recruitment of a different circuit centered on the medial orbitofrontal cortex (OFC), where we showed that monkeys represent chosen and unchosen reward prediction errors. Overall, our study shows how ACC/MCC-dlPFC and OFC circuits together could support exploitation of available information to the fullest and drive behavior towards finding more information through exploration when it is beneficial.