Neurons in the monkey frontopolar cortex encode learning stage and goal during a fast learning task.

The frontopolar cortex (FPC) is, to date, one of the least understood regions of the prefrontal cortex. The current understanding of its function suggests that it plays a role in the control of exploratory behaviors by coordinating the activities of other prefrontal cortex areas involved in decision-making and exploiting actions based on their outcomes. Based on this hypothesis, FPC would drive fast-learning processes through a valuation of the different alternatives. In our study, we used a modified version of a well-known paradigm, the object-in-place (OIP) task, to test this hypothesis in electrophysiology. This paradigm is designed to maximize learning, enabling monkeys to learn in one trial, which is an ability specifically impaired after a lesion of the FPC. We showed that FPC neurons presented an extremely specific pattern of activity by representing the learning stage, exploration versus exploitation, and the goal of the action. However, our results do not support the hypothesis that neurons in the frontal pole compute an evaluation of different alternatives. Indeed, the position of the chosen target was strongly encoded at its acquisition, but the position of the unchosen target was not. Once learned, this representation was also found at the problem presentation, suggesting a monitoring activity of the synthetic goal preceding its acquisition. Our results highlight important features of FPC neurons in fast-learning processes without confirming their role in the disengagement of cognitive control from the current goals.

Human Brain Project Partnering Projects Meeting: Status Quo and Outlook.

As the European Flagship Human Brain Project (HBP) ends in September 2023, a meeting dedicated to the Partnering Projects (PPs), a collective of independent research groups that partnered with the HBP, was held on September 4-7, 2022. The purpose of this meeting was to allow these groups to present their results, reflect on their collaboration with the HBP and discuss future interactions with the European Research Infrastructure (RI) EBRAINS that has emerged from the HBP. In this report, we share the tour-de-force that the Partnering Projects that were present in the meeting have made in furthering knowledge concerning various aspects of Brain Research with the HBP. We describe briefly major achievements of the HBP Partnering Projects in terms of a systems-level understanding of the functional architecture of the brain and its possible emulation in artificial systems. We then recapitulate open discussions with EBRAINS representatives about the evolution of EBRAINS as a sustainable Research Infrastructure for the Partnering Projects after the HBP, and also for the wider scientific community.

Social monitoring of actions in the macaque frontopolar cortex.

The frontopolar cortex (FPC) of primates appeared as a main innovation in the evolution of anthropoid primates and it has been placed at the top of the prefrontal hierarchy. The only study to date that investigated the activity of FPC neurons in monkeys performing a cognitive task suggested that these cells were involved in the monitoring of self-generated actions. We recorded the activity of neurons in the FPCs of two rhesus monkeys while they performed a social variant of a nonmatch-to-goal task that required monitoring the actions of a human or computer agent. We discovered that the role of FPC neurons extends beyond self-generated actions to include monitoring others' actions. Their monitoring activity was very specific. First, neurons in the FPC encoded the spatial position of the target but not its object features. Second, a dedicated representation of the human agent actions was tied to the time of target acquisition, while it was reduced or absent in the successive epochs of the trial. Finally, this other-specific neural substrate did not emerge during the interaction with a virtual agent such as the computer. These results provide a new perspective on the functions of a uniquely primate brain area, suggesting that FPC might play an important role in social behaviors.

Neurons in the Monkey's Subthalamic Nucleus Differentially Encode Motivation and Effort.

The understanding of the electrophysiological properties of the subthalamic nucleus (STN) neurons is crucial since it represents the main target of deep brain stimulation for the treatment of Parkinson's disease and obsessive-compulsive disorders. The study of its nonmotor properties could shed light on the cognitive and motivational alterations possibly encountered after stimulation. In this study, we recorded the activity of STN neurons in two male behaving monkeys (Macaca mulatta) while they performed a visuomotor motivational task in which visual cues indicated which amount of force was required to obtain which amount of reward. Our results evidenced force- and reward-modulated neurons. After the occurrence of the visual stimuli, the force-modulated neurons mainly fired when a high effort was required. Differently, the activity of the population of reward-modulated neurons encoded the motivational value of the stimuli. This population consisted of neurons increasing or decreasing their activity according to the motivational ranking of the task conditions. Both populations could play complementary roles, one in the implementation of the difficulty of the action and the other in enhancing or slowing its execution based on the subjective value of each condition.SIGNIFICANCE STATEMENT An increasing number of studies confers a role to the subthalamic nucleus (STN) in motivational and reward-related processes. However, the electrophysiological bases of such properties at the neuronal level remain unclear. The present study investigated the modulation of STN neuronal activity in monkeys performing a motivational task in which the force to produce and the reward obtained were manipulated. We found two main populations of neurons, one modulated by the effort required and the other integrating the motivational subjective value of the stimuli. This last population could help at improving decision-making to act or not, depending on the subjective value set by the motivational context. This highlights the pivotal role of STN in the valuation of cost/benefit for decision-making processes.

Dedicated Representation of Others in the Macaque Frontal Cortex: From Action Monitoring and Prediction to Outcome Evaluation.

Social neurophysiology has increasingly addressed how several aspects of self and other are distinctly represented in the brain. In social interactions, the self-other distinction is fundamental for discriminating one's own actions, intentions, and outcomes from those that originate in the external world. In this paper, we review neurophysiological experiments using nonhuman primates that shed light on the importance of the self-other distinction, focusing mainly on the frontal cortex. We start by examining how the findings are impacted by the experimental paradigms that are used, such as the type of social partner or whether a passive or active interaction is required. Next, we describe the 2 sociocognitive systems: mirror and mentalizing. Finally, we discuss how the self-other distinction can occur in different domains to process different aspects of social information: the observation and prediction of others' actions and the monitoring of others' rewards.

Intrinsic timescales across the basal ganglia.

Recent studies have shown that temporal stability of the neuronal activity over time can be estimated by the structure of the spike-count autocorrelation of neuronal populations. This estimation, called the intrinsic timescale, has been computed for several cortical areas and can be used to propose a cortical hierarchy reflecting a scale of temporal receptive windows between areas. In this study, we performed an autocorrelation analysis on neuronal populations of three basal ganglia (BG) nuclei, including the striatum and the subthalamic nucleus (STN), the input structures of the BG, and the external globus pallidus (GPe). The analysis was performed during the baseline period of a motivational visuomotor task in which monkeys had to apply different amounts of force to receive different amounts of reward. We found that the striatum and the STN have longer intrinsic timescales than the GPe. Moreover, our results allow for the placement of these subcortical structures within the already-defined scale of cortical temporal receptive windows. Estimates of intrinsic timescales are important in adding further constraints in the development of computational models of the complex dynamics among these nuclei and throughout cortico-BG-thalamo-cortical loops.

Macaque monkeys learn and perform a non-match-to-goal task using an automated home cage training procedure.

In neurophysiology, nonhuman primates represent an important model for studying the brain. Typically, monkeys are moved from their home cage to an experimental room daily, where they sit in a primate chair and interact with electronic devices. Refining this procedure would make the researchers' work easier and improve the animals' welfare. To address this issue, we used home-cage training to train two macaque monkeys in a non-match-to-goal task, where each trial required a switch from the choice made in the previous trial to obtain a reward. The monkeys were tested in two versions of the task, one in which they acted as the agent in every trial and one in which some trials were completed by a "ghost agent". We evaluated their involvement in terms of their performance and their interaction with the apparatus. Both monkeys were able to maintain a constant involvement in the task with good, stable performance within sessions in both versions of the task. Our study confirms the feasibility of home-cage training and demonstrates that even with challenging tasks, monkeys can complete a large number of trials at a high performance level, which is a prerequisite for electrophysiological studies of monkey behavior.

Effects of reward size and context on learning in macaque monkeys.

The outcome of an action plays a crucial role in decision-making and reinforcement learning processes. Indeed, both human and animal behavioural studies have shown that different expected reward values, either quantitatively or qualitatively, modulate the motivation of subjects to perform an action and, as a consequence, affect their behavioural performance. Here, we investigated the effect of different amounts of reward on the learning of macaque monkeys using a modified version of the object-in-place task. This task offers the opportunity to shape rapid learning based on a set of external stimuli that enhance an animal's accuracy in terms of solving a problem. We compared the learning of three monkeys among three different reward conditions. Our results demonstrate that the larger the reward, the better the monkey's ability to learn the associations starting with the second presentation of the problem. Moreover, we compared the present results with those of our previous work using the same monkeys in the same task but with a unique reward condition, the intermediate one. Interestingly, the performance of our animals in our previous work matched with their performance in the largest and not intermediate reward condition of the present study These results suggest that learning is mostly influenced by the reward context and not by its absolute value.

Role of the social actor during social interaction and learning in human-monkey paradigms.

The social interactions between primates is drawn by their ability to predict others' behaviours, to learn from others' actions and to represent others' intentions. It allows them to extract information by observation to understand which action is leading to which outcome and to maximize the efficiency of their own future behaviours. These processes have mainly been investigated studying non-human primates observing conspecifics, but more recently an increasing body of work has adopted a human-monkey paradigm, and some have now convincingly shown that macaque monkeys understand human choices, consider them and can act accordingly. Two main hypotheses have been developed to explain macaque monkeys' ability to learn from humans: 1) the similarity between the behaviours of both species 2) the presence of a non-ambiguous link between the observed action and its outcome. Based on the literature examined the recent evidence appears to supports the second. The non-social observational learning, meaning the learning by observation of an inanimate agent, can be a powerful tool to understand the mechanisms underlying the social interactions.

Macaque monkeys learn by observation in the ghost display condition in the object-in-place task with differential reward to the observer.

Observational learning has been investigated in monkeys mainly using conspecifics or humans as models to observe. Some studies attempted to clarify the social agent's role and to test whether non-human primates could learn from observation of a non-social agent, usually mentioned as a 'ghost display' condition, but they reported conflicting results. To address this question, we trained three rhesus monkeys in an object-in-place task consisting of the presentation of five subsequent problems composed of two objects, one rewarded and one unrewarded, for six times, or runs. Three types of learning conditions were tested. In the individual learning condition, the monkeys performed the first run, learned from it and improved their performance in the following runs. In the social and non-social learning conditions, they observed respectively a human model and a computer performing the first run and learned by the observation of their successes or errors. In all three conditions, the monkeys themselves received the reward after correct choices only. One-trial learning occurred in all three conditions. The monkeys performed over chance in the second run in all conditions, providing evidence of non-social observational learning with differential reward in macaque monkeys using a "ghost display" condition in a cognitive task.

Learning the meaning of new stimuli increases the cross-correlated activity of prefrontal neurons.

The prefrontal cortex (PF) has a key role in learning rules and generating associations between stimuli and responses also called conditional motor learning. Previous studies in PF have examined conditional motor learning at the single cell level but not the correlation of discharges between neurons at the ensemble level. In the present study, we recorded from two rhesus monkeys in the dorsolateral and the mediolateral parts of the prefrontal cortex to address the role of correlated firing of simultaneously recorded pairs during conditional motor learning. We trained two rhesus monkeys to associate three stimuli with three response targets, such that each stimulus was mapped to only one response. We recorded the neuronal activity of the same neuron pairs during learning of new associations and with already learned associations. In these tasks after a period of fixation, a visual instruction stimulus appeared centrally and three potential response targets appeared in three positions: right, left, and up from center. We found a higher number of neuron pairs significantly correlated and higher cross-correlation coefficients during stimulus presentation in the new than in the familiar mapping task. These results demonstrate that learning affects the PF neural correlation structure.

Dynamic Encoding of Effort and Reward throughout the Execution of Action by External Globus Pallidus Neurons in Monkeys.

Humans and animals must evaluate the costs and expected benefits of their actions to make adaptive choices. Prior studies have demonstrated the involvement of the basal ganglia in this evaluation. However, little is known about the role of the external part of the globus pallidus (GPe), which is well positioned to integrate motor and reward-related information, in this process. To investigate this role, the activity of 126 neurons was recorded in the associative and limbic parts of the GPe of two monkeys performing a behavioral task in which different levels of force were required to obtain different amounts of liquid reward. The results first revealed that the activity of associative and limbic GPe neurons could be modulated not only by cognitive and limbic but also motor information at the same time, both during a single period or during different periods throughout the trial, mainly in an independent way. Moreover, as a population, GPe neurons encoded these types of information dynamically throughout the trial, when each piece of information was the most relevant for the achievement of the action. Taken together, these results suggest that GPe neurons could be dedicated to the parallel monitoring of task parameters essential to adjusting and maintaining goal-directed behavior.

Outcome Modulation Across Tasks in the Primate Dorsolateral Prefrontal Cortex.

Animals need to learn and to adapt to new and changing environments so that appropriate actions that lead to desirable outcomes are acquired within each context. The prefrontal cortex (PF) is known to underlie such function that directly implies that the outcome of each response must be represented in the brain for behavioral policies update. However, whether such PF signal is context dependent or it is a general representation beyond the specificity of a context is still unclear. Here, we analyzed the activity of neurons in the dorsolateral PF (PFdl) recorded while two monkeys performed two perceptual magnitude discrimination tasks. Both tasks were well known by the monkeys and unexpected changes did not occur but the difficulty of the task varied from trial to trial and thus the monkeys made mistakes in a proportion of trials. We show a context-independent coding of the response outcome with neurons maintaining similar selectivity in both task contexts. Using a classification method of the neural activity, we also show that the trial outcome could be well predicted from the activity of the same neurons in the two contexts. Altogether, our results provide evidence of high degree of outcome generality in PFdl.

Modulation of Tonically Active Neurons of the Monkey Striatum by Events Carrying Different Force and Reward Information.

The role of basal ganglia in motivational processes has been under scrutiny in recent decades, with increasing evidence from clinical studies of cognitive and motivational deficits in patients with basal ganglia lesions. Tonically active neurons (TANs), the presumed striatal cholinergic interneurons, could be important actors in integrating and relaying motivational information arising from various modalities. Their multiphasic responses to rewards and to conditioned stimuli associated with reward conferred them a role in limbic processes. They are also modulated by a task's motor aspect. Recent studies suggest they are influenced by the context in which behavioral responses are expressed. To investigate the role of TANs in motor-limbic interaction processes, we recorded 169 TANs in the striatum of two monkeys performing a motivational task, in which they had to develop a variable force to receive different amounts of reward in response to visual stimuli. Our results reveal new features of TANs response properties. First, TANs usually responded either by a pause or an elevation of discharge rate to the visual cues and the reward, with few neurons combining both pause and rebound. Second, the elevations of discharge rate after the cues were most sensitive to the least valuable (high force or small reward) task conditions. Finally, the responses of TANs to the visual cues were time locked on the onset of the animal's movement. TANs' population and responses could thus play a role in signaling less attractive situations, those with either a high motor demand and/or small reward. SIGNIFICANCE STATEMENT: Tonically active neurons (TANs) are known for their responses to unpredictable positive or negative events. However, here we show that TANs respond by a pause or an increase in their activity to all rewarding events in a task in which combined visual cues indicate to the monkeys the levels of force to produce and the upcoming reward. Unlike the pause, the increase in activity is modulated by task parameters and is most sensitive to the least attractive task conditions (high force and/or small reward). TANs' responses triggered by cue occurrence are also modulated by movement-related information (movement onset). We therefore propose here that TANs could play a role, via their action on striatal projections neurons, in maintaining high cost/low benefit ratio behaviors.