Atomoxetine and reward size equally improve task engagement and perceptual decisions but differently affect movement execution.

Our ability to engage and perform daily activities relies on balancing the associated benefits and costs. Rewards, as benefits, act as powerful motivators that help us stay focused for longer durations. The noradrenergic (NA) system is thought to play a significant role in optimizing our performance. Yet, the interplay between reward and the NA system in shaping performance remains unclear, particularly when actions are driven by external incentives (reward). To explore this interaction, we tested four female rhesus monkeys performing a sustained Go/NoGo task under two reward sizes (low/high) and three pharmacological conditions (saline and two doses of atomoxetine, a NA reuptake inhibitor: ATX-0.5 mg/kg and ATX-1 mg/kg). We found that increasing either reward or NA levels equally enhanced the animal's engagement in the task compared to low reward saline; the animals also responded faster and more consistently under these circumstances. Notably, we identified differences between reward size and ATX. When combined with ATX, high reward further reduced the occurrence of false alarms (i.e., incorrect go trials on distractors), implying that it helped further suppress impulsive responses. In addition, ATX (but not reward size) consistently increased movement duration dose-dependently, while high reward did not affect movement duration but decreased its variability. We conclude that noradrenaline and reward modulate performance, but their effects are not identical, suggesting differential underlying mechanisms. Reward might energize/invigorate decisions and action, while ATX might help regulate energy expenditure, depending on the context, through the NA system.

Developmental Trajectory of Anticipation: Insights from Sequential Comparative Judgments.

Reaction time (RT) is a critical measure of performance, and studying its distribution at the group or individual level provides useful information on the cognitive processes or strategies used to perform a task. In a previous study measuring RT in children and adults asked to compare two successive stimuli (quantities or words), we discovered that the group RT distribution was bimodal, with some subjects responding with a mean RT of around 1100 ms and others with a mean RT of around 500 ms. This bimodal distribution suggested two distinct response strategies, one reactive, the other anticipatory. In the present study, we tested whether subjects' segregation into fast and slow responders (1) extended to other sequential comparative judgments (2) evolved from age 8 to adulthood, (3) could be linked to anticipation as assessed using computer modeling (4) stemmed from individual-specific strategies amenable to instruction. To test the first three predictions, we conducted a distributional and theoretical analysis of the RT of 158 subjects tested earlier using four different sequential comparative judgment tasks (numerosity, phonological, multiplication, subtraction). Group RT distributions were bimodal in all tasks, with the two strategies differing in speed and sometimes accuracy too. The fast strategy, which was rare or absent in 8- to 9-year-olds, steadily increased through childhood. Its frequency in adolescence remained, however, lower than in adulthood. A mixture model confirmed this developmental evolution, while a diffusion model corroborated the idea that the difference between the two strategies concerns anticipatory processes preceding decision processes. To test the fourth prediction, we conducted an online experiment where 236 participants made numerosity comparisons before and after an instruction favoring either reactive or anticipatory responses. The results provide out-of-the-lab evidence of the bimodal RT distribution associated with sequential comparisons and demonstrated that the proportions of fast vs. slow responders can be modulated simply by asking subjects to anticipate or not the future result of the comparison. Although anticipation of the future is as important for cognition as memory of the past, its evolution after the first year of life is much more poorly known. The present study is a step toward meeting this challenge. It also illustrates how analyzing individual RT distributions in addition to group RT distributions and using computational models can improve the assessment of decision making cognitive processes.

Task-independent neural bases of peer presence effect on cognition in children and adults.

There is ample behavioral evidence that others' mere presence can affect any behavior in human and non-human animals, generally facilitating the expression of mastered responses while impairing the acquisition of novel ones. Much less is known about i) how the brain orchestrates the modulation of such a wide array of behaviors by others' presence and ii) when these neural underpinnings mature during development. To address these issues, fMRI data were collected in children and adults alternately observed and unobserved by a familiar peer. Subjects performed a numerosity comparison task and a phonological comparison task. While the former involves number-processing brain areas, the latter involves language-processing areas. Consistent with previous behavioral findings, adults' and children's performance improved in both tasks when observed by a peer. Across all participants, task-specific brain regions showed no reliable change in activity under peer observation. Rather, we found task-independent changes in domain-general brain regions typically involved in mentalizing, reward, and attention. Bayesian analyses singled out the attention network as the exception to the close child-adult resemblance of peer observation neural substrates. These findings suggest that i) social facilitation of some human education-related skills is primarily orchestrated by domain-general brain networks, rather than by task-selective substrates, and ii) apart from attention, peer presence neural processing is largely mature in children.

BioSimia, France CNRS network for nonhuman primate biomedical research in infectiology, immunology, and neuroscience.

Research and developments based on nonhuman primate models have a specific place in biomedical sciences, and nonhuman primate species also have a specific place in the public opinion on the use of animal in research. While nonhuman primates are used in very limited number compared to other animal models, they are rightly the focus of deep ethical concerns. The importance of nonhuman primates in neuroscientific fundamental and preclinical discoveries together with the targeting of such research by activist groups well illustrate this fact. Nonhuman primates also highly contribute to other biomedical fields including immunology, virology, or metabolic and respiratory physiology. In all these fields, researchers, engineers and technicians face similar matters and share the same needs for optimal animal welfare, handling, and veterinary care, the same quest for first-rate research infrastructure and funding, and the same yearning for more public understanding and support. In this article, we give an overview of the evolution of human-animal relationships and public attitudes to animal research in France, and we recount the creation of BioSimia, France network for nonhuman primate biomedical research which now links all academic laboratories nationwide in all the domains for which nonhuman primates remain essential. We explain the principles as well as the outcomes of networking across disciplines. As a perspective, we outline the potential benefits of extending such network to a European scale.

Peer Presence Effect on Numerosity and Phonological Comparisons in 4th Graders: When Working with a SchoolMate Makes Children More Adult-like.

Little is known about how peers' mere presence may, in itself, affect academic learning and achievement. The present study addresses this issue by exploring whether and how the presence of a familiar peer affects performance in a task assessing basic numeracy and literacy skills: numerosity and phonological comparisons. We tested 99 fourth-graders either alone or with a classmate. Ninety-seven college-aged young adults were also tested on the same task, either alone or with a familiar peer. Peer presence yielded a reaction time (RT) speedup in children, and this social facilitation was at least as important as that seen in adults. RT distribution analyses indicated that the presence of a familiar peer promotes the emergence of adult-like features in children. This included shorter and less variable reaction times (confirmed by an ex-Gaussian analysis), increased use of an optimal response strategy, and, based on Ratcliff's diffusion model, speeded up nondecision (memory and/or motor) processes. Peer presence thus allowed children to at least narrow (for demanding phonological comparisons), and at best, virtually fill in (for unchallenging numerosity comparisons) the developmental gap separating them from adult levels of performance. These findings confirm the influence of peer presence on skills relevant to education and lay the groundwork for exploring how the brain mechanisms mediating this fundamental social influence evolve during development.

Optic flow selectivity in the macaque parieto-occipital sulcus.

In humans, several neuroimaging studies have demonstrated that passive viewing of optic flow stimuli activates higher-level motion areas, like V6 and the cingulate sulcus visual area (CSv). In macaque, there are few studies on the sensitivity of V6 and CSv to egomotion compatible optic flow. The only fMRI study on this issue revealed selectivity to egomotion compatible optic flow in macaque CSv but not in V6 (Cotterau et al. Cereb Cortex 27(1):330-343, 2017, but see Fan et al. J Neurosci. 35:16303-16314, 2015). Yet, it is unknown whether monkey visual motion areas MT + and V6 display any distinctive fMRI functional profile relative to the optic flow stimulation, as it is the case for the homologous human areas (Pitzalis et al., Cereb Cortex 20(2):411-424, 2010). Here, we described the sensitivity of the monkey brain to two motion stimuli (radial rings and flow fields) originally used in humans to functionally map the motion middle temporal area MT + (Tootell et al. J Neurosci 15: 3215-3230, 1995a; Nature 375:139-141, 1995b) and the motion medial parietal area V6 (Pitzalis et al. 2010), respectively. In both animals, we found regions responding only to optic flow or radial rings stimulation, and regions responding to both stimuli. A region in the parieto-occipital sulcus (likely including V6) was one of the most highly selective area for coherently moving fields of dots, further demonstrating the power of this type of stimulation to activate V6 in both humans and monkeys. We did not find any evidence that putative macaque CSv responds to Flow Fields.

Atomoxetine modulates the contribution of low-level signals during free viewing of natural images in rhesus monkeys.

Visuo-spatial attentional orienting is fundamental to selectively process behaviorally relevant information, depending on both low-level visual attributes of stimuli in the environment and higher-level factors, such as goals, expectations and prior knowledge. Growing evidence suggests an impact of the locus-cœruleus-norepinephrine (LC-NE) system in attentional orienting that depends on taskcontext. Nonetheless, most of previous studies used visual displays encompassing a target and various distractors, often preceded by cues to orient the attentional focus. This emphasizes the contribution of goal-driven processes, at the expense of other factors related to the stimulus content. Here, we aimed to determine the impact of NE on attentional orienting in more naturalistic conditions, using complex images and without any explicit task manipulation. We tested the effects of atomoxetine (ATX) injections, a NE reuptake inhibitor, on four monkeys during free viewing of images belonging to three categories: landscapes, monkey faces and scrambled images. Analyses of the gaze exploration patterns revealed, first, that the monkeys spent more time on each fixation under ATX compared to the control condition, regard less of the image content. Second, we found that, depending on the image content, ATX modulated the impact of low-level visual salience on attentional orienting. This effect correlated with the effect of ATX on the number and duration of fixations. Taken together, our results demonstrate that ATX adjusts the contribution of salience on attentional orienting depending on the image content, indicative of its role in balancing the role of stimulus-driven and top-down control during free viewing of complex stimuli.

Atomoxetine modulates the relationship between perceptual abilities and response bias.

Elucidation of how neuromodulators influence motivated behaviors is a major challenge of neuroscience research. It has been proposed that the locus-cœruleus-norepinephrine system promotes behavioral flexibility and provides resources required to face challenges in a wide range of cognitive processes. Both theoretical models and computational models suggest that the locus-cœruleus-norepinephrine system tunes neural gain in brain circuits to optimize behavior. However, to the best of our knowledge, empirical proof demonstrating the role of norepinephrine in performance optimization is scarce. Here, we modulated norepinephrine transmission in monkeys performing a Go/No-Go discrimination task using atomoxetine, a norepinephrine-reuptake inhibitor. We tested the optimization hypothesis by assessing perceptual sensitivity, response bias, and their functional relationship within the framework of the signal detection theory. We also manipulated the contingencies of the task (level of stimulus discriminability, target stimulus frequency, and decision outcome values) to modulate the relationship between sensitivity and response bias. We found that atomoxetine increased the subject's perceptual sensitivity to discriminate target stimuli regardless of the task contingency. Atomoxetine also improved the functional relationship between sensitivity and response bias, leading to a closer fit with the optimal strategy in different contexts. In addition, atomoxetine tended to reduce reaction time variability. Taken together, these findings support a role of norepinephrine transmission in optimizing response strategy.

Atomoxetine improves attentional orienting in a predictive context.

The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes influenced by atomoxetine (ATX) injections, a NE-reuptake inhibitor that boosts the level of NE in the brain, and to characterize these influences. We tested the effects of ATX injections, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more inconsistent. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

Peer Presence Effects on Eye Movements and Attentional Performance.

"Social facilitation" refers to the enhancement or impairment of performance engendered by the mere presence of others. It has been demonstrated for a diversity of behaviors. This study assessed whether it also concerns attention and eye movements and if yes, which decision-making mechanisms it affects. Human volunteers were tested in three different tasks (saccades, visual search, and continuous performance) either alone or in the presence of a familiar peer. The results failed to reveal any significant peer influence on the visual search and continuous performance tasks. For saccades, by contrast, they showed a negative or positive peer influence depending on the complexity of the testing protocol. Pro-and anti-saccades were both inhibited when pseudorandomly mixed, and both facilitated when performed separately. Peer presence impaired or improved reaction times, i.e., the speed to initiate the saccade, as well as peak velocity, i.e., the driving force moving the eye toward the target. Effect sizes were large, with Cohen's d-values ranging for reaction times (RTs) from 0.50 to 0.95. Analyzing RT distributions using the LATER (Linear Approach to Threshold with Ergodic Rate) model revealed that social inhibition of pro- and anti-saccades in the complex protocol was associated with a significant increase in the rate of rise. The present demonstration that the simple presence of a familiar peer can inhibit or facilitate saccades depending on task difficulty strengthens a growing body of evidence showing social modulations of eye movements and attention processes. The present lack of effect on visual search and continuous performance tasks contrasts with peer presence effects reported earlier using similar tasks, and future studies are needed to determine whether it is due to an intermediate level of difficulty maximizing individual variability. Together with an earlier study of the social inhibition of anti-saccades also using the LATER model, which showed an increase of the threshold, the present increase of the rate of rise suggests that peer presence can influence both the top-down and bottom-up attention-related processes guiding the decision to move the eyes.

An Open Resource for Non-human Primate Imaging.

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

Could LC-NE-Dependent Adjustment of Neural Gain Drive Functional Brain Network Reorganization?

The locus coeruleus-norepinephrine (LC-NE) system is thought to act at synaptic, cellular, microcircuit, and network levels to facilitate cognitive functions through at least two different processes, not mutually exclusive. Accordingly, as a reset signal, the LC-NE system could trigger brain network reorganizations in response to salient information in the environment and/or adjust the neural gain within its target regions to optimize behavioral responses. Here, we provide evidence of the co-occurrence of these two mechanisms at the whole-brain level, in resting-state conditions following a pharmacological stimulation of the LC-NE system. We propose that these two mechanisms are interdependent such that the LC-NE-dependent adjustment of the neural gain inferred from the clustering coefficient could drive functional brain network reorganizations through coherence in the gamma rhythm. Via the temporal dynamic of gamma-range band-limited power, the release of NE could adjust the neural gain, promoting interactions only within the neuronal populations whose amplitude envelopes are correlated, thus making it possible to reorganize neuronal ensembles, functional networks, and ultimately, behavioral responses. Thus, our proposal offers a unified framework integrating the putative influence of the LC-NE system on both local- and long-range adjustments of brain dynamics underlying behavioral flexibility.

Social modulation of cognition: Lessons from rhesus macaques relevant to education.

Any animal, human or non-human, lives in a world where there are others like itself. Individuals' behaviors are thus inevitably influenced by others, and cognition is no exception. Long acknowledged in psychology, social modulations of cognition have been neglected in cognitive neuroscience. Yet, infusing this classic topic in psychology with brain science methodologies could yield valuable educational insights. In recent studies, we used a non-human primate model, the rhesus macaque, to identify social influences representing ancient biases rooted in evolution, and neuroimaging to shed light on underlying mechanisms. The behavioral and neural data garnered in humans and macaques are summarized, with a focus on two findings relevant to human education. First, peers' mistakes stand out as exceptional professors and seem to have devoted areas and neurons in the primates' brain. Second, peers' mere presence suffices to enhance performance in well-learned tasks, possibly by boosting activity in the brain network involved in the task at hand. These findings could be translated into concrete pedagogical interventions in the classroom.

Boosting Norepinephrine Transmission Triggers Flexible Reconfiguration of Brain Networks at Rest.

The locus coeruleus-norepinephrine (LC-NE) system is thought to act as a reset signal allowing brain network reorganization in response to salient information in the environment. However, no direct evidence of NE-dependent whole-brain reorganization has ever been described. We used resting-state functional magnetic resonance imaging in monkeys to investigate the impact of NE-reuptake inhibition on whole-brain connectivity patterns. We found that boosting NE transmission changes functional connectivity between and within resting-state networks. It modulated the functional connectivity pattern of a brainstem network including the LC region and interactions between associative and sensory-motor networks as well as within sensory-motor networks. Among the observed changes, those involving the fronto-parietal attention network exhibited a unique pattern of uncoupling with other sensory-motor networks and correlation switching from negative to positive with the brainstem network that included the LC nucleus. These findings provide the first empirical evidence of NE-dependent large-scale brain network reorganization and further demonstrate that the fronto-parietal attention network represents a central feature within this reorganization.

Others' Sheer Presence Boosts Brain Activity in the Attention (But Not the Motivation) Network.

The sheer presence of another member of the same species affects performance, sometimes impeding it, sometimes enhancing it. For well-learned tasks, the effect is generally positive. This fundamental form of social influence, known as social facilitation, concerns human as well as nonhuman animals and affects many behaviors from food consumption to cognition. In psychology, this phenomenon has been known for over a century. Yet, its underlying mechanism (motivation or attention) remains debated, its relationship to stress unclear, and its neural substrates unknown. To address these issues, we investigated the behavioral, neuronal, and endocrinological markers of social facilitation in monkeys trained to touch images to obtain rewards. When another animal was present, performance was enhanced, but testing-induced stress (i.e., plasma cortisol elevation) was unchanged, as was metabolic activity in the brain motivation network. Rather, task-related activity in the (right) attention frontoparietal network encompassing the lateral prefrontal cortex, ventral premotor cortex, frontal eye field, and intraparietal sulcus was increased when another individual was present compared with when animals were tested alone. These results establish the very first link between the behavioral enhancement produced by the mere presence of a peer and an increase of metabolic activity in those brain structures underpinning attention.

Social Facilitation of Cognition in Rhesus Monkeys: Audience Vs. Coaction.

Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect), or a passive spectator (audience effect) changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad) performed a simple cognitive task consisting in touching images to obtain food treats, alone vs. in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however four times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

Model-observer similarity, error modeling and social learning in rhesus macaques.

Monkeys readily learn to discriminate between rewarded and unrewarded items or actions by observing their conspecifics. However, they do not systematically learn from humans. Understanding what makes human-to-monkey transmission of knowledge work or fail could help identify mediators and moderators of social learning that operate regardless of language or culture, and transcend inter-species differences. Do monkeys fail to learn when human models show a behavior too dissimilar from the animals' own, or when they show a faultless performance devoid of error? To address this question, six rhesus macaques trained to find which object within a pair concealed a food reward were successively tested with three models: a familiar conspecific, a 'stimulus-enhancing' human actively drawing the animal's attention to one object of the pair without actually performing the task, and a 'monkey-like' human performing the task in the same way as the monkey model did. Reward was manipulated to ensure that all models showed equal proportions of errors and successes. The 'monkey-like' human model improved the animals' subsequent object discrimination learning as much as a conspecific did, whereas the 'stimulus-enhancing' human model tended on the contrary to retard learning. Modeling errors rather than successes optimized learning from the monkey and 'monkey-like' models, while exacerbating the adverse effect of the 'stimulus-enhancing' model. These findings identify error modeling as a moderator of social learning in monkeys that amplifies the models' influence, whether beneficial or detrimental. By contrast, model-observer similarity in behavior emerged as a mediator of social learning, that is, a prerequisite for a model to work in the first place. The latter finding suggests that, as preverbal infants, macaques need to perceive the model as 'like-me' and that, once this condition is fulfilled, any agent can become an effective model.

The helmet head restraint system: a viable solution for resting state fMRI in awake monkeys.

In monkey neuroimaging, head restraint is currently achieved via surgical implants. Eradicating such invasive head restraint from otherwise non-invasive monkey studies could represent a substantial progress in terms of Reduction and Refinement. Two non-invasive helmet-based methods are available but they are used exclusively by the pioneering research groups who designed them. In the absence of independent replication, they have had little impact in replacing the surgical implants. Here, we built a modified version of the helmet system proposed by Srihasam et al. (2010 NeuroImage, 51(1), 267-73) and tested it for resting state fMRI in awake monkeys. Extremely vulnerable to motion artifacts, resting state fMRI represents a decisive test for non-invasive head restraint systems. We compared two monkeys restrained with the helmet to one monkey with a surgically implanted head post using both a seed-based approach and an independent component analysis. Technically, the helmet system proved relatively easy to develop. Scientifically, although it allowed more extensive movements than the head post system, the helmet proved viable for resting state fMRI, in particular when combined with the independent component analysis that deals more effectively with movement-related noise than the seed-based approach. We also discuss the pros and cons of such device in light of the European Union new 2013 regulation on non-human primate research and its firm Reduction and Refinement requests.

Social learning as a way to overcome choice-induced preferences? Insights from humans and rhesus macaques.

Much theoretical attention is currently devoted to social learning. Yet, empirical studies formally comparing its effectiveness relative to individual learning are rare. Here, we focus on free choice, which is at the heart of individual reward-based learning, but absent in social learning. Choosing among two equally valued options is known to create a preference for the selected option in both humans and monkeys. We thus surmised that social learning should be more helpful when choice-induced preferences retard individual learning than when they optimize it. To test this prediction, the same task requiring to find which among two items concealed a reward was applied to rhesus macaques and humans. The initial trial was individual or social, rewarded or unrewarded. Learning was assessed on the second trial. Choice-induced preference strongly affected individual learning. Monkeys and humans performed much more poorly after an initial negative choice than after an initial positive choice. Comparison with social learning verified our prediction. For negative outcome, social learning surpassed or at least equaled individual learning in all subjects. For positive outcome, the predicted superiority of individual learning did occur in a majority of subjects (5/6 monkeys and 6/12 humans). A minority kept learning better socially though, perhaps due to a more dominant/aggressive attitude toward peers. Poor learning from errors due to over-valuation of personal choices is among the decision-making biases shared by humans and animals. The present study suggests that choice-immune social learning may help curbing this potentially harmful tendency. Learning from successes is an easier path. The present data suggest that whether one tends to walk it alone or with a peer's help might depend on the social dynamics within the actor/observer dyad.

Advanced Parkinson's disease effect on goal-directed and habitual processes involved in visuomotor associative learning.

The present behavioral study re-addresses the question of habit learning in Parkinson's disease (PD). Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding vs. following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under 60 years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by PD. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced PD stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed actions.