Contribution of the subthalamic nucleus to motor, cognitive and limbic processes: an electrophysiological and stimulation study in monkeys

Deep brain stimulation of the subthalamic nucleus (STN) has become the gold standard surgical treatment for Parkinson’s disease and is being investigated for obsessive compulsive disorders. Even if the role of the STN in the behavior is well documented, its organization and especially its division into several functional territories is still debated. A better characterization of these territories and a better knowledge of the impact of stimulation would address this issue. We aimed to find specific electrophysiological markers of motor, cognitive and limbic functions within the STN and to specifically modulate these components. Two healthy non-human primates (Macaca fascicularis) performed a behavioral task allowing the assessment of motor, cognitive and limbic reward-related behavioral components. During the task, four contacts in the STN allowed recordings and stimulations, using low frequency stimulation (LFS) and high frequency stimulation (HFS). Specific electrophysiological functional markers were found in the STN with beta band activity for the motor component of behavior, theta band activity for the cognitive component, and, gamma and theta activity bands for the limbic component. For both monkeys, dorsolateral HFS and LFS of the STN significantly modulated motor performances, whereas only ventromedial HFS modulated cognitive performances. Our results validated the functional overlap of dorsal motor and ventral cognitive subthalamic territories, and, provide information that tends toward a diffuse limbic territory sensitive to the reward within the STN

Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinson's Disease

It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms.Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12–56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5–7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested.Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits

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

APPRENTISSAGE ET RESOLUTION DE PROBLEMES SEQUENTIELS CHEZ LE SINGE RHESUS : Etude comportementale et enregistrements unitaires dans les aires oculomotrices frontales et le cortex cingulaire antérieur

rédigée de janvier à mai 1999.Bibliographic review and behavioural and neurophpysiological data on organisation and learning of sequential behaviours in primatesCe mémoire présente une revue bibliographique et des données sur les bases comportementales et neurophysiologiques de l'apprentissage de comportement séquentiels chez le primat

The primate working memory networks.

International audienceWorking memory has long been associated with the prefrontal cortex, since damage to this brain area can critically impair the ability to maintain and update mnemonic information. Anatomical and physiological evidence suggests, however, that the prefrontal cortex is part of a broader network of interconnected brain areas involved in working memory. These include the parietal and temporal association areas of the cerebral cortex, cingulate and limbic areas, and subcortical structures such as the mediodorsal thalamus and the basal ganglia. Neurophysiological studies in primates confirm the involvement of areas beyond the frontal lobe and illustrate that working memory involves parallel, distributed neuronal networks. In this article, we review the current understanding of the anatomical organization of networks mediating working memory and the neural correlates of memory manifested in each of their nodes. The neural mechanisms of memory maintenance and the integrative role of the prefrontal cortex are also discussed

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

International audienceResearch 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

Investigating Confidence Judgments using Reviews in Human and Monkeys

Confidence judgments are self-assessments of the quality of one’s own performance, and are a crucial aspect of metacognitive abilities. The underlying neurobiological mechanisms are poorly understood. One approach to understanding these mechanisms would be to take advantage of putative metacognitive abilities in non-human models. However, many discrepancies exist between human and non-human studies on metacognition due to the mode of reporting judgements. We here present an attempt to directly compare human and non-human primates’ metacognitive abilities using a protocol assessing confidence judgments. After performing a categorization test, subjects could either validate their choice or review the test. We could assess whether subjects detected their errors and how they corrected them according to their confidence, and importantly did so in both human and non-human primates. 14 humans and 2 macaque monkeys were tested. Humans showed a well-adapted use of the review option by reviewing more after incorrect choices or difficult stimuli. Non-human primates did not demonstrate a convincing use of the review or validate opportunity. In both species, reviewing did not improve performance. This study shows that decisions to review under uncertainty are not naturally beneficial to performance and is rather perturbed by biases and alternative low-cognitive cost strategies