Learning In Non-human Primates Research Articles

M1-selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates

Acetylcholine (ACh) in cortical neural circuits mediates how selective attention is sustained in the presence of distractors and how flexible cognition adjusts to changing task demands. The cognitive domains of attention and cognitive flexibility might be differentially supported by the M1 muscarinic acetylcholine receptor (mAChR) subtype. Understanding how M1 mAChR mechanisms support these cognitive subdomains is of highest importance for advancing novel drug treatments for conditions with altered attention and reduced cognitive control including Alzheimer's disease or schizophrenia. Here, we tested this question by assessing how the subtype-selective M1 mAChR positive allosteric modulator (PAM) VU0453595 affects visual search and flexible reward learning in nonhuman primates. We found that allosteric potentiation of M1 mAChRs enhanced flexible learning performance by improving extradimensional set shifting, reducing latent inhibition from previously experienced distractors and reducing response perseveration in the absence of adverse side effects. These procognitive effects occurred in the absence of apparent changes of attentional performance during visual search. In contrast, nonselective ACh modulation using the acetylcholinesterase inhibitor (AChEI) donepezil improved attention during visual search at doses that did not alter cognitive flexibility and that already triggered gastrointestinal cholinergic side effects. These findings illustrate that M1 mAChRpositive allosteric modulation enhances cognitive flexibility without affecting attentional filtering of distraction, consistent with M1 activity boosting the effective salience of relevant over irrelevant objects specifically during learning. These results suggest that M1 PAMs are versatile compounds for enhancing cognitive flexibility in disorders spanning schizophrenia and Alzheimer's diseases.

Behavioral metrics of reward learning in nonhuman primates provide a framework for human neurophysiological recordings

Behavioral metrics of reward learning in nonhuman primates provide a framework for human neurophysiological recordings

Understanding Imitation in Papio papio: The Role of Experience and the Presence of a Conspecific Demonstrator.

What factors affect imitation performance? Varying theories of imitation stress the role of experience, but few studies have explicitly tested its role in imitative learning in non-human primates. We tested several predictions regarding the role of experience, conspecific presence, and action compatibility using a stimulus-response compatibility protocol. Nineteen baboons separated into two experimental groups learned to respond by targeting on a touch screen the same stimulus as their neighbor (compatible) or the opposite stimulus (incompatible). They first performed the task with a conspecific demonstrator (social phase) and then a computer demonstrator (ghost phase). After reaching a predetermined success threshold, they were then tested in an opposite compatibility condition (i.e., reversal learning conditions). Seven baboons performed at least two reversals during the social phase, and we found no significant difference between the compatible and incompatible conditions, although we noticed slightly faster response times (RTs) in the compatible condition that disappeared after the first reversal. During the ghost phase, monkeys showed difficulties in learning the incompatible condition, and the compatible condition RTs tended to be slower than during the social phase. Together, these results suggest that (a) there is no strong movement compatibility effect in our task and that (b) the presence of a demonstrator plays a role in eliciting correct responses but is not essential as has been previously shown in human studies.

Collective knowledge and the dynamics of culture in chimpanzees.

Social learning in non-human primates has been studied experimentally for over 120 years, yet until the present century this was limited to what one individual learns from a single other. Evidence of group-wide traditions in the wild then highlighted the collective context for social learning, and broader ‘diffusion experiments’ have since demonstrated transmission at the community level. In the present article, we describe and set in comparative perspective three strands of our recent research that further explore the collective dimensions of culture and cumulative culture in chimpanzees. First, exposing small communities of chimpanzees to contexts incorporating increasingly challenging, but more rewarding tool use opportunities revealed solutions arising through the combination of different individuals' discoveries, spreading to become shared innovations. The second series of experiments yielded evidence of conformist changes from habitual techniques to alternatives displayed by a unanimous majority of others but implicating a form of quorum decision-making. Third, we found that between-group differences in social tolerance were associated with differential success in developing more complex tool use to exploit an increasingly inaccessible resource. We discuss the implications of this array of findings in the wider context of related studies of humans, other primates and non-primate species.This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.

Nonhuman primates learn adjacent dependencies but fail to learn nonadjacent dependencies in a statistical learning task with a salient cue.

There is ample evidence that humans and nonhuman animals can learn complex statistical regularities presented within various types of input. However, humans outperform their nonhuman primate counterparts when it comes to recognizing relationships that exist across one or several intervening stimuli (nonadjacent dependencies). This is especially true when the two elements in the dependency do not share any perceptual similarity (arbitrary associations). In the present study, we investigated whether manipulating the saliency of the predictive stimulus would enhance nonadjacent dependency learning in nonhuman primates. Rhesus macaques and tufted capuchins engaged in a computerized signal detection task that included sequences that were random in nature, included an adjacent dependency, or included a nonadjacent dependency. We manipulated the saliency of the predictive stimulus, such that the predictor jittered in place on the screen in some grammar blocks, as well as the transitional probability (the likelihood of the stimulus preceding the target to accurately predict the target's appearance) from block to block. Some monkeys evidenced learning of adjacent dependencies by faster response times to targets that followed a predictive stimulus compared to targets that were not preceded by a predictor. However, consistent with the body of evidence that indicates that nonhuman animals' statistical learning mechanisms are not at the same level of sophistication as humans', there was no evidence that monkeys learned nonadjacent dependencies of arbitrary associations, even when the salient cue was present.

The Emergence of Language: a Review of Ljiljana Progovac (2019); A Critical Introduction to Language Evolution: Current Controversies and Future Prospects

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Combined model-free and model-sensitive reinforcement learning in non-human primates.

Contemporary reinforcement learning (RL) theory suggests that potential choices can be evaluated by strategies that may or may not be sensitive to the computational structure of tasks. A paradigmatic model-free (MF) strategy simply repeats actions that have been rewarded in the past; by contrast, model-sensitive (MS) strategies exploit richer information associated with knowledge of task dynamics. MF and MS strategies should typically be combined, because they have complementary statistical and computational strengths; however, this tradeoff between MF/MS RL has mostly only been demonstrated in humans, often with only modest numbers of trials. We trained rhesus monkeys to perform a two-stage decision task designed to elicit and discriminate the use of MF and MS methods. A descriptive analysis of choice behaviour revealed directly that the structure of the task (of MS importance) and the reward history (of MF and MS importance) significantly influenced both choice and response vigour. A detailed, trial-by-trial computational analysis confirmed that choices were made according to a combination of strategies, with a dominant influence of a particular form of model sensitivity that persisted over weeks of testing. The residuals from this model necessitated development of a new combined RL model which incorporates a particular credit assignment weighting procedure. Finally, response vigor exhibited a subtly different collection of MF and MS influences. These results provide new illumination onto RL behavioural processes in non-human primates.

Adaptive coordination of working-memory and reinforcement learning in non-human primates performing a trial-and-error problem solving task

Accumulating evidence suggest that human behavior in trial-and-error learning tasks based on decisions between discrete actions may involve a combination of reinforcement learning (RL) and working-memory (WM). While the understanding of brain activity at stake in this type of tasks often involve the comparison with non-human primate neurophysiological results, it is not clear whether monkeys use similar combined RL and WM processes to solve these tasks. Here we analyzed the behavior of five monkeys with computational models combining RL and WM. Our model-based analysis approach enables to not only fit trial-by-trial choices but also transient slowdowns in reaction times, indicative of WM use. We found that the behavior of the five monkeys was better explained in terms of a combination of RL and WM despite inter-individual differences. The same coordination dynamics we used in a previous study in humans best explained the behavior of some monkeys while the behavior of others showed the opposite pattern, revealing a possible different dynamics of WM process. We further analyzed different variants of the tested models to open a discussion on how the long pretraining in these tasks may have favored particular coordination dynamics between RL and WM. This points towards either inter-species differences or protocol differences which could be further tested in humans.

Implicit Memory in Monkeys: Development of a Delay Eyeblink Conditioning System with Parallel Electromyographic and High-Speed Video Measurements.

Delay eyeblink conditioning, a cerebellum-dependent learning paradigm, has been applied to various mammalian species but not yet to monkeys. We therefore developed an accurate measuring system that we believe is the first system suitable for delay eyeblink conditioning in a monkey species (Macaca mulatta). Monkey eyeblinking was simultaneously monitored by orbicularis oculi electromyographic (OO-EMG) measurements and a high-speed camera-based tracking system built around a 1-kHz CMOS image sensor. A 1-kHz tone was the conditioned stimulus (CS), while an air puff (0.02 MPa) was the unconditioned stimulus. EMG analysis showed that the monkeys exhibited a conditioned response (CR) incidence of more than 60% of trials during the 5-day acquisition phase and an extinguished CR during the 2-day extinction phase. The camera system yielded similar results. Hence, we conclude that both methods are effective in evaluating monkey eyeblink conditioning. This system incorporating two different measuring principles enabled us to elucidate the relationship between the actual presence of eyelid closure and OO-EMG activity. An interesting finding permitted by the new system was that the monkeys frequently exhibited obvious CRs even when they produced visible facial signs of drowsiness or microsleep. Indeed, the probability of observing a CR in a given trial was not influenced by whether the monkeys closed their eyelids just before CS onset, suggesting that this memory could be expressed independently of wakefulness. This work presents a novel system for cognitive assessment in monkeys that will be useful for elucidating the neural mechanisms of implicit learning in nonhuman primates.

Effects of self‐administered methamphetamine on learning‐to‐learn in the squirrel monkey (661.1)

Long‐term chronic exposure to methamphetamine (MA) has been related to profound neural impact including, but not limited to, damage to monoamine nerve terminals. In turn, neural changes following repeated MA administration may be related to adverse effects on learning and other cognitive performance. However, the characterization of such neurobehavioral deficits remains incomplete. The present study assessed the effects of ongoing MA self‐administration on touchscreen‐based discrimination learning in nonhuman primates. Prior to daily sessions of MA self‐administration (i.e., 20‐hr after the previous day’s session), monkeys engaged in a repeated acquisition task in which changes in the rate of discrimination learning for a stimulus pair were assessed over the successive presentation of novel stimulus pairs. Results thus far indicate that ongoing MA self‐administration produces markedly deleterious effects on the development of learning sets in discrimination learning. Importantly, the magnitude of adverse effects on learning appears to be correlated with the level of daily MA intake among individual subjects.Grant Funding Source: Supported by grant K01‐DA035974 from NIDA

Chronic manganese exposure impairs visuospatial associative learning in non-human primates

Manganese (Mn) is an essential trace metal nutrient, however, excess Mn can be neurotoxic. The degree to which chronic environmental or occupational exposures to Mn in adults cause neuropsychological dysfunction is of considerable interest. Descriptions of neuropsychological dysfunction following chronic Mn exposure have been somewhat inconsistent though, likely owing to different measures of exposure in different populations, complicated by factors of mixed exposures and differences in neuropsychological tests administered. We previously described up-regulation of the mRNA expression for amyloid-beta (A-beta) precursor-like protein 1 (APLP1) and the presence of A-beta diffuse plaques in frontal cortex of Mn-exposed monkeys. The present study examined Mn-induced changes in performance on a paired associate learning (PAL) task that has been suggested as a marker for preclinical Alzheimer's disease. Aspects of performance of this task were affected early following initiation of Mn exposure. Thus, PAL performance may be a sensitive and valuable tool for the early, preclinical detection of incipient dementia and it may also be a sensitive tool for detecting cognitive dysfunction from Mn exposure. The current cognitive data, combined with our previous findings, suggest that frontal cortex may be a particularly sensitive target for the effects of Mn on cognition and that chronic Mn exposure may initiate or accelerate a process that could lead to or predispose to Alzheimer's like pathology and cognitive dysfunction.

On the pursuit of the brain network for proto-syntactic learning in non-human primates: conceptual issues and neurobiological hypotheses

Songbirds have become impressive neurobiological models for aspects of human verbal communication because they learn to sequence their song elements, analogous, in some ways, to how humans learn to produce spoken sequences with syntactic structure. However, mammals such as non-human primates are considered to be at best limited-vocal learners and not able to sequence their vocalizations, although some of these animals can learn certain ‘artificial grammar’ sequences. Thus, conceptual issues have slowed the progress in exploring potential neurobiological homologues to language-related processes in species that are taxonomically closely related to humans. We consider some of the conceptual issues impeding a pursuit of, as we define them, ‘proto-syntactic’ capabilities and their neuronal substrates in non-human animals. We also discuss ways to better bridge comparative behavioural and neurobiological data between humans and other animals. Finally, we propose guiding neurobiological hypotheses with which we aim to facilitate the future testing of the level of correspondence between the human brain network for syntactic-learning and related neurobiological networks present in other primates. Insights from the study of non-human primates and other mammals are likely to complement those being obtained in birds to further our knowledge of the human language-related network at the cellular level.

Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication

Comparative analyses used to reconstruct the evolution of traits associated with the human language faculty, including its socio-cognitive underpinnings, highlight the importance of evolutionary constraints limiting vocal learning in non-human primates. After a brief overview of this field of research and the neural basis of primate vocalizations, we review studies that have addressed the genetic basis of usage and structure of ultrasonic communication in mice, with a focus on the gene FOXP2 involved in specific language impairments and neuroligin genes (NL-3 and NL-4) involved in autism spectrum disorders. Knockout of FoxP2 leads to reduced vocal behavior and eventually premature death. Introducing the human variant of FoxP2 protein into mice, in contrast, results in shifts in frequency and modulation of pup ultrasonic vocalizations. Knockout of NL-3 and NL-4 in mice diminishes social behavior and vocalizations. Although such studies may provide insights into the molecular and neural basis of social and communicative behavior, the structure of mouse vocalizations is largely innate, limiting the suitability of the mouse model to study human speech, a learned mode of production. Although knockout or replacement of single genes has perceptible effects on behavior, these genes are part of larger networks whose functions remain poorly understood. In humans, for instance, deficiencies in NL-4 can lead to a broad spectrum of disorders, suggesting that further factors (experiential and/or genetic) contribute to the variation in clinical symptoms. The precise nature as well as the interaction of these factors is yet to be determined.

Neural correlates of observational learning in non human primates

Neural correlates of observational learning in non human primates

Acquisition and memory of sequence order in young and adult chimpanzees (Pan troglodytes)

There is no research about age difference in the process of sequential learning in non-human primates. Is there any difference between young and adults in sequential learning process? Six chimpanzees (Pan troglodytes), 3 young and 3 adults, learned the Arabic numeral sequence 1 to 9 by touching the numerals on a touch-screen monitor in ascending order. Initially, the sequence always started with the numeral 1, i.e. 'start-fixed task'. Training began with the sequence 1-2, 1-2-3, and continued sequentially up to 1-2-3-4-5-6-7-8-9. Later, the subjects were introduced to sequences that started with a random numeral, but always ended with 9, i.e. 'end-fixed task'. Performance in the end-fixed task was worse relative to the familiar start-fixed task. After training with various sequences of adjacent numerals, the subjects were given a transfer test for the non-adjacent numerals. The results suggested that all chimpanzees indeed mastered sequential ordering, and although there was no fundamental difference in the acquisition process between the two age groups, there was a significant age difference in memory capacity. Based on their knowledge of sequential ordering, the subjects were then asked to perform a masking task in which once a subject touched the lowest numeral, the other numeral(s) turned to white squares. Performance of the masking task by young chimpanzees was better than that of adults in accuracy and degree of difficulty (number of numerals). Taken together, these data clearly demonstrate a similarity among subjects in the way chimpanzees acquire knowledge of sequential order regardless of age differences in sequential learning. Moreover, they reveal that once knowledge of sequential order is established, it can be a good index used to evaluate memory capacity in young and adult chimpanzees.

Acoustic analysis of vocal development in a New World primate, the common marmoset (Callithrix jacchus)

In contrast to humans and songbirds, there is limited evidence of vocal learning in nonhuman primates. While previous studies suggested that primate vocalizations exhibit developmental changes, detailed analyses of the extent and time course of such changes across a species' vocal repertoire remain limited. In a highly vocal primate, the common marmoset (Callithrix jacchus), we studied developmental changes in the acoustic structure of species-specific communication sounds produced in a social setting. We performed detailed acoustic analyses of the spectral and temporal characteristics of marmoset vocalizations during development, comparing differences between genders and twin pairs, as well as with vocalizations from adult marmosets residing in the same colony. Our analyses revealed significant changes in spectral and temporal features as well as variability of particular call types over time. Infant and juvenile vocalizations changed progressively toward the vocalizations produced by adult marmosets. Call types observed early in development that were unique to infants disappeared gradually with age, while vocal exchanges with conspecifics emerged. Our observations clearly indicate that marmoset vocalizations undergo both qualitative and quantitative postnatal changes, establishing the basis for further studies to delineate contributions from maturation of the vocal apparatus and behavioral experience.

Prenatal Stress Alters Early Neurobehavior, Stress Reactivity and Learning in Non-human Primates: A Brief Review

In this paper we review three prospective longitudinal studies from our laboratory examining the effects of prenatal stress on early neurobehavior, stress reactivity and learning performance in rhesus monkeys. Either a noise stressor or ACTH treatment was administered to pregnant monkeys during specific periods of pregnancy and offspring were examined repeatedly across development. In all three studies, the prenatally stressed monkeys showed reduced attention and impaired neuromotor functioning during the first month of life compared to controls from undisturbed pregnancies. When the monkeys were separated from their mothers or peers at 6–8 months of age, prenatally stressed monkeys exhibited more disturbance behavior and showed hypothalamic-pituitary-adrenal axis dysregulation. During adolescence, they exhibited impairments in learning, compared to controls.

Vocal communication as a function of differential rearing experiences inPan paniscus: A preliminary report

There is little evidence of vocal learning in nonhuman primates despite the well-documented abilities found in avian species. We describe the vocal repertoire of five bonobos (Pan paniscus), four of which live in a seminatural environment. The fifth subject, Kanzi, has been reared with humans during the course of language training. The data indicated that the four bonobos living in a seminatural environment exhibit a variety of species-typical vocalizations. In addition to producing all the species-typical vocalization, Kanzi produced four structurally unique vocalizations that were not heard among the other subjects. These data suggest that Kanzi has learned vocalizations that are novel due to his unique rearing experience. Discussion is focused on the flexibility of vocal communication and vocal comprehension inPan paniscus.

Poison-based avoidance learning in nonhuman primates: Use of visual cues

A series of experiments was designed to evaluate the use of visual cues in the acquisition, persistence, and extinction of a poison-based aversion in a nonhuman primate species. The initial experiments examined the acquisition of the aversion as well as the influence of variations in the dosage of the malaise inducing agent (LiCl). Data indicated one-trial visually-cued aversion learning that was quite persistent. The final experiment was designed to investigate extinction parameters. The experimental animals were found to be extremely resistent to extinction and this aversion was maintained even after forced-choice experience. These results are interpreted within the framework of an adaptive-evolutionary theory of poison-based avoidance learning.