Cognition In Nonhuman Primates Research Articles

May the force be with you: exploring force discrimination in chimpanzees using the force-feedback device.

While force-feedback devices have been developed in areas such as virtual reality, there have been very few comparative cognitive studies in nonhuman animals using these devices. In addition, although cross-modal perception between vision and touch has been actively studied in nonhuman primates for several decades, there have been no studies of their active haptic perception. In this study, we attempted to train force discrimination in chimpanzees using a force-feedback device modified from a trackball. Chimpanzees were given different levels of force feedback (8.0 vs. 0.5N) when moving the on-screen cursor to the target area by manipulating the trackball and were required to select one of two choice stimuli based on the force cue. The experiment was conducted using a trial-block procedure in which the same force stimulus was presented for a fixed number of trials, and the force stimulus was changed between blocks. The block size was progressively reduced from ten trials. Four chimpanzees were trained, but none reached the learning criterion (80% or more correct responses under the condition that the force stimuli were presented randomly). However, a detailed analysis of the chimpanzees' performance before and after the trial-block switching revealed that their choice behavior could not be explained by a simple win-stay/lose-shift strategy, suggesting that the switching of the force stimuli affected the chimpanzees' choice behavior. It was also found that the chimpanzees performed better when switching from small to large force stimuli than when switching from large to small force stimuli. Although none of the chimpanzees in this study acquired force discrimination, future studies using such force-feedback devices will provide new insights for understanding haptic cognition in nonhuman primates from a comparative cognitive perspective.

Behavioral and Cognitive Outcomes of Rhesus Macaques Following Neonatal Exposure to Antiseizure Medications.

Exposure of neonatal macaques to the antiseizure medications phenobarbital and midazolam (PbM) causes widespread apoptotic death of neurons and oligodendrocytes. We studied behavior and neurocognitive performance in 12 to 24 month-old macaques treated as neonates with PbM. A total of 14 monkeys received phenobarbital and midazolam over 24 hours under normothermia (n = 8) or mild hypothermia (n = 6). Controls (n = 8) received no treatment. Animals underwent testing in the human intruder paradigm at ages 12 and 18 months, and a 3-step stimulus discrimination task at ages 12, 18, and 24 months. Animals treated with PbM displayed lower scores for environmental exploration, and higher scores for locomotion and vocalizations compared with controls. Combined PbM and hypothermia resulted in lower scores for aggression and vigilance at 12 months compared with controls and normothermic PbM animals. A mixed-effects generalized linear model was used to test for differences in neurocognitive performance between the control and PbM groups in the first step of the stimulus discrimination task battery (shape center baited to shape center non-baited). The odds of passing this step differed by group (p = 0.044). At any given age, the odds of passing for a control animal were 9.53-fold (95% CI 1.06-85) the odds for a PbM animal. There was also evidence suggesting a higher learning rate in the shape center non-baited for the control relative to the PbM group (Cox model HR 2.13, 95% CI 1.02-4.43; p = 0.044). These findings demonstrate that a 24-hour-long neonatal treatment with a clinically relevant combination of antiseizure medications can have long-lasting effects on behavior and cognition in nonhuman primates. ANN NEUROL 2023.

Preliminary Assessment of Siamang (Symphalangus syndactylus) Cognition Using Digital Cognition Testing Software and Touchscreen Technology

Studies of nonhuman primate cognition have traditionally employed subjects from the monkey (Cercopithecoidea) and ape (Hominidae) lineages, with relatively much less examination of the phylogenetically intermediate gibbons (Hylobatidae). To begin to rectify this gap in our understanding of primate cognition, we used a short-term training and testing method to preliminarily evaluate siamang gibbon (Symphalangus syndactylus) performance on a battery of standardized cognitive tasks, using Monkey CANTAB cognition testing software (Lafayette-Campden Neuroscience) and a computer touchscreen apparatus. Five different operant tasks examining distinct perceptual and cognitive functions were used to train and test each subject over a period of five weeks. Over 1900 cognitive testing trials were completed with three subjects. Despite limited training and testing opportunity, all siamangs achieved proficiency scores well above chance (> 65%) in both Concurrent Discrimination and Spatial Working Memory tasks. Over the limited training opportunities available, our subjects did not achieve proficiency in Delayed Match-to-Sample, Paired Associates Learning, or Conditional Visual Discrimination tasks; however, subjects did exhibit (to varying degrees) improved performance in these tasks, suggesting that additional training may lead to higher proficiency and that siamangs demonstrate effective, task-based learning capabilities. We present one of the first successful tests of a hylobatid ape using touchscreen cognitive testing methods and demonstrate that hylobatids can be evaluated using the same methods now commonly employed in tests of other nonhuman primates. Further, our testing regime proved to be behaviorally rewarding for our subjects, suggesting that hylobatids may benefit from advanced forms of interactive cognitive enrichment.

The evolutionary origins of syntax: Event cognition in nonhuman primates.

Languages tend to encode events from the perspective of agents, placing them first and in simpler forms than patients. This agent bias is mirrored by cognition: Agents are more quickly recognized than patients and generally attract more attention. This leads to the hypothesis that key aspects of language structure are fundamentally rooted in a cognition that decomposes events into agents, actions, and patients, privileging agents. Although this type of event representation is almost certainly universal across languages, it remains unclear whether the underlying cognition is uniquely human or more widespread in animals. Here, we review a range of evidence from primates and other animals, which suggests that agent-based event decomposition is phylogenetically older than humans. We propose a research program to test this hypothesis in great apes and human infants, with the goal to resolve one of the major questions in the evolution of language, the origins of syntax.

Long term study of motivational and cognitive effects of low-intensity focused ultrasound neuromodulation in the dorsal striatum of nonhuman primates

Noninvasive brain stimulation using transcranial focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2–0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.

Assessing the reliability of an automated method for measuring dominance hierarchy in non-human primates

Among animal societies, dominance is an important social factor that influences inter-individual relationships. However, assessing dominance hierarchy can be a time-consuming activity which is potentially impeded by environmental factors, difficulties in the recognition of animals, or disturbance of animals during data collection. Here we took advantage of novel devices, machines for automated learning and testing (MALT), designed primarily to study non-human primate cognition, to additionally measure the dominance hierarchy of a semi-free-ranging primate group. When working on a MALT, an animal can be replaced by another, which could reflect an asymmetric dominance relationship. To assess the reliability of our method, we analysed a sample of the automated conflicts with video scoring and found that 74% of these replacements included genuine forms of social displacements. In 10% of the cases, we did not identify social interactions and in the remaining 16% we observed affiliative contacts between the monkeys. We analysed months of daily use of MALT by up to 26 semi-free-ranging Tonkean macaques (Macaca tonkeana) and found that dominance relationships inferred from these interactions strongly correlated with the ones derived from observations of spontaneous agonistic interactions collected during the same time period. An optional filtering procedure designed to exclude chance-driven displacements or affiliative contacts suggests that the presence of 26% of these interactions in data sets did not impair the reliability of this new method. We demonstrate that this method can be used to assess the dynamics of both individual social status, and group-wide hierarchical stability longitudinally with minimal research labour. Further, it facilitates a continuous assessment of dominance hierarchies in captive groups, even during unpredictable environmental or challenging social events, which underlines the usefulness of this method for group management purposes. Altogether, this study supports the use of MALT as a reliable tool to automatically and dynamically assess dominance hierarchy within captive groups of non-human primates, including juveniles, under conditions in which such technology can be used.

Age-related changes in chimpanzee (Pan troglodytes) cognition: Cross-sectional and longitudinal analyses.

Chimpanzees are the species most closely related to humans, yet age-related changes in brain and cognition remain poorly understood. The lack of studies on age-related changes in cognition in chimpanzees is particularly unfortunate in light of the recent evidence demonstrating that this species naturally develops Alzheimer's disease (AD) neuropathology. Here, we tested 213 young, middle-aged, and elderly captive chimpanzees on the primate cognitive test battery (PCTB), a set of 13 tasks that assess physical and social cognition in nonhuman primates. A subset of these chimpanzees (n = 146) was tested a second time on a portion of the PCTB tasks as a means of evaluating longitudinal changes in cognition. Cross-sectional analyses revealed a significant quadratic association between age and cognition with younger and older chimpanzees performing more poorly than middle-aged individuals. Longitudinal analyses showed that the oldest chimpanzees at the time of the first test showed the greatest decline in cognition, although the effect was mild. The collective data show that chimpanzees, like other nonhuman primates, show age-related decline in cognition. Further investigations into whether the observed cognitive decline is associated with AD pathologies in chimpanzees would be invaluable in understanding the comparative biology of aging and neuropathology in primates.

Monkeys Show Theory of Mind

Hayashi etal. (2020) provide evidence that Japanese macaques show theory of mind abilities in an anticipatory-looking variant of the canonical false belief task. This study paves the way to investigate the neuronal basis of social cognition in non-human primates.

Structure-Guided Design and Procognitive Assessment of a Potent and Selective Phosphodiesterase 2A Inhibitor.

Herein we describe the development of a series of pyrazolopyrimidinone phosphodiesterase 2A (PDE2) inhibitors using structure-guided lead identification and design. The series was derived from informed chemotype replacement based on previously identified internal leads. The initially designed compound 3, while potent on PDE2, displayed unsatisfactory selectivity against the other PDE2 isoforms. Compound 3 was subsequently optimized for improved PDE2 activity and isoform selectivity. Insights into the origins of PDE2 selectivity are described and verified using cocrystallography. An optimized lead, 4, demonstrated improved performance in both a rodent and a nonhuman primate cognition model.

Visual stimulation-induced mild stress enhances cognitive behavior in cynomolgus monkey

Cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.

Studying primate cognition in a social setting to improve validity and welfare: a literature review highlighting successful approaches.

BackgroundStudying animal cognition in a social setting is associated with practical and statistical challenges. However, conducting cognitive research without disturbing species-typical social groups can increase ecological validity, minimize distress, and improve animal welfare. Here, we review the existing literature on cognitive research run with primates in a social setting in order to determine how widespread such testing is and highlight approaches that may guide future research planning.Survey MethodologyUsing Google Scholar to search the terms “primate” “cognition” “experiment” and “social group,” we conducted a systematic literature search covering 16 years (2000–2015 inclusive). We then conducted two supplemental searches within each journal that contained a publication meeting our criteria in the original search, using the terms “primate” and “playback” in one search and the terms “primate” “cognition” and “social group” in the second. The results were used to assess how frequently nonhuman primate cognition has been studied in a social setting (>3 individuals), to gain perspective on the species and topics that have been studied, and to extract successful approaches for social testing.ResultsOur search revealed 248 unique publications in 43 journals encompassing 71 species. The absolute number of publications has increased over years, suggesting viable strategies for studying cognition in social settings. While a wide range of species were studied they were not equally represented, with 19% of the publications reporting data for chimpanzees. Field sites were the most common environment for experiments run in social groups of primates, accounting for more than half of the results. Approaches to mitigating the practical and statistical challenges were identified.DiscussionThis analysis has revealed that the study of primate cognition in a social setting is increasing and taking place across a range of environments. This literature review calls attention to examples that may provide valuable models for researchers wishing to overcome potential practical and statistical challenges to studying cognition in a social setting, ultimately increasing validity and improving the welfare of the primates we study.

The M1 Muscarinic Positive Allosteric Modulator PQCA Improves Performance on Translatable Tests of Memory and Attention in Rhesus Monkeys.

Improved treatment of Alzheimer disease (AD) is a significant unmet medical need that is becoming even more critical given the rise in the number of patients and the substantial economic burden. The current standards of care, acetylcholinesterase inhibitors (AChEIs), are hindered by gastrointestinal side effects owing to their nonselective activation of muscarinic and nicotinic receptors. Recently, the highly selective M1 positive allosteric modulator PQCA (1-((4-cyano-4-(pyridine-2-yl)piperidin-1-yl)methyl-4-oxo-4 H-quinolizine-3-carboxylic acid) has been demonstrated to improve cognition in a variety of rodent and nonhuman primate cognition models without producing significant gastrointestinal side effects. Here we describe the effect of PQCA and the AChEI donepezil on two clinically relevant and highly translatable touchscreen cognition tasks in nonhuman primates: paired-associates learning (PAL) and the continuous-performance task (CPT). Blockade of muscarinic signaling by scopolamine produced significant impairments in both PAL and CPT. PQCA and donepezil attenuated the scopolamine deficits in both tasks, and the action of these two compounds was similar in magnitude. In addition, the combination of subeffective doses of PQCA and donepezil enhanced PAL performance. These results further suggest that M1-positive allosteric modulators, either as monotherapy or as an add-on to current standards of care, have potential to reduce the cognitive deficits associated with AD.

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device (ALDM) Test Systems

Fagot & Paleressompoulle1 and Fagot & Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys maintained in semi-free ranging conditions. Data accumulated during the last five years have consistently demonstrated the efficiency of this protocol to investigate individual/physical cognition in monkeys, and have further shown that this procedure reduces stress level during animal testing3. This paper demonstrates that networks of ALDM can also be used to investigate different facets of social cognition and in-group expressed behaviors in monkeys, and describes three illustrative protocols developed for that purpose. The first study demonstrates how ethological assessments of social behavior and computerized assessments of cognitive performance could be integrated to investigate the effects of socially exhibited moods on the cognitive performance of individuals. The second study shows that batteries of ALDM running in parallel can provide unique information on the influence of the presence of others on task performance. Finally, the last study shows that networks of ALDM test units can also be used to study issues related to social transmission and cultural evolution. Combined together, these three studies demonstrate clearly that ALDM testing is a highly promising experimental tool for bridging the gap in the animal literature between research on individual cognition and research on social cognition.

Assessment of Social Cognition in Non-human Primates Using a Network of Computerized Automated Learning Device (ALDM) Test Systems

Fagot & Paleressompoulle1 and Fagot & Bonte2 have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys maintained in semi-free ranging conditions. Data accumulated during the last five years have consistently demonstrated the efficiency of this protocol to investigate individual/physical cognition in monkeys, and have further shown that this procedure reduces stress level during animal testing3. This paper demonstrates that networks of ALDM can also be used to investigate different facets of social cognition and in-group expressed behaviors in monkeys, and describes three illustrative protocols developed for that purpose. The first study demonstrates how ethological assessments of social behavior and computerized assessments of cognitive performance could be integrated to investigate the effects of socially exhibited moods on the cognitive performance of individuals. The second study shows that batteries of ALDM running in parallel can provide unique information on the influence of the presence of others on task performance. Finally, the last study shows that networks of ALDM test units can also be used to study issues related to social transmission and cultural evolution. Combined together, these three studies demonstrate clearly that ALDM testing is a highly promising experimental tool for bridging the gap in the animal literature between research on individual cognition and research on social cognition.

Comparative Developmental Psychology: How is Human Cognitive Development Unique?

The fields of developmental and comparative psychology both seek to illuminate the roots of adult cognitive systems. Developmental studies target the emergence of adult cognitive systems over ontogenetic time, whereas comparative studies investigate the origins of human cognition in our evolutionary history. Despite the long tradition of research in both of these areas, little work has examined the intersection of the two: the study of cognitive development in a comparative perspective. In the current article, we review recent work using this comparative developmental approach to study non-human primate cognition. We argue that comparative data on the pace and pattern of cognitive development across species can address major theoretical questions in both psychology and biology. In particular, such integrative research will allow stronger biological inferences about the function of developmental change, and will be critical in addressing how humans come to acquire species-unique cognitive abilities.

Povinelli’s Problem and Introspection

Povinelli’s Problem is a well-known methodological problem confronting those researching nonhuman primate cognition. In this paper I add a new wrinkle to this problem. The wrinkle concerns introspection, i.e., the ability to detect one’s own mental states. I argue that introspection either creates a new obstacle to solving Povinelli’s Problem, or creates a slightly different, but closely related, problem. I apply these arguments to Robert Lurz and Carla Krachun’s (Review of Philosophy and Psychology 2: 449–481, 2011) recent attempt at solving Povinelli’s Problem.

Effects of anandamide and other CB1 ligands on cognitive function

The primary psychoactive ingredient of marijuana, Δ9‐ tetrahydrocannabinol (THC), has medicinal effects that promote continued development of CB1 agonists as therapeutics but also produces well‐documented deleterious effects on cognitive endpoints. In the present study, CB1 agonists—THC (0.03–1.8 mg/kg), WIN 55,212 (0.3–1.8 mg/kg), AM4054 (0.003–0.1 mg/kg), anandamide (3.0–32 mg/kg alone and after the FAAH inhibitor URB 597)—were further evaluated by comparing their effects on cognition in nonhuman primates. Drugs were studied using touchscreen procedures to assay learning (repeated acquisition, reversal), motivation (progressive ratio), and, with novel methodology, attention (titrating vigilance). THC, WIN, and AM4054 produced dose‐related impairment of each type of complex behavior. However, drug potency varied across tasks, i.e., particular cognitive endpoints appeared more vulnerable to drug action (e.g., learning<reversal). Anandamide had negligible effects and, even after URB597, produced only moderate dose‐related impairments. These data suggest that anandamide may offer a therapeutically advantageous alternative to other CB1 agonists for further development. (supported by DA031020, DA007252)

Mediodorsal thalamus and cognition in non-human primates

Several recent studies in non-human primates have provided new insights into the role of the medial thalamus in different aspects of cognitive function. The mediodorsal nucleus of the thalamus (MD), by virtue of its connectivity with the frontal cortex, has been implicated in an array of cognitive functions. Rather than serving as an engine or relay for the prefrontal cortex, this area seems to be more specifically involved in regulating plasticity and flexibility of prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate the effects of damage to other subcortical relays. Thus, a wide range of distributed circuits and cognitive functions may be disrupted from focal damage within the medial thalamus (for example as a consequence of stroke or brain injury). Conversely, this region may make an interesting target for neuromodulation of cognitive function via deep brain stimulation or related methods, in conditions associated with dysfunction of these neural circuits.

A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia

Dopamine D1 receptors play an important role in memory and cognition in non-human primates. Dopamine D1 agonists have been shown to reverse performance deficits in both aged non-human primates and in primates with lesions to dopamine systems. This study explored whether a single dose of the first full D1 agonist dihydrexidine (DAR-0100) would cause changes in brain activity (perfusion) in dopamine-rich brain regions. We used a new gadolinium-contrast magnetic resonance perfusion scanning technique to measure brain activity. A within-subject cross-over double-blind randomized design was used in 20 adults with SCID-diagnosed schizophrenia. Each morning at 0800 h, they were scanned on a 3.0 T MRI scanner for perfusion. They then received either 20 mg of dihydrexidine, or placebo, subcutaneously over 15 min. Over the next 45 min, they had intermittent MRI scans. Two days later, they had a repeat of the Day 1 schedule, but received the opposite treatment from that given on the first day. Within-day, as well as between-day, comparisons were made to test for perfusion effects of dihydrexidine. Analysis revealed that dihydrexidine induced a significant increase in both prefrontal and non-prefrontal perfusion compared to placebo. The greatest increases occurred approximately 20 min after dihydrexidine infusion, consistent with the short pharmacokinetic half-life of dihydrexidine. These data are consistent with the hypothesis formulated from studies of non-human primates that dihydrexidine and other D1 agonists may be able to modulate prefrontal dopaminergic function.

Do Some Taxa Have Better Domain-General Cognition than others? A Meta-Analysis of Nonhuman Primate Studies

Although much recent attention has focused on identifying domain-specific taxonomic differences in cognition, little effort has been directed towards investigating whether domain-general differences also exist. We therefore conducted a meta-analysis of published nonhuman primate cognition studies, testing the prediction that some taxa outperform others across a range of testing situations. First, within each of nine experimental paradigms with interspecific variation, we grouped studies by their procedures and the characteristics of their study subjects. Then, using Bayesian latent variable methods, we tested whether taxonomic differences consistently held within or across paradigms. No genus performed especially well within particular paradigms, but genera differed significantly in overall performance. In addition, there was evidence of variation at higher taxonomic levels; most notably, great apes significantly outperformed other lineages. These results cannot be readily explained by perceptual biases or any other contextual confound and instead suggest that primate taxa differ in some kind of domain-general ability.