Wisconsin General Test Apparatus Research Articles

Assessment of brain imaging and cognitive function in a modified rhesus monkey model of depression

Depression incurs a huge personal and societal burden, impairing cognitive and social functioning and affecting millions of people worldwide. A better understanding of the biological basis of depression could facilitate the development of new and improved therapies. Rodent models have limitations and do not fully recapitulate human disease, hampering clinical translation. Primate models of depression help to bridge this translational gap and facilitate research into the pathophysiology of depression. Here we optimized a protocol for administering unpredictable chronic mild stress (UCMS) to non-human primates and evaluated the influence of UCMS on cognition using the classical Wisconsin General Test Apparatus (WGTA) method. We used resting-state functional MRI to explore changes in amplitude of low-frequency fluctuations and regional homogeneity in rhesus monkeys. Our work highlights that the UCMS paradigm effectively induces behavioral and neurophysiological (functional MRI) changes in monkeys but without significantly impacting cognition. The UCMS protocol requires further optimization in non-human primates to authentically simulate changes in cognition associated with depression.

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2

Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

Feasibility of repeated testing for learning ability in juvenile primates for pediatric safety assessment

Assessment of learning ability in nonhuman primate (NHP) models is sometimes requested by regulatory authorities. The double choice object discrimination task using a Wisconsin General Testing Apparatus (WGTA) approach is typically being applied. In this study, the WGTA approach was performed on 66 juvenile cynomolgus monkeys aged 8–9 months in the predose phase of juvenile toxicity assessment. In addition, reversal learning data of seven control animals/gender were obtained for the weeks 25 and 52 of dosing. Gender differences in the number of days required to pass the habituation, learning or reversal learning phases were statistically comparable, males and females may be combined for statistical analysis. At first instance, the habituation phase was passed on average after 6.4 days, and the learning test on average after 8.6 days with improvement to 2.0–2.6 days for habituation and 6.4–6.7 days for learning in weeks 52. Power analysis (α = 0.05, one-sided t-test) revealed a sample size of 8 and 41 to predict a 50% and 20% difference, respectively. In conclusion, examination for learning ability, but not for memory ability (during repeated testing) is feasible in juvenile NHPs using the WGTA approach.

Use of a non-navigational, non-verbal landmark task in children

Two hundred and twenty two children (104 females), 1–8 years of age and young adults, were tested for up to 25 days on five versions of a non-verbal, non-navigational landmark task that had previously been used for monkeys. In monkeys, performance on this task is severely impaired following damage to the parietal cortex. For the basic task, the positive of two identical stimuli concealed a food reward and was designated by spatial proximity of a salient landmark. None of the 1- and 2-year-old children learned the task, i.e., they failed to consistently reach for and displace the positive stimulus in 25 test days. Of the 3-, 4-, and 5- year-old groups, 56%, 70%, and 77% of the children, respectively, mastered the task within 25 days. Children older than 5 and adults rapidly mastered the task. In Experiment #2, all subjects, 1–6 years of age, rapidly mastered a non-relational task when the choice stimulus was attached to the landmark, but the youngest children failed to transfer performance when the landmark was subsequently detached. Children under the age of 5 did not tolerate relational ambiguity as well as adults did. Replications of the first two experiments produced virtually identical results and indicated that the tests have a high degree of reliability. In Experiment #5, there were two distinct proximal landmarks, one of which always designated the positive stimulus. This manipulation did not improve performance of younger children. As compared to results from navigational landmark tasks, results obtained in the Wisconsin General Testing Apparatus (WGTA) indicate a very narrow focus of attention on the response site. Thus, small separations between discriminative cue and response site significantly affect performance, especially in younger children. By comparing the present results with those from monkeys, we speculate that components of the parietal pathways involved with attention and reaching mature between 1 and 5 years of age in children.

Object discrimination and reversal learning in infant and juvenile non‐human primates in a non‐clinical laboratory

Biopharmaceutical development necessitates use of non-human primates in toxicology, leading to adoption of non-traditional methods including cognitive function assessment. A two-object discrimination and reversal test in cynomolgus monkeys (Macaca fascicularis) was performed using a Wisconsin General Testing Apparatus (WGTA). Non-clinical study design and regulatory considerations dictate that infants are raised by their biological mothers until weaning at 6 months. Thirty-four animals (6-21 months of age) were trained to discriminate between two randomly selected stimulus objects to retrieve a reward. Following training, days to first reversal after interchanging the reward were measured. Both sexes acquired visual discrimination skills at similar rates. Trends in learning and reversals completed were uniform across age groups. Completing training early in some subjects had no impact on subsequent testing phases. Weaned cynomolgus monkey infants can be successfully tested for cognitive abilities using the WGTA in a non-clinical laboratory setting.

Interactive effects of morphine and dopaminergic compounds on spatial working memory in rhesus monkeys

Opiates and dopamine (DA) play key roles in learning and memory in humans and animals. Although interactions between these neurotransmitters have been found, their functional roles remain to be fully elucidated, and their dysfunction may contribute to human diseases and addiction. Here we investigated the interactions of morphine and dopaminergic neurotransmitter systems with respect to learning and memory in rhesus monkeys by using the Wisconsin General Test Apparatus (WGTA) delayed-response task. Morphine and DA agonists (SKF-38393, apomorphine and bromocriptine) or DA antagonists (SKF-83566, haloperidol and sulpiride) were co-administered to the monkeys 30 min prior to the task. We found that dose-patterned co-administration of morphine with D1 or D2 antagonists or agonists reversed the impaired spatial working memory induced by morphine or the compounds alone. For example, morphine at 0.01 mg/kg impaired spatial working memory, while morphine (0.01 mg/kg) and apomorphine (0.01 or 0.06 mg/kg) co-treatment ameliorated this effect. Our findings suggest that the interactions between morphine and dopaminergic compounds influence spatial working memory in rhesus monkeys. A better understanding of these interactive relationships may provide insights into human addiction.

Object Discrimination Reversal As a Method to Assess Cognitive Impairment in Nonhuman Primate Enhanced Pre‐ and Postnatal Developmental (ePPND) Studies: Statistical Power Analysis

An important aspect of the enhanced pre- and postnatal developmental (ePPND) toxicity study in nonhuman primates (NHP) is that it combines in utero and postnatal assessments in a single study. However, it is unclear if NHP ePPND studies are suitable to perform all of the evaluations incorporated into rodent PPND studies. To understand the value of including cognitive assessment in a NHP ePPND toxicity study, we performed a power analysis of object discrimination reversal task data using a modified Wisconsin General Testing Apparatus (ODR-WGTA) from two NHP ePPND studies. ODR-WGTA endpoints evaluated were days to learning and to first reversal, and number of reversals. With α = 0.05 and a one-sided t-test, a sample of seven provided 80% power to predict a 100% increase in all three of the ODR-WGTA endpoints; a sample of 25 provided 80% power to predict a 50% increase. Similar power analyses were performed with data from the Cincinnati Water Maze (CWM) and passive avoidance tests from three rat PPND toxicity studies. Groups of 5 and 15 in the CWM and passive avoidance test, respectively, provided 80% power to detect a 100% change. While the power of the CWM is not far superior to the NHP ODR-WGTA, a clear advantage is the routine use of larger sample size, with a group of 20 rats the CWM provides ~90% power to detect a 50% change. Due to the limitations on the number of animals, the ODR-WGTA may not be suitable for assessing cognitive impairment in NHP ePPND studies.

Behavioral tests as indicator for pain and distress in a primate endometriosis model

As common marmosets (Callithrix jacchus) are frequently used experimental animals, sensitive test systems are needed to evaluate impairment and pain caused by procedures and diseases. A diurnal profile of healthy animals was obtained by videotaping. Differences in social behavior and cognitive skills between marmosets with established endometriosis and healthy monkeys were investigated using the videotaping, the Wisconsin General Test Apparatus (WGTA), and a food tree. The marmosets showed a mostly trimodal course of activity. Social grooming and activity were significantly decreased in animals with endometriosis; furthermore, the diseased monkeys habituated significantly worse to the cognitive test settings. The food tree experiments offered no differences between diseased and control animals. The videotaping and the WGTA are suitable methods to detect disease-related impairments in common marmosets, which is essential for the refinement of experiments.

Clonidine improves attentional and memory components of delayed response performance in a model of early Parkinsonism

Cognitive deficits, including attention and working memory deficits, are often described in Parkinson's disease (PD) patients even during the early stages of the disease. However, cognitive deficits associated with PD have proven difficult to treat and often do not respond well to the dopaminergic therapies used to treat the motor symptoms of the disease. Chronic administration of low doses of the neurotoxin 1-methy,4-phenyl,1,2,3,6-tetrahydropyridine (MPTP) can induce cognitive dysfunction in non-human primates, including impaired performance on a variable delayed response (VDR) task with attentional and memory components. Since alpha-2 adrenergic receptor agonists have been suggested to improve attention and working memory in a variety of conditions, the present study assessed the extent to which the alpha-2 noradrenergic agonist clonidine might influence VDR performance in early Parkinsonian non-human primates. Clonidine (0.02–0.10 mg/kg) improved performance on both attentional and memory components of the task, performed in a modified Wisconsin General Test Apparatus, in a dose-dependent manner and the cognition enhancing effects of clonidine were blocked by co-administration of the alpha-2 noradrenergic antagonist idazoxan (0.10 mg/kg). These data suggest that clonidine or drugs of this class, perhaps with greater receptor subtype selectivity and low sedation liability, might be effective therapeutics for cognitive dysfunction associated with PD.

Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys

This study examined whether regular exercise training, at a level that would be recommended for middle-aged people interested in improving fitness could lead to improved cognitive performance and increased blood flow to the brain in another primate species. Adult female cynomolgus monkeys were trained to run on treadmills for 1 h a day, 5 days a week, for a 5 month period (n=16; 1.9±0.4 miles/day). A sedentary control group sat daily on immobile treadmills (n=8). Half of the runners had an additional sedentary period for 3 months at the end of the exercise period (n=8). In all groups, half of the monkeys were middle-aged (10–12 years old) and half were more mature (15–17 years old). Starting the fifth week of exercise training, monkeys underwent cognitive testing using the Wisconsin General Testing Apparatus (WGTA). Regardless of age, the exercising group learned to use the WGTA significantly faster (4.6±3.4 days) compared to controls (8.3±4.8 days; P=0.05). At the end of 5 months of running monkeys showed increased fitness, and the vascular volume fraction in the motor cortex in mature adult running monkeys was increased significantly compared to controls (P=0.029). However, increased vascular volume did not remain apparent after a 3-month sedentary period. These findings indicate that the level of exercise associated with improved fitness in middle-aged humans is sufficient to increase both the rate of learning and blood flow to the cerebral cortex, at least during the period of regular exercise.

A comparative neuropsychological test battery differentiates cognitive signatures of Fragile X and Down syndrome

Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and weaknesses as well as the affected brain areas. To evaluate the utility and feasibility of six non-verbal comparative neuropsychological (CN) tasks administered in a modified version of the Wisconsin General Test Apparatus (WGTA) to confirm and extend our knowledge of unique cognitive signatures of Fragile X syndrome (FXS) and Down syndrome (DS). A test battery of CN tasks adapted from the animal literature was administered in a modified WGTA. Tasks were selected that have established or emerging brain-behaviour relationships in the domains of visual-perceptual, visual-spatial, working memory and inhibition. Despite the fact that these tasks revealed cognitive signatures for the two ID groups, only some hypotheses were supported. Results suggest that whereas individuals with DS were relatively impaired on visual-perceptual and visual-spatial reversal learning tasks they showed strengths in egocentric spatial learning and object discrimination tasks. Individuals with FXS were relatively impaired on object discrimination learning and reversal tasks, which was attributable to side preferences. In contrast, these same individuals exhibited strengths in egocentric spatial learning and reversal tasks as well as on an object recognition memory task. Both ID groups demonstrated relatively poor performance for a visual-spatial working memory task. Performance on the modified WGTA tasks differentiated cognitive signatures between two of the most common forms of ID. Results are discussed in the context of the literature on the cognitive and neurobiological features of FXS and DS.

Selective Impairment of Cognitive Performance in the Young Monkey Following Recovery from Iron Deficiency

While poor nutrition during development is an obvious concern, the magnitude and duration of the neural and cognitive deficits that occur after moderate iron deficiency in infancy have remained controversial. A nonhuman primate model of infancy anemia was refined to investigate the effects on cognitive performance. Young rhesus monkeys that experienced a delimited period of iron deficiency were tested on a series of cognitive tasks following normalization of their hematological status. Beginning at 8 to 9 months of age, 2 months after weaning from their mothers and consumption of solid food, the previously iron-deficient (ID) monkeys (n = 17) were compared to age- and gender-matched, iron-sufficient (IS) (n = 27) monkeys on a series of three tests of cognitive performance. Using the Wisconsin General Testing Apparatus, a Black/White Discrimination task was followed by acquisition of Black/White Reversal (BWR). ID monkeys were significantly slower at mastering the BWR task (p < .04), which required reversing and inhibiting the previously learned response. In addition, ID infants were significantly less object oriented (p < .017) and more distractible (p < .018). However, on two subsequent tests, the Concurrent Object Discrimination and Delayed Non-Match-to-Sample, there were no differences in acquisition, performance, or behavioral reactivity. The initial cognitive and behavioral deficits are similar to those seen in follow-up evaluations of anemic children, but the limited extent of the impairment after this moderate iron deficiency that involved a select nutrient deficiency is encouraging for the benefits attainable through early identification and iron supplementation.

Measuring reward assessment in a semi-naturalistic context: The effects of selective amygdala, orbital frontal or hippocampal lesions

Studying the neural mechanisms underlying complex goal-directed behaviors, such as social behavior, reward seeking or punishment avoidance, has become increasingly tractable in humans, nonhuman primates and rodents. In most experiments, however, goal-directed behaviors are measured in a laboratory setting, which is vastly different from the context in which these behaviors naturally occur. This study adapted a reward assessment paradigm, previously conducted with rhesus monkeys (Macaca mulatta) in the controlled environment of a Wisconsin General Testing Apparatus (WGTA) [Machado CJ, Bachevalier J (2007) The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates. Eur J Neurosci 25:2885–2904], to a more naturalistic context. We used this new paradigm to examine the effects of bilateral amygdaloid, hippocampal or orbital frontal cortex lesions on established food and nonfood preferences. Behavioral modification following reinforcer devaluation was also measured. Consistent with our previous study, none of the lesions produced changes in preference for palatable foods relative to pre-surgery, but animals with amygdala lesions displayed heightened preference for unpalatable foods that control or other operated animals typically avoided. In contrast to several previous WGTA-based experiments, nonfood preference was not affected by any of the lesions. Finally, animals with orbital frontal cortex lesions continued to select preferred foods after satiation, but those with amygdala, hippocampal or sham lesions altered their foraging behavior appropriately and selected less of the sated food. These findings parallel food devaluation results obtained with these same animals when tested in the WGTA. Overall, this study stresses the importance of testing context when measuring decision-making abilities in nonhuman primates with selective brain lesions.

Dopamine D2/D3 Receptors Play a Specific Role in the Reversal of a Learned Visual Discrimination in Monkeys

Converging evidence supports a role for mesocorticolimbic dopaminergic systems in a subject's ability to shift behavior in response to changing stimulus-reward contingencies. To characterize the dopaminergic mechanisms involved in this function, we quantified the effects of subtype-specific dopamine (DA) receptor antagonists on acquisition, retention, and reversal of a visual discrimination task in non-human primates (Chlorocebus aethiops sabaeus). We used a modified Wisconsin General Test Apparatus that was equipped with three food boxes, each fitted with a lid bearing a unique visual cue; one of the cues concealed a food reward, whereas the other two concealed an empty box. The monkeys were trained first to acquire a novel discrimination (eg A(+), B(-), C(-)) in a single session, before experiencing either a reversal of the discrimination (eg A(-), B(+), C(-)) or the acquisition of a completely new discrimination (eg D(+), E(-), F(-)), on the following day. Systemic administration of the D(2)/D(3) receptor antagonist raclopride (0.001-0.03 mg/kg) failed to significantly affect the performance of reversal learning when reversal sessions were run without a retention session. But, raclopride (0.03 mg/kg) significantly impaired performance under the reversal condition when reversal sessions were run right after a retention session; however, it did not affect acquisition of a novel visual discrimination. Specifically, raclopride significantly increased the number of reversal errors made before reaching the performance criterion in the reversal, but not in new learning sessions. In contrast, the D(1)/D(5) receptor antagonist SCH 23390 did not significantly modulate acquisition of a novel discrimination or reversal learning at doses (0.001-0.03 mg/kg, i.m.) that did not suppress behavior generally. In addition, none of the drug treatments affected retention of a previously learned discrimination. The results strongly suggest that D(2)/D(3) receptors, but not D(1)/D(5) receptors, selectively mediate reversal learning, without affecting the capacity to learn a new stimulus-reward association. These data support the hypothesis that phasic DA release, acting through D(2)-like receptors, mediates behavioral flexibility.

One-trial visual recognition in cats

The ability of normal cats to perform delayed matching- and nonmatching-to-sample with trial-unique stimuli was investigated both in a modified Wisconsin General Testing Apparatus requiring manipulatory responses and in a Nencki-type testing room requiring locomotor responses. Cats trained in the WGTA learned the two tasks at about the same rate, on average, as that reported for monkeys. However, unlike monkeys, whose strong preference for novelty facilitates their learning of the nonmatching rule and retards their learning of the matching rule, the cats learned the two different rules at about the same rate, suggesting that cats do not share the monkey's strong preference for novelty. In contrast to their relatively rapid learning of the manipulatory versions of the two tasks, cats learned the locomotor versions only slowly or even failed to learn. Experimental analysis indicated that a major source of the cats' difficulty on these locomotor versions was interference from a strong tendency in the large testing room to use visuospatial strategies. Nevertheless, once the matching or nonmatching rule was learned at short delays, whether in the WGTA or the testing room, the cats performed at criterion levels without further training even at delays of 10 minutes, indicating that this species, like monkeys, has a highly developed long-term recognition memory ability.

Learning and memory as a function of age in Down syndrome: A study using animal-based tasks

Individuals with Down syndrome (DS) are at a high risk for developing Alzheimer disease (AD) after the age 40; however, low levels of intellectual functioning, coupled with impaired language ability, confound the detection of AD. Comparative neuropsychological tests developed in animal models of aging and cognition do not require intact language function and can be useful for detecting changes in cognition. Experimental paradigms used to detect age-dependent cognitive deficits in animal models were applied in the present study to measure cognitive function in a group of 20 adults with DS ranging in age from 22 to 58 years. Object discrimination, reversal learning, and spatial and object memory were administered using a modified Wisconsin General Testing Apparatus and reinforcement (penny rewards). When considering age as the only clinical variable to parallel the animal studies, age was significantly correlated with performance on object memory and marginally related to performance on reversal learning and spatial memory. However, when evaluating multiple clinical variables including age, a measure of intellectual ability (FSIQ), scores on the Dementia Questionnaire for Persons with Mental Retardation (DMR), and gender using regression analysis, scores on the DMR were the best predictors of errors of reversal learning, whereas FSIQ was the best predictor of performance on object memory. These results suggest that while age may be related to performance on learning and memory tasks, other clinical variables may be stronger predictors of performance in adults with DS. These changes may reflect prefrontal and medial temporal lobe dysfunction that is associated with the development of AD pathology in DS.

Two methods for teaching simple visual discriminations to learners with severe disabilities

Simple discriminations are involved in many functional skills; additionally, they are components of conditional discriminations (identity and arbitrary matching-to-sample), which are involved in a wide array of other important performances. Many individuals with severe disabilities have difficulty acquiring simple discriminations with standard training procedures, such as differential reinforcement. Errorless training methods may be more effective with this population. We used multiple-probe designs to compare two potentially errorless procedures for teaching simple discriminations among three pairs of photos of preferred items (S+) and colored rectangles (S−) to three youths with severe disabilities. In Experiment 1, baseline trials conducted with differential reinforcement yielded near-chance performances on all stimulus sets. A progressive delayed prompt training procedure was then implemented, with stimuli presented flat on the tabletop for one participant and at a 45° angle to the tabletop for the other participants. After 120 teaching trials, accuracy remained near chance. Next, a stimulus control shaping procedure was implemented using an adapted Wisconsin General Test Apparatus (WGTA), with stimuli at a 45° angle to the tabletop. Accuracy increased when this procedure was implemented with each stimulus pair in succession. In Experiment 2, for the participant whose stimuli were presented flat on the tabletop during the progressive delayed prompt training procedure, baseline trials were presented on the WGTA as at the end of Experiment 1, with differential reinforcement; accuracy remained high. On probe trials with stimuli placed flat on the tabletop, accuracy decreased to near-chance levels, indicating that the orientation of the stimulus array was a controlling variable.

Love at Goon Park: Harry Harlow and the Science of Affection

Love at Goon Park: Harry Harlow and the Science of Affection

Part III. Behavioral Changes in Rhesus Monkeys Following Experimental Whiplash

AbstractIntroduction. Previous studies, summarized in Parts I and II, have shown that the injection of radio-opaque isotope and implantation of flexible electrodes into the brain of rhesus monkeys introduced an additional independent variable into the experiment, thus confounding the certitude of the dependent variable. A behavioral study, where trauma was the only intervention, would greatly add to our understanding of the clinical/cognitive responses of whiplashed primates with possible implications for humans.Materials and Method. Three female, feral-raised rhesus monkeys that were experimentally naive were used as subjects. A modified Wisconsin General Testing Apparatus (Harlow (4)) with two Plexiglass partitions was used to measure the types of mental functioning evaluated by the Halstead-Reitan Scale (Reitan (9)) in suspected cases of brain injury. These were attention, memory, and perception. The 3 testing phases were: learning set discriminations, reversal learning, and delayed responding. Each su...

Working memory in capuchin monkeys ( Cebus apella)

It has been suggested that delayed (non-) matching to sample (DNMTS/DMTS) tasks using trial-unique stimuli and short, as well as longer delay intervals, can provide important insights into animal cognition. Therefore, this research examined the capability of the New World capuchin monkey ( Cebus apella) in perform trial-unique DMTS and DNMTS tasks across delay intervals ranging between 8 s and 10 min. Subjects were tested using a version of the Wisconsin General Test Apparatus mounted in front of the animal's home cage. They were first trained on a basic DMTS/DNMTS task with an 8 s interval until they reached a learning criterion of nine correct responses in ten consecutive trials. All subjects reached the learning criterion in both DMTS/DNMTS tasks, and the number of trials to criterion did not differ between tasks. After reaching the criterion, subject's memory performance was successively assessed at delay intervals of 15 s, 60 s, 120 s and 10 min. For both DMTS/DNMTS tasks, the mean percentage of correct responses across delays was above chance and, interestingly, performance did not significantly decrease as function of delay increments. Comparisons based on each group's scores, averaged across the four delays, showed no difference between DMTS and DNMTS memory performance. These results indicate that capuchin monkeys are able to learn DMTS/DNMTS tasks in which they are required to respond to new pairs of stimuli on every trial. This demonstrates the capability of ‘concept’ learning in this species. Moreover, above chance performance on the memory tests indicates a working memory ability similar to that reported for the genus Macaca. Taken together, these data indicates that capuchin monkeys can be a valuable alternative model for investigations of the neuropsychological basis of memory.