Brown Capuchins (Cebus apella) Exhibit Self-Control on a Delay of Gratification Food Exchange Task When Food Options Differ Qualitatively

Self-control allows an individual to obtain a more preferred outcome by forgoing an immediate interest. Self-control is an advanced cognitive process because it involves the ability to weigh the costs and benefits of impulsive versus restrained behavior, determine the consequences of such behavior, and make decisions based on the most advantageous course of action. Self-control has been thoroughly explored in Old World primates, but less so in New World monkeys. There are many ways to test self-control abilities in non-human primates, including exchange tasks in which an animal must forgo an immediate, less preferred reward to receive a delayed, more preferred reward. I examined the self-control abilities of six capuchin monkeys using a task in which a monkey was given a less preferred food and was required to wait a delay interval to trade the fully intact less preferred food for a qualitatively higher, more preferred food. Partially eaten pieces of the less preferred food were not rewarded, and delay intervals increased on an individual basis based on performance. All six monkeys were successful in inhibiting impulsivity and trading a less preferred food for a more preferred food at the end of a delay interval. The maximum duration each subject postponed gratification instead of responding impulsively was considered their delay tolerance. This study was the first to show that monkeys could inhibit impulsivity in a delay of gratification food exchange task in which the immediate and delayed food options differed qualitatively and a partially eaten less preferred food was not rewarded with the more preferred food at the end of a delay interval. These results show that New World monkeys possess advanced cognitive abilities similar to those of Old World primates.

The Use of Human and Conspecific Gestures By Capuchin Monkeys to Solve an Object-Choice Task

Most primates live in highly complex social systems, and therefore have evolved similarly complex methods of communicating with each other. One type of communication is the use of manual gestures, which are only found in primates. No substantial evidence exists indicating that monkeys use communicative gestures in the wild. However, monkeys may demonstrate the ability to learn and/or use gestures in certain experimental paradigms since they¿ve been shown to use other visual cues such as gaze. The purpose of this study was to investigate if ten brown capuchin monkeys (Cebus apella) were able to use gestural cues from monkeys and a pointing cue from a human to obtain a hidden reward. They were then tested to determine if they could transfer this skill from monkeys to humans and from humans to monkeys. One group of monkeys was trained and tested using a conspecific as the cue giver, and was then tested with a human cue-giver. The second group of monkeys began training and testing with a human cue giver, and was then tested with a monkey cue giver. I found that two monkeys were able to use gestural cues from conspecifics (e.g., reaching) to obtain a hidden reward and then transfer this ability to a pointing cue from a human. Four monkeys learned to use the human pointing cue first, and then transferred this ability to use the gestural cues from conspecifics to obtain a hidden reward. However, the number of trials it took for each monkey to transfer the ability varied considerably. Some subjects spontaneously transferred in the minimum number of trials needed to reach my criteria for successfully obtaining hidden rewards (N = 40 trials), while others needed a large number of trials to do so (e.g. N = 190 trials). Two subjects did not perform successfully in any of the conditions in which they were tested. One subject successfully used the human pointing cue and a human pointing plus vocalization cue, but did not learn the conspecific cue. One subject learned to use the conspecific cue but not the human pointing cue. This was the first study to test if brown capuchin monkeys could use gestural cues from conspecifics to solve an object choice task. The study was also the first to test if capuchins could transfer this skill from monkeys to humans and from humans to monkeys. Results showed that capuchin monkeys were able to flexibly use communicative gestures when they were both unintentionally given by a conspecific and intentionally given by a human to indicate a source of food.

Capuchin Monkeys (Cebus apella) Fail to Be Equitable in an Ultimatum Game

The ultimatum game is a commonly used economics game testing humans' sense of fairness. In the game, a "proposer" is given a sum of money and is told they can split it however they want with another human partner. The partner can then either accept the division and both proposer and responder receive the proposed amounts, or the responder can reject the offer and neither player will get anything. Human subjects from most western cultures typically share almost half of an allotted amount, but it remains unknown whether our close primate relatives share this generosity. Recent attempts to present chimpanzees with the ultimatum game have provided inconclusive results, with some studies finding the animals share humans' disposition to behave 'fairly' and others concluding that chimpanzees act selfishly to maximize their own rewards. Capuchin monkeys are known to share many human and chimpanzee social and cooperative behaviors, and this study was the first to present capuchin monkeys with a version of the ultimatum game. Subjects were presented with two differently colored tokens representing different qualitative reward contingencies, one equitable and the other inequitable in favor of the subject proposer. Subjects could select and place one of the tokens in a transfer container. The capuchins were first tested with a "dictator game" where, after the subject monkey selected a token, the rewards (equitable or inequitable) were distributed to the subject and a nearby partner monkey that was not an active participant. The capuchins were then tested on an ultimatum game in which after the subject selected and placed a token in the container, the container was moved to the partner. The partner needed to remove the token and transfer it back to the experimenter for the rewards to be distributed. As such, the partner could reject the subject's offer by refusing to participate and neither would receive a reward. The experiment was conducted to determine if the subject monkey would select the equitable reward option rather than the selfish option in order to maintain the partner's cooperation in the task. Capuchin subjects behaved selfishly and selected the inequitable token significantly more often than the equitable token in both the dictator and ultimatum game with no significant difference in preference between the two games. Interestingly, despite the occasional occurrence of rejection by the partner monkeys (resulting in no reward for the subject), subjects never altered their strategy, continuing to prefer the selfish token. The study may indicate that capuchin monkeys have an inability to judge the effect of their behavior on a conspecific's reward outcome, or an indifference to the outcome if there is an individual cost associated with behaving prosocially.

Modulating the granularity of category formation by global cortical states

The unsupervised categorization of sensory stimuli is typically attributed to feedforward processing in a hierarchy of cortical areas. This purely sensory-driven view of cortical processing, however, ignores any internal modulation, e.g., by top-down attentional signals or neuromodulator release. To isolate the role of internal signaling on category formation, we consider an unbroken continuum of stimuli without intrinsic category boundaries. We show that a competitive network, shaped by recurrent inhibition and endowed with Hebbian and homeostatic synaptic plasticity, can enforce stimulus categorization. The degree of competition is internally controlled by the neuronal gain and the strength of inhibition. Strong competition leads to the formation of many attracting network states, each being evoked by a distinct subset of stimuli and representing a category. Weak competition allows more neurons to be co-active, resulting in fewer but larger categories. We conclude that the granularity of cortical category formation, i.e., the number and size of emerging categories, is not simply determined by the richness of the stimulus environment, but rather by some global internal signal modulating the network dynamics. The model also explains the salient non-additivity of visual object representation observed in the monkey inferotemporal (IT) cortex. Furthermore, it offers an explanation of a previously observed, demand-dependent modulation of IT activity on a stimulus categorization task and of categorization-related cognitive deficits in schizophrenic patients.

Learning flexible sensori-motor mappings in a complex network

Given the complex structure of the brain, how can synaptic plasticity explain the learning and forgetting of associations when these are continuously changing? We address this question by studying different reinforcement learning rules in a multilayer network in order to reproduce monkey behavior in a visuomotor association task. Our model can only reproduce the learning performance of the monkey if the synaptic modifications depend on the pre- and postsynaptic activity, and if the intrinsic level of stochasticity is low. This favored learning rule is based on reward modulated Hebbian synaptic plasticity and shows the interesting feature that the learning performance does not substantially degrade when adding layers to the network, even for a complex problem.

Transbilayer Phospholipid Asymmetry in Plasmodium knowlesi- Infected Host Cell Membrane

The membranes from normal and Plasmodium knowlesi-infected rhemsus monkey erythrocytes (90 to 95 percent infected with early ring stage) were analyzed for transbilayer distribution of phosphatidylcholine (PC). hosphatidylethanolamine (PE). and hosphatidylserine (PS). by means of chemical and enzymatic probes. The external monolayer of the normal red cell membrane contained at least 68 to 72 percent of the total phosphatidylcholine and 15 to 20 percent of the total phosphati dylethanolamine. In the infected cell, the transmembrane phosphatidylcholine distribution appeared to be reversed, with only 20 to 30 percent of it being externally localized, whereas roughly equal amounts of phosphatidylethanolamine were present in the outer and'inner surfaces. However, total pho.~phatid)'lserine in both the infected and normal red cells was exc/usi~'ely internal. Unlike that in the normal intact cell, external phosphatidylethanolamine in the parasitized cell was readily accessible to phospholipase A2. These results indicate that significant changes in molecular architecture of the host cell membrane are the result of varasitization.

Spatial modulation of primate inferotemporal responses by eye position.

BACKGROUND: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information. METHODOLOGY/PRINCIPAL FINDINGS: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of recorded neurons with small gaze angle shifts from central fixation. Although eye position modulates responses, it does not change shape selectivity. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that spatial information is available in AIT for the representation of objects and scenes within a non-retinocentric frame of reference. More generally, the availability of spatial information in AIT calls into questions the classic dichotomy in visual processing that associates object shape processing with ventral structures such as AIT but places spatial processing in a separate anatomical stream projecting to dorsal structures.

Elevated albumin in retinas of monkeys with experimental glaucoma.

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina. METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this protein and glaucoma severity was investigated by regression analyses. Protein localization in retina was evaluated by immunohistochemistry with confocal imaging. RESULTS: The abundant protein was identified as Macaca mulatta serum albumin precursor (67 kDa) from eight non-overlapping proteolytic fragments, and the identity was confirmed by Western blot. The average increase in retinal albumin content was 2.3 fold (P = 0.015). In glaucoma eyes, albumin was localized to some neurons of the inner nuclear layer, in the inner plexiform layer, and along the vitreal surface, but it was only found in blood vessels in control retinas. CONCLUSIONS: Albumin is the abundant protein found in the glaucomatous monkey retinas. The increased albumin is primarily localized to the inner retina where oxidative damage associated with experimental glaucoma is known to be prominent. Since albumin is a major antioxidant, the increase of albumin in the retinas of eyes with experimental glaucoma may serve to protect the retina against oxidative damage.

Change Detection Memory in Rhesus Monkeys and Humans

Visual short-term memory (VSTM) is the storage of visual information over a brief time period (usually a few seconds or less). Over the past decade, the most popular task for studying VSTM in humans has been the change detection task. In this task, subjects must remember several visual items per trial in order to identify a change following a brief delay interval. Results from change detection tasks have shown that VSTM is limited; humans are only able to accurately hold a few visual items in mind over a brief delay. However, there has been much debate in regard to the structure or cause of these limitations. The two most popular conceptualizations of VSTM limitations in recent years have been the fixed-capacity model and the continuous-resource model. The fixed-capacity model proposes a discrete limit on the total number of visual items that can be stored in VSTM. The continuous-resource model proposes a continuous-resource that can be allocated among many visual items in VSTM, with noise in item memory increasing as the number of items to be remembered increases. While VSTM is far from being completely understood in humans, even less is known about VSTM in non-human animals, including the rhesus monkey (Macaca mulatta). Given that rhesus monkeys are the premier medical model for humans, it is important to understand their VSTM if they are to contribute to understanding human memory. The primary goals of this study were to train and test rhesus monkeys and humans in change detection in order to directly compare VSTM between the two species and explore the possibility that direct species comparison might shed light on the fixed-capacity vs. continuous-resource models of VSTM. The comparative results suggest qualitatively similar VSTM for the two species through converging evidence supporting the continuous-resource model and thereby establish rhesus monkeys as a good system for exploring neurophysiological correlates of VSTM.

Origins and evolution of VNTR loci: The apolipoprotein B 3$\sp\prime$ VNTR

I studied the apolipoprotein (apo) B 3$\sp\prime$ variable number tandem repeat (VNTR) and did computer simulations of the stepwise mutation model to address four questions: (1) How did the apo B VNTR originate? (2) What is the mutational mechanism of repeat number change at the apo B VNTR? (3) To what extent are population and molecular level events responsible for the determination of the contemporary apo B allele frequency distribution? (4) Can VNTR allele frequency distributions be explained by a simple and conservative mutation-drift model? I used three general approaches to address these questions: (1) I characterized the apo B VNTR region in non-human primate species; (2) I constructed haplotypes of polymorphic markers flanking the apo B VNTR in a sample of individuals from Lorrain, France and studied the associations between the flanking-marker haplotypes and apo B VNTR size; (3) I did computer simulations of the one-step stepwise mutation model and compared the results to real data in terms of four allele frequency distribution characteristics.^ The results of this work have allowed me to conclude that the apo B VNTR originated after an initial duplication of a sequence which is still present as a single copy sequence in New World monkey species. I conclude that this locus did not originate by the transposition of an array of repeats from somewhere else in the genome. It is unlikely that recombination is the primary mutational mechanism. Furthermore, the clustered nature of these associations implicates a stepwise mutational mechanism. From the high frequencies of certain haplotype-allele size combinations, it is evident that population level events have also been important in the determination of the apo B VNTR allele frequency distribution. Results from computer simulations of the one-step stepwise mutation model have allowed me to conclude that bimodal and multimodal allele frequency distributions are not unexpected at loci evolving via stepwise mutation mechanisms. Short tandem repeat loci fit the stepwise mutation model best, followed by microsatellite loci. I therefore conclude that there are differences in the mutational mechanisms of VNTR loci as classed by repeat unit size. (Abstract shortened by UMI.) ^

CHARACTERIZATION AND COMPARISON OF SUBHUMAN PRIMATE AND HUMAN TYPE C RETROVIRAL GENE PRODUCTS

The viral specific precursor polyproteins of simian sarcoma/simian associated virus (SiSV/SiAV), baboon endogenous viruses (BaEV), and three human isolate retroviruses, have been analyzed by radioimmunoprecipitation and tryptic peptide mapping. Cells infected with the BaEV isolates are characterized by identical precursor polyproteins: gPr80-85('env), Pr70-71('gag), and Pr65-67('gag). By tryptic digest mapping, m7-BaEV and 455K-BaEV were shown to be highly related. By comparison, mapping studies showed that BILN-BaEV was less highly related to m7-BaEV than was 455K-BaEV. Chase-incubated cells infected with BaEV also contained a stable, p28-related polyprotein termed P72('gag). This polyprotein appeared to arise by posttranslational modification of Pr70-71('gag). Tryptic digest mapping of BaEV and HL23V precursor polyproteins suggested that the BaEV-like component of HL23V was more closely related to m7-BaEV than to 455K-BaEV or BILN-BaEV.^ The intracellular precursor polyproteins of SiSV(SiAV) and gibbon ape leukemia virus (GaLV) were compared to the intracellular proteins of the human retrovirus isolates, HL23V, HEL12V, and A1476V. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200('gag-pol), gPr80('env), Pr80('gag), pr60('gag), and Pr40('gag). We have found that the human isolates are identical to true SiAV with regard to the size and structure of their precursor polyproteins. Both gPr80('env) and Pr60('gag) of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retroviral isolates examined. We have also shown that these viruses differ significantly from each of the GaLV isolates studied. Since SiAV differs substantially from any known GaLV isolate, we feel that it is unlikely that SiAV is a subtype of GaLV which exists today in the gibbon gene pool. The experimental evidence suggests that SiAV may be an exogenous human retrovirus that was transmitted originally into the human gene pool in the distant past by cross-species infection with GaLV(,SF) or with the GaLV(,SF) progenitor virus. It is, therefore, quite possible that SiAV expression in the pet woolly monkey arose from a recent infection of that monkey with SiAV from humans.^

CHARACTERIZATION OF HIGH MOBILITY GROUP AND HISTONE H1 PROTEIN LEVELS AND SYNTHESIS DURING SPERMATOGENESIS IN THE RAT

In order to propose a role for internucleosomal high mobility group proteins (HMGs), and HI histone variants study of their levels and synthesis in a system of development and differentiation--rat spermatogenesis--was undertaken. HMG1, 2, 14, and 17 were isolated from rat testes and found to be very similar to calf thymus HMGs. Testis levels of HMGs, relative to DNA, were equivalent to other rat tissues for HMG1 (13 ug/mg DNA), HMG14 (2 ug/mg DNA), and HMG17 (5 ug/mg DNA). HMG2 levels were different among rat tissues, with three groups observed: (1) nonproliferating tissues (1-5 ug/mg DNA); (2) proliferating tissues (8-13 ug/mg DNA); and (3) the testis (32 ug/mg DNA). Other species (toad, opposum, mouse, dog, and monkey) showed the same testis-specific increase of HMG2. Populations of purified testis cell types were separated by centrifugal elutriation and density gradient centrifugation from adult and immature rat testes. Pachytene spermatocytes and early spermatids (56 and 47 ug/mg DNA, respectively) caused the testis-specific increase of HMG2 levels. Cell types preceding pachytenes (types A and B spermatogonia, mixtures of spermatogonia and early primary spermatocytes, and early pachytenes contained HMG2 levels similar to proliferating tissues (12 ug/mg DNA). Late spermatids did not contain HMGs. Somatic Sertoli and Leydig cells (2 ug/mg DNA) exhibited HMG2 levels similar to nonproliferating tissues. HMGs synthesized in spermatogonia and spermatocytes had similar specific activities, but early spermatids did not synthesize HMGs. Germ cells also contained an HMG2 species (on acid-urea gels) not found in somatic tissues. Other investigators have shown that HMGs may be associated with transcriptional or replicative processes. Thus, it is proposed that HMG2 plays a role in modulatable gene expression, while HMG1 is associated with housekeeping functions.^ HI histone variants were also studied throughout spermatogenesis. The minor somatic variant, HIa, is the predominant variant in spermatogonia and early primary spermatocytes. In early pachytenes, the testis-specific variant, HIt, is first synthesized and appears, largely replacing somatic variants HIbcd and e by late pachytene stage. Early spermatids contain the same HI composition as pachytenes, but do not synthesize HI histones. HI('0) is present in low amounts in all germ cells. These results suggest that expression of HI variants is developmentally controlled.^

Function of histaminergic retinopetal axons in rat and primate retinas

Mammalian retinas receive input from histaminergic neurons in the posterior hypothalamus. These neurons are most active during the waking state of the animal, but their role in retinal information processing is not known. To determine the function of these retinopetal axons, their targets in the rat and monkey retina were identified. Using antibodies to three histamine receptors, HR1, HR2, and HR3, the immunolabeling was analyzed by confocal and electron microscopy. These experiments showed that mammalian retinas possess histamine receptors. In macaques and baboons, diurnal species, HR3 receptors were found at the apex of ON-bipolar cell dendrites in cone pedicles and rod spherules, sclerad to the other neurotransmitter receptors that have been localized there. In addition, HR1 histamine receptors were localized to large puncta in the inner plexiform layer, a subset of ganglion cells and retinal blood vessels. In rats, a nocturnal species, the localization of histamine receptors in the retina was markedly different. Most HR1 receptors were localized to dopaminergic amacrine cells and on elements in the rod spherule. To determine how histaminergic retinopetal axons contribute to retinal information processing, responses of retinal ganglion cells to histamine were analyzed. The effects of histamine on the maintained and light-evoked activity of retinal ganglion cells were analyzed. In monkeys, histamine and the HR3 agonist, methylhistamine, increased or decreased the maintained activity of most ganglion cells, but a few did not respond. The responses of a subset of ganglion cells to light stimuli were decreased by histamine, a finding suggesting that histaminergic retinopetal axons contribute to light adaptation during the day. In rats, histamine nearly always increased the maintained activity and produced both increases and decreases in the light responses. The effects of histamine on maintained activity of ganglion cells in the rat can be partially attributed to HR1-mediated changes in the activity of dopaminergic amacrine cells, at night. Together, these experiments provide the first indication of the function of retinopetal axons in mammalian retinas. ^

Effects of early and late lesion of orbital frontal cortex on visual processing of faces in rhesus macaques (Macaca mulatta)

Many mental disorders disrupt social skills, yet few studies have examined how the brain processes social information. Functional neuroimaging, neuroconnectivity and electrophysiological studies suggest that orbital frontal cortex plays important roles in social cognition, including the analysis of information from faces, which are important cues in social interactions. Studies in humans and non-human primates show that damage to orbital frontal cortex produces social behavior impairments, including abnormal aggression, but these studies have failed to determine whether damage to this area impairs face processing. In addition, it is not known whether damage early in life is more detrimental than damage in adulthood. This study examined whether orbital frontal cortex is necessary for the discrimination of face identity and facial expressions, and for appropriate behavioral responses to aggressive (threatening) facial expressions. Rhesus monkeys (Macaca mulatta) received selective lesions of orbital frontal cortex as newborns or adults. As adults, these animals were compared with sham-operated controls on their ability to discriminate between faces of individual monkeys and between different facial expressions of emotion. A passive visual paired-comparison task with standardized rhesus monkey face stimuli was designed and used to assess discrimination. In addition, looking behavior toward aggressive expressions was assessed and compared with that of normal control animals. The results showed that lesion of orbital frontal cortex (1) may impair discrimination between faces of individual monkeys, (2) does not impair facial expression discrimination, and (3) changes the amount of time spent looking at aggressive (threatening) facial expressions depending on the context. The effects of early and late lesions did not differ. Thus, orbital frontal cortex appears to be part of the neural circuitry for recognizing individuals and for modulating the response to aggression in faces, and the plasticity of the immature brain does not allow for recovery of these functions when the damage occurs early in life. This study opens new avenues for the assessment of rhesus monkey face processing and the neural basis of social cognition, and allows a better understanding of the nature of the neuropathology in patients with mental disorders that disrupt social behavior, such as autism. ^

Pediatric obesity: Managed care collaborating with providers to improve diagnosis and treatment

Child overweight and obesity reaches across ethnic, cultural, socioeconomic and regional barriers. It must be assessed, diagnosed and treated to help families make sustainable behavior changes. Treatment recommendations have been made to address pediatric overweight and obesity. They include screening for risk factors, monitoring BMI trends and educating patients and families to make small sustainable changes. Health insurance companies can play a meaningful role in supporting and facilitating provider education and behavior change to diagnose, treat and prevent pediatric overweight and obesity.^ The aims of this thesis were: (1) Describe a disease management program that uses evidence-based practices to create provider behavior change related to pediatric obesity screening, diagnosis and treatment. (2) Identify ways to improve the implementation of the program based on the perceptions of participating clinicians.^ A literature review was completed to evaluate current recommendations for screening and treating pediatric obesity using the Ovid data base. The evidenced-based recommendations were compared against the practices of the Healthy Lifestyles Program (HeLP). The literature confirmed that HeLP is following evidence-based recommendations for assessment, diagnosis and treatment of pediatric obesity.^ A Children’s Mercy Family Health Partners focus group was convened to create a provider survey. The goals of the survey were to assess providers’ perception of the Healthy Lifestyles Program (HeLP). The survey was sent out through email using Survey Monkey. All survey responses were anonymous. The survey was sent to a total of 80 providers who had completed HeLP. Twenty-five percent responded. The survey results were evaluated to make recommendations for HeLP.^ Results of the survey included motivating factors for participation in HeLP. Concern about the increasing prevalence of pediatric obesity was a frequent motivator for participation. Provider barriers to obesity diagnosis were evaluated. Lack of time during clinic visits a frequent barrier to obesity diagnosis. ^ In conclusion several recommendations for the HeLP were made based on survey results. It is recommended that the program evaluate methods and tools for facilitating effective weight management follow up visits. Promotional materials should highlight the increasing prevalence of pediatric obesity when advertising HeLP. These recommendations will be used to refine the current Healthy Lifestyles Program.^