Primate Experiments Research Articles

The roles of dopamine and serotonin in decision making: evidence from pharmacological experiments in humans.

Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of drugs to healthy controls, experiments that have tested genotypic influences upon dopamine and serotonin function, and, finally, some of those experiments that have examined the effects of drugs on the decision making of clinical samples. Pharmacological experiments in humans are few in number and face considerable methodological challenges in terms of drug specificity, uncertainties about pre- vs post-synaptic modes of action, and interactions with baseline cognitive performance. However, the available data are broadly consistent with current computational models of dopamine function in decision making and highlight the dissociable roles of dopamine receptor systems in the learning about outcomes that underpins value-based decision making. Moreover, genotypic influences on (interacting) prefrontal and striatal dopamine activity are associated with changes in choice behavior that might be relevant to understanding exploratory behaviors and vulnerability to addictive disorders. Manipulations of serotonin in laboratory tests of decision making in human participants have provided less consistent results, but the information gathered to date indicates a role for serotonin in learning about bad decision outcomes, non-normative aspects of risk-seeking behavior, and social choices involving affiliation and notions of fairness. Finally, I suggest that the role played by serotonin in the regulation of cognitive biases, and representation of context in learning, point toward a role in the cortically mediated cognitive appraisal of reinforcers when selecting between actions, potentially accounting for its influence upon the processing salient aversive outcomes and social choice.

“Counting” serially presented stimuli by human and nonhuman primates and pigeons

Much of Stewart Hulse's career was spent analyzing how animals can extract patterned information from sequences of stimuli. Yet an additional form of information contained in a sequence may be the number of times different elements occurred. Experiments that required numerical discrimination between different stimulus items presented in sequence are analyzed for primates and pigeons. It is shown that a model based on magnitude discrimination can account well for data from human and nonhuman primate experiments. Similar experiments carried out with pigeons showed a strong recency effect not found with primates. The pigeon data are modeled successfully, however, by assuming that representations of events decay as other events are presented.

Update on mucosal HIV vaccine vectors

HIV's primary site of infection is at mucosal surfaces. To successfully defend against sexually transmitted diseases (STDs), including HIV, protection may need to be specifically elicited at the mucosal interface, where the organism enters the host. Recent advances in measuring adaptive responses at mucosal sites and optimization of techniques for low-dose repeated mucosal challenge in nonhuman primate animal models allow more in depth studies of mucosal vaccine vectors. Although parenterally administered vaccines can elicit responses at mucosal sites, vaccination of mucosal sites is being explored in an attempt to increase the frequency, strength and distribution of the adaptive mucosal response. Recent studies in nonhuman primates involve vaccination of the gastrointestinal tract and rectum, as well as the nose, oropharynx or respiratory tree in an attempt to elicit responses at the distal mucosal sites where HIV transmission occurs, the rectum and genital tract. Recent experiments in nonhuman primates indicate that vaccination at mucosal sites can elicit robust responses in the periphery and at mucosal sites, although the response pattern varies widely by route and regimen used. For most regimens, disease course after challenge did not differ by route of vaccination.

Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971.

In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical 'Studies on Human Reproduction'. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology. The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision. We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants' high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support. This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research.

Integration of EEG source imaging and fMRI during continuous viewing of natural movies

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an estimate of the current density at every time point. We then carried out a correlation between the time series of visual contrast changes in the movie with that of EEG voxels. We found the most significant correlations in visual area V1, just as seen in previous fMRI studies (Bartels A, Zeki, S, Logothetis NK. Natural vision reveals regional specialization to local motion and to contrast-invariant, global flow in the human brain. Cereb Cortex 2008;18(3):705–717), but on the time scale of milliseconds rather than of seconds. To obtain an estimate of how the EEG signal relates to the BOLD signal, we calculated the IRF between the BOLD signal and the estimated current density in area V1. We found that this IRF was very similar to that observed using combined intracortical recordings and fMRI experiments in nonhuman primates. Taken together, these findings open a new approach to noninvasive mapping of the brain. It allows, firstly, the localization of feature-selective brain areas during natural viewing conditions with the temporal resolution of EEG. Secondly, it provides a tool to assess EEG/BOLD transfer functions during processing of more natural stimuli. This is especially useful in combined EEG/fMRI experiments, where one can now potentially study neural-hemodynamic relationships across the whole brain volume in a noninvasive manner.

RATIONALE AND RECOMMENDATIONS FOR TREATMENT OF RADIATION INJURY WITH CYTOKINES

Treatment of the hematopoietic syndrome includes replacement with blood products, stem cell transplantation, and the use of hematopoietic cytokines. Cytokines have predictable effects based upon their mechanism of action. Those acting on early hematopoietic stem/progenitor cells have multilineage effects, while those acting upon more differentiated progenitor cells have lineage restricted activity. The selection of cytokines for treatment of acute hematopoietic toxicity in man is largely based upon results of experiments in non-human primates and canines. Since randomized controlled trials are unable to be performed in man after accidental radiation exposure, recommendations for therapy are largely based upon expert opinion. There is general agreement that granulocyte colony-stimulating factor (G-CSF) is an acceptable choice for treatment of individuals receiving a whole-body dose of 3 Gy or more, or 2 Gy or more in the presence of mechanical trauma and/or burns (i.e., combined injury). G-CSF is available in radiation stockpiles that have been developed in the U.S. and by the World Health Organization.

25 years after discovering HIV as the cause of aids: prospects for a vaccine

Live attenuated HIV vaccines cannot be tested in humans because of their danger. Inactivated virions are still dangerous and also poorly immunogenic. For that reason subunit vaccines in one form or another have been the approach of almost all investigators since 1984 when adequate HIV culture systems became available. With the exception of using small animals for testing immune responses all in vivo experimental vaccine testing research utilize subhuman primates, especially macaques, challenged with SIV or the chimeric SHIV (using an HIV envelope with SIV). Thus, we begin with two handicaps -- a limitation to subunit vaccines and a limitation in our animal model. However, the limits of the animal model in my view are not due to any inadequacy of the model but rather the limitation of monkeys. This has been a problem from the beginning, but is one that could have been overcome long ago with adequate investments from funders. Instead, we witness most quality investigators limited in their experiments to 4 to 6 animals per group, so as to require multiple repeated experiments and years of delay, while a few groups can afford 20 to 30 animals per group. Obviously, this needs to change. A third handicap is HIV variation. Generally, investigators have challenged macaques with homologous SIV (or SHIV), but this is inadequate. However, in recent years the need for heterologous viral challenges has finally been recognized. It would be ideal to challenge with several different heterologous challenges, but there are serious limitations in available primate viral stocks, particularly SHIV. The best protocol for testing a candidate vaccine in macaques is controversial. Many have favored a single relatively high dose challenge, while recently several groups argue for multiple low dose challenges. The fact is arguments can be made for either, and no one knows which one will be more predictable for a HIV vaccine in man. By far the greatest hurdle to an effective vaccine is the retrovirus characteristics of HIV, namely its capacity to rapidly integrate its genes into our DNA. This establishes life-long infection, rapid diminished function of immune responses, and the emergence of variants. This feature has major implications all too often forgotten in the 1984 to 2008 period of HIV vaccine research, namely an effective HIV vaccine: (1) must protect against infection not just reduce HIV after infection; (2) must be long lasting; and (3) must be broad. Early in HIV vaccine history (roughly 1984-1990) the candidate immunogen was focused on the gp120 envelope delivered as protein, DNA, or vector with an HIV env gene insert. Mostly these led to type specific immune responses so vaccines of this type failed in the monkey model when challenges were made with heterologous strains of SIV or SHIV, especially with protein alone. Nonetheless, a company (VaxGen) still went forward with a gp120 protein clinical trial, and all too predictably, completely failed, and caused much negativity for HIV vaccine research. Many investigators then turned to CMI based vaccines. Though CMI is important and likely helpful to any vaccine candidate, CMI alone is a predictable failure, and indeed such vaccines have failed (e.g., recent NIAID -- Merck trials in Africa). We and some other groups think the answers will be in finding, fixing, and properly presenting conserved sequences of gp120 which are functionally required for HIV infection. Finding conserved sequences is an obvious need and a readily achievable one. Fixing means making a constrained envelope because the mobile envelope is a difficult and ever changing target. We have chosen the CCR5 binding domains of gp120 as the conserved and functionally necessary region. This region of gp120 contains novel epitopes called CD4i epitodes and Abs to them are known as CD4i Abs. We approach this by linking gp120 to domains of CD4 that bind gp120. We have developed a candidate vaccine based on inducing CD4i Abs. These Abs are often broadly reactive, and although we have not as yet reached sterilizing immunity, the vaccine ultimately protects against a high dose heterologous challenge and often has ADCC activity [1]. From our primate experiments and our studies in human elite viral suppressors [2] we predict that a successful HIV vaccine may consist of an immunogen that induces CD4i Abs and ADCC type responses.

The brain's router: a cortical network model of serial processing in the primate brain.

The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100–500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a “router” network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates.

SNOM fluorescence techniques applied to cytoskeleton study in cell cultures

Introduction Scanning near field optical microscope (SNOM) is a tool which overcomes the diffraction limit of conventional optical microscopy and allows optical imaging with a resolution of less than 100 nm without having to go through any special sample preparation. Moreover one of the best advantages of SNOM is to produce topographic, transmission and reflection images simultaneously [1]. Several studies have been carried out by SNOM in the last years on biological specimens, but the fluorescence SNOM technique has been rarely applied on cell culture investigations. Here we set up a TriA-SNOM with a specific fluorescence equipment to develop the performance of this probe microscope and identify cytoskeleton elements in cell cultures, mainly primary rat podocytes cultures. Materials and methods The microscope used were a TriA-SNOM (APE Research, Trieste, Italy) equipped with a specific fluorescence set-up that allowed to obtain different SNOM images of the samples simultaneously: topography, SNOM fluorescence in reflection and SNOM-fluorescence in transmission. Cell cultures: Primary culture of rat podocytes were treated by immunofluorescence techniques with TRITC-phalloidin to visualize cytoskeletal elements such as actin filaments. Actin filaments were analyzed by SNOM-fluorescence and compared with conventional fluorescence. Results SNOMfluorescence, unlike all other techniques, may reconstruct a fluorescence mapping of the sample, and obtain a direct measure in height of the fluorescence structures. The major technical problem in this kind of microscopy is to reduce of the optical background noise. We actually obtained a SNOM-fluorescence set-up to adequately visualize the specimens, producing images with low background noise and high resolution. SNOM moreover allowed to discriminate the superficial actin filaments from the deep filaments by reflection system. Conclusions SNOM with fluorescence technique may be suitable method for detection of specific molecules in cell cultures, providing an overlapping of the fluorescence image on the 3D mapping of the sample. These studies open further possibilities for application of SNOM to biological materials, especially in cells observed in liquid environment.

Depolarising Primate Experimentation: The Good, the Bad and the Determined

Until I began working at FRAME, I was not really aware of the Three Rs or FRAME's work to promote and progress them. It soon became clear to me that it made scientific sense and that it could make a difference to many thousands of laboratory animals. As an alternatives advocate, I regularly experience optimism, frustration and determination. This is illustrated most clearly by the primate research dilemma. Here, I describe the positive and negative experiences I have had whilst working toward the goal of replacing primate experiments, and how these have led me to undertake a multidisciplinary PhD project on primate use in biomedical research. The aim is to examine how research scientists view the opportunities and challenges involved in the use of primates in biomedical science, and to investigate the feasibility of phasing out their use. As a result of the research, I hope to provide a new perspective, to depolarise the debate and bring about a constructive dialogue between all parties as to how and when primate research could be replaced.

The end of monkey research?

Kevan A. C. Martin, a neurobiologist and director of the Institute of Neuroinformatics—a joint institute of the University of Zurich and the Swiss Federal Institute of Technology—has a moral dilemma. For the past four years, he has not hired any postdoctoral fellows or PhD students. He feels he cannot take them on in good conscience because he cannot guarantee they will be able to do research. It was another moral debate that put him in this position; his work on rhesus macaques has been put on hold and he is uncertain when, or if, it will resume in Switzerland. > …the real impact on primate labs might come from pending revisions to legislation in Europe and the USA that could potentially end research on apes and monkeys altogether In 2004, the Swiss Constitution was changed to acknowledge “the dignity of living beings,” which, according to Martin, was intended to address concerns about transgenic experimentation, rather than animal research in general. Nevertheless, the change resulted in some members of a local external advisory committee on animal experimentation legally challenging the 2006 renewal of Martin's license to use the monkeys for neurobiological research. Similar legal action was taken against Daniel Kiper at the same institute, whose research on brain plasticity in monkeys has relevance for stroke patients. A third researcher, whose work on motor systems has implications for patients with spinal cord damage, has decided to leave Switzerland (Staub, 2007). All three of these projects were approved by the Zurich Canton's Veterinary Office, which controls experiments on animals. Martin's case has been working its way through the Swiss courts and is finally before Switzerland's Federal Supreme Court. In the meantime, Martin, who established the Institute in Zurich with Rodney Douglas 13 years ago, has been limited to using post‐mortem monkey brains. These are …

A Human Anti-CD40 Monoclonal Antibody, 4D11, for Kidney Transplantation in Cynomolgus Monkeys: Induction and Maintenance Therapy

Blockade of CD40-CD154 signaling pathway is an attractive strategy to induce potent immunosuppression and tolerance in organ transplantation. Due to its strong immunosuppressive effect shown in nonhuman primate experiments, anti-CD154 monoclonal antibodies (mAbs) have been tried in clinical settings, but it was interrupted by unexpected thromboembolic complications. Thus, inhibition of the counter molecule, CD40, has remained an alternative approach. In the previous preliminary study, we have shown that 4D11, a novel fully human anti-CD40 mAb, has a fairly potent immunosuppressive effect on kidney allograft in nonhuman primates. In this study, we aimed to confirm the efficacy and untoward events of the 2-week induction and 180-day maintenance 4D11 treatments. In both, 4D11 significantly suppressed T-cell-mediated alloimmune responses and prolonged allograft survival. Addition of weekly 4D11 administration after the induction treatment further enhanced graft survival. Complete inhibition of both donor-specific Ab and anti-4D11 Ab productions was obtained only with higher-dose maintenance therapy. No serious side effect including thromboembolic complications was noted except for a transient reduction of hematocrit in one animal, and decrease of peripheral B-cell counts in all. These results indicate that the 4D11 appears to be a promising candidate for immunosuppression in clinical organ transplantation.

Refinements in husbandry, care and common procedures for non-human primates

Preface Whenever animals are used in research, minimizing pain and distress and promoting good welfare should be as important an objective as achieving the experimental results. This is important for humanitarian reasons, for good science, for economic reasons and in order to satisfy the broad legal principles in international legislation. It is possible to refine both husbandry and procedures to minimize suffering and improve welfare in a number of ways, and this can be greatly facilitated by ensuring that up-to-date information is readily available. The need to provide such information led the British Veterinary Association Animal Welfare Foundation (BVAAWF), the Fund for the Replacement of Animals in Medical Experiments (FRAME), the Royal Society for the Prevention of Cruelty to Animals (RSPCA) and the Universities Federation for Animal Welfare (UFAW) to establish a Joint Working Group on Refinement (JWGR) in the UK. The chair is Professor David Morton and the secretariat is provided by the RSPCA. This report is the ninth in the JWGR series. The RSPCA is opposed to the use of animals in experiments that cause pain, suffering, distress or lasting harm and together with FRAME has particular concerns about the continued use of non-human primates. The replacement of primate experiments is a primary goal for the RSPCA and FRAME. However, both organizations share with others in the Working Group, the common aim of replacing primate experiments wherever possible, reducing suffering and improving welfare while primate use continues. The reports of the refinement workshops are intended to help achieve these aims. This report produced by the British Veterinary Association Animal Welfare Foundation (BVAAWF)/Fund for the Replacement of Animals in Medical Experiments (FRAME)/Royal Society for the Prevention of Cruelty to Animals (RSPCA)/Universities Federation for Animal Welfare (UFAW) Joint Working Group on Refinement (JWGR) sets out practical guidance on refining the husbandry and care of non-human primates (hereinafter primates) and on minimizing the adverse effects of some common procedures. It provides a valuable resource to help understand the physical, social and behavioural characteristics and needs of individual primates, and is intended to develop and complement the existing literature and legislative guidelines. Topics covered include refinements in housing, husbandry and common procedures such as restraint, identification and sampling, with comprehensive advice on issues such as primate communication, assessing and facilitating primate wellbeing, establishing and maintaining social groups, environmental and nutritional enrichment and animal passports. The most commonly used species are the key focus of this resource, but its information and recommendations are generally applicable to other species, provided that relevant individual species characteristics are taken into account.

Three-dimensional, automated, real-time video system for tracking limb motion in brain–machine interface studies

Collection and analysis of limb kinematic data are essential components of the study of biological motion, including research into biomechanics, kinesiology, neurophysiology and brain–machine interfaces (BMIs). In particular, BMI research requires advanced, real-time systems capable of sampling limb kinematics with minimal contact to the subject's body. To answer this demand, we have developed an automated video tracking system for real-time tracking of multiple body parts in freely behaving primates. The system employs high-contrast markers painted on the animal's joints to continuously track the three-dimensional positions of their limbs during activity. Two-dimensional coordinates captured by each video camera are combined and converted to three-dimensional coordinates using a quadratic fitting algorithm. Real-time operation of the system is accomplished using direct memory access (DMA). The system tracks the markers at a rate of 52 frames per second (fps) in real-time and up to 100 fps if video recordings are captured to be later analyzed off-line. The system has been tested in several BMI primate experiments, in which limb position was sampled simultaneously with chronic recordings of the extracellular activity of hundreds of cortical cells. During these recordings, multiple computational models were employed to extract a series of kinematic parameters from neuronal ensemble activity in real-time. The system operated reliably under these experimental conditions and was able to compensate for marker occlusions that occurred during natural movements. We propose that this system could also be extended to applications that include other classes of biological motion.

“Like-Me” Simulation as an Effective and Cognitively Plausible Basis for Social Robotics

We present a successful design approach for social robotics based on a computational cognitive architecture and mental simulation. We discuss an approach to a Theory of Mind known as a “like-me” simulation in which the agent uses its own knowledge and capabilities as a model of another agent to predict that agent’s actions. We present three examples of a “like-me” mental simulation in a social context implemented in the embodied version of the Adaptive Control of Thought-Rational (ACT-R) cognitive architecture, ACT-R/E (for ACT-R Embodied). Our examples show the efficacy of a simulation approach in modeling perspective taking (identifying another’s left or right hand), teamwork (simulating a teammate for better team performance), and dominant-submissive social behavior (primate social experiments). We conclude with a discussion of the cognitive plausibility of this approach and our conclusions.

Neural correlates of learning and working memory in the primate posterior parietal cortex

The posterior parietal cortex has been traditionally associated with coordinate transformations necessary for interaction with the environment and with visual-spatial attention. More recently, involvement of posterior parietal cortex in other cognitive functions such as working memory and task learning has become evident. Neurophysiological experiments in non-human primates and human imaging studies have revealed neural correlates of memory and learning at the single neuron and at the brain network level. During working memory, posterior parietal neurons continue to discharge and to represent stimuli that are no longer present. This activation resembles the responses of prefrontal neurons, although important differences have been identified in terms of the ability to resist stimulation by distracting stimuli, which is more evident in the prefrontal than the posterior parietal cortex. Posterior parietal neurons also become active during tasks that require the organization of information into larger structured elements and their activity is modulated according to learned context-dependent rules. Neural correlates of learning can be observed in the mean discharge rate and spectral power of neuronal spike trains after training to perform new task sets or rules. These findings demonstrate the importance of posterior parietal cortex in brain networks mediating working memory and learning.

Measles studies in the macaque model.

Much of our current understanding of measles has come from experiments in non-human primates. In 1911, Goldberger and Anderson showed that macaques inoculated with filtered secretions from measles patients developed measles, thus demonstrating that the causative agent of this disease was a virus. Since then, different monkey species have been used for experimental measles virus infections. Moreover, infection studies in macaques demonstrated that serial passage of the virus in vivo and in vitro resulted in virus attenuation, providing the basis for all current live-attenuated measles vaccines. This chapter will review the macaque model for measles, with a focus on vaccination and immunopathogenesis studies conducted over the last 15 years. In addition, recent data are highlighted demonstrating that the application of a recombinant measles virus strain expressing enhanced green fluorescent protein dramatically increased the sensitivity of virus detection, both in living and sacrificed animals, allowing new approaches to old questions on measles vaccination and pathogenesis.

FEF neural responses during uninstructed, optimal eye movements in a free-viewing scan task

Event Abstract Back to Event FEF neural responses during uninstructed, optimal eye movements in a free-viewing scan task The majority of primate electrophysiological experiments begin gathering neural data only after the animal is well trained. In this experiment we recorded from the frontal eye fields (FEF), prefrontal cortex (PFC), and caudate nucleus (CN) of two monkeys throughout the acquisition of a novel free-viewing scan task. In this task monkeys were required to maintain their eye position in the space occupied by a 4- or 9-target (depending on the stage of training) grid of dots until, by freely making saccades in that space, they fixated on or passed through the target randomly chosen to be rewarded. We previously reported that monkeys form habitual patterns of eye movements without explicit shaping or instruction of any kind (Feledy, et al. Cosyne 2007). Furthermore, we found that these patterns of eye movements, or scan paths, gradually evolve to be more optimal through training where optimality was defined as the shortest distance and time to cover all the grid targets in a loop. Here we focus on recording results from a single cortical area, FEF, obtained at the end of training. Because of the free-viewing nature of this task, we first categorized FEF units according to those properties found in the FEF of over-trained monkeys performing single saccade tasks. We found similar kinds of general responses, as defined by modulation of mean firing rate, e.g. direction selectivity and visual selectivity. In addition, we found units that had more complex firing properties that may be novel and could indicate as yet undocumented properties of FEF units that emerge with uninstructed learning of a naturalistic task. This work is supported by: NEI EY12848, Friends of the McGovern Institute Graduate Fellowship, NDSEG Fellowship Conference: Computational and systems neuroscience 2009, Salt Lake City, UT, United States, 26 Feb - 3 Mar, 2009. Presentation Type: Poster Presentation Topic: Poster Presentations Citation: (2009). FEF neural responses during uninstructed, optimal eye movements in a free-viewing scan task. Front. Syst. Neurosci. Conference Abstract: Computational and systems neuroscience 2009. doi: 10.3389/conf.neuro.06.2009.03.177 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Feb 2009; Published Online: 03 Feb 2009. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Google Google Scholar PubMed Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Samuel Fernberger's rejected doctoral dissertation: A neglected resource for the history of ape research in America.

I summarize a never-completed 1911 doctoral dissertation on ape behavior by Samuel Fernberger of the University of Pennsylvania. Included are observations on many behavioral patterns including sensory and perceptual function, learning, memory, attention, imagination, personality, and emotion in an orangutan and two chimpanzees. There are examples of behavior resembling insight, conscience, tool use and imitation. Language comprehension was good but speech production was minimal. The document appears to contradict a brief published article on the project by William Furness in that punishment was frequently used. The document is important for understanding Fernberger's early career, for anticipations of later research, and for understanding the status of ape research at the time.

A non-invasive technique to monitor wakefulness during electrophysiologic recording experiments in primates

Although the state of wakefulness has an impact on many physiological parameters, this variable is seldom controlled for in in vivo experiments, because the existing techniques to identify periods of wakefulness are laborious and difficult to implement. We here report on a simple non-invasive technique to achieve this goal, using the analysis of video material, collected along with the electrophysiologic data, to analyze eyelid movements. The technique was applied to recordings in non-human primates, and allowed us to automatically identify periods during which the subject has its eyes open. A comparison with frontal electroencephalographic records confirmed that such periods corresponded to wakefulness.