Conserved fMRI and LFP signals during new associative learning in the human and macaque monkey medial temporal lobe

We measured local field potential (LFP) and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in the medial temporal lobes of monkeys and humans, respectively, as they performed the same conditional motor associative learning task. Parallel analyses were used to examine both data sets. Despite significantly faster learning in humans relative to monkeys, we found equivalent neural signals differentiating new versus highly familiar stimuli, first stimulus presentation, trial outcome, and learning strength in the entorhinal cortex and hippocampus of both species. Thus, the use of parallel behavioral tasks and analyses in monkeys and humans revealed conserved patterns of neural activity across the medial temporal lobe during an associative learning task.     

Specificity of sensorimotor learning and the neural code: Neuronal representations in the primary motor cortex

Human studies show that the learning of a new sensorimotor mapping that requires adaptation to directional errors is local and generalizes poorly to untrained directions. We trained monkeys to learn new visuomotor rotations for only one target in space and recorded neuronal activity in the primary motor cortex before, during and after learning. Similar to humans, the monkeys showed poor transfer of learning to other directions, as observed by behavioral aftereffects for untrained directions. To test for internal representations underlying these changes, we compared two features of neuronal activity before and after learning: changes in firing rates and changes in information content. Specific elevations of firing rate were only observed in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation; namely cells only showed plasticity if their preferred direction was near the training one. We applied measures from information theory to probe for learning-related changes in the neuronal code. Single cells conveyed more information about the direction of movement and this specific improvement in encoding was correlated with an increase in the slope of the neurons' tuning curve. Further, the improved information after learning enabled a more accurate reconstruction of movement direction from neuronal populations. Our findings suggest a neural mechanism for the confined generalization of a newly acquired internal model by showing a tight relationship between the locality of learning and the properties of neurons. They also provide direct evidence for improvement in the neural code as a result of learning.     

Typological characteristics of conditioned reflex learning in monkeys

Three types of conditioned learning dynamics were singled out in males of the rhesus monkeys by the speed of formation of a positive motor instrumental reflex and differentiation. Type I is characterized by the fastest mastering of separate subprograms and of the whole test program of conditioned behaviour, by optimal functional characteristics in the process of learning and by a high adaptivity in new conditions. The most prolonged formation of the conditioned reflexes occurs in monkeys of the III-d type; 50% of them do not master the whole learning program; monkeys with such type of learning dynamics have no adaptation of previously acquired conditioned stereotype to new environmental conditions. Monkeys of the II-nd type of learning dynamics possess intermediate characteristics. A notion is substantiated of interconnection of higher nervous activity properties with typological characteristics of conditioned learning dynamics in monkeys.     

Motor and cognitive functions of the ventral premotor cortex

Recent data show that the ventral premotor cortex in both humans and monkeys has motor and cognitive functions. The cognitive functions include space perception, action understanding and imitation. The data also show a clear functional homology between monkey area F5 and human area 44. Preliminary evidence suggests that the ventral part of the lateral premotor cortex in humans may correspond to monkey area F4. A tentative map of the human lateral premotor areas founded on the reviewed evidence is presented.     

The mirror system and its role in social cognition

Experiments in monkeys have shown that coding the goal of the motor acts is a fundamental property of the cortical motor system. In area F5, goal-coding motor neurons are also activated by observing motor acts done by others (the 'classical' mirror mechanism); in area F2 and area F1, some motor neurons are activated by the mere observation of goal-directed movements of a cursor displayed on a computer screen (a 'mirror-like' mechanism). Experiments in humans and monkeys have shown that the mirror mechanism enables the observer to understand the intention behind an observed motor act, in addition to the goal of it. Growing evidence shows that a deficit in the mirror mechanism underlies some aspects of autism.     

Thermal and EMG Biofeedback Learning in Nonhuman Primates

Four monkeys were found able to learn to raise and lower hand temperature and to reduce muscle tension to low levels using feedback from the target physiological system. The establishment of this model of biofeedback learning in monkeys enables work on mechanisms mediating the modes of biofeedback most used in clinical practice. Results suggest that biofeedback learning does not need to be mediated by the type of human-specific cognitive strategies employed by humans.     

Individual and social learning processes involved in the acquisition and generalization of tool use in macaques

Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning.     

Motoring ahead with rodents

How neural circuits underlie the acquisition and control of learned motor behaviors has traditionally been explored in monkeys and, more recently, songbirds. The development of genetic tools for functional circuit analysis in rodents, the availability of transgenic animals with well characterized phenotypes, and the relative ease with which rats and mice can be trained to perform various motor tasks, make rodents attractive models for exploring the neural circuit mechanisms underlying the acquisition and production of learned motor skills. Here we discuss the advantages and drawbacks of this approach, review recent trends and results, and outline possible strategies for wider adoption of rodents as a model system for complex motor learning.     

The role of ventral premotor cortex in action execution and action understanding

The human ventral premotor cortex overlaps, at least in part, with Broca's region in the dominant cerebral hemisphere, that is known to mediate the production of language and contributes to language comprehension. This region is constituted of Brodmann's areas 44 and 45 in the inferior frontal gyrus. We summarize the evidence that the motor related part of Broca's region is localized in the opercular portion of the inferior frontal cortex, mainly in area 44 of Brodmann. According to our own data, there seems to be a homology between Brodmann area 44 in humans and the monkey area F5. The non-language related motor functions of Broca's region comprise complex hand movements, associative sensorimotor learning and sensorimotor integration. Brodmann's area 44 is also a part of a specialized parieto-premotor network and interacts significantly with the neighbouring premotor areas. In the ventral premotor area F5 of monkeys, the so called mirror neurons have been found which discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding not only to the observation of mouth actions, but also to sounds characteristic to actions have been found. In humans, through an fMRI study, it has been shown that the observation of actions performed with the hand, the mouth and the foot leads to the activation of different sectors of Broca's area and premotor cortex, according to the effector involved in the observed action, following a somatotopic pattern which resembles the classical motor cortex homunculus. On the other hand the evidence is growing that human ventral premotor cortex, especially Brodmann's area 44, is involved in polymodal action processing. These results strongly support the existence of an execution-observation matching system (mirror neuron system). It has been proposed that this system is involved in polymodal action recognition and might represent a precursor of language processing. Experimental evidence in favour of this hypothesis both in the monkey and humans is shortly reviewed.     

Does Presentation Format Influence Visual Size Discrimination in Tufted Capuchin Monkeys (Sapajus spp.)?

Most experimental paradigms to study visual cognition in humans and non-human species are based on discrimination tasks involving the choice between two or more visual stimuli. To this end, different types of stimuli and procedures for stimuli presentation are used, which highlights the necessity to compare data obtained with different methods. The present study assessed whether, and to what extent, capuchin monkeys’ ability to solve a size discrimination problem is influenced by the type of procedure used to present the problem. Capuchins’ ability to generalise knowledge across different tasks was also evaluated. We trained eight adult tufted capuchin monkeys to select the larger of two stimuli of the same shape and different sizes by using pairs of food items (Experiment 1), computer images (Experiment 1) and objects (Experiment 2). Our results indicated that monkeys achieved the learning criterion faster with food stimuli compared to both images and objects. They also required consistently fewer trials with objects than with images. Moreover, female capuchins had higher levels of acquisition accuracy with food stimuli than with images. Finally, capuchins did not immediately transfer the solution of the problem acquired in one task condition to the other conditions. Overall, these findings suggest that – even in relatively simple visual discrimination problems where a single perceptual dimension (i.e., size) has to be judged – learning speed strongly depends on the mode of presentation.     

Easy Rider: Monkeys Learn to Drive a Wheelchair to Navigate through a Complex Maze

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in real world environments. There is some incertitude, however, regarding the extrapolation of rodent spatial navigation strategies to primates. Here we present an entirely new platform for investigating real spatial navigation in rhesus monkeys. We showed that monkeys can learn a pathway by using different strategies. In these experiments three monkeys learned to drive the wheelchair and to follow a specified route through a real maze. After learning the route, probe tests revealed that animals successively use three distinct navigation strategies based on i) the place of the reward, ii) the direction taken to obtain reward or iii) a cue indicating reward location. The strategy used depended of the options proposed and the duration of learning. This study reveals that monkeys, like rodents and humans, switch between different spatial navigation strategies with extended practice, implying well-conserved brain learning systems across different species. This new task with freely driving monkeys provides a good support for the electrophysiological and pharmacological investigation of spatial navigation in the real world by making possible electrophysiological and pharmacological investigations.     

Nonhuman primates are relevant models for research in hematology, immunology and virology

Nonhuman primates have been used for biomedical research for several decades. They have proved to be models that are relevant to humans because of the high level of gene homology which underlies physiological and biochemical similarities. The similarity of monkeys to humans has been used to investigate pathophysiological mechanisms in hematology, immunology and virology. New therapeutic procedures can be assessed in primates by using materials, in particular pharmacological reagents, and methods designed for humans. The relevance of these models also relies on the use of species-specific pathogens and the availability of recombinant, homologous cytokines. The introduction of more and more sophisticated cell and gene therapy protocols in hematopoietic cell transplantation and immunotherapy requires the development of preclinical trials similar to clinical settings. For several decades now, baboons and cynomolgus/rhesus monkeys have been the most useful primate models in experimental hematology, and this has contributed to numerous therapeutic advances. Primate models of AIDS have been developed to study the pathogenesis, transmission and immune responses to infection, and to test vaccines and drugs. Primate research should be restricted in quantity, and mainly designed with the aim of removing uncertainty as to the safety and clinical benefit to the patient, of new biomedical protocols.     

Discrimination strategies of humans and rhesus monkeys for complex visual displays

By learning to discriminate among visual stimuli, human observers can become experts at specific visual tasks. The same is true for Rhesus monkeys, the major animal model of human visual perception. Here, we systematically compare how humans and monkeys solve a simple visual task. We trained humans and monkeys to discriminate between the members of small natural-image sets. We employed the "Bubbles" procedure to determine the stimulus features used by the observers. On average, monkeys used image features drawn from a diagnostic region covering about 7% +/- 2% of the images. Humans were able to use image features drawn from a much larger diagnostic region covering on average 51% +/- 4% of the images. Similarly for the two species, however, about 2% of the image needed to be visible within the diagnostic region on any individual trial for correct performance. We characterize the low-level image properties of the diagnostic regions and discuss individual differences among the monkeys. Our results reveal that monkeys base their behavior on confined image patches and essentially ignore a large fraction of the visual input, whereas humans are able to gather visual information with greater flexibility from large image regions.     

Effect of cannabis on learning in the cynocephalic monkey (Papio Papio)]

Chronic treatment of monkeys with Cannabis reduce the speed of acquisition of learned behavior, yet, learning is nevertheless possible. After acquisition, Cannabis administration disturb the responses in the learning test. In this two experimental procedures, tolerance occurs to the effects of Cannabis.     

Characteristic features of adaptation to experimental conditions in primates with various initial keeping conditions

Ethological study of emotional state and behavior was carried out in male macaques of two species (Macaca mulatta and Macaca fascicularis), which were divided in three groups according to their initial keeping: isolated, family, and gregarious. During instrumental conditioning, the initial keeping was changed for identical conditions (individual caging or sitting in a primatological chair). It was shown that adaptation to stress associated with a sharp enviromental change depended on initial keeping conditions. Monkeys brought up in family with experience of both intra- and interspecies interactions (for example, monkey--human) had the highest adaptation and learning abilities. Individual and gregarious keeping of monkeys impoverished their individual experience, and their adaptation to experimental conditions required additional efforts. The learning of individually caged monkeys was successful, if their keeping conditions were not changed. Initially gregarious monkeys were successfully trained after their habituation to contact with humans.     

Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex

Many recent studies describe learning-related changes in sensory and motor areas, but few have directly probed for improvement in neuronal coding after learning. We used information theory to analyze single-cell activity from the primary motor cortex of monkeys, before and after learning a local rotational visuomotor task. We show that after learning, neurons in the primary motor cortex conveyed more information about the direction of movement and did so with relation to their directional sensitivity. Similar to recent findings in sensory systems, this specific improvement in encoding is correlated with an increase in the slope of the neurons' tuning curve. We further demonstrate that the improved information after learning enables a more accurate reconstruction of movement direction from neuronal populations. Our results suggest that similar mechanisms govern learning in sensory and motor areas and provide further evidence for a tight relationship between the locality of learning and the properties of neurons; namely, cells only show plasticity if their preferred direction is near the training one. The results also suggest that simple learning tasks can enhance the performance of brain–machine interfaces.     

Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey

Aged individuals experience decreased fine motor function of the hand and digits, which could result, in part, from the chronic, systemic state of inflammation that occurs with aging. Recent research for treating age-related inflammation has focused on the effects of nutraceuticals that have anti-inflammatory properties. One particular dietary polyphenol, curcumin, the principal curcuminoid of the spice turmeric, has been shown to have significant anti-inflammatory effects and there is mounting evidence that curcumin may serve to reduce systemic inflammation. Therefore, it could be useful for alleviating age-related impairments in fine motor function. To test this hypothesis we assessed the efficacy of a dietary intervention with a commercially available optimized curcumin to ameliorate or delay the effects of aging on fine motor function of the hand of rhesus monkeys. We administered oral daily doses of curcumin or a control vehicle to 11 monkeys over a 14- to 18-month period in which they completed two rounds of fine motor function testing. The monkeys receiving curcumin were significantly faster at retrieving a food reward by round 2 of testing than monkeys receiving a control vehicle. Further, the monkeys receiving curcumin demonstrated a greater degree of improvement in performance on our fine motor task by round 2 of testing than monkeys receiving a control vehicle. These findings reveal that fine motor function of the hand and digits is improved in middle-aged monkeys receiving chronic daily administration of curcumin.     

Prostaglandins in cerebrospinal fluid of healthy human volunteers, abstinent alcoholics and rhesus monkeys

A sensitive and selective assay for measuring prostaglandins in cerebrospinal fluid has been developed, based on the selected-ion-monitoring, electron-capture negative ionization GC/MS detection for the MO-PFB-TMS derivatives of prostaglandins E2, E1, F2 alpha, F1 alpha, and 6-keto-F1 alpha. Improvements over previously published assay procedures have been made, and the new assay has been applied to measurement of prostaglandin concentrations in lumbar CSF of healthy human volunteers, abstinent alcoholic patients, in cisternal CSF of Rhesus monkeys, and continuously sampled lumbar CSF of awake Rhesus monkeys. Results indicated that the concentrations of PGE2, PGE1, PGF1 alpha, and 6-keto-PGF1 alpha were below 15 pg/mL CSF in lumbar CSF of healthy humans and abstinent alcoholics, and in cisternal CSF of Rhesus monkeys. In contrast, continuously sampled lumbar CSF of awake Rhesus monkeys contained more than 200 pg/mL of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha, probably present as a result of local production.     

A comparative study of the adrenergic nerves to the anterior eye segment of some primates

Summary The distribution of adrenergic terminals to the anterior eye segment of humans, Cynomolgue monkeys, squirrel monkeys, owl monkeys, Cebus monkeys, vervets, tamarins, and baboons has been investigated. The cornea is normally devoid of adrenergic terminals, except in a plexus near the limbus. The trabecular meshwork contains varying numbers of adrenergic terminals: usually none in Cynomolgus monkeys, patas monkeys, vervets, and humans, although fibres have very rarely been observed in Cynomolgus monkeys, vervets, and humans; a few in owl monkeys, squirrel monkeys, and tamarins; and moderate numbers in Cebus monkeys and baboons. From the evidence, however, it seems premature to presume an adrenergic innervation of the trabecular mechanism regulating the outflow resistance. The dilatator pupillae is regularly supplied with numerous adrenergic terminals and in the iris stroma there is probably an adrenergic innervation of the melanophores. The sphincter pupillae regularly contains adrenergic terminals with notable species differences; most fibres occur in baboons and fewest in humans, with the remaining species forming a middle class. The ciliary processes in all species contain a moderate number of adrenergic terminals, presumably primarily associated with the epithelium. Intraepithelial adrenergic terminals have been observed on the pars plana of the ciliary body of humans, Cebus monkeys, vervets, baboons, and patas monkeys. The ciliary muscle of baboons and Cynomolgus monkeys contains numerous adrenergic terminals. Moderate numbers occur in Cebus monkeys and vervets, and still less in (in falling order) tamarins, squirrel monkeys, humans, and patas monkeys.     

Smells are no surer: rapid improvement in olfactory discrimination is not due to the acquisition of a learning set.

The claim that rats can demonstrate the 'primate-like' learning capacity of learning set formation when trained with olfactory cues, rather than visual or auditory cues, has generated considerable interest in recent years. In this study, the claim is evaluated in detail by using a series of experimental and control procedures to determine whether rats do indeed develop the abstract 'win-stay, lose-shift' strategy which underlies learning set formation in monkeys. We report here that although exposure to a series of novel olfactory discrimination problems gives rise to progressive improvement in the rate of learning, it is not a necessary condition for the development of that rapid learning. Furthermore, even rats which fail to display progressive improvement in olfactory reversal learning show rapid learning on novel olfactory discrimination problems. Each of these findings suggests that although olfactory learning may be rapid, learning set formation does not occur over a short series of problems.