Disorders of cognitive processes in simulation of Alzheimer's disease in monkeys

Two groups of monkeys were learned to differentiate stimuli with different types of information and to make a spatial choice. Characteristics of the operative memory were revealed in the delayed differentiation tasks prior to and after administration of p75-saporin (I group) and saline (II group). For the first time the Alzheimer disease in monkeys was shown to entail a deficit of operative memory due to disorders in the sensory and cognitive components of the memory. The degree of reduction of the correct decision making was shown to depend on the delay duration and the type of visual information. Following the saline administration, no significant changes occurred in the monkeys (II group). The data obtained suggest that structural-functional organisation of the cholinergic and noradrenergic mechanisms predetermining the sensory processing, differs from those involved in decision-making.     

Interaction between sensory and cognitive processes in visual recognition: the role of the associative areas of the cerebral cortex

Monkeys were taught to differentiate stimuli with different types of information and to perform a spatial choice. Development of Alzheimer's disease in experimental monkeys entailed a deficit of operative memory, a considerable enhancement of entropy related to correct decisions. In control monkeys, no significant changes of these characteristics occurred. In monkeys, following a bilateral removal of the sulcus principalis, the 7th field, or both, the operative memory deficit was also determined by two components. The specifics of disorders in the operative memory due to Alzheimer's disease suggest that cholinergic mechanisms determining the sensory processing differ from those involved in decision-making. The structural-functional organization of interaction between sensory and cognitive processes controlled by the motivation and attention system, is discussed.     

Patterns in the ontogenetic development of certain forms of higher nervous activity in rhesus macaques

Studies have been made on ontogenetic development of simple and complex behavioural forms, realization of certain sequence of motor feeding conditioned reflexes, visual differentiation of signals, short-term memory and probability prediction in rhesus monkeys. Evolutionary features of ontogenetic development of some of the forms of the higher nervous activity were revealed. Both similarities and differences were noted in animals from three age groups. In ontogenesis of lower monkeys, the development of the main nervous processes of the higher nervous activity (learning, memory, etc.) takes place gradually depending on the age of a baby and the level of integrative activity of the brain.     

The role of the prefrontal and parietal cortex in learning and memory in monkeys

Removal of the 7th field of parietal cortex and sulcus principalis of prefrontal cortex did not affect learning processes for images with such properties as spatial frequency, orientation, geometrical form, but worsen learning characteristics in visual differentiation of spatial information making the learning processes unstable, longer and below the 85% level. Removal of sulcus principalis also affects learning of differentiation among various colour stimuli. The short-term memory in these monkeys are also much worse than in intact animals. A scheme of learning involving interacting sensory and cognitive processes controlled by motivation system, is proposed.     

Effect of a dopamine agonist on working memory in monkeys

Prior to and after pharmacological effect of Agroclavine (a dopamine receptors' agonist) following its per os administration, its optimal dose (5 mg/kg) for cognitive processes was established in monkeys. Psychotropic effect of Agroclavine resulting in cognitive dysfunction manifested itself to a greater of lesser extent in all the experimental animals. Correctness of visual differentiation, probability of refusal to solve a task, time of a correct motor response were assumed as the behavioural criteria. In fact, all the animals revealed absence of any increase in the number of wrong solutions in visual differentiation or spatial choice, although the time of correct morot response and the number of refusal to solve the task mostly increased. The Agroclavine effect was found to be rather variable in respect to different types of visual information. A possible structural-functional organisation of the working memory processes is discussed.     

Behavioral compensations in a positional learning and memory task by aged monkeys

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.     

Genotype-dependent mice behavior in cognitive tasks. Effect of noopept

The interstrain differences in performance of C57BL/6J, BALB/c and DBA/2J male mice in two cognitive tasks were found. Mice C57BL/6J showed good learning ability and preservation of memory traces tested 10 days after performance in a simplified version of Morris water maze. Mice BALB/c learned the task but, virtually, no long-term memory traces were revealed, whereas DBA/2J demonstrated poor learning. The effect of nootropic drug Noopept (GVS-111, N-phenil-acetyl-L-prolylglycin ethyl ether) was shown to be genotype-dependent. Its administration (0.5 mg/kg i.p., 15 min before learning) improved the long-term memory in Morris test in BALB/c mice but failed to produce any improvement in C57BL/6J. The ability of mice for extrapolation of the direction of stimulus movement differently changed after Noopept injections: the proportion of correct task solutions increased in C57BL/6J and BALB/c mice, whereas the performance of DBA/2J did not change.     

Effects of testosterone on spatial learning and memory in adult male rats

A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting 7 days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.     

Dynamics of population code for working memory in the prefrontal cortex

Some neurons (delay cells) in the prefrontal cortex elevate their activities throughout the time period during which the animal is required to remember past events and prepare future behavior, suggesting that working memory is mediated by continuous neural activity. It is unknown, however, how working memory is represented within a population of prefrontal cortical neurons. We recorded from neuronal ensembles in the prefrontal cortex as rats learned a new delayed alternation task. Ensemble activities changed in parallel with behavioral learning so that they increasingly allowed correct decoding of previous and future goal choices. In well-trained rats, considerable decoding was possible based on only a few neurons and after removing continuously active delay cells. These results show that neural activity in the prefrontal cortex changes dynamically during new task learning so that working memory is robustly represented and that working memory can be mediated by sequential activation of different neural populations.     

Working Memory in the Processing of the Iowa Gambling Task: An Individual Differences Approach

The Iowa Gambling Task (IGT) is a sequential learning task in which participants develop a tendency towards advantageous options arising from the outcomes associated with their previous decisions. The role of working memory in this complex task has been largely debated in the literature. On one hand, low working memory resources lead to a decrease in the number of advantageous decisions and make a significant part of participants unable to report explicitly which options are the most profitable. On the other hand, several studies have shown no contribution of working memory to the IGT decision patterns. In order to investigate this apparent incompatibility of results, we used an individual differences approach, which has proven an effective method to investigate the role of working memory in cognition. We compared the IGT decision patterns of participants as a function of their working memory capacity (WMC). As expected, contrary to low WMC participants, high WMC participants developed a tendency towards advantageous decisions. These findings lead us to discuss the role of WMC in decision making tasks.     

Forming of the visual cognitive structures in the monkey conditioned-reflex behaviour: the dependence on the sensory information

In monkeys, changes in size and shape of figures led to a significant decrease of correct solutions in training and a considerable increase of refusals from solution of tasks as well as the time of their motor response. The invariance of differentiation in this case was achieved after additional training. The data obtained show that, based on the stimulus sensory processing in conditioned-reflex training, in the long-term memory some differentiating signs are formed: the cognitive structures (the functional neurophysiological mechanisms) maintaining the classification of visual images. With these structures, temporary conditioned connection will be established. Their formation will be determined by the type of sensory information and provided for by existence in the long-term memory of separate subsystems for spatial as well as non-spatial information.     

Functional specifics of cortical associative regions participating in learning to differentiate visual information in monkeys

In 3 groups of monkeys: intact, those with their 7th field bilaterally removed, and those with bilateral removal of the sulcus principalis, functional specifics of the cortex' associative areas were studied. Removal of the 7th field practically does not affect processes of training for images with such features as spatial frequency, colour, and images of animals, but considerably impairs the learning characteristics in visual differentiation of objects' size and spatial interrelationships among objects. Removal of the sulcus principalis considerably impairs the characteristics of differentiation of objects' size and spatial interrelationships among them, as well as differently coloured stimuli. In both these groups, the stable motor response term and the probability of refusal increase. The data obtained suggest that the sensory processing results in forming a few (at least three) functional visual informational flows with which different cortical areas operate.     

Concerning a conflict nature of the "spatial delayed response" test

Neuropsychological analysis of rats' performance of the spatial delayed response (SDR) in different testing conditions revealed a conflict nature of the indirect variation of the SDR task. It was found that the execution of the response based on the image short-term memory interferes with the response differentiation acquired during learning the rule of indirect SDR performance, i.e., during acquisition of the spatial discrimination. It is evident that the maximization of conditions, which promote the acquisition of response differentiation (additional training of animals for spatial discrimination), makes it difficult to perform the indirect variation of the SDR task, while the minimization of these conditions facilitates the correct task performance.     

When to use social information: the advantage of large group size in individual decision making

Correct decision making is crucial for animals to maximize foraging success and minimize predation risk. Group-living animals can make such decisions by using their own personal information or by pooling information with other group members (i.e. social information). Here, we investigate how individuals might best balance their use of personal and social information. We use a simple modelling approach in which individual decisions based upon social information are more likely to be correct when more individuals are involved and their personal information is more accurate. Our model predicts that when the personal information of group members is poor (accurate less than half the time), individuals should avoid pooling information. In contrast, when personal information is reliable (accurate at least half the time), individuals should use personal information less often and social information more often, and this effect should grow stronger in larger groups. One implication of this pattern is that social information allows less well-informed members of large groups to reach a correct decision with the same probability as more well-informed members of small groups. Thus, animals in larger groups may be able to minimize the costs of collecting personal information without impairing their ability to make correct decisions.     

Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 μg), CEE-Medium (20 μg) or CEE-High (30 μg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 β-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.     

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.     

Generalization of Auditory Sensory and Cognitive Learning in Typically Developing Children

Despite the well-established involvement of both sensory (“bottom-up”) and cognitive (“top-down”) processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported “far-transfer” to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills.     

Human implicit memory for irrelevant dimension values is similar to rats' incidental memory in simultaneous discrimination tasks

Participants completed a category-learning task in which they needed to discover which of three stimulus dimensions (shape, color or size) was relevant. After meeting a learning criterion (nine of 10 consecutive correct responses), participants continued making categorization choices and response latencies associated with these trials were examined. In both Experiments 1 and 2, people responded reliably faster when correct responses matched the previous responses with respect to irrelevant dimension values. Thus, they demonstrated a form of incidental short-term memory analogous to that we previously reported in studies of rats. In Experiment 2, participants' explicit memory for irrelevant dimension values was assessed after category learning was complete. The results indicated that people were unaware of the irrelevant dimension values encountered on trials preceding surprise probe trials. This indicates that memory for the irrelevant dimension values was implicit (i.e. unconscious). The findings are discussed with respect to both human and non-human studies of hippocampus-independent memory and implicit memory.     

Analysing neuronal correlates of the comparison of two sequentially presented sensory stimuli

In a typical sequential sensory discrimination task, subjects are required to make a decision based on comparing a sensory stimulus against the memory trace left by a previous stimulus. What is the neuronal substrate for such comparisons and the resulting decisions? This question was studied by recording neuronal responses in a variety of cortical areas of awake monkeys (Macaca mulatta), trained to carry out a vibrotactile sequential discrimination task. We describe methods to analyse responses obtained during the comparison and decision phases of the task, and describe the resulting findings from recordings in secondary somatosensory cortical area (S2). A subset of neurons in S2 become highly correlated with the monkey''s decision in the task.