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Deficits in water escape performance and alterations in hippocampal cholinergic mechanisms associated with neonatal monosodium glutamate treatment in mice.

Mice treated neonatally with monosodium glutamate (MSG) were found to have learning and memory deficits in performing a non-spatial water escape task. Scopolamine impaired the water-escape performance of the control mice but not that of the MSG-treated mice. It was suggested that the water-escape performance deficit in the MSG-treated mice was a result of impaired central cholinergic mechanisms. As such, scopolamine was unable to further incapacitate an already impaired cholinergic system. This is strongly supported by the decreased affinity of the sodium-dependent high-affinity choline uptake observed in the hippocampus. D-Cycloserine, a partial agonist at the glycine site of the NMDA receptor, did not affect the water-escape performance of the MSG-treated and control mice; nor did it alter the effects of scopolamine. This lack of effect of D-Cycloserine may imply that the NMDA receptors are not involved in non-spatial learning, in contrast to their reported involvement in spatial learning.

Animals↗

Depth of understanding and excellence of practice: the question of wholeness and problem-based learning.

The paper evaluates the importance of conceptions underlying practices in medicine and in medical education. It uses a study of anaesthetists' approaches to practice, and of lectures in problem-based learning, to illustrate the influence of a conception of 'applying knowledge in, or to, practice' and of its apparently serious limitations reflected in practice. A brief background to the pervasiveness of the conception is given, together with discussion of an alternative, and arguably better, conception and its realization in rigorous problem-based learning in contrast to transitional, semi-problem-based learning.

Anesthesiology↗

Attention-gated reinforcement learning of internal representations for classification.

Animal learning is associated with changes in the efficacy of connections between neurons. The rules that govern this plasticity can be tested in neural networks. Rules that train neural networks to map stimuli onto outputs are given by supervised learning and reinforcement learning theories. Supervised learning is efficient but biologically implausible. In contrast, reinforcement learning is biologically plausible but comparatively inefficient. It lacks a mechanism that can identify units at early processing levels that play a decisive role in the stimulus-response mapping. Here we show that this so-called credit assignment problem can be solved by a new role for attention in learning. There are two factors in our new learning scheme that determine synaptic plasticity: (1) a reinforcement signal that is homogeneous across the network and depends on the amount of reward obtained after a trial, and (2) an attentional feedback signal from the output layer that limits plasticity to those units at earlier processing levels that are crucial for the stimulus-response mapping. The new scheme is called attention-gated reinforcement learning (AGREL). We show that it is as efficient as supervised learning in classification tasks. AGREL is biologically realistic and integrates the role of feedback connections, attention effects, synaptic plasticity, and reinforcement learning signals into a coherent framework.

Animals↗

Take-home informed consent for intravenous contrast media: do patients learn more?

RATIONALE AND OBJECTIVES: In 1978, Morrow et al published the results of a simple technique for raising radiation oncology patients' levels of awareness about medical options. They reported that providing written information at least 24 hours in advance was an effective tool for increasing the baseline knowledge in this patient group. However, Morrow's cohort consisted exclusively of cancer patients receiving radiation therapy. The authors of this article are concerned with whether the encouraging results reported by Morrow are reproducible when applied to patients awaiting invasive radiologic procedures. METHODS: One hundred sixty consecutive outpatients awaiting contrast were block randomized into one of eight groups based on age, sex, and previous contrast exposure. For each group, half were given their consent form at least 24 hours prior, and the other half at the time of their procedure. All patients were tested at the time of their procedure to evaluate knowledge retention. RESULTS: Comparison between the two study groups showed no overall statistically significant differences either in knowledge (experimental group 4.7 +/- 1.32 versus 4.38 +/- 1.30 control group) or level of satisfaction. Additionally, individuals experienced with contrast failed to outperform those who had never previously been given contrast. There is no significant difference in the performance between the two sexes regardless of group. CONCLUSIONS: The providing of information 24 to 72 hours in advance of an invasive procedure does not have a beneficial effect over just providing the same information at the time of the study.

Age Factors↗

Chronic ethanol and chlordiazepoxide: contrasting effects on reward learning.

Rats were exposed for one week to increasing concentrations of ethanol in a liquid diet, and were then maintained for a further 4 weeks on a 10% ethanol diet. Ten weeks after return to normal diet they were trained in a learning task in which three out of nine holes were consistently rewarded. The ex-ethanol-treated rats were slower to complete the task during the first week, compared with their control group and the differences were most marked on days 3 and 4, which were the days of most rapid improvement. On day 4 the ex-ethanol-treated rats made significantly more errors at rewarded holes. In contrast, rats that had been treated for 4 weeks with chlordiazepoxide (10 mg/kg/day) and then trained 10 weeks later on days 2 and 3 made significantly fewer errors of reference memory, and on day 2 made significantly fewer errors of working memory, compared with their control group.

Alcoholism↗

Effects of repetition learning on upright, inverted and contrast-reversed face processing using ERPs.

The effects of short-term learning on memory for inverted, contrast-reversed and upright faces were investigated using event-related potentials (ERPs) in a target/nontarget discrimination task following a learning phase of the target. Subjects were equally accurate for all three face types although responding more slowly to inverted and negative faces compared to upright faces. Face type affected both early ERP components P1 and N170, and long-latency components at frontal and parietal sites, reflecting the difficulty of processing inverted faces. Different effects of face type were found for P1 and N170 latencies and amplitudes, suggesting face processing could start around 100-120 ms and is sensitive to facial configuration. Repetition effects were also found on both early and long-latency components. Reduced N170 latency and amplitude for repeated targets are likely due to perceptual priming. Repetition effects on the N250 were delayed for inverted and negative faces, suggesting delayed access to stored facial representations for these formats. Increased frontopolar positivity at 250-300 ms and parietal positivity from 300 to 500 ms reflected familiarity 'old-new' repetition effects that were of similar magnitude for all three face types, indexing the accurate recognition of all faces. Thus, while structural encoding was disrupted by inversion and contrast-reversal, the learning phase was sufficient to abolish the effects of these configural manipulations behaviourally; all three face types were equally well recognised and this was reflected as equally large parietal old-new effects.

Adult↗

Successive negative contrast in one-way avoidance learning in rats.

In three experiments, successive negative contrast was examined in one-way avoidance learning. Reward magnitude in first (pre-shift) and second (post-shift) phases was manipulated by time spent in the safe compartment. Experiment 1 demonstrated that when time in the danger compartment was held constant, a group shifted from a large reward--30 sec spent in the safe compartment--to a small reward--1 sec--showed poor performance and longer response latency than a group conditioned with the small reward in both phases. Experiment 2 replicated this effect with a less intense shock and also demonstrated that a group shifted from large to small reward performed more poorly than a group exposed to large reward--30 sec--in both phases. Finally, Experiment 3 showed that changes in intertrial interval, defined as total time spent in the safe compartment and the danger compartment before the onset of the warning signal, were not responsible for this contrast effect. These results suggest that time spent in a safe place can act as appetitive incentive during one-way avoidance learning.

Animals↗

Concurrent learning of temporal and spatial sequences.

In a serial reaction time task, stimulus events simultaneously defined spatial and temporal sequences. Responses were based on the spatial dimension. The temporal sequence was incidental to the task, defined by the response-to-stimulus intervals in Experiment 1 and stimulus onset asynchronies in Experiment 2. The two sequences were either of equal length and correlated or of unequal length. In both experiments, spatial learning occurred regardless of sequence length condition. In contrast, temporal learning occurred only in the correlated condition. These results suggest that timing is an integrated part of action representations and that incidental learning for a temporal pattern does not occur independently from the action. Interestingly, sequence learning was enhanced in the correlated condition, reflecting the integration of spatial-temporal information.

Analysis of Variance↗

Adult age differences in the rate of learning serial patterns: evidence from direct and indirect tests.

Subjects performed a serial reaction time task (adopted from Nissen & Bullemer, 1987) that contained a repeating pattern of spatial locations. In Experiment 1, following 20 repetitions of a 10- or 16-element pattern, reaction time was equally disrupted for both younger and older people when the sequence became random. In Experiment 2, the response times for subjects encountering the 10-element pattern were compared with those of subjects encountering a random sequence. These response time functions diverged at the same point in training for the 2 age groups. Thus, on this indirect measure of response time facilitation, both experiments revealed age similarity in the rate of pattern learning. In contrast, on a subsequent direct test of pattern learning that required prediction, the younger people earned a higher percentage correct score than the older in both experiments. Age-related dissociations between direct and indirect measures of learning and comparisons with memory-impaired populations are discussed.

Adolescent↗

Contrasting effects on discrimination learning after hippocampal lesions and conjoint hippocampal-caudate lesions in monkeys.

Eighteen monkeys with lesions of the hippocampal region (the hippocampus proper, the dentate gyrus, and the subiculum) made by an ischemic procedure, radio frequency, or ibotenic acid were tested on a simple, two-choice object discrimination learning task that has been shown to be sensitive to large lesions of the medial temporal lobe. The monkeys were also tested on two other discrimination tasks (pattern discrimination and eight-pair concurrent discrimination) that can be learned normally by monkeys with large medial temporal lobe lesions. All of the lesion groups were impaired at learning the simple object discrimination task. Seven of the monkeys who had sustained damage to the hippocampal region also sustained damage to the tail of the caudate nucleus. These seven monkeys, but not the other 11 monkeys with hippocampal lesions, were impaired on pattern discrimination and concurrent discrimination learning. The results suggest that the hippocampal region is important for learning easy, two-choice discriminations, whereas the caudate nucleus is necessary for the normal learning of more difficult, gradually acquired discrimination tasks. The findings support the distinction between declarative memory, which depends on the hippocampus and related medial temporal lobe structures, and habit learning, which depends on the caudate nucleus.

Animals↗

Contrast agents provide a faster learning curve in dipyridamole stress echocardiography.

AIM: Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo. METHODS AND RESULTS: Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a kappa index of 0.58 and 0.83 without and with contrast administration, respectively. CONCLUSIONS: The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

Clinical Competence↗

Differential effect of buspirone and diazepam on negative contrast in one-way avoidance learning.

The main aim of the present work was to investigate the effect of buspirone, a 5-HT1A receptor agonist, on successive negative contrast in one-way avoidance learning. Successive negative contrast was induced by shifting rats from a large reward (30 s spent in the safe compartment) to a small reward (1 s). Acute administration of buspirone (0.25, 0.5, 0.75 and 1.0 mg/kg i.p.) did not attenuate the contrast effect, as opposed to that observed for diazepam (1 mg/kg i.p.). The highest dose of buspirone used, however, did interfere with the learning of the avoidance response itself. Chronic buspirone (20 days, 0.5 and 0.75 mg/kg i.p.) did not have any effect on successive negative contrast either. Overall, these results could suggest that the 5-HT1A receptor is not involved in the negative contrast effect studied, quite different to that observed for the gamma-aminobutyric acid (GABA) system. The findings are compared to results obtained with animal models selectively sensitive to some anxiolytic drugs, as are the so-called 'conflict models'.

Animals↗

Physiological deactivation after two contrasting tasks at a video display terminal: learning vs repetitive data entry .

Two contrasting 90 min VDT work situations were simulated in the laboratory: (1) a machine-paced, repetitive data entry task; and (2) a stimulating, self-paced learning task with successive feedback. Thirty non-smoking male students (20-34 years), without previous experience of VDT work, participated individually in each condition on two consecutive days (balanced order) and in a task-free baseline condition. Self-reports and successive measurements (ambulatory recordings) of systolic and diastolic blood pressure and heart rate were obtained during work and during a subsequent 60 min period of deactivation. Urine samples were obtained after each period for the determination of catecholamines and cortisol. In the baseline condition, measurements were obtained at corresponding times of the day. As expected, the data entry task was associated with self-reports of boredom, irritation, and unpleasantness; the learning task wtih alertness, interest, and ability to concentrate. Similar elevations of physiological measurements occurred in both work situations. However, differences between conditions were found after work. Following data entry, deactivation was slower in five of the six variables (significant for epinephrine).

Adult↗

Successive positive contrast in one-way avoidance learning.

The main finding of these experiments was a positive contrast effect in one-way avoidance learning. Experiment 1 showed that increasing safety time during one-way avoidance training led to improved performance, surpassing that of a control group that had received the high reward (safe time) from the beginning of training. Experiment 2 showed that a similar positive contrast effect occurred when the time spent in the danger compartment before the onset of the warning signal was shortened. These results suggest that time spent in a safe context acts as a reinforcer of the avoidance response; however, its incentive value depends not only on its duration, but also on the length of the time spent in the danger compartment before the onset of the signal. Overall, results also suggest that the avoidance response is a mixture of flight (motivated by fear) and approach (to a safe place) behaviour. The specific weight of the flight or approach component may be a function of the time and the amount of activation of each emotional state (fear or relief) due to opponent homeostatic compensatory processes that occur in the danger and safe compartments during one-way avoidance learning.

Animals↗

The neuropharmacological and neurochemical basis of place learning in the Morris water maze.

The Morris water maze (MWM) offers several advantages over other methods of studying the neurochemical basis of learning and memory, particularly with respect to its ability to dissociate deficits in memory formation from deficits in sensory, motor, motivational and retrieval processes. The contributions of nearly all of the major neurotransmitter systems have been investigated and consistent patterns have emerged. Normal function in glutamatergic and cholinergic systems is necessary for spatial learning, as blockade of NMDA receptors and cholinergic hypofunction prevents spatial learning but does not impair recall. Peptides such as adrenal and sex hormones and somatostatin may also be necessary for spatial learning. In contrast, activity in either GABAergic or opioidergic systems impairs spatial learning, though by quite different means. GABAergic activity prevents memory function, whereas opioidergic activity reduces motivation. Normal monoaminergic activity is necessary for normal performance in the MWM, but not for spatial learning per se. However, noradrenergic and serotonergic systems may enhance cholinergic-mediated mnemonic processes. Further research into the relative contributions of different receptor subtypes as well as interactions between neurochemical systems should provide significant advances in our understanding of the neural basis of learning and memory in mammals.

Animals↗

Molecular, cellular, and neuroanatomical substrates of place learning.

Learning and remembering the location of food resources, predators, escape routes, and immediate kin is perhaps the most essential form of higher cognitive processing in mammals. Two of the most frequently studied forms of place learning are spatial learning and contextual conditioning. Spatial learning refers to an animal's capacity to learn the location of a reward, such as the escape platform in a water maze, while contextual conditioning taps into an animal's ability to associate specific places with aversive stimuli, such as an electric shock. Recently, transgenic and gene targeting techniques have been introduced to the study of place learning. In contrast with the abundant literature on the neuroanatomical substrates of place learning in rats, very little has been done in mice. Thus, in the first part of this article, we will review our studies on the involvement of the hippocampus in both spatial learning and contextual conditioning. Having demonstrated the importance of the hippocampus to place learning, we will then focus attention on the molecular and cellular substrates of place learning. We will show that just as in rats, mouse hippocampal pyramidal cells can show place specific firing. Then, we will review our evidence that hippocampal-dependent place learning involves a number of interacting physiological mechanisms with distinct functions. We will show that in addition to long-term potentiation, the hippocampus uses a number of other mechanisms, such as short-term-plasticity and changes in spiking, to process, store, and recall information. Much of the focus of this article is on genetic studies of learning and memory (L&M). However, there is no single experiment that can unambiguously connect any cellular or molecular mechanism with L&M. Instead, several different types of studies are required to determine whether any one mechanism is involved in L&M, including (i) the development of biologically based learning models that explain the involvement of a given mechanism in L&M, (ii) lesion experiments (genetics and pharmacology), (iii) direct observations during learning, and (iv) experiments where learning is triggered by turning on the candidate mechanism. We will show how genetic techniques will be key to unraveling the molecular and cellular basis of place learning.

Animals↗

Baseline performance and learning rate of procedural and declarative memory tasks: younger versus older adults.

Twenty-five older and 25 younger adults were compared on declarative (i.e., Rey Auditory-Verbal Learning Test and Visual Pair Associations) and procedural (i.e., Tower of Hanoi puzzle and Porteus mazes) learning tasks. A dissociation between learning rate on declarative and procedural tasks was demonstrated for the elderly participants. The younger group showed a steeper learning rate than the older group on the declarative tasks. By contrast, the learning rate of both groups on the procedural tasks did not differ consistently, whether the measure was number of errors/moves or time elapsed (with one exception in which the older group showed a steeper learning rate than the younger group). The younger group's baseline performance was better than that of the older group on all tasks employed in this study. These results reinforce the importance of distinguishing between baseline performance and the rate of learning on procedural learning tasks.

Adult↗

[The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats].

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.

Animals↗