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Autoimmunity and age-associated cognitive decline.

It is suggested that the immune system may play a role in the etiology of age-associated cognitive decline and/or Alzheimer's disease. The relationship between brain-reactive antibodies (BRA) and age-associated cognitive dysfunction is reviewed and discussed. A parallel relationship between BRA increases with age and decline of avoidance learning capacity is described in mouse models. Transfer of immunity from old to young mice was found to accelerate both age-related formation of brain-reactive antibodies and age-related decline of avoidance learning capacity. Short-lived mouse genotypes with accelerated autoimmunity were found to show accelerated age-related declines in their ability to acquire an avoidance response when compared with nonautoimmune mice. Overall, these findings suggest that the immune system could be an important target for development of intervention strategies aimed at extending the intellectually competent period of life. Mice in which autoimmunity is accelerated may be useful as models for the development of such interventions.

Aging↗

Spatial relational learning in rufous hummingbirds (Selasphorus rufus).

There is increasing evidence that animals can learn abstract spatial relationships, and successfully transfer this knowledge to novel situations. In this study, rufous hummingbirds (Selasphorus rufus) were trained to feed from either the lower or the higher of two flowers. When presented with a test pair of flowers, one of which was at a novel height, they chose the flower in the appropriate spatial position rather than the flower at the correct height. This response may also have been influenced by a preference for taller flowers as acquisition of the task during experimental training occurred more readily when the reward flower was the taller of the pair. Thus, it appears that although learning abstract relationships may be a general phenomenon across contexts, and perhaps across species, the ease with which they are learned and the context in which they are subsequently used may not be the same.

Animals↗

Transfer of stimulus control: measuring the moment of transfer.

Three severely retarded boys acquired simple form discriminations errorlessly. Each was first taught to press a red key versus a simultaneously present white key. After this discrimination had been established, black figures were superimposed on the red and white keys. Each correct response affected the next trial by delaying the onset of the red stimulus an additional 0.5 sec. Transfer of stimulus control to the figures was indicated when the subjects responded correctly before the onset of the red stimulus. A series of errorless discrimination reversals was accomplished with this technique, during which the number of trials to transfer systematically decreased with successive reversals.

Adolescent↗

Function transfer in human operant experiments: the role of stimulus pairings.

Although function transfer often has been studied in complex operant procedures (such as matching to sample), whether operant reinforcement actually produces function transfer in such settings has not been established. The present experiments, with high school students as subjects, suggest that stimulus pairings can promote function transfer in conditions that closely approximate those of matching to sample. In Experiment 1, the subjects showed transfer of operant responding from three geometric figures (C1, C2, C3) to three colored shapes (B1, B2, B3) when the latter were paired with the former. Experiment 2 involved two groups of subjects. In the matching group, subjects matched the colored shapes with the geometric figures; in the yoked group, the shapes were merely paired with the geometric figures, and the schedule of stimulus pairing was yoked to the performance of the subjects in the matching group. Both groups of subjects showed function transfer. Experiment 3 documented function transfer from C stimuli to B stimuli through indirect stimulus pairings (A-B, A-C). In Experiment 4, function transfer was obtained even though the subjects vocalized continuously during the pairing trials, presumably preventing covert verbalization that might mediate transfer effects. Our results are consistent with a Pavlovian account and raise difficulties for current operant theories of function transfer.

Adolescent↗

Teaching an amnesic a complex cognitive skill.

G.P., a Korsakoff's amnesic, was able to learn an algorithm for squaring two-digit numbers mentally over a 7-day period at a rate comparable to that of age-matched controls. He failed to show normal positive transfer to specific problems or to specific numbers used in components of the task. He also exhibited slight improvement in simple naming speed, forward digit span, simple multiplication speed, but no apparent improvement for the recall of repeated supraspan digit strings. He was unable to state the algorithm he had learned to square two-digit numbers, though he could implement it successfully. The results suggest that the compilation of a skill may involve two dissociable components: composition and proceduralization, with the former, but not the latter, occurring at normal rates for Korsakoff's amnesics.

Aged↗

Effects of stimulus familiarity on the rehearsal strategies transfer mechanism in retarded and nonretarded individuals.

The possibility that the familiarity value of stimuli might be a component of the rehearsal strategies mechanism in Ellis' (1970) multiprocess theory of short-term memory was investigated. Retarded and nonretarded subjects of equal CA were given either PA pretraining of nonsense pictures with colors or were presented with nonsense pictures alone. They were then compared in their performance on either an experimenter- or subject-paced serial memory task in which the nonsense pictures were employed as stimuli. It was expected that pretraining would increase the familiarity value of nonsense stimuli for nonretarded and, to a lesser extent, retarded subjects, facilitating transfer of information from primary to secondary memory in both groups. Although predictions about the effects of pretraining on retention were not substantiated, the results of the experiment did support the hypothesis that a production deficiency in active encoding can account for the poor secondary memory of mentally retarded subjects.

Achievement↗

Transfer of negative occasion setting and conditioned inhibition across conditioned and unconditioned stimuli.

The transfer of negative occasion setting and conditioned inhibition across conditioned stimuli (CSs) and unconditioned stimuli (USs) was examined in four experiments that used Pavlovian appetitive feature negative discrimination training procedures with rats. After training with simultaneous compounds (A+, XA-), X inhibited conditioned responding (CRs) elicited by other CSs and CRs supported by other appetitive USs that had not been involved in discrimination training. After training with serial compounds (A+, X----A-), X's power to set the occasion for nonresponding transferred across CSs and USs only if those events had also been involved in serial feature negative discrimination training. The results supported the suggestion that the acquisition of negative occasion setting involves the representation of individual events in a higher order memory system, separate from that involved in simple association, and that negative occasion setters act only on events that are represented in that system.

Animals↗

The variability of practice hypothesis in motor learning: does it apply to Alzheimer's disease?

Based on Schmidt's (1975) variability of practice hypothesis, this study examined acquisition and transfer of a gross motor skill, namely tossing, in 58 patients with Alzheimer's disease (AD) and 58 healthy older adults under constant, blocked, and random practice conditions. While healthy older adults were able to learn the tossing task equally well under the three practice conditions, only AD patients receiving constant practice showed significant improvements. Tests of intermediate transfer yielded the expected random practice advantage in healthy controls but not AD patients. None of the practice conditions facilitated intermediate transfer in AD patients; however, constant practice did benefit these impaired individuals on tests of near transfer. These results indicate that the variability of practice hypothesis does not extend to AD patients. As motor learning and transfer were clearly a function of constant practice, future attempts to retrain basic activities of daily living in AD patients should emphasize consistency in training.

Aged↗

Virtual environments for motor rehabilitation: review.

In this paper, the current "state of the art" for virtual reality (VR) applications in the field of motor rehabilitation is reviewed. The paper begins with a brief overview of available equipment options. Next, a discussion of the scientific rationale for use of VR in motor rehabilitation is provided. Finally, the major portion of the paper describes the various VR systems that have been developed for use with patients, and the results of clinical studies reported to date in the literature. Areas covered include stroke rehabilitation (upper and lower extremity training, spatial and perceptual-motor training), acquired brain injury, Parkinson's disease, orthopedic rehabilitation, balance training, wheelchair mobility and functional activities of daily living training, and the newly developing field of telerehabilitation. Four major findings emerge from these studies: (1) people with disabilities appear capable of motor learning within virtual environments; (2) movements learned by people with disabilities in VR transfer to real world equivalent motor tasks in most cases, and in some cases even generalize to other untrained tasks; (3) in the few studies (n = 5) that have compared motor learning in real versus virtual environments, some advantage for VR training has been found in all cases; and (4) no occurrences of cybersickness in impaired populations have been reported to date in experiments where VR has been used to train motor abilities.

Persons with Disabilities↗

The sales learning curve.

When a company launches a new product into a new market, the temptation is to immediately ramp up sales force capacity to gain customers as quickly as possible. But hiring a full sales force too early just causes the firm to burn through cash and fail to meet revenue expectations. Before it can sell an innovative product efficiently, the entire organization needs to learn how customers will acquire and use it, a process the authors call the sales learning curve. The concept of a learning curve is well understood in manufacturing. Employees transfer knowledge and experience back and forth between the production line and purchasing, manufacturing, engineering, planning, and operations. The sales learning curve unfolds similarly through the give-and-take between the company--marketing, sales, product support, and product development--and its customers. As customers adopt the product, the firm modifies both the offering and the processes associated with making and selling it. Progress along the manufacturing curve is measured by tracking cost per unit: The more a firm learns about the manufacturing process, the more efficient it becomes, and the lower the unit cost goes. Progress along the sales learning curve is measured in an analogous way: The more a company learns about the sales process, the more efficient it becomes at selling, and the higher the sales yield. As the sales yield increases, the sales learning process unfolds in three distinct phases--initiation, transition, and execution. Each phase requires a different size--and kind--of sales force and represents a different stage in a company's production, marketing, and sales strategies. Adjusting those strategies as the firm progresses along the sales learning curve allows managers to plan resource allocation more accurately, set appropriate expectations, avoid disastrous cash shortfalls, and reduce both the time and money required to turn a profit.

Commerce↗

Domestic pigeons (Columba livia) discriminate between photographs of individual pigeons.

In two experiments, we examined the discrimination of photographs of individual pigeons by pigeons, using go/no-go discrimination procedures. In Experiments 1A and 1B, the pigeons were trained to discriminate 4 photographs of one pigeon from those of a number of pigeons. The subjects learned the discrimination, but their discriminative behavior did not transfer to new photographs taken from novel perspectives. When the pigeons were trained to discriminate between 20 photographs of five pigeons taken from four perspectives as the S+ and 20 photographs of five different pigeons as the S-, the subjects learned the discrimination, and this discriminative behavior partially transferred to new photographs taken from novel perspectives (Experiments 2A-2C). The results suggest that pigeons are able to discriminate among conspecific individuals, using stationary visual cues. This strengthens the assumption in evolutionary theory that animals can discriminate among individuals and encourages further investigation as to how this ability is used in various behaviors of animals.

Animals↗

Preserved sigma1 (sigma1) receptor expression and behavioral efficacy in the aged C57BL/6 mouse.

The sigma(1) (sigma(1)) receptor represents a unique intracellular neuronal protein modulating several neurotransmitter responses with relevant effects on cognitive functions. We examined here its expression and behavioral efficacy during aging. The sigma(1) receptor expression was examined in young (2 months old) and aged (24 months old) C57BL/6 mouse brain using comparative RT-PCR and immunohistochemistry. The promnesic effect of PRE-084, a selective sigma(1) agonist, was assessed using a water-maze procedure. The sigma(1) mRNA expression was not affected during aging in the olfactory bulb, hippocampus, hypothalamus, cortex or cerebellum. The sigma(1) immunolabeling was intense in the olfactory bulb, hippocampus, hypothalamus and midbrain of the young mouse and the distribution appeared unchanged in the aged. The subcellular localization was similar in aged and younger animals, the protein being present on nuclear, mitochondrial, endoplasmic reticular and plasmic membranes. At the behavioral level, aged C57BL/6 mice showed deficits in the invisible platform learning, but not when the platform was visible. Animals subjected to a transfer test under repeated treatment with saline or PRE-084 significantly learned the new platform location. This study shows that sigma(1) receptor expression is preserved in aged animals and demonstrates the efficacy of a selective sigma(1) agonist against age-related memory deficits. Targeting this unique receptor may offer an original drug strategy during aging.

Aging↗

Learning words through overhearing.

Recent research indicates that toddlers can monitor others' conversations, raising the possibility that they can acquire vocabulary in this way. Three studies examined 2-year-olds' (N = 88) ability to learn novel words when overhearing these words used by others. Children aged 2,6 were equally good at learning novel words-both object labels and action verbs-when they were overhearers as when they were directly addressed. For younger 2-year-olds (2,1), this was true for object labels, but the results were less clear for verbs. The findings demonstrate that 2-year-olds can acquire novel words from overheard speech, and highlight the active role played by toddlers in vocabulary acquisition.

Age Factors↗

Revealing hidden covariation detection: evidence for implicit abstraction at study.

Four experiments in the brain scans paradigm (P. Lewicki, T. Hill, & I. Sasaki, 1989) investigated hidden covariation detection (HCD). In Experiment 1 HCD was found in an implicit- but not in an explicit-instruction group. In Experiment 2 HCD was impaired by nonholistic perception of stimuli but not by divided attention. In Experiment 3 HCD was eliminated by interspersing stimuli that deviated from the critical covariation. In Experiment 4 a transfer procedure was used. HCD was found with dissimilar test stimuli that preserved the covariation but was almost eliminated with similar stimuli that were neutral as to the covariation. Awareness was assessed both by objective and subjective tests in all experiments. Results suggest that HCD is an effect of implicit rule abstraction and that similarity processing plays only a minor role. HCD might be suppressed by intentional search strategies that induce inappropriate aggregation of stimulus information.

Adult↗

Computational models of the hippocampal region: implications for prediction of risk for Alzheimer's disease in non-demented elderly.

We have pursued an interdisciplinary research program to develop novel behavioral assessment tools for evaluating specific memory impairments following damage to the medial temporal lobe, including the hippocampus and associated structures that show pathology early in the course of Alzheimer's disease (AD). Our approach uses computational models to identify the functional consequences of hippocampal-region damage, leading to testable predictions in both rodents and humans. Our modeling argues that hippocampal-region dysfunction may selectively impair the ability to generalize when familiar information is presented in novel recombinations. Previous research has shown that specific reductions in hippocampal volume in non-demented elderly individuals correlate with future development of AD. In two previous studies, we tested non-demented elderly with and without mild hippocampal atrophy (HA) on stimulus-response learning tasks. Individuals with and without HA could learn the initial information, but the HA group was selectively impaired on transfer tests where familiar features and objects were recombined. This suggests that such generalization deficits may be behavioral markers of HA, and an early indicator of risk for subsequent cognitive decline. Converging support for the relevance of these tasks to aging and Alzheimer's disease comes from our recent fMRI studies of individuals with mild cognitive impairment (MCI). Activity in the hippocampus declines with progressive training on these tasks, suggesting that the hippocampus is important for learning new stimulus representations that support subsequent transfer. Individuals with HA may be able to learn, but in a more hippocampal-independent fashion that does not support later transfer. Ultimately, this line of research could lead to a novel battery of behavioral tests sensitive to very mild hippocampal atrophy and risk for decline to AD, allowing early diagnosis and also allowing researchers to test new Alzheimer's drugs that target individuals in the earliest stages of the disease - before significant cognitive decline. A new mouse version of one of our tasks shows promise for translating these paradigms into rodents, allowing for future studies of therapeutic interventions in transgenic mouse models of AD.

Aged↗

Perceptual learning of highly demanding visual search tasks.

Inefficient visual search can become efficient with practice [Vision Research 35 (1995) 2037; 40 (2000) 2925]. In this study, we wondered whether this improvement depends on unique visual features associated with the target, on differences in item-specific brightness distribution between target and distractors, or only on a change in the allocation of attention and thus global search strategy. We found that both, unique visual features and differences in brightness distribution lead to parallelisation with practice of originally inefficient search. Prolonged practice of inefficient search tasks lacking both unique visual features and differences in brightness distribution (conjunctions) does not lead to improved performance, thus indicating that perceptual learning in visual search does not solely reflect an unspecific global improvement in search strategy. Changing the brightness polarity of the stimuli leads to instantaneous, complete transfer to the new task. There is no transfer but rather trade-off between the learning based on unique visual features or on differences in brightness distribution between target and distractors.

Attention↗

7-Nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat.

Nitric oxide (NO) is an intercellular messenger that has been suggested to have a role in learning and memory formation. Previous studies with nonselective NO synthase inhibitors have produced contradictory results in learning experiments. However, these drugs also produced blood pressure changes, as NO is an endothelial-derived relaxing factor. A novel NO synthase inhibitor, 7-nitro indazole (7-NI), as a dose (30 mg/kg i.p.) shown previously to inhibit neuronal NO synthase by 85% without affecting blood pressure, produced amnesic effects both in a water maze and in an 8-arm radial maze. Latency as well as distance was greater in the 7-NI group in the water maze while swim speed was not affected. Latency, working memory (WM), and reference memory (RF) errors were also higher in the 7-NI group in the 8-arm maze. At the end of the second training day, these differences were no longer apparent. However, on the fourth training day, a transfer test in the water maze showed that 7-NI had produced a spatial memory deficit, reducing quadrant bias and the number of annulus crossings. Learning of a visual cue task was not affected. No difference between groups was visible in an open field test. We conclude that neuronal NO synthase activity plays a role in learning and memory formation in the rat.

Animals↗