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An artificial neural network analogue of learning in autism.

An artificial neural network is simulated that shares formal qualitative similarities with the selective attention and generalization deficits seen in people with autism. The model is based on neuropathological studies which suggest that affected individuals have either too few or too many neuronal connections in various regions of the brain. In simulations where the model was taught to discriminate children with autism from children with mental retardation, having too few simulated neuronal connections led to relatively inferior discrimination of the two groups in a training set and, consequently, relatively inferior generalization of the discrimination to a novel test set. Too many connections produced excellent discrimination but inferior generalization because of overemphasis on details unique to the training set. It is concluded that, within the context of the current model, the neuropathological observations that have been described in the literature are sufficient to explain some of the unique pattern recognition and discrimination learning abilities seen in some people with autism as well as their problems with generalization and concept acquisition. The model generates testable hypotheses that have implications for understanding the pathogenesis, treatment, and phenomenology of autism.

Analysis of Variance↗

Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging.

Memory decline in human aging and dementia is linked to dysfunction of the cholinergic system. Aging dogs demonstrate cognitive impairments and neuropathology that models human aging and dementia. This paper reviews recent evidence suggesting cholinergic involvement in canine cognitive aging based on studies with the anti-cholinergic drug, scopolamine, and a novel acetylcholinesterase inhibitor, phenserine. In particular, we examine: (1) the cognitive specificity of scopolamine's impairment in dogs, (2) the effect of age on scopolamine impairment and (3) the effect of phenserine on cognitive performance in dogs. Our findings indicate that working memory performance is disrupted by scopolamine at doses that do not disrupt non-cognitive behavior or long-term, semantic-like, memory, as indicated by performance of previously learned discriminations. This pattern of deficits is also seen in human and canine aging. We demonstrate that aged dogs are more sensitive to the impairing effects of scopolamine than young dogs, suggesting a decrease in cholinergic tone with increasing age. Dogs receiving phenserine demonstrate improved learning and memory compared to placebo controls. Our findings suggest that cholinergic decline could result in memory impairment, but that the memory impairment may be secondary to deficits in attention and/or encoding of new information. Together, these results suggest that the canine cholinergic system declines with age and that the aged dog is a unique model for screening therapeutics and for examining the relationship between amyloid pathology and cholinergic dysfunction in age-dependent cognitive decline.

Acetylcholine↗

Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia.

Groups of patients with Hungington's disease and probable dementia of Alzheimer type (DAT) matched for level of dementia on the basis of mini mental state examination scores were compared in several tests of visual memory and tests sensitive to frontal lobe dysfunction. Whereas recall of patients with DAT tended to be worse on the Kendrick object learning test, the two groups were equivalent on tests of sensorimotor ability and delayed matching to sample performance. By contrast, the patients with Huntington's disease were significantly worse on tests of pattern and spatial recognition, simultaneous matching to sample, visuospatial paired associates, and on three tests sensitive to frontal lobe dysfunction--namely, the Tower of London test of planning, spatial working memory, and a visual discrimination learning and reversal paradigm. The impairments in these tests, however, did not always qualitatively resemble those seen in patients with frontal lobe damage and may be more characteristic of primary neostriatal deficit. In the visual discrimination paradigm the patients with Hungtington's disease were significantly worse than the patients with DAT at the simple reversal stage, where they displayed significant preservation to the previously rewarded alternative. The results are consistent with the hypothesis that patients with Huntington's disease exhibit deficits in tests sensitive to frontostriatal dysfunction and that this form of intellectual deterioration is qualitatively distinct from that seen in Alzheimer's disease.

Aged↗

Visual activation of neurons in inferotemporal cortex depends on striate cortex and forebrain commissures.

Neurons in inferotemporal cortex respond only to visual stimuli and a majority have receptive fields that extend well into both visual half-fields. After bilateral removal of striate cortex, no inferotemporal neurons responded to visual stimuli. After unilateral removal of striate cortex, inferotemporal neurons in both hemispheres responded only to stimuli in the hemifield contralateral to the intact striate cortex. After section of the corpus callosum and anterior commissure, inferotemporal neurons in both hemispheres responded only to stimuli in the hemifield contralateral to the recording site. These results indicate that inferotemporal cortex visual information from striate cortex and that the pathway from striate cortex to the contralateral inferotemporal cortex includes the forebrain commissures. This same striate-temporal pathway is also necessary for normal discrimination learning. We suggest that the converging input onto single inferotemporal neurons from widely separated retinal areas may provide a mechanism for stimulus equivalence over different parts of the visual field, and it may be the absence of such a mechanism that contributes to the visual discrimination deficit that follows inferotemporal lesions.

Animals↗

Learning-induced reduction in post-burst after-hyperpolarization (AHP) is mediated by activation of PKC.

We studied the role of protein kinase C (PKC) and protein kinase A (PKA) in mediating learning-related long lasting reduction of the post-burst after-hyperpolarization (AHP) in cortical pyramidal neurons. We have shown previously that pyramidal neurons in the rat piriform (olfactory) cortex from trained (TR) rats have reduced post-burst AHP for 3 days after odour-discrimination learning, and that this reduction is due to decreased conductance of calcium-dependent potassium current. In the present study, we examined whether this long-lasting reduction in AHP is mediated by second messenger systems. The broad-spectrum kinase inhibitor, H7, increased the AHP in neurons from TR rats, but not in neurons from pseudo-trained (pseudo-TR) and naive rats. Consequently, the difference in AHP amplitude between neurons from TR and control animals was diminished. This effect was also obtained by application of the specific PKC inhibitor, GF-109203x. The PKC activator, 1-Oleoyl-2-acetyl-sn-glycerol (OAG), significantly reduced the AHP in neurons from naive and pseudo-TR rats, but not in neurons from TR rats, so that the difference between the groups was abolished. The PKA-specific inhibitor, H-89, increased the AHP in neurons from all groups to a similar extent, and the difference in AHP amplitude between neurons from TR rats and neurons from controls was maintained. We suggest that while the post-burst AHP in piriform cortex pyramidal neurons is modulated by both PKC and PKA, a PKC-dependent process maintains the learning-related reduction of the AHP in these cells.

Action Potentials↗

Perceptual learning in contrast discrimination: the effect of contrast uncertainty.

Performance in perceptual tasks improves with repetition (perceptual learning), eventually reaching a saturation level. Typically, when perceptual learning effects are studied, stimulus parameters are kept constant throughout the training and during the pre- and post-training tests. Here we investigate whether learning by repetition transfers to testing conditions in which the practiced stimuli are randomly interleaved during the post-training session. We studied practice effects with a contrast discrimination task, employing a number of training methods: (i) practice with a single, fixed pedestal (base-contrast), (ii) practice with several pedestals, and (iii) practice with several pedestals that included a spatial context. Pre- and post-training tests were carried out with the base contrast randomized across trials, under conditions of contrast uncertainty. The results showed that learning had taken place with the fixed pedestal method (i) and with the context method (iii), but only the latter survived the uncertainty test. In addition, we were able to identify a very fast learning phase in contrast discrimination that improved performance under uncertainty. We contend that learned tasks that do not pass the uncertainty test involve modification of decision strategies that require exact knowledge of the stimulus.

Contrast Sensitivity↗

Challenges of organizational learning: perpetuation of discrimination against employees with disabilities.

This article examines why organizations struggle with learning how to prevent discrimination against their employees with disabilities. To explore this issue, qualitative archival data were collected and analyzed from 53 Americans with Disabilities Act (ADA) lawsuits filed against 44 organizations. Theoretical analysis of the qualitative data suggests that several organizationally based learning theories explain the difficulty organizations have with creating a disability-friendly work environment. These barriers to learning are embedded in complex defense mechanisms and discriminatory organizational routines. Furthermore, organizations have difficulties engaging in higher-order and vicarious learning. We conclude the article with examples of successful learning practices as they relate to barriers identified in the qualitative analysis.

Persons with Disabilities↗

Recovery of function after brain damage: differences in aged rats?

Age at the time of brain injury is generally considered an important determinant in recovery of function. The implication is that older individuals show less recovery. Existing data challenge this common notion, but suggest differential effects of brain damage in aged subjects. To assess these differences old rats were trained on a two-choice brightness discrimination, subjected to visual decortication, and retrained with nonreversed or reversed reinforcement contingencies. A significant reversal impairment established that sparing of function in aged rats was similar to that in adult rats. However, a significant reversal X brightness interaction suggested that the progress of recovery of function in aged rats is influenced not only by what is spared but also by whether the expression of what is spared is consistent with or antagonistic to competing innate response biases.

Age Factors↗

Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit.

The effects of discrete bilateral ibotenic acid lesions to 3 areas of striatum were examined on a conditional visual discrimination task involving temporal frequency (SLOW vs FAST flashes) that had previously been shown to be sensitive to the effects of dorsal striatal dopamine depletion. Two of the groups, namely, those with nucleus accumbens (ACC) and lateral caudate-putamen (LCP) lesions, were very disrupted in the acquisition of the task. The nature of the respective impairments of the 2 groups was dissociable, however. The performance of the ACC group could be improved either by manipulations of stimulus duration or inter-stimulus interval, implying an attentional deficit. In contrast, the rats with lesions of the LCP were not significantly improved by any of the behavioural challenges. Their performance was characterised by a bias to respond to the SLOW discriminandum. Under conditions of non-reward, the LCP group extinguished their responding at a similar rate to control rats whereas the ACC group were very much more persistent. Lesions of the medial caudate-putamen failed to affect any index of performance significantly. These data suggest that the LCP is necessary for the acquisition of arbitrary stimulus-response rules and that damage to an equivalent area in humans, such as in Huntington's disease, may explain deficits of procedural memory. The second part of the experiment investigated the effects of ACC lesions on established performance of the schedule. The lesioned group behaved identically to the ACC group that had been lesioned prior to acquisition, both in terms of accuracy and degree of persistence in extinction, further implying the role of attentional factors and inflexibility in the lesion-induced deficit.

Animals↗

Lesions of the mammillothalamic tract impair the acquisition of spatial but not nonspatial contextual conditional discriminations.

This study examined the influence of selective mammillothalamic tract lesions in rats on the acquisition of two kinds of contextual conditional discrimination: one involving two contexts (A and B) that differed in their visuo-spatial properties and another involving two contexts (C and D) that differed in temperature. In contexts A (and C) presentations of a tone were paired with food whereas presentations of a clicker were not; and in contexts B (and D) presentations of the clicker were paired with food whereas those of the tone were not. Mammillothalamic tract lesions disrupted initial acquisition of the conditional discrimination involving visual contexts (A and B), but not the formally equivalent discrimination involving thermal contexts (C and D). These results provide support for the suggestion that mammillothalamic tract lesions disrupt visuo-spatial encoding.

Acoustic Stimulation↗

Comparison of the cognitive palatability assessment protocol and the two-pan test for use in assessing palatability of two similar foods in dogs.

OBJECTIVE: To compare preferences of dogs for 2 similar foods by use of 2 distinct methods (the cognitive palatability assessment protocol [CPAP] and the 2-pan test). ANIMALS: 13 Beagles. PROCEDURE: 6 dogs were trained in a 3-choice object-discrimination-learning task in which their nonpreferred objects were associated with a reward of a lamb-based or chicken-based food. The number of choices for each object was used to determine food preferences. Preference of the same foods was also assessed by use of a 2-pan test in which all 13 dogs were provided the 2 foods in identical bowls. The amount of each food consumed in 10 minutes was used to determine food preference. RESULTS: All dogs had a noticeable preference for the chicken-based food during the CPAP. Once established, preferences remained consistent and were not affected by satiety. The 2-pan test identified a preference for the chicken-based food in dogs with previous exposure to the food but only a weak and nonsignificant preference for the same food in dogs without previous exposure. Food preferences in the 2-pan test varied considerably. Total food consumption and the ability to detect a preference were reduced when dogs were fed prior to testing. CONCLUSIONS AND CLINICAL RELEVANCE: The CPAP provides a reliable measure of food preference that requires few test subjects. The 2-pan test reveals similar preferences but with variability in data that requires larger numbers of subjects and is susceptible to effects from prior exposure and feeding of the test foods to the subjects.

Analysis of Variance↗

Effects of classifier structures and training regimes on integrated segmentation and recognition of handwritten numeral strings.

In integrated segmentation and recognition of character strings, the underlying classifier is trained to be resistant to noncharacters. We evaluate the performance of state-of-the-art pattern classifiers of this kind. First, we build a baseline numeral string recognition system with simple but effective presegmentation. The classification scores of the candidate patterns generated by presegmentation are combined to evaluate the segmentation paths and the optimal path is found using the beam search strategy. Three neural classifiers, two discriminative density models, and two support vector classifiers are evaluated. Each classifier has some variations depending on the training strategy: maximum likelihood, discriminative learning both with and without noncharacter samples. The string recognition performances are evaluated on the numeral string images of the NIST Special Database 19 and the zipcode images of the CEDAR CDROM-1. The results show that noncharacter training is crucial for neural classifiers and support vector classifiers, whereas, for the discriminative density models, the regularization of parameters is important. The string recognition results compare favorably to the best ones reported in the literature though we totally ignored the geometric context. The best results were obtained using a support vector classifier, but the neural classifiers and discriminative density models show better trade-off between accuracy and computational overhead.

Algorithms↗

Punished and unpunished responding in multiple variable-interval schedules.

The performance of rats trained on multiple variable-interval schedules was examined before, during, and after punishment. The same linear function related relative response rates to relative density of reinforcement both in the presence and absence of punishment. Equal relative suppression was seen in both the high and low reinforcement density components. The intercept value of the function was zero. Each component of the schedule was programmed on a separate lever: thus during any component, there was an opportunity for responses on the nonoperative lever (errors). The proportions of these errors declined to a near-zero value during punishment and did not regain their prepunishment values after punishment was removed, suggesting that some discrimination learning occurred during punishment. Recovery of response rate during punishment was seen only where a greater-than-zero probability of reinforcement was associated with the response.

Animals↗

Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions.

To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli. Postoperatively, this visual recognition memory task was given twice. As compared to a sham-operated group, the RH group showed good retention of rule learning and were unimpaired on the Delay memory subtest. Performance on the List Length memory subtest was, however, severely impaired at both postoperative evaluations, with a significant negative correlation between cognitive performance and neuronal loss in rhinal areas. Visual habit memory and spatial working memory were assessed postoperatively only, using a concurrent discrimination learning task and both a delayed-response task (with a two- and four-location choice) and a delayed alternation task, respectively. The RH group was unimpaired on the first two tasks and was even faster than the controls in learning the delayed-response task with four locations. Finally, most RH baboons failed to learn the delayed alternation task within the limits of testing. These results indicate that neuronal loss in the rhinal cortex is sufficient to impair visual recognition memory, and extend the implication of this area to spatial executive functions. Furthermore, the observation of impaired recognition memory and executive processes with preserved procedural memory and retrograde memory suggests that damage to the rhinal cortex probably participates in the cognitive deficits typical of the early stages of Alzheimer's disease.

Animals↗