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PubMed1990

Unsupervised learning and discriminant analysis applied to identification of high risk postoperative cardiac patients.

A set of 200 patients in the 6 hours immediately following cardiac surgery was analysed within a multidimensional space of 13 commonly monitored physiological variables in order to identify high risk patterns. The application of an unsupervised learning (clustering) method to these data clearly showed the existence of two well-separated classes of low and high risk patients. A stepwise discriminant analysis was then applied to patients representative of the two classes in order to find those variables which, over time, possessed the greatest separation power. The latter always included the oxygen delivery (DO2), an index related to the oxygen content in the blood (Pv(-)O2 or avO2D) and a myocardial contractility index (VF or LAP).

Algorithms↗
PubMed2001

Effects of prenatal exposure to cocaine on the developing brain: anatomical, chemical, physiological and behavioral consequences.

Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the pharmacokinetics of crack cocaine in humans. At this dose, cocaine had no effect on the body weight gain of dams, time to delivery, litter size and body weight or other physical characteristics of the offspring. In spite of an otherwise normal appearance, cocaine-exposed neonates displayed a permanent impairment in signal transduction via the D1 dopamine receptor in caudate nucleus, frontal cortex and cingulate cortex due to an uncoupling of the receptor from its associated Gs protein. This uncoupling in the caudate nucleus was shown to have behavioral consequences in that young or adult rabbits, exposed to cocaine in utero, failed to demonstrate amphetamine-elicited motor responses normally seen after activation of D1 receptors in the caudate. The cocaine progeny also demonstrated permanent morphological abnormalities in the anterior cingulate cortex due to uncoupling of the D1 receptor and the consequent inability of dopamine to regulate neurite outgrowth during neuronal development. Consistent with the known functions of the anterior cingulate cortex, adult cocaine progeny demonstrated deficits in attentional processes. This was reflected by impairment in discrimination learning during classical conditioning that was due to an inability to ignore salient stimuli even when these were not relevant to the task. The impairment in discrimination learning also occurred in an instrumental avoidance task and could be shown to be due to an impairment of cingulothalamic learning-related neuronal coding. It was proposed that the selective loss of D1-related neurotransmission in the anterior cingulate cortex prevented an appropriate activation of GABA neurons and thus a loss of inhibitory regulation that is necessary for processes involved in associative attention. Taken together, these findings suggest that the uncoupling of the D1 receptor from its G protein may be the fundamental source of the anatomic, cognitive and motor disturbances seen in rabbits exposed to cocaine in utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with the recent reports indicating that persistent attentional and other behavioral deficits may be evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.

Journal Article↗
PubMed1989

Rats can learn a roughness discrimination using only their vibrissal system.

Rats learned to discriminate between two degrees of roughness, detecting the stimuli only with their vibrissal system. After bilateral trimming of the vibrissae, performance abruptly dropped to chance levels and remained there throughout the period in which the vibrissae were kept trimmed. After the vibrissae regrew to approximately normal lengths, rats again exhibited high performance levels and demonstrated retention of the task. This discriminative procedure would appear to be appropriate for psychophysical assessment of vibrissal system function.

Afferent Pathways↗
PubMed1978

Learning performance varies with brain weight in heterogeneous mouse lines.

Three lines of unselected heterogeneous stocks of mice were tested for learning and activity in active avoidance acquisition and extinction, water-maze discrimination learning and reversal learning, operant discrimination, and passive avoidance acquisition tasks. Ambulation in the open field was also measured. Small to moderate correlations (absolute values of .17 to .42) between brain weight and learning measures were obtained for all tasks except passive avoidance. A moderate correlation between brain weight and activity was found only in the open field (r = .39). Partialing out differences in operant level and body weight and learning performance. When ambulation in the open field was partialed out, however, all correlations between brain weight and learning performance decreased. Previous research has suggested a positive relation between brain weight and learning scores across mammalian orders and species. The results reported here extend this relation to within-species variation in brain size. The results also emphasize the limitations of estimating genetic associations between brain and behavior from comparisons between small numbers of inbred strains or selected lines.

Animals↗
PubMed2000

Scale-invariant superiority of foveal vision in perceptual categorization.

The recognition of objects is exceedingly difficult in indirect view. This complication cannot be explained in terms of retino-cortical magnification, as size scaling fails to establish position invariance both for character recognition [Strasburger, H. & Rentschler, I. (1996) Eur. J. Neurosci., 8 1787-1791] and pattern classification [Jüttner, M. & Rentschler, I. (1996) Vision Res., 36, 1007-1021]. Thus we compared, for two tasks of discrimination learning and category learning with respect to a common set of grey-level patterns, how humans perform in foveal and extrafoveal vision. Observers learnt to discriminate (size-scaled) images equally well in foveal and extrafoveal view, whereas they displayed profound deficiencies in extrafoveal category learning for the same patterns. From the behavioural learning data, internal representations of the learning signals were reconstructed by means of computer simulations. For foveal view, these representations were found to be veridical to their physical counterparts for both learning tasks. For extrafoveal view, they were severely distorted for category learning but not for discrimination learning. A variance reduction of the pattern classes by a factor of 100 reduced the dissociation between extrafoveal categorization and discrimination but did not remove it. These observations suggest a scale-invariant superiority of foveal vision for learning object categories. This implies a high degree of space variance of visual cognition which is vastly underestimated by classical measures of visual performance, e.g. acuity, visual field and contrast sensitivity.

Adult↗
PubMed2000

Morphine discriminative control is mediated by the mu opioid receptor: assessment of delta opioid substitution and antagonism.

Morphine is an effective training drug in drug discrimination procedures. In subsequent generalization tests in which other opioids are administered, mu opioid agonists selectively substitute for the training drug. Given the relative selectivity of morphine for the mu receptor, such substitution patterns suggest that the mu opioid receptor is mediating the discriminative control of this compound. The present study assessed this selective mediation by examining the ability of the delta opioid agonist SNC80 to substitute for (and the delta opioid antagonist naltrindole to antagonize) morphine stimulus effects in rats trained to discriminate morphine from its vehicle in the conditioned taste aversion baseline of drug discrimination learning. Although morphine and methadone produced dose-related substitution for morphine (10 mg/kg), there was no evidence of substitution for morphine by SNC80 at any dose tested. Further, although naloxone (3.2 mg/kg) completely blocked the discriminative effects of morphine, naltrindole (3.2-10 mg/kg) did not significantly affect the morphine stimulus. These data suggest that the discriminative control established to morphine is mediated by its activity at the mu, but not the delta, receptor.

Animals↗
PubMed1995

FR discrimination training effects in SHR and microencephalic rats.

Fixed-ratio (FR) discrimination learning in adult male spontaneously hypertensive rats (SHR), methylazoxymethanol-induced microencephalic Sprague-Dawley (MAM), and Sprague-Dawley control rats was examined. SHR and MAM rats had little problem learning incrementally more difficult FR discriminations (FR1 vs. FR16, FR4 vs. FR16, and FR8 vs. FR16) that resulted in parallel increases in errors in all animals, and displayed only modest learning deficits during a subsequent FR4 vs. FR16 position reversal. When training involved nonincremental changes in difficulty (FR8 vs. FR16, FR4 vs. FR16, FR8 vs. FR16, FR12 vs. FR16, and FR14 vs. FR16), SHR and MAM rats evidenced relatively large learning deficits during the initial FR8 vs. FR16 discrimination but had no difficulty with the last two discriminations. Furthermore, training selectively and significantly elevated hippocampal weight in MAM rats. These findings: a) question prior suggestions that MAM and SHR model separate human developmental disabilities; b) indicate that manifestation of learning deficits in even markedly brain-damaged organisms depends on initial task difficulty and can be overcome by experience; and c) are the first indicating that training-induced antagonism of prenatally induced hippocampal hypoplasia and its consequences is possible.

Animals↗
PubMed1985

Pharmacological dissociation of memory: anisomycin, a protein synthesis inhibitor, and leupeptin, a protease inhibitor, block different learning tasks.

Inhibition of protein synthesis by anisomycin for a short duration impairs memory of a one-trial inhibitory avoidance task in rats. Memory of escape conditioning involving eight trials is disrupted only if the duration of protein synthesis is prolonged by repeated injections. In marked contrast, olfactory memory of rats trained on two odor discriminations is not affected by anisomycin even if the duration of inhibition is prolonged and the number of trials is reduced to a minimum. In previous work, leupeptin, a thiol proteinase inhibitor, was shown to impair olfactory discrimination learning, but left inhibitory and avoidance conditioning intact. Together, these results provide a pharmacological double dissociation of memory, and suggest that the same chemistries, or mixtures of chemistries, may not be involved in all types of memory.

Animals↗
PubMed2006

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

Analysis of Variance↗
PubMed1996

A high linoleate and a high alpha-linolenate diet induced changes in learning behavior of rats. Effects of a shift in diets and reversal of training stimuli.

Rats fed from weaning on semi-purified diets supplemented either with linoleate-rich safflower oil (S) or alpha-linolenate-rich perilla oil (P) were mated. Half of the progeny were weaned to the original diet of the dams (SS and PP), the other two groups were shifted to diets enriched in the other fatty acid (SP and PS). Brightness-discrimination learning ability was tested daily for 30 d beginning at 11 weeks of age, with a bright light as the positive stimulus. The learning performance was inferior in the group fed the safflower diet through two generations (SS) as compared with groups fed the perilla diet through two generations (PP) or for which the diets were shifted at weaning (PS and SP). The docosahexaenoate content of brain phospholipids was significantly less in the SS group compared with the three other groups. After 30 d of the learning test, the effect of shifting the stimulus was tested for another 30 d, this time using a dim light as the positive stimulus. The learning performance was superior in the PP group to the SS group throughout the latter 30 sessions, the difference being even more obvious than during the first 30 d. These results indicate that the decrease in the discrimination-learning ability induced by alpha-linolenate deficiency is a relatively reversible process; both the docosahexaenoate content in brain and the learning performance were restored by supplementing alpha-linolenate after the weaning.

Animals↗
PubMed2005

Learning-stage dependent Fos expression in the rat brain during acquisition of an olfactory discrimination task.

By using Fos immunocytochemistry, we investigated the activation in olfactory-related areas at three stages (the first and fourth days of conditioning and complete acquisition) of an olfactory discrimination learning task. The trained rats (T) had to associate one odour of a pair with water-reward within a four-arm maze whereas pseudo-trained (P) rats were only submitted to the olfactory cues without any reinforcement. In the piriform cortex, both T and P rats exhibited a higher immunoreactivity on the first day, which seemed to indicate a novelty-related Fos expression in this area, but whatever the learning-stage, no significant difference in Fos expression between T and P rats was observed. In hippocampus, Fos expression was significantly different between T and P rats in CA1 and CA3 on the first and fourth days respectively. Thus we showed a differential activation of CA1 and CA3 subfields which might support a possible functional heterogeneity. In the orbitofrontal cortex, Fos immunoreactivity was significantly higher in T rats compared to P rats when mastery of the discrimination task was complete. In contrast, no learning-related Fos expression was found in infralimbic and prelimbic cortices. The present data suggest an early implication of the hippocampal formation and a later involvement of neocortical areas throughout different stages of a progressively acquired olfactory learning task.

Analysis of Variance↗
PubMed2025

N6-methyladenine identification using deep learning and discriminative feature integration.

N6-methyladenine (6 mA) is a pivotal DNA modification that plays a crucial role in epigenetic regulation, gene expression, and various biological processes. With advancements in sequencing technologies and computational biology, there is an increasing focus on developing accurate methods for 6 mA site identification to enhance early detection and understand its biological significance. Despite the rapid progress of machine learning in bioinformatics, accurately detecting 6 mA sites remains a challenge due to the limited generalizability and efficiency of existing approaches. In this study, we present Deep-N6mA, a novel Deep Neural Network (DNN) model incorporating optimal hybrid features for precise 6 mA site identification. The proposed framework captures complex patterns from DNA sequences through a comprehensive feature extraction process, leveraging k-mer, Dinucleotide-based Cross Covariance (DCC), Trinucleotide-based Auto Covariance (TAC), Pseudo Single Nucleotide Composition (PseSNC), Pseudo Dinucleotide Composition (PseDNC), and Pseudo Trinucleotide Composition (PseTNC). To optimize computational efficiency and eliminate irrelevant or noisy features, an unsupervised Principal Component Analysis (PCA) algorithm is employed, ensuring the selection of the most informative features. A multilayer DNN serves as the classification algorithm to identify N6-methyladenine sites accurately. The robustness and generalizability of Deep-N6mA were rigorously validated using fivefold cross-validation on two benchmark datasets. Experimental results reveal that Deep-N6mA achieves an average accuracy of 97.70% on the F. vesca dataset and 95.75% on the R. chinensis dataset, outperforming existing methods by 4.12% and 4.55%, respectively. These findings underscore the effectiveness of Deep-N6mA as a reliable tool for early 6 mA site detection, contributing to epigenetic research and advancing the field of computational biology.

Deep Learning↗
PubMed2005

Dynamics of learning-induced cellular modifications in the cortex.

This aim of this review is to describe the dynamics of learning-induced cellular modifications in the rat piriform (olfactory) cortex after olfactory discrimination learning and to describe their functional significance to long-term memory consolidation. The first change to occur is in the intrinsic properties of the neurons. One day after learning, pyramidal neurons show enhanced neuronal excitability. This enhancement results from reduction in calcium-dependent conductance that mediates the post burst after-hyperpolarization. Such enhanced excitability lasts for 3 days and is followed by a series of synaptic modifications. Several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons in the piriform cortex accompany olfactory learning. Enhanced synaptic release is indicated by reduced paired-pulse facilitation. Post-synaptic enhancement of synaptic transmission is indicated by reduced rise time of post-synaptic potentials and formation of new synaptic connections is indicated by increased spine density along dendrites of these neurons. Such modifications last for up to 5 days. Thus, olfactory discrimination rule learning is accompanied by a series of cellular modifications which occur and then disappear at different times. These modifications overlap partially, allowing the maintenance of the cortical system in a 'learning mode' in which memories for specific odors can be acquired rapidly and efficiently.

Animals↗
PubMed1982

The effects of haloperidol on learning and behavior in autistic children.

The effects of haloperidol on behavioral symptoms and learning were critically assessed in autistic children in an ongoing double-blind placebo-controlled clinical trial. Children were randomly assigned to haloperidol-placebo-haloperidol or placebo-haloperidol-placebo treatment sequences. Statistically, haloperidol was significantly superior to placebo in reducing behavioral symptoms. In discrimination learning paradigm, children receiving haloperidol learned the discrimination while those on placebo did not. Discrimination attained on haloperidol was retained when the children were switched to placebo.

Autistic Disorder↗
PubMed1986

The nature of the visual discrimination impairment after neonatal or adult ablation of superior colliculi in rats.

The superior colliculi were removed in rats at either one or five days of age or in adulthood. Seven months later they were tested on four successively presented two-choice intensity discriminations. The intensity difference between the discriminanda was reduced across the four problems to encourage choice by comparison. The purpose was to establish whether impoverished scanning is a feature of rats with collicular lesions and whether the age at which the lesion is incurred is important. The number of door-push and approach errors made in reaching criterion were used as measures of performance and the number of head-scans during acquisition was counted. The results provide no evidence that either one- or five-day operated rats exhibit sparing or recovery of the ability to scan discriminanda since all operated animals were impaired. Furthermore, novel retinal projections, present in one-day operated animals, fail to mediate such sparing. Finally, the results did not demonstrate a selective increase in approach errors following collicular lesions and were therefore inconsistent with the view that the impairment is one of visually-guided locomotion. It is concluded that visual discrimination learning is impaired following collicular lesions in circumstances where scanning of discriminanda is required for efficient performance.

Age Factors↗
PubMed1982

The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats.

In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning: motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varying complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy was either 2.5, 5, of 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dose-dependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam- and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.

Animals↗