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PubMed1969

Some determinants of inhibitory stimulus control.

Interspersed reinforcement and extinction during discrimination learning generate a U-shaped gradient of inhibition about the stimulus correlated with extinction. The present work showed that extinction is not a necessary determinant of inhibitory stimulus control. In Exp. I, a reduction in the rate of reinforcement, through a shift from a multiple variable-interval 1-min variable-interval 1-min schedule to a multiple variable-interval 1-min variable-interval 5-min schedule, resulted in a post-discrimination line orientation gradient of inhibition about the stimulus correlated with the variable-interval 5-min schedule. In Exp. II, the rates of reinforcement, correlated with a pair of stimuli, were held constant during a shift from a multiple variable-interval 1-min variable-interval 1-min schedule to a multiple variable-interval 1-min differential-reinforcement-of-low-rate schedule. Inhibitory stimulus control about the stimulus correlated with the differential reinforcement of low rate was obtained. In both experiments, a reduction in the rate of responding during one stimulus and behavioral contrast during the other stimulus preceded the observation of inhibitory stimulus control.

Journal Article↗
PubMed1971

Pavlovian pattern learning by nonlinear neural networks.

This note describes laws for the anatomy, potentials, spiking rules, and transmitters of some networks of formal neurons that enable them to learn spatial patterns by Pavlovian conditioning. Applications to spacetime pattern learning and operant conditioning are then possible, if the conditioning is viewed as multi-channel Pavlovian conditioning in a highly inhomogeneous anatomy. In suitable anatomies, biases in learning because of axon collaterals with nonuniformly distributed diameters can be corrected if one properly couples the action potential to transmitter potentiation, and chooses signal velocity proportional to axon diameter. These anatomies can contain any number of cells. Anatomies exist in which patterns may be learned without their being practiced overtly, whereas persistent recall of old patterns without the learning of newly imposed patterns is impossible. Physiologically, this constraint has the trivial interpretation that signals from one cell to another first pass through the intervening synaptic knob. Mechanisms that control learning rates at times important to the network (e.g., reward and punishment times) can be discussed. Serial behavior like that described by Lashley is possible: this consists of sequential learning and performance of patterns faster than would be allowed by a motor-feedback control, at velocities influenced by arousal level, with the possibility of abrupt termination of performance if conflicting environmental demands arise. Analogs of pattern completion and mass action exist, as do phase transitions in memory (for some rate parameters and anatomies, memory is rigid, for others, it is plastic). The laws limit the ways in which these networks can be interconnected to yield specific discrimination, learning, memory, and recall capabilities.

Action Potentials↗
PubMed1996

Recovery of function after brain damage: differential effects of blocking calcium uptake during the recovery of a learned behavior and the performance of the recovered behavior following neocortical brain injury.

The recovery of a learned behavior following brain damage is typically considered to have occurred when the brain-injured individual reattains the performance criterion that defined original preoperative learning. While this is obviously correct from an operational point of view, it does not necessarily mean that the consequences of the brain injury have been reversed, particularly with regard to the sustained performance of the supposedly recovered behavior. The present research attempted a more comprehensive evaluation of the behavioral effects of localized neocortical injury by investigating how a calcium channel blocker would effect (a) the original preoperative acquisition, (b) the initial postoperative recovery, and (c) the subsequent long-term performance of a brightness discrimination learned by rats subjected to injuries of their visual neocortex. The results demonstrated that notwithstanding the brain-injured rat's ability to reattain the performance criterion used to define preoperative learning, its long-term performance of this recovered behavior was significantly inferior to that of a normal rat. More importantly, the present data suggest that there are important differences between the initial postoperative recovery of a behavior and its long-term performance since the same drug that will facilitate initial recovery has just the opposite effect with respect to the animals long-term postoperative performance of the behavior.

Analysis of Variance↗
PubMed1998

The diabolo classifier

We present a new classification architecture based on autoassociative neural networks that are used to learn discriminant models of each class. The proposed architecture has several interesting properties with respect to other model-based classifiers like nearest-neighbors or radial basis functions: it has a low computational complexity and uses a compact distributed representation of the models. The classifier is also well suited for the incorporation of a priori knowledge by means of a problem-specific distance measure. In particular, we will show that tangent distance (Simard, Le Cun, & Denker, 1993) can be used to achieve transformation invariance during learning and recognition. We demonstrate the application of this classifier to optical character recognition, where it has achieved state-of-the-art results on several reference databases. Relations to other models, in particular those based on principal component analysis, are also discussed.

Journal Article↗
PubMed1990

Naltrexone in autistic children: a double-blind and placebo-controlled study.

A double-blind, placebo-controlled study was designed to assess critically the effects of naltrexone on behavioral symptoms and learning in autistic children, and its safety. This is a preliminary report on 18 children, ages 3.08 to 7.99 years, who completed this ongoing study. Subjects were randomly assigned to naltrexone or placebo and received daily doses over a period of 21 days. Naltrexone was superior to placebo according to blind Clinical Global Consensus Ratings (unpublished scale). However, other behavioral rating measures did not confirm this result. There was only a suggestion that naltrexone reduced fidgety and hyperactive behavior and tended to alleviate overall symptomatology in older children. Naltrexone did not appear to affect discrimination learning. Results are preliminary and, owing to the small sample size, can be considered only suggestive until this study is completed or replication is obtained from independent research.

Autistic Disorder↗
PubMed2003

Towards an understanding of the mechanisms of weak central coherence effects: experiments in visual configural learning and auditory perception.

The weak central coherence hypothesis of Frith is one of the most prominent theories concerning the abnormal performance of individuals with autism on tasks that involve local and global processing. Individuals with autism often outperform matched nonautistic individuals on tasks in which success depends upon processing of local features, and underperform on tasks that require global processing. We review those studies that have been unable to identify the locus of the mechanisms that may be responsible for weak central coherence effects and those that show that local processing is enhanced in autism but not at the expense of global processing. In the light of these studies, we propose that the mechanisms which can give rise to 'weak central coherence' effects may be perceptual. More specifically, we propose that perception operates to enhance the representation of individual perceptual features but that this does not impact adversely on representations that involve integration of features. This proposal was supported in the two experiments we report on configural and feature discrimination learning in high-functioning children with autism. We also examined processes of perception directly, in an auditory filtering task which measured the width of auditory filters in individuals with autism and found that the width of auditory filters in autism were abnormally broad. We consider the implications of these findings for perceptual theories of the mechanisms underpinning weak central coherence effects.

Asperger Syndrome↗
PubMed1992

Canonical and non-canonical syllable discrimination by two-day-old infants.

Canonical syllables may be important units in early speech perception as well as production. Twenty infants (mean age 51 hours) (and twenty controls) were tested for their ability to discriminate between members of syllable pairs which were either canonical (paet and taep) or non-canonical (pst and tsp). A discrimination learning method was used in which syllables signalled the availability of either a recording of the mother's voice or silence--one of which was presented if the infant began a sucking burst. Infants in the canonical condition changed sucking patterns during signals over an 18-minute experimental session and activated their mother's voice more than silence, consistent with previous experiments using mother's voice as a reinforcer. In the non-canonical condition, infants also changed sucking patterns but sucked more during the signal for quiet than mother's voice, contrary to previous findings. Differential sucking during the syllables indicated discrimination in both conditions, but infants responded differently depending upon whether the syllables were canonical or non-canonical. The activation of silence in the non-canonical condition may be the result of a preference for quiet, but it is better explained as a failure to progress to a level of differential responding that was reached by the canonical group.

Age Factors↗
PubMedDate not supplied

The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys.

The serotonin 5-HT3 receptor antagonists ondansetron and SEC-579 were tested over a wide dose range (0.000001-0.5 mg/kg, PO) for cognitive-enhancing effects in aged rhesus monkeys. Animals were tested on the following cognitive and motor tasks: 1) acquisition of a visual object discrimination; 2) reversal of a visual object discrimination; 3) the delayed response task, a spatial working memory task; and 4) a fine motor task. This study found enhanced acquisition of a visual object discrimination following very low doses (0.000001-0.00001 mg/kg, PO) of either 5-HT3 receptor antagonist. This finding replicates a previous study in marmosets. However, unlike the marmoset research, no reliable improvement was found on the reversal condition. Similarly, no improvement was observed on the delayed response or fine motor tasks. No side effects were observed at any dose, consistent with reports in both animals and humans. These results suggest that 5-HT3 receptor antagonists may be helpful in treating a subset of cognitive functions.

Aging↗
PubMed1991

Amnesia following damage to the left fornix and to other sites. A comparative study.

Two memory-impaired patients, who had suffered damage to the left or both fornix columns during removal of a ventricular cyst, were compared with 3 others having left-sided hippocampal or thalamic lesions, and with normal controls. The tests used were nonverbal--scene recognition, delayed matching-to-sample and concurrent pattern and object discrimination learning. The last two are differentially sensitive to fornix transection and to hippocampal or thalamic ablations in monkeys; however, the patients with fornix damage did not show a distinctive pattern of impairment. The reasons for this discrepancy are discussed. The study adds to the evidence that fornix transection can cause wide-ranging memory disturbances in man.

Adult↗
PubMed2006

Behavioral methods in cannabinoid research.

In the absence of any specific behavioral assay for cannabinoids or endocannabinoids, a cannabinoid-induced profile in a series of four in vivo assays in mice is most commonly used to assess a specific cannabinoid activity at the behavioral level. Thus, when a given compound produces motor depression in an open field, catalepsy on an elevated ring, analgesia on a hot plate, as well as hypothermia, cannabinoid CB1 receptor activation is assumed, although exceptions are possible. The full cannabinoid profile, however, includes for example ataxia in dogs and discrimination learning in rats. In view of (1) the addictive/reward potential of cannabis and the cannabinoids and (2) the multiple roles of the endocannabinoid physiological control system (EPCS) in behavioral functions, including memory, emotionality, and feeding, a number of behavioral techniques have been used to assess the effects of cannabinoids in these functions. In this chapter we will describe the tetrad of cannabinoid-induced effects as well as a series of behavioral assays used in the behavioral pharmacology of marijuana-cannabinoid research. Since the EPCS plays an important role in the developing organism, methods used in the assessment of physical and behavioral development will also be discussed. The techniques include the tetrad, drug discrimination, self-stimulation and self-administration, conditioned place preference/aversion, the plus-maze, chronic mild stress (CMS), ultrasonic vocalizations, cognitive behaviors, and developmental assessment in mouse (and rat) pups.

Animals↗
PubMed1994

Restoration of cognitive abilities by cholinergic grafts in cortex of monkeys with lesions of the basal nucleus of Meynert.

Three groups of marmosets were trained to perform a series of visual discrimination tasks in a Wisconsin General Test Apparatus. Two groups then received bilateral lesions of the basal nucleus of Meynert using the excitotoxin N-methyl-D-aspartate and were found to be severely impaired on relearning a visual discrimination first learnt prior to surgery. One lesioned group then received grafts of acetylcholine-rich tissue dissected from the basal forebrain of fetal marmosets. Three months later the marmosets with lesion alone remained impaired on a number of retention and reversal tasks whereas the transplanted animals were no longer significantly impaired. Histological examination of the brains indicated that all lesioned animals had sustained substantial loss of the cholinergic neurons of the basal nucleus of Meynert (assessed by nerve growth factor receptor immunoreactivity) and that the lesion-alone animals showed marked loss of the cholinergic marker acetylcholinesterase in the dorsolateral frontal and parietal cortex. All transplanted animals had surviving graft tissue (visualized by Cresyl Violet staining, dense acetylcholinesterase staining and the presence of a limited number of nerve growth factor receptor-immunoreactive neurons) in the neocortex and 5/6 transplanted animals showed near complete restitution of acetylcholinesterase staining in frontal and parietal cortex. Examination of individual animal data showed that the animal without this restitution performed very poorly. The performance of the remaining transplanted animals was significantly better than that of the animals with lesion alone. There was a significant positive correlation between the degree of acetylcholinesterase staining and good performance on tasks sensitive to frontal lobe damage. These results demonstrate that acetylcholine-rich tissue transplanted into the neocortex of primates with damage to the cholinergic projections to the neocortex can produce substantial restitution of function provided that an appropriate level of interaction between graft and host tissue is achieved.

Acetylcholine↗
PubMed1991

Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdala.

Structures and connections in the medial temporal lobe of humans and nonhuman primates have long been recognized as important for normal memory and emotional behavior. The present study investigated memory and emotional behavior in normal monkeys and six groups of monkeys with lesions of the medial temporal lobe. Two groups had damage to the hippocampal formation (or adjacent perirhinal and parahippocampal cortex) but not the amygdaloid complex; two groups had either partial or complete damage to the amygdaloid complex but not the hippocampal formation; and two groups had damage to both the hippocampal formation and the amygdaloid complex. Memory was evaluated with three tasks sensitive to human amnesia: (1) delayed nonmatching to sample; (2) retention of object discriminations; and (3) concurrent discrimination learning. Emotional behavior was assessed by measuring the responsiveness of monkeys to 12 different stimulus situations. Damage to the hippocampal formation or anatomically related cortex impaired memory but did not affect emotional behavior. Partial or complete damage to the amygdaloid complex affected emotional behavior but not memory. These findings show that memory impairment and abnormal emotional behavior are anatomically dissociable and independent effects of damage to the medial temporal lobe.

Amygdala↗
PubMed2000

Influence of diet and occlusal support on learning memory in rats behavioral and biochemical studies.

In order to verify the relationship between tooth loss and the learning memory in rat, male Wistar rats (25 weeks old) were divided into three separate groups: a control group (fed with a solid diet); a soft diet group (fed with a powder diet containing the same components as the solid one) and a molarless group (all molars were removed at 25 weeks and then fed with a powder diet). To evaluate both learning ability and memory, rats were tested with a one-way step through type of passive avoidance apparatus divided into light and dark chambers at 40-weeks. After the passive avoidance test, determination of acetylcholine (ACh) concentration of the cerebral cortex and hippocampus was performed. There was no significant difference between the molarless group and the control group in the response latency before the acquisition trails (non-stimulated period). At day 4 and 7 after the acquisition trials, the response latency of the molarless group was significantly shorter than that in the control group (p<0.05). The ACh levels of the molarless group in the cerebral cortex and hippocampus were significantly lower than that of the control group (p<0.05). It was apparent that tooth loss had an association with a loss of discriminative learning ability. This study suggested that the decrease of masticatory function caused by tooth loss leads to a decrease of ACh synthesis resulting in a learning memory disorder.

Acetylcholine↗
PubMed1990

Repeated exposure to diisopropylfluorophosphate (DFP) produces increased sensitivity to cholinergic antagonists in discrimination retention and reversal.

This experiment examined the effects of repeated exposure to diisopropylfluorophosphate (DFP), an organophosphate anticholinesterase, on the retention and reversal of a visual discrimination and on the number of muscarinic receptors in the brain. Rats were trained in a serial reversal procedure. After achieving stable performance, the rats were divided into two groups. One group received repeated injections of DFP, the other group received injections. To determine whether DFP-treated rats would be more sensitive than normal rats to stresses on the cholinergic system, each rat was injected with saline or one of three doses of scopolamine, a muscarinic receptor blocker, prior to testing on every 6th day. DFP alone caused no impairment in performance. Scopolamine produced a greater impairment in DFP-treated rats than in control rats. Similar results were obtained in a second behavioral task, match-to-sample in a water maze, using the same DFP treatment protocol and only one dose of scopolamine. The number of muscarinic receptors and acetylcholinesterase activity levels were reduced on the 2nd and 15th day after the end of DFP treatment. These results demonstrate that although repeated exposure to organophosphate anticholinesterases may not alter discrimination behavior directly, it may compromise the central nervous system so that it cannot react normally when challenged.

Acetylcholinesterase↗
PubMed1994

Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on physiological development, reflexes, locomotor activity and learning behaviour in Wistar rats.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat offspring were studied after administration of a loading dose of 300 or 1000 ng TCDD/kg body wt on day 19 of pregnancy, followed by weekly maintenance doses of 120 or 400 ng TCDD/kg body wt. The dose regimens led to a fluctuation of average TCDD concentrations in the liver of the offspring of 4.9-14.9 ng/g (TCDD1000/400 group) or 1.4-6.3 ng/g (TCDD300/120 group) during the course of the experiment. In both TCDD-exposed groups the body weight of the offspring was significantly lower on postnatal day 7 (PND 7); in the high dose group from PND 7 to PND 31. Some landmarks of postnatal development were retarded in the exposed groups; in particular, the vaginal opening was delayed for several days in both TCDD-exposed groups. The TCDD-exposed animals revealed a reduced ability to remain on a rotating rod. During reflex testing, the rate of successfully responding animals was higher in the exposed groups. No statistically significant differences in the locomotor activity between controls and TCDD-exposed offspring were detectable under our experimental conditions. In a discrimination learning test no effects on the learning ability were found. However, TCDD-exposed offspring showed an increase in unanswered trials during critical phases of the task. They also exhibited increased locomotor activity in a novel environment; prior to an amphetamine challenge dose of 1 mg/kg body weight. Amphetamine-induced activity was decreased in a dose-dependent manner.

Animals↗