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PubMed2005

Response reversal and children with psychopathic tendencies: success is a function of salience of contingency change.

BACKGROUND: Previous work has inconsistently reported difficulties with response reversal/extinction in children with psychopathic tendencies. METHOD: We tested the hypothesis that the degree of impairment seen in children with psychopathic tendencies is a function of the salience of contingency change. We investigated the performance of children with psychopathic tendencies on a novel probabilistic response reversal task involving four conditions with gradated reward-punishment contingencies (100-0, 90-10, 80-20 and 70-30; i.e., for the 100-0 contingency, responding to one object is always rewarded while responding to the other is always punished). RESULTS: In line with predictions, the impairment seen in the children with psychopathic tendencies was an inverse function of the salience of the contingency change. CONCLUSIONS: We suggest that this data is consistent with suggestions of subtle orbital frontal cortex impairment in children with psychopathic tendencies.

Adolescent↗
PubMed1992

Texture segregation in the cat: a parametric study.

We have investigated how different texture parameters affect texture segregation in the cat, and which strategies cats use to solve the segregation task. Five cats were presented with stimuli consisting of two adjacent panels. One side contained a square area of a particular texture embedded in a different background texture; the other side was filled with only the background texture. The animal's task was to detect at which side the texture difference was presented. Sensitivity for the texture difference was assessed by making one aspect of the texture (in most instances the size of the texture elements) dependent upon performance by means of a staircase procedure. Among the most prominent parametric effects are those of density and element position randomization. In general, segregation was optimal at intermediate densities and deteriorated at larger and smaller densities. Element position randomization caused a slight but systematic decrease in segregation performance. Furthermore, we found texture elements at the border between different textures to be of primary importance for segregation. Which strategy the animals used for solving the segregation task depended upon the presence of random figure/background reversals in subsequent stimulus presentations during training. The animals learned to detect texture differences if these reversals were present, and without reversals, they learned to identify the particular texture in the target square. Interestingly, parameter dependencies of segregation did not depend upon the detection strategy used. We have speculated that the two different strategies used by the cats to solve the segregation tasks are related to different hierarchical levels of texture segregation which can be traced back to different stages of texture processing in human models of segregation performance.

Animals↗
PubMed1996

Learning and recall of form discriminations during reversible cooling deactivation of ventral-posterior suprasylvian cortex in the cat.

Extrastriate visual cortex of the ventral-posterior suprasylvian gyrus (vPS cortex) of freely behaving cats was reversibly deactivated with cooling to determine its role in performance on a battery of simple or masked two-dimensional pattern discriminations, and three-dimensional object discriminations. Deactivation of vPS cortex by cooling profoundly impaired the ability of the cats to recall the difference between all previously learned pattern and object discriminations. However, the cats' ability to learn or relearn pattern and object discriminations while vPS was deactivated depended upon the nature of the pattern or object and the cats' prior level of exposure to them. During cooling of vPS cortex, the cats could neither learn the novel object discriminations nor relearn a highly familiar masked or partially occluded pattern discrimination, although they could relearn both the highly familiar object and simple pattern discriminations. These cooling-induced deficits resemble those induced by cooling of the topologically equivalent inferotemporal cortex of monkeys and provides evidence that the equivalent regions contribute to visual processing in similar ways.

Animals↗
PubMed1997

Effect of chronic treatment with piracetam and tacrine on some changes caused by thymectomy in the rat brain.

Thymectomized rats, 5 weeks after surgery, showed a significant impairment in learning and memory as shown by deficits in passive avoidance and in the Morris water maze test. The behaviour of the thymectomized rats in the "open field" apparatus was largely unchanged. Following treatment for 20 days with either piracetam (500 mg/kg) or tacrine (3.0 mg/kg), the deficit in passive avoidance learning was largely reversed. Chronic treatment with tacrine also reversed the deficit in the behaviour of the thymectomized rats in the Morris water maze. The effects of thymectomy on the biogenic amines and some of their metabolites in the amygdaloid cortex, hypothalamus, striatum and olfactory bulbs were also determined. Relative to the sham-operated controls, thymectomy resulted in a reduction in the noradrenaline concentration in the amygdala, hypothalamus, and olfactory bulbs. This effect was reversed by chronic piracetam and tacrine treatments. The concentration of dopamine was also reduced in the olfactory bulbs after thymectomy whereas in the striatum the concentration of 5-hydroxytryptamine (5-HT; serotonin) was increased. The concentration of gamma amino butyric acid (GABA) was determined in amygdaloid cortex and hippocampus only. The only significant change occurred following chronic treatment of thymectomized rats with tacrine, when a significant elevation of GABA was found. Neither piracetam nor tacrine produced any change in the amines of their metabolites in the sham-operated controls. Tacrine, however, elevated the dopamine and reduced the 5-HT content of the hypothalamus and increased the 3,4-dihydroxylphenylacetic acid concentration of the striatum of thymectomized rats. Examination of the differential white blood cell count of the thymectomized rats showed that the percentage of lymphocytes was decreased, and the percentage of neutrophils increased, relative to the sham-operated controls. Chronic lacrine, but not piracetam, treatment reversed the lesion-induced changes.

Animals↗
PubMed2005

Behavioral effects and drug vulnerability in rats exposed to Pfiesteria toxin.

Pfiesteria piscicida is a dinoflagellate which has a lethal effect on fish and also causes a syndrome of toxic effects in humans. Cognitive impairment is a prominent aspect of Pfiesteria's toxicity, and this neurocognitive effect resulting from toxin exposure has been demonstrated previously in a rat model. Four experiments are presented here, which replicate, confirm and extend some of the initial research and also show that similar cognitive deficits result from exposure to the toxin of another species, Pfiesteria shumwayae. Rats were given intraperitoneal injections of filtered water taken from toxic Pfiesteria cultures and tested in the radial arm maze (RAM). In two experiments, exposure to toxin from either species (piscicida or shumwayae) retarded acquisition of RAM performance in a non-interrupted win-shift RAM paradigm. A scopolamine challenge showed increased vulnerability to anticholinergic effects in exposed rats, even after nondrugged RAM performance was not different from controls. A third experiment featured a more difficult RAM test which included a 150-min interruption-delay. Toxin exposure also degraded performance in this version of the RAM, and the impairment was potentiated by the scopolamine challenge. The fourth experiment demonstrated retarded learning of the reversal of a RAM procedure which tested reference memory. In agreement with earlier research, these results indicate that Pfiesteria toxin interferes with the learning required to adapt to changing behavioral requirements. They also demonstrate that a latent toxin-produced CNS dysfunction persists after behavior appears normal, as revealed by potentiation of scopolamine's impairment of efficient RAM performance.

Animals↗
PubMedDate not supplied

Reversal of long-delay conditioned taste aversion learning in rats by sex hormone manipulation.

Conditioned taste aversion (CTA) learning is an adaptive, robust, well-established learning and memory paradigm. Strong taste aversions develop to the conditioned stimulus (CS = saccharin) despite long delays between exposure to the CS and unconditioned stimulus (US = LiCl). Rats display a sexually dimorphic pattern of long-delay CTA learning (Foy et al., 1996). The present study examines whether this sex difference is a result of activational or organizational hormone action, because here we implanted gonadectomized rats with their normal hormone replacements, or with opposing hormones prior to testing in a 4-hr delayed CTA learning task. We found that gonadally intact male rats displayed a more robust CTA response than intact female rats. Gonadectomy essentially eliminated this sex difference; gonadectomized males and gonadectomized females displayed similar CTA responses. In gonadectomized rats, when their normal sex hormones were replaced with implanted hormone pellets, the sex difference in CTA learning was reinstated. In contrast, when gonadectomized rats were implanted with opposing hormones, the sex difference was reversed. Gonadectomized female rats implanted with 5alpha-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17beta-estradiol pellets. Regardless of the original developmental hormonal environment, our study suggests that an activational manipulation of circulating hormones serves to significantly influence long-delay CTA learning in rats.

Androgens↗
PubMed2006

Molecular studies on the protective effect of nicotine in adult-onset hypothyroidism-induced impairment of long-term potentiation.

We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning and memory impairment. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of long-term potentiation (LTP). Analysis of LTP associated key signaling molecules revealed that chronic nicotine treatment prevented the hypothyroidism-induced reduction of the basal phosphotransferase activity of CaMKII and protein levels of P-CaMKII. In addition, the failure of high frequency stimulation to increase the levels of P-CaMKII in hypothyroid rats was reversed by nicotine treatment, suggesting that the neuroprotective effect of nicotine during hypothyroidism involved activation of CaMKII. Furthermore, chronic nicotine treatment reverses the hypothyroidism-induced elevated phosphatase activity and protein levels of calcineurin, a phosphatase that regulates CaMKII activation. We conclude that the neuroprotective effects of nicotine in adult-onset hypothyroidism may result from restoration of CaMKII and calcineurin activity.

Age Factors↗
PubMed1991

Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice.

The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions. In contrast to control mice, they failed to improve their performance from the first to the last session. Nevertheless, when later required to repeatedly learn the same discrimination over several days (repetitive testing), animals with ACC lesions no longer exhibited any learning deficit. The converse pattern of results was found in mice with PCC lesions. These animals performed much more poorly than control animals during the acquisition and first reversal of the discrimination, but displayed remarkable improvement over the subsequent four reversal sessions, gradually overcoming their initial impairment. However, when later submitted to repetitive testing, these animals again showed a substantial learning deficit. Neither ACC nor PCC cingulate lesions significantly affected the animals' retention capacities as measured by single test-trials over a 24-h interval. Yet, mice with PCC lesions were retarded in reversal learning after a long intersession interval (10 days), indicating that PCC, but not ACC, lesions did interfere with some long-term retention processes. These results imply that the ACC, as a part of the medial frontal cortex, may play a crucial role in temporally ordering a series of spatial responses, whereas the PCC seems to contribute to the formation and retention of each individual spatial response, probably by transmitting information from limbic structures such as the anterior thalamus and hippocampal formation to posterior neocortical association areas.

Adaptation, Psychological↗
PubMed1997

Hippocampal activity during classical discrimination--reversal eyeblink conditioning in rabbits.

Multiple-unit neuronal recordings were taken from the hippocampi of 10 male, New Zealand white rabbits during classical discrimination and reversal eyeblink conditioning using 2 tones as the conditioned stimuli (CS+ and CS-) and an air-puff unconditioned stimulus. During discrimination training, characteristic learning-related activity was seen in the hippocampus on trials when a conditioned response (CR) was executed. During early phases of reversal training, however, when high numbers of CRs were evident to both the new CS+ (the former CS-) and the new CS- (the former CS+), no learning-related activity was observed. Characteristic CR-related hippocampal activity to the CS+ was observed only after the rabbits began to learn the reversal response. These results suggest that the hippocampus may encode different features of eyeblink conditioning during discrimination and reversal learning.

Animals↗
PubMed1977

Operant discriminative conditioning of vertical eye movements in the midpontine pretrigeminal cat.

In the acute midpontine pretrigeminal cat, either upward or downward eye movements above a certain preset amplitude were reinforced by electrical stimulation of the lateral hypothalamic (LHT) reward area, which did not induce a significant eye movement by itself. During the course of the reinforcement procedure, eye movements greatly increased. In a yoked control test where LHT stimulation was delivered to a cat, independently of its own eye movements, no significant enhancement of the eye movements was observed. However, when reinforcement was given contingently on each large eye movement, eye movement rate became much higher. When cats were trained for an operant discrimination between an S+ (light-off or light-on) and an S- (light-on or light-off), 5 cats acquired clearly differential responses to the S + and S-. They also learned a discrimination reversal. Furthermore, removal of the visual cue eliminated differential responses during the reinforcement and nonreinforcement periods. These data strongly suggest that, in its preparation, a real learning process in the form of a visual discrimination is maintained and an operant conditioning of eye movements with hypothalamic stimulation was achieved without feedback from the peripheral nerve or caudal central nervous system.

Animals↗
PubMed2006

Neural activation during successful and unsuccessful verbal learning in schizophrenia.

Successful and unsuccessful intention to learn words was assessed by means of event-related functional MRI. Eighteen patients with schizophrenia and 15 healthy control participants were scanned while being given two word lists to read and another seven to learn with immediate recall. Neural activation patterns were segregated according to whether words were subsequently recalled or forgotten and these conditions were contrasted with each other and reading. Compared to controls, patients with schizophrenia showed deficits with regard to neural recruitment of right hippocampus and of cerebellar structures during successful verbal learning. Furthermore, a reversal of activated structures was evident in the two groups: Controls showed activation of right frontal and left middle temporal structures during the unsuccessful intention to learn. During successful learning, there was additional activation of right superior parietal lobule. In contrast, patients showed activation of right superior parietal lobule during unsuccessful and successful intention to learn. There were additional frontal and left middle temporal lobe activations during successful learning. We conclude that increased parietal activity may reflect a mechanism which compensates for the lack of hippocampal and cerebellar contributions to verbal learning in schizophrenia.

Adult↗
PubMed2002

A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP.

Long-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell synapses must be balanced by long-term potentiation (LTP) to prevent saturation and allow reversal of motor learning. The only previously analyzed form of cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not nitric oxide. It is a poor candidate to reverse LTD because it is presynaptically expressed whereas LTD is postsynaptic. We now characterize a new form of LTP induced by 1 Hz PF stimulation for at least 300 s. This LTP is postsynaptically expressed, enhanced by chelating postsynaptic Ca(2+), and depends on nitric oxide but not cAMP or cGMP, making it a plausible anti-Hebbian counterpart to Hebbian LTD.

Animals↗
PubMed1998

Ginseng improves strategic learning by normal and brain-damaged rats.

Adult rats were prepared with either sham or medial prefrontal cortex lesions and administered, beginning on the third post-operative day, either, 0, 40, or 80 mg kg-1 crude ginseng extract suspended in saline daily for the next 30 days. Later, kinetic functions were evaluated on an elevated rotating rod. No long-term influences of the treatments were observed on this task. Significant positive influences of ginseng were observed in the position reversal task. The learning deficits observed in the saline control brain-damaged rats were significantly attenuated in the ginseng-treated animals. An analysis of trial 2 response accuracy across reversals revealed enhanced cognitive abilities (i.e. acquisition of a win-stay, lose-shift strategy) in both the brain damaged and sham control rats administered ginseng. Generally, administration of the higher dose resulted in better performance in the learning paradigm. The exact mechanism responsible for these promising results remains to be discovered. Several possible mechanisms are discussed.

Analysis of Variance↗
PubMed1999

Cognitive deficits in a genetic mouse model of the most common biochemical cause of human mental retardation.

Phenylalanine hydroxylase (Pah)-deficient "PKU mice" have a mutation in the Pah gene that causes phenylketonuria (PKU) in humans. PKU produces cognitive deficits in humans if it is untreated. We report here the first evidence that the genetic mouse model of PKU (Pah(enu2)) also produces cognitive impairments. PKU mice were impaired on both odor discrimination reversal and latent learning compared with heterozygote littermates and with wild-type mice of the same BTBR strain. A small container of cinnamon-scented sand was presented on the right or left, and nutmeg-scented sand was presented on the other side; left-right location varied over trials. Digging in sand of the correct scent was rewarded by finding phenylalanine-free chocolate. To prevent scent cuing, new containers were used on every trial, and both containers always contained chocolate. Digging in the incorrect choice was stopped before the chocolate was uncovered. Once criterion was reached, the other scent was rewarded. PKU mice were impaired on reversals 2, 3, and 4. They were also impaired in latent learning. On day 1, half the mice were allowed to explore a maze and discover the location of water. On day 2, all mice were water-deprived and were placed in the maze. Whereas pre-exposed wild-type and heterozygous mice showed evidence that they remembered the location of the water and hence could find the water faster on day 2, pre-exposed PKU mice showed no significant benefit from their pre-exposure on day 1.

Animals↗
PubMedDate not supplied

Effects of desmopressin acetate (DDAVP) on the learning of a brightness discrimination.

Sixty male albino rats received DDAVP, a placebo, or control treatment and were tested on a brightness discrimination task. Three groups (DDAVP, placebo, and control) were tested in the morning and three groups were tested in the evening. The acquisition and reversal of the brightness discrimination, along with the retention of the reversal problem after a 5-day retention interval were analyzed. Inspection of forward and backward learning curves plotted for each task revealed facilitated acquisition along with an initial impairment of reversal learning in those animals treated with DDAVP. These results support a memorial interpretation of DDAVP's effects. This was short-term in duration, as no retention effects were obtained. It was also found that DDAVP's effects were not influenced by diurnal processes.

Adrenocorticotropic Hormone↗
PubMed1991

Perceptual learning following a long-lasting tactile reversal.

Crossing 2 adjacent fingers produces a distorted perception when 2 tactile stimuli are touched to the crossed fingertips. This is because a given pair of fingers has a functional range of action within which spatial perception is correct (uncrossed fingers) and beyond which perceived location of tactile stimuli is wrong (crossed fingers). The present study tested the possibility that this range of action could be modified following a long-lasting crossing. Therefore, the functional range of action of the 2nd and 3rd fingers was tested every month in 6 volunteers who maintained the finger crossing for as long as 6 months. The results show that after a variable period of time the range of action was enlarged such that spatial perception was correct with crossed fingers as well. The perceptual organization of the human hand therefore depends on experience and is not rigidly determined on a genetic basis.

Adult↗
PubMed1981

Learning improvement of appetitively or aversively reinforced light-dark discrimination and reversal four weeks after electrical stimulation of the lateral hypothalamus of the rat.

The experiments reported here point out the effect of electrical stimulation of the lateral hypothalamus on the acquisition and reversal of a simultaneous light-dark discrimination performed 4 weeks later. The stimulation was applied on 15-day-old rats. There were two control groups, implanted but not stimulated and non-implanted rats. In the first experiment, the light-dark discrimination task was food-reinforced. As already reported in the case of an appetitively reinforced operant task, stimulation of the lateral hypothalamus induced an important improvement of performance in discrimination and reversal. This improvement was already apparent at the beginning of acquisition. In the reversal task the mean response latency of stimulated rats was greater than tht of control animals. In the second experiment with naive rats we used the same discrimination but the task was aversively reinforced by an electric foot-shock. In spite of the different type of reinforcement used, the stimulated rats performed better than the control rats in the three behavioral situations studied: avoidance, discrimination and reversal. As in the first experiment the improvement appeared at the onset of acquisition in the three situations. Thus the long-term effect of lateral hypothalamic stimulation does not depend on the type of reinforcement, nor the behavioral task. These results are briefly discussed.

Animals↗