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At least 469 records · Page 26Linked to original sources
PubMed2000

Medial frontal cortex mediates perceptual attentional set shifting in the rat.

If rodents do not display the behavioral complexity that is subserved in primates by prefrontal cortex, then evolution of prefrontal cortex in the rat should be doubted. Primate prefrontal cortex has been shown to mediate shifts in attention between perceptual dimensions of complex stimuli. This study examined the possibility that medial frontal cortex of the rat is involved in the shifting of perceptual attentional set. We trained rats to perform an attentional set-shifting task that is formally the same as a task used in monkeys and humans. Rats were trained to dig in bowls for a food reward. The bowls were presented in pairs, only one of which was baited. The rat had to select the bowl in which to dig by its odor, the medium that filled the bowl, or the texture that covered its surface. In a single session, rats performed a series of discriminations, including reversals, an intradimensional shift, and an extradimensional shift. Bilateral lesions by injection of ibotenic acid in medial frontal cortex resulted in impairment in neither initial acquisition nor reversal learning. We report here the same selective impairment in shifting of attentional set in the rat as seen in primates with lesions of prefrontal cortex. We conclude that medial frontal cortex of the rat has functional similarity to primate lateral prefrontal cortex.

Animals↗
PubMed1975

[The effect of striatectomy on retraining rats to an avoidance habit in a U-shaped maze].

The capacity of rats to reversal learning changing of the direction of the avoidance response was determined in the Y-shaped maze. Four training sessions--each time in a new direction (to the right or to the left) for running were conducted in the course of one experiment. The results obtained in 4 groups of animals were compared: intact, with bi- and unilateral striatectomy and with bilateral destruction of the parietal cortex. The majority of the intact rats preferred running in the right direction. The character of the preference changed after striectomy: the rats ran more regularly in the direction at the side of which the striatum was injured more. Bilateral striatectomy also led to increase in the number of errors, to the increase in the latency and disturbance of a passive component of the avoidance response.

Animals↗
PubMed1986

Amphetamine and the overtraining reversal effect.

Rats were trained in a Y-maze on a two choice simultaneous brightness discrimination with light as S+ and dark as S- (position irrelevant). Animals in the Mastery group were trained until they reached criterion and were then switched to reversal, where the reinforcement contingencies of the original training were reversed. Animals in the Overtraining group received a further 110 trials before being switched to reversal. The administration of 1 mg/kg d-amphetamine facilitated dramatically reversal learning in Mastery group. Overtraining improved reversal in saline injected animals and slowed down reversal in amphetamine-treated animals. The drug also facilitated the acquisition of the initial brightness discrimination.

Amphetamine↗
PubMed2006

The role of the ventromedial prefrontal cortex in abstract state-based inference during decision making in humans.

Many real-life decision-making problems incorporate higher-order structure, involving interdependencies between different stimuli, actions, and subsequent rewards. It is not known whether brain regions implicated in decision making, such as the ventromedial prefrontal cortex (vmPFC), use a stored model of the task structure to guide choice (model-based decision making) or merely learn action or state values without assuming higher-order structure as in standard reinforcement learning. To discriminate between these possibilities, we scanned human subjects with functional magnetic resonance imaging while they performed a simple decision-making task with higher-order structure, probabilistic reversal learning. We found that neural activity in a key decision-making region, the vmPFC, was more consistent with a computational model that exploits higher-order structure than with simple reinforcement learning. These results suggest that brain regions, such as the vmPFC, use an abstract model of task structure to guide behavioral choice, computations that may underlie the human capacity for complex social interactions and abstract strategizing.

Action Potentials↗
PubMed2002

Motivation, reward, and Parkinson's disease: influence of dopatherapy.

"Orbitofrontal" and "cingulate" striatofrontal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in motivation and sensitivity to reinforcement in animals. Parkinson's disease (PD) provides a model to assess their implications in humans. The aims of the study were to investigate motivation and sensitivity to reinforcement in non-demented and -depressed PD patients and to evaluate the influence of dopaminergic therapy by comparing patients in "on" (with L-Dopa) and "off" (without L-Dopa) states. Twenty-three PD patients were compared, in both the "on" and "off" states, to 28 controls, using: (1) an Apathy Scale; (2) Stimulus-Reward Learning, Reversal, and Extinction tasks; and (3) a Gambling task. PD patients were found: (1) mildly apathetic; (2) impaired on Stimulus-Reward Learning and Reversal, but not on Extinction; and (3) able to progress in the Gambling task during the first, but not the second assessment. There was no significant correlation between these various deficits. L-Dopa treatment clearly improved motivation, but had more limited and contrasting effects on other variables, decreasing the number of omission errors in Reversal, but increasing the number of perseveration errors in Extinction. These results suggest: (1) an implication of striatofrontal loops in human motivation and explicit and implicit sensitivity to reinforcement; (2) a positive influence of L-Dopa treatment on the subjective evaluation of motivation, but contrasting effects on reward sensitivity.

Adult↗
PubMed2004

Role of hippocampal CA3 mu-opioid receptors in spatial learning and memory.

The dorsal CA3 region of the hippocampus is unique in its connectivity, sensitivity to neurotoxic lesions, and its ability to encode and retrieve episodic memories. Computational models of the CA3 region predict that blocking mossy-fiber and/or perforant path activity to CA3 would cause impairments in learning and recall of spatial memory, respectively. Because the CA3 region contains micro-opioid receptors and receives inputs from the mossy-fiber and lateral perforant pathways, both of which contain and release opioid peptides, we tested the hypothesis that inactivating micro-opioid receptors in the CA3 region would cause spatial learning and memory impairments and retrieval deficits. In this study, male Sprague Dawley rats were trained in a Morris water maze after a single bilateral intrahippocampal injection of either saline or the selective and irreversible micro-opioid receptor antagonist beta-funaltrexamine (beta-FNA) into area CA3. We found that micro-opioid receptor binding decreased 24 hr after beta-FNA injection and returned to control levels 11 d after injection. Injections of beta-FNA into the CA3 region, but not into the ventricles, caused a significant impairment in the acquisition of spatial learning without causing sensory or motor deficits. New learning was not affected once micro-opioid receptor levels replenished (>11 d after injection). In pretrained animals, beta-FNA significantly impaired spatial memory retrieval and new (reversal) learning. These data are consistent with theoretical models of CA3 function and suggest that CA3 micro-opioid receptors play an important role in the acquisition and retrieval of spatial memory.

Animals↗
PubMed2006

Dose-dependent reductions in spatial learning and synaptic function in the dentate gyrus of adult rats following developmental thyroid hormone insufficiency.

Thyroid hormones are critical for the development and maturation of the central nervous system. Although somatic and neurological effects are well documented following severe thyroid hormone deprivation, much less is known of the functional consequences of moderate levels of hormone insufficiency. We have previously demonstrated that severe thyroid hormone reductions in the postnatal period are associated with impairments in synaptic transmission in the dentate gyrus. The present study was performed to examine the dose-response relationships of moderate levels of hormone disruption on synaptic function in the dentate gyrus in an in vivo preparation and to determine the effects on spatial learning. Pre- and postnatal thyroid hormone insufficiency was induced by administration of 3 or 10 ppm propylthiouracil (PTU) to pregnant and lactating dams via the drinking water from gestation day (GD) 6 until postnatal day (PN) 30. This regimen produced a 47% and 65% reduction in serum T4, in the dams of the low and high-dose groups, respectively. At the time of testing of adult offspring, hormone status had returned to control levels. In littermates, field potentials evoked in the dentate gyrus in response to stimulation of the perforant path were assessed under urethane anesthesia. The data reveal dose-dependent reductions in synaptic transmission and impairments in long-term potentiation (LTP) of the EPSP component of the compound field potential. In contrast, LTP of the population spike measure was paradoxically enhanced. Spatial learning in the Morris water maze was profoundly impaired in high-dose animals. Although the majority of subjects in the low-dose group eventually acquired the task, their acquisition rate lagged behind control values. Reversal learning was assessed in all animals reaching criterion performance and found to be impaired in PTU-exposed animals relative to controls. These data support previous findings in area CA1 in vitro, extend observations associated with dentate gyrus synaptic function to a lower dose range, and provide correlative evidence of behavioral disruption in a hippocampal-dependent learning task following developmental thyroid hormone insufficiency.

Age Factors↗
PubMed2001

Abstract reward and punishment representations in the human orbitofrontal cortex.

The orbitofrontal cortex (OFC) is implicated in emotion and emotion-related learning. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activation in human subjects doing an emotion-related visual reversal-learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward and choice of the incorrect stimulus led to a monetary loss. Distinct areas of the OFC were activated by monetary rewards and punishments. Moreover, in these areas, we found a correlation between the magnitude of the brain activation and the magnitude of the rewards and punishments received. These findings indicate that one emotional involvement of the human orbitofrontal cortex is its representation of the magnitudes of abstract rewards and punishments, such as receiving or losing money.

Adult↗
PubMed1988

Effects of bilateral lesions of the central and lateral amygdala on free operant successive discrimination.

Male rats received either ibotenic acid (IBO) or sham lesions bilaterally into the central or lateral amygdala or were assigned to an unoperated control group. After the postoperation recovery period all lesioned and unoperated animals were tested for open field behaviour and for the ability to master a free operant successive discrimination. Retention of the discrimination learning was evaluated 48 h later for the original and reversal problem. After the reversal learning retention test the unoperated animals were assigned at random to one unoperated control and two IBO amygdaloid lesioned groups (central and lateral) and these, unoperated and lesioned animals, received additional free operant successive discrimination retraining after the surgery recovery period. Significant lesion effects were found in the emotional indices in the open field test. The lesions significantly impaired the postoperative acquisition of a free operant successive discrimination and its reversal and diminished its retention but did not impair the retention of such a discrimination task acquired before the lesion. The contribution of central and lateral amygdala in open field behaviour and in the major components of a free operant successive discrimination is discussed. In order to know how the amygdala is involved in association of sensorial stimuli with reinforcement we suggest experimental designs controlling the detailed components of such an association.

Amygdala↗
PubMed2005

Impaired memory and olfactory performance in NaSi-1 sulphate transporter deficient mice.

In the present study, NaSi-1 sulphate transporter knock-out (Nas1-/-) mice, an animal model of hyposulphataemia, were examined for spatial memory and learning in a Morris water maze, and for olfactory function in a cookie test. The Nas1-/- mice displayed significantly (P<0.05) increased latencies to find an escape platform in the reversal learning trials at 2 days but not 1 day after the last acquisition trial in a Morris water maze test, suggesting that Nas1-/- mice may have proactive memory interference. While the wild-type (Nas1+/+) mice showed a significant (P<0.02) decrease in time to locate a hidden food reward over four trials after overnight fasting, Nas1-/- mice did not change their performance, resulting in significantly (P<0.05) higher latencies when compared to their Nas1+/+ littermates. There were no significant differences between Nas1-/- and Nas1+/+ mice in the cookie test after moderate food deprivation. In addition, both Nas1-/- and Nas1+/+ mice displayed similar escape latencies in the acquisition phase of the Morris water maze test, suggesting that learning, motivation, vision and motor skills required for the task may not be affected in Nas1-/- mice. This is the first study to demonstrate an impairment in memory and olfactory performance in the hyposulphataemic Nas1-/- mouse.

Animals↗
PubMed1975

Interactive effects of training condition and septal lesions on perseverative responding in the rat.

Rats that had received septal lesions either prior to acquisition of a position habit (Group SAR) or immediately after position habit acquisition (Group SR) were tested on two reversals of the task. Compared with control-operated rats, both groups of rats with septal lesions exhibited position-habit reversal deficits. The two groups with septal lesions could not be distinguished in terms of the total number of errors made during reversal learning, but could be distinguished on the basis of the type of error committed. Compared with Group SR, Group SAR made significantly more perservative errors on the first reversal and significantly fewer perserverative errors on the second reversal. Group SR made significantly more nonperservative errors than Group SAR on both reversals.

Animals↗
PubMed1981

Effects of neonatal undernutrition and cold stress on behavior and biochemical brain parameters in rats.

This study was conducted to investigate the separate and combined effects of neonatal undernutrition (U) and cold stress (S) on the behavioral and cerebral development of postweaning rats. A severe U was imposed by feeding dams a low protein diet. Postweaning all pups were fed a control diet. S consisted of daily exposure to 5 degrees for 3 minutes from day 2 to 11. Behavioral data show that U animals, stressed (S) + nonstressed (NS), exhibited a significant deficit in reversal learning of T-maze at 21 days, an enhanced passive avoidance response, but no difference in active-avoidance at 35 days when compared to controls of the same age. S had no effect on behavior development. At death (110 days), the brains were dissected into five sections and assay for acetylcholinesterase (AChE) and cholinesterase (ChE) activities. Brain weights of U animals (NS + S) were significantly lower in all sections except dorsal cortex (DC). AChE and ChE activities were significantly higher in all sections (except DC) of U animals relative to controls. S resulted in lower cerebellar weight and ChE:AChE ratios in some sections. Our results suggest a delayed behavioral maturation in U animals and an association between early postweaning behavior and brain parameters in adult rehabilitated animals.

Acetylcholinesterase↗
PubMed1998

Effects of MK-801 on vicarious trial-and-error and reversal of olfactory discrimination learning in weanling rats.

The effects of dizocilpine maleate (MK-801) on vicarious trial-and-error (VTE), and on simultaneous olfactory discrimination learning and its reversal, were observed in weanling rats. The term VTE was used by Tolman (The determiners of behavior at a choice point. Psychol. Rev. 1938;46:318-336), who described it as conflict-like behavior at a choice-point in simultaneous discrimination learning. It takes the form of head movements from one stimulus to the other, and has recently been proposed by Amsel (Hippocampal function in the rat: cognitive mapping or vicarious trial-and-error? Hippocampus, 1993;3:251-256) as related to hippocampal, nonspatial function during this learning. Weanling male rats received systemic MK-801 either 30 min before the onset of olfactory discrimination training and its reversal, or only before its reversal. The MK-801-treated animals needed significantly more sessions to acquire the discrimination and showed significantly fewer VTEs in the acquisition phase of learning. Impaired reversal learning was shown only when MK-801 was administered during the reversal-learning phase, itself, and not when it was administered throughout both phases.

Animals↗
PubMed2004

Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour.

While prefrontal lesions in rodents serve as models for frontal lobe syndromes, neonatal lesions are considered as models for disconnection syndromes, such as schizophrenia. We investigated the effect of neonatal lesions of the rat medial prefrontal cortex (mPFC) together with pubertal dexamethasone-challenge on adult rat behaviour and on apomorphine-induced behavioural changes. Adult lesions were used as controls. Rats with neonatal (postnatal day 7) or adult excitotoxic lesions or sham-lesions of the mPFC were tested 9 weeks after surgery. At postnatal day 49 one group of neonatal operated rats were systemically injected with the glucocorticoid receptor agonist dexamethasone (20 mg/kg), in order to simulate stress-induced glucocorticoid receptor activation. Working memory and perseveration was tested in T-maze tasks (continuous delayed alternation and reversal learning). Additionally, locomotor activity and prepulse inhibition (PPI) of startle was tested with and without apomorphine-treatment. Brain tissue damage was assessed using Nissl-staining and parvalbumine-immunocytochemistry. Pronounced thinning of the prelimbic-infralimbic subregion of the mPFC accompanied by altered cytoarchitecture and reduced number of parvalbumine-immunopositive neurones was found after neonatal lesions while adult lesions resulted in loss of neurones accompanied by gliosis. Neonatal lesions increased perseveration in the T-maze tasks and enhanced PPI, while adult lesions induced a working memory deficit. This differential behavioural outcome presumably reflects neurodevelopmentally induced alterations in neuronal circuits after neonatal lesions versus damage to mPFC alone after adult lesions. Dexamethasone-injection at day 49 did not alter behaviour in these tasks. Motor activity was not affected by neonatal or adult lesions but dexamethasone reduced apomorphine-induced hyperlocomotion.

Analysis of Variance↗
PubMed1978

Use of the Jordan Left-Right Reversal Test with learning disabled children.

This investigation established the reliability of the Jordan Left-Right Reversal Test for learning disabled children. Test-retest reliability coefficients ranged from .89 to .92 for a sample of 91 children, 5 through 12 yr., attending private schools for children with learning disabilities. Reversal errors decreased with age for boys and girls, although girls 9 through 12 made significantly fewer errors than did boys in the same age range. Learning disabled children made more errors at all ages than normal children. This test instrument was determined to be a measure of the global tendency to make visual reversal errors and was viewed as an appropriate part of the learning disabilities diagnostic procedure.

Age Factors↗
PubMed2000

Prenatal cocaine exposure impairs selective attention: evidence from serial reversal and extradimensional shift tasks.

This study assessed the effects of prenatal cocaine exposure on cognitive functioning, using an intravenous (IV) rodent model that closely mimics the pharmacokinetics seen in humans after smoking or IV injection and that avoids maternal stress and undernutrition. Cocaine-exposed males were significantly impaired on a 3-choice, but not 2-choice, olfactory serial reversal learning task. Both male and female cocaine-exposed rats were significantly impaired on extradimensional shift tasks that required shifting from olfactory to spatial cues; however, they showed no impairment when required to shift from spatial to olfactory cues. In-depth analyses of discrete learning phases implicated deficient selective attention as the basis of impairment in both tasks. These data provide clear evidence that prenatal cocaine exposure produces long-lasting cognitive dysfunction, but they also underscore the specificity of the impairment.

Animals↗
PubMed2006

Assessment of cognitive function in the heterozygous reeler mouse.

RATIONALE: The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined. OBJECTIVE: Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients. METHODS: Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task, (2) impulsivity in an inhibitory control task, (3) attentional function in a three-choice serial reaction time task, and (4) working memory in a delayed matching-to-position task. RESULTS: No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning. CONCLUSIONS: These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.

Animals↗