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PubMedDate not supplied

Human temporal behavior and discrimination-reversal learning.

The present study demonstrates that a relationship exists between individual differences in temporal behavior and individual differences in human discrimination-reversal learning behavior. When the results of performance on a time-estimation task employing the method of reproduction are compared with the results of acquisition performance on a complex form of discrimination-reversal learning task is can be demonstrated that underestimation of time is associated with faster learning and overestimation of time is associated with slower learning of the discrimination task. The experimental design was based on the historical fact that the Sechenov-Pavlov and Spence-Hull formulations assigned a primary role in learning to excitation and inhibition as intervening variables between the input of stimulation and output of response. The present study also used the tasks of time estimation and discrimination learning as dependent variables; and the concept that underestimation of time is associated with and underlying predominance of excitatory processes as a hypothetical construct. The conclusion was reached that one of the many theoretical processes which may be used to explain discrimination learning is the concept that acquisition of the correct response may be viewed as a function of the individual rates at which excitatory processes come to be conditioned to a predominance over existing inhibitory processes.

Adult↗
PubMed1984

Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.

To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.

Animals↗
PubMed2006

Early discrimination reversal learning impairment and preserved spatial learning in a longitudinal study of Tg2576 APPsw mice.

To understand the relationship between amyloid-beta and cognitive decline in Alzheimer's disease, we evaluated cortical and hippocampal function in a transgenic mouse model of amyloid over-expression in Alzheimer's disease, the Tg2576 mouse. Tg2576 mice and their non-transgenic littermates were assessed at both 6 and 14 months of age in a battery of cognitive tests: attentional set-shifting, water maze spatial reference memory and T-maze working memory. Spatial reference memory was not affected by Tg status at either age. Working memory was only affected by age, with 6-month-old mice performing better than 14-month-old ones. Older mice were also significantly impaired on reversal learning and on the intra- and extra-dimensional shift in attentional set-shifting. A significant transgene effect was apparent in reversal learning, with Tg2576 mice requiring more trials to reach criterion at 6 months old. These data indicate that the effects of normal aging in C57B6xSJL F1 mice are most pronounced on putative frontal cortex-dependent tasks and that increasing Abeta load only affects discrimination reversal learning in our study.

Age Factors↗
PubMed1979

Persistence of impaired reversal learning in young monkeys exposed to low levels of dietary lead.

Lead acetate in milk was fed daily to infant rhesus monkeys at doses averaging 0 (control), 0.287 (low-Pb), or 0.880 (high-Pb) mg/kgd for the first year of life. Pb concentrations in whole blood (PbB) averaged 4.15, 31.71, and 65.17 microgram/dl for the control, low-Pb, and high-Pb groups, respectively, during the year of treatment and declined toward control levels when Pb dosing was stopped. Behavioral observations during the year of treatment had shown that both experimental groups were retarded in their acquisition of object-cue discrimination reversal learning sets. At 4 yr of age, when PbB levels in all animals were normal, the ability of the same monkeys to acquire a series of 3 spatial-cue reversal learning sets was examined; these data form the basis for this report. In the first problem, the high-Pb group was significantly retarded in acquisition of the original discrimination and of most reversals, and the low-Pb group was retarded on reversal 1 only. These deficits declined in severity across the three problems administered, in a manner similar to that seen in the tests given during the first year of life. These data demonstrate that reversal learning retardation, observed early in life, can recur in postadolescent primates with a history of chronic, low-level Pb intoxication during infancy.

Animals↗
PubMed2000

Reversal learning deficit in a spatial task but not in a cued one after telencephalic ablation in goldfish.

The fish telencephalon seems to be involved in spatial learning and memory in a similar manner to the hippocampus of the land vertebrates. For instance, telencephalon ablated goldfish are impaired in the post-operative retention of a 'spatial constancy' task, which requires the use of mapping strategies, but not in a directly cued task in which responses are based in a guidance strategy. In this regard, previous experiments showed that intact goldfish trained in the spatial constancy task presented considerable behavioral flexibility, as they showed fast reversal learning, that is, they required less training compared with animals trained in the directly cued task and made a lower number of errors to master the reversal than in acquisition. The purpose of the present work was to investigate if the goldfish telencephalon is involved in the faster reversal learning of the animals trained in the spatial constancy task. Goldfish with bilateral telencephalic ablation, sham operated or intact, were trained in the spatial constancy task or in the directly cued task. Telencephalic ablation selectively impaired reversal learning in the animals trained in the spatial constancy procedure. Ablated animals in this procedure reversed more slowly than control animals. By contrast, telencephalic ablation did not produce any significant deficit during reversal in the animals trained in the directly cued task. These results provide additional evidence that the fish telencephalon, as the land vertebrate hippocampus, plays a crucial role in the use of flexible spatial representations.

Animals↗
PubMed2006

Reversal learning after prenatal or early postnatal alcohol exposure in juvenile and adult rats.

Learning tasks that require the reversal of a previously learned contingency are disrupted in animals and humans exposed to alcohol during the perinatal period. The current experiments examined how varying the time of alcohol exposure and the age at which subjects were tested would affect the expression of reversal deficits in a T-maze task. Groups of rats were exposed to alcohol from gestational day (GD) 8 to GD20 or from postnatal day (PN) 4 to PN9, and then tested in a spatial reversal task at either PN28 or PN63. Results indicate that exposure to alcohol during the prenatal period did not lead to substantial dose-dependent reversal learning deficits in males or females at either age tested. However, exposure to alcohol during the early postnatal period, a period that corresponds to the third trimester in human neural development, selectively disrupted reversal learning performance in male rats at PN28 but not PN63. Statistically significant sex differences were seen when subjects were tested at PN63. These results demonstrate how the timing of alcohol exposure leads to variability in the age-dependent expression of learning deficits associated with fetal alcohol effects.

Aging↗
PubMed2004

Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice.

BACKGROUND: Dopamine modulation of neuronal signaling in the frontal cortex, midbrain, and striatum is essential for processing and integrating diverse external sensory stimuli and attaching salience to environmental cues that signal causal relationships, thereby guiding goal-directed, adaptable behaviors. At the cellular level, dopamine signaling is mediated through D1-like or D2-like receptors. Although a role for D1-like receptors in a variety of goal-directed behaviors has been identified, an explicit involvement of D2 receptors has not been clearly established. To determine whether dopamine D2 receptor-mediated signaling contributes to associative and reversal learning, we compared C57Bl/6J mice that completely lack functional dopamine D2 receptors to wild-type mice with respect to their ability to attach appropriate salience to external stimuli (stimulus discrimination) and disengage from inappropriate behavioral strategies when reinforcement contingencies change (e.g. reversal learning). RESULTS: Mildly food-deprived female wild-type and dopamine D2 receptor deficient mice rapidly learned to retrieve and consume visible food reinforcers from a small plastic dish. Furthermore, both genotypes readily learned to dig through the same dish filled with sterile sand in order to locate a buried food pellet. However, the dopamine D2 receptor deficient mice required significantly more trials than wild-type mice to discriminate between two dishes, each filled with a different scented sand, and to associate one of the two odors with the presence of a reinforcer (food). In addition, the dopamine D2 receptor deficient mice repeatedly fail to alter their response patterns during reversal trials where the reinforcement rules were inverted. CONCLUSIONS: Inbred C57Bl/6J mice that develop in the complete absence of functional dopamine D2 receptors are capable of olfaction but display an impaired ability to acquire odor-driven reinforcement contingencies. Furthermore, the ability of dopamine D2 receptor deficient mice to adjust their responding to a previously reinforced stimulus when unexpected outcomes are encountered is significantly impaired. These findings suggest that signaling mediated by the dopamine D2 receptor is important for regulating associative and reversal learning and may have implications for the treatment of human attention disorders.

Animals↗
PubMed1990

Visual discrimination and reversal learning in the aged monkey (Macaca mulatta).

Visual discrimination and reversal learning were assessed in young adult (10-12 years old, n = 4) and aged (23-27 years old, n = 5) female rhesus monkeys. Performance was comparable across age groups in many tasks, suggesting that the acquisition of stimulus-reward associations remains largely intact in the aged monkey. Most older subjects, however, required more training than any young animal to learn an initial pattern discrimination. In combination with previous findings from the same groups of monkeys, these data suggest that deficits in attending to the relevant stimulus features in novel testing procedures may contribute to poor performance in aged subjects across a variety of learning and memory tasks. In addition, preliminary findings from a discrimination probe procedure raise the possibility that aged subjects may adopt alternate testing strategies that compensate for some aspects of age-dependent cognitive dysfunction.

Aging↗
PubMed1995

The nucleus accumbens in monkeys (Macaca fascicularis). III. Reversal learning.

The nucleus accumbens (NA), which receives inputs from limbic structures and projects to the motor system, may be important for the association of reinforcement with action. There are projections to the NA from the amygdala and hippocampus. Discrimination and reversal learning tasks which are known to be disrupted by lesions to these areas in monkeys were given to monkeys with lesions of the NA. Twelve monkeys (Macaca fascicularis) were used in the present study. Six of these received ibotenic acid lesions which resulted in considerable cell loss in the NA; the remaining six acted as controls. The first group of six monkeys were taught a visual discrimination task pre-operatively. Post-operatively, these monkeys were tested on visual and spatial discrimination and reversal tasks. A second group of six monkeys were tested on a motor reversal task. The results indicate that ibotenic acid lesions of the NA transiently impair spatial but not visual reversal learning in monkeys. The NA lesions did not impair a monkey's ability to perform visual or spatial discriminations, or the ability to perform the motor learning or motor reversal tasks. Our results suggest that bilateral lesions of the NA in monkeys do not disrupt the ability to discriminate basic properties of reward-related stimuli or the formation of visual stimulus-reward associations. In addition, our results argue against theories which suggest that the NA is important for behavioural switching or general behavioural flexibility. We conclude that the NA may play a more specific role in the association of temporal and spatial cues with movement and reward.

Animals↗
PubMed2003

Improved reversal learning and altered fear conditioning in transgenic mice with regionally restricted p25 expression.

Cleavage of the cyclin-dependent kinase 5 activator p35 generates the protein fragment p25, which accumulates in the forebrain of patients with Alzheimer's disease. Although p25 expression has been suggested to affect learning and memory, this hypothesis has not been tested to date. To investigate the role of p25 in hippocampus-dependent learning and memory we have generated transgenic mice expressing p25 preferentially in postnatal forebrain. p25 expression was highest in hippocampus where it averaged approximately 33% of endogenous p35 expression. This low level of p25 expression did not seem to result in hyperphosphorylation of tau, but increased the phosphorylation of neurofilament M and enhanced the expression of tau protein. These molecular changes did not correlate with neurodegeneration or motor abnormalities. In the Morris water maze the p25 mutants were normal in learning an initial platform location, but surprisingly reversal learning was improved when the platform position was changed. The p25 mutants were normal in contextual fear conditioning. However, when trained with a tone presentation the mutants showed reduced contextual conditioning and enhanced tone fear conditioning. We conclude that low p25 expression has pleiotropic effects on learning and memory. As p25 expression can improve learning and memory, p25 formation could be a compensatory mechanism for learning and memory deficits in Alzheimer's disease.

Alzheimer Disease↗
PubMed2005

Rapid tryptophan depletion improves decision-making cognition in healthy humans without affecting reversal learning or set shifting.

Rapid tryptophan (Trp) depletion (RTD) has been reported to cause deterioration in the quality of decision making and impaired reversal learning, while leaving attentional set shifting relatively unimpaired. These findings have been attributed to a more powerful neuromodulatory effect of reduced 5-HT on ventral prefrontal cortex (PFC) than on dorsolateral PFC. In view of the limited number of reports, the aim of this study was to independently replicate these findings using the same test paradigms. Healthy human subjects without a personal or family history of affective disorder were assessed using a computerized decision making/gambling task and the CANTAB ID/ED attentional set-shifting task under Trp-depleted (n=17; nine males and eight females) or control (n=15; seven males and eight females) conditions, in a double-blind, randomized, parallel-group design. There was no significant effect of RTD on set shifting, reversal learning, risk taking, impulsivity, or subjective mood. However, RTD significantly altered decision making such that depleted subjects chose the more likely of two possible outcomes significantly more often than controls. This is in direct contrast to the previous report that subjects chose the more likely outcome significantly less often following RTD. In the terminology of that report, our result may be interpreted as improvement in the quality of decision making following RTD. This contrast between studies highlights the variability in the cognitive effects of RTD between apparently similar groups of healthy subjects, and suggests the need for future RTD studies to control for a range of personality, family history, and genetic factors that may be associated with 5-HT function.

Adolescent↗
PubMed2004

Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs.

The effects of long-term treatment with both antioxidants and a program of behavioral enrichment were studied as part of a longitudinal investigation of cognitive aging in beagle dogs. Baseline performance on a battery of cognitive tests was used to assign 48 aged dogs (9-12 years) into four cognitively equivalent groups, of 12 animals per group: Group CC (control food-control environment), group CE (control food-enriched environment); Group AC (antioxidant fortified food-control environment); Group AE (fortified food-enriched environment). We also tested a group of young dogs fed the control food and a second group fed the fortified food. Both groups of young dogs received a program of behavioral enrichment. To evaluate the effects of the interventions on cognition after 1 year, the dogs were tested on a size discrimination learning task and subsequently on a size discrimination reversal learning task. Both tasks showed age-sensitivity, with old dogs performing more poorly than young dogs. Both tasks were also improved by both the fortified food and the behavioral enrichment. However, in both instances the treatment effects largely reflected improved performance in the combined treatment group. These results suggest that the effectiveness of antioxidants in attenuating age-dependent cognitive decline is dependent on behavioral and environmental experience.

Aging↗
PubMed2005

Polydrug abusers display impaired discrimination-reversal learning in a model of behavioural control.

Long-term cocaine and alcohol use is associated with neuropsychological impairments that implicate poor inhibitory mechanisms of behavioural control. This study tested acquisition and discrimination-reversal learning in a group of polydrug users (n 20) with a history of cocaine and heavy alcohol use and a group of age-matched controls (n 20). A cued go/nogo task measured subjects' ability to learn stimulus-response associations that involved the quick activation and sudden inhibition of responses. Compared with controls, drug users displayed similar acquisition, but impaired discrimination-reversal learning of both inhibitory and activational responses. The results suggest that some drug-related neuropsychological deficits might reflect specific impairments of the ability to inhibit interference from prior learning. The findings contribute to growing evidence that suggests cocaine and alcohol use could produce broad inhibitory impairments that increase the risk for learning deficits and poor impulse control.

Adolescent↗
PubMed1992

Reversal learning of the rabbit nictitating membrane response following kindling-induced potentiation within the hippocampal dentate gyrus.

The following experiment examined the effects of kindled seizures on reversal learning and the effects of both kindling and classical conditioning of the rabbit nictitating membrane on granule cell responsivity to perforant path input. Kindling resulted in significant potentiation of the population spike, the excitatory postsynaptic potential (EPSP) and the magnitude of twin pulse inhibition. Following kindling, rabbits were trained in a discrimination-reversal paradigm with either a tone or light paired with a corneal airpuff. Kindling did not affect acquisition of the initial discriminative response but did retard the rate of reversal learning. Kindling-induced potentiation, within dentate excitatory and inhibitory circuits, persisted for the duration of training. Thus, these results do not distinguish between the contribution of kindling-induced potentiation within dentate excitatory and inhibitory circuits to discrimination-reversal training. Spikes evoked during tone presentations were of reduced amplitude compared to spikes evoked either between trials or during light trials. The EPSP was not affected by stimulus conditions. In control rabbits, the magnitude of both the spike and EPSP increased across training. Training-related potentiation, in kindled rabbits, could not be separated from kindling-induced potentiation. These results demonstrate that an LTP-like effect of both the population spike and EPSP occurs with discrimination-reversal training.

Animals↗
PubMed2003

The NMDA-receptor antagonist MK-801 selectively disrupts reversal learning in rats.

We tested the hypothesis that inhibition of NMDA-receptors in rats would lead to a selective impairment of reversal learning in a serial reversal task in the Skinner box. Low doses of MK-801 (0.025 and 0.05 mg/kg) did not affect acquisition of the two-lever discrimination, but impaired performance during the first reversal more than during the third reversal. Similar effects were observed during the series of extinction sessions. The high dose (0.1 mg/kg) completely inhibited reversal and extinction learning, as the rats perseverated in pressing the previously rewarded lever(s). We conclude that NMDA receptor blockade leads to a selective impairment in cognitive flexibility, and shows some similarity to transient inactivation of the medial prefrontal cortex in this respect.

Animals↗
PubMed2003

Neural correlates of rapid reversal learning in a simple model of human social interaction.

Humans and other primates spend much of their time engaged in social interactions where a crucial ability is to decode face expressions and act accordingly. This rapid reversal learning has been proposed to be important in the relative evolutionary success of primates. Here we provide the first neuroimaging evidence that the ability to change behaviour based on face expression in a model of social interactions is not reflected in the activity in the fusiform face area, but is specifically correlated with activity in the orbitofrontal and anterior cingulate/paracingulate cortices. These brain regions are particularly involved in reversal learning, such that the activations described occurred specifically at the time of reversal, and were also found when different face expressions other than angry were used to cue reversal. The evidence that the orbitofrontal and anterior cingulate/paracingulate cortices are specifically activated at the time of reversal is important for understanding changes in affect and emotional processing in patients with lesions to these brain regions.

Adult↗
PubMed2001

Improved short-term spatial memory but impaired reversal learning following the dopamine D(2) agonist bromocriptine in human volunteers.

RATIONALE: Studies in humans of cognitive effects of dopaminergic drugs have largely focused on tasks of working memory, with a few studies also examining executive function. OBJECTIVES: This study was designed to investigate the effects of 1.25 mg of the dopamine D(2) agonist bromocriptine on spatial working memory, planning and discrimination reversal learning in young healthy volunteers. METHODS: Twenty volunteers were tested in a double-blind, placebo-controlled, cross-over design. The cognitive assessment included tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB) designed to test visuo-spatial recognition memory and spatial working memory. In addition, tests of spatial planning and discrimination reversal learning were used to assess the more general effects of bromocriptine. Tests of subjective feelings and motivation were also incorporated into the battery. RESULTS: Bromocriptine enhanced the spatial memory span of subjects, whilst impairing their ability to reverse a learned probabilistic discrimination. Tests of recognition memory and planning were unaffected by the drug. The findings were not explained by changes in subjective mood or motivational measures. CONCLUSIONS: The pattern of findings observed here mirror medication-dependent observations seen in Parkinson's disease. The results are discussed with reference to the different anatomical networks known to subserve performance of the differentially affected tasks.

Adult↗
PubMedDate not supplied

Reversal learning tasks may provide rapid determination of cognitive deficits in lead-exposed children.

An historical cohort study of twins, aged 6 to 15 years, found reduced cognitive performance related to subclinical exposure to lead (Pb) much earlier in life. Pairs of twins discordant for blood Pb (low-Pb twins ranged from 30-50 micrograms/dl and high-Pb twins ranged from 43-80 micrograms/dl) exhibited reduced learning of a computer-administered visual discrimination and reversal by the twin having the higher exposure. There was no evidence that sensory or motor impairment contributed to the cognitive deficit. Performance of a reference group indicated that test's validity for age-related cognitive development and the method's suitability for children of varying socio-economic or racial status. Because the reversal learning approach required only one 20-min test session and was powerful enough to document Pb-related deficits in a small sample (n = 8), it may indicate a practical method for obtaining early evidence of environmentally induced developmental delays. An advantage of the test is that it can be used with both humans and animals. Tests capable of direct comparison of behavioral data from humans and animals can guide the search for behavioral and biological mechanisms in experiments that can be done only with animals. They also can augment the clinical procedures currently used.

Adolescent↗