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Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning.

The behavior of aged rhesus monkeys (18 years and older) was compared to that of young monkeys (3 to 6 years old) to evaluate their relative abilities to learn a series of visual discrimination and discrimination reversal problems. Using a subject-paced, automated experimental procedure designed to optimize stimulus control and facilitate execution of choice responses, no consistent age-related differences were observed in the ability to learn new color and pattern discrimination problems of varying difficulty. However, a severe and consistent deficity on reversal learning did occur. A detailed analysis of this deficit revealed that not only did the aged monkeys take longer to extinguish the old habit and return to chance performance, but they continued to display a deficit in establishing accurate performance at above-chance levels as well. Since no reliable age differences were observed on the original discrimination learning problems, these data suggest that aging impairs mechanisms involved with response rigidity and/or susceptibility to intertrial proactive interference, more severely than those involved with the simple formation of new associations.

Aging

Serial spatial reversal learning in rats: comparison of instrumental and automaintenance procedures.

Serial reversals of a spatial discrimination were trained in rats under automaintenance conditions, in which food reward occurred regardless of responding. This automaintained reversal learning was compared to instrumental reversal learning in other rats trained under a similar procedure which required responding for reward. In the automaintenance (AU) procedure, rats received food after every retraction of a "positive" response lever (S+); retraction of a second, "neutral" lever (So) was not paired with food delivery. Responses to the S+ were elicited at fairly constant rates during daily 100-trial conditioning sessions. Responses to the So occurred early in each session but rapidly diminished across trials. When the valences of the levers were reversed, responding shifted to the new S+ and diminished on the new So. Criterion for reversal was defined as a discrimination ratio (DR) of at least 90% responding to the S+ in two consecutive 10-trial blocks. With repeated reversals, acquisition of criterion performance occurred with increasing rapidity, reaching an asymptote below that required for the original discrimination. A second group of rats was trained on a similar instrumental schedule, in which at least one response to the S+ was required for food delivery. Response rates in this instrumental (IN) group were approximately double those of the AU group. However, ratios of S+ to So response rates were similar to those of the AU group, and the serial reversal curves generated were qualitatively similar. Thus rats can show improvement across serial reversals of a spatial discrimination based entirely on pairings of stimulus events (automaintenance), in a manner similar to that observed in instrumental procedures, in which reward is contingent upon correct responding.

Animals

Reversal learning deficits in young monkeys exposed to lead.

The reversal learning capacity of young rhesus monkeys in visual discrimination tasks was examined during daily exposure to dietary lead acetate throughout the first year of life. While not affected in physical development, all lead-treated monkeys showed performance deficits on reversal learning tasks. These deficits were independent of lead-induced changes in motivation. Over a series of problems, the overall learning rate of monkeys with blood lead concentrations in the range of 70-90 microgram/dl was retarded, which resulted partly from a pronounced difficulty in attaining criterion on the first of a series of reversals within a given problem. This latter deficit resulted from an increase in errors, balks, and total trials to criterion on the first reversal. Monkeys exposed to blood lead concentrations of 40-60 microgram/dl required significantly more trials to finish all problems, but did not show the first-reversal deficit. Theoretical implications of these data were discussed.

Aging

Delay-dependent impairment of reversal learning in rats treated with trimethyltin.

Recent theories of hippocampal function focus on its role in the formation of associations in the temporal domain. A reversal learning paradigm based on leverpress automaintenance was developed to vary the CS-US relationship along two independent dimensions, one temporal and one not: CS(+)-US delay and the probability of reinforcement [P(RFT)] following the CS+. Eight male hooded Long-Evans rats were trained to reverse these automaintained discriminations repeatedly, until stable performance was achieved. The neurotoxicant trimethyltin (TMT) was used to induce lesions in the CNS, including the CA3-4 region of Ammon's Horn in dorsal hippocampus. Following iv injection of 7 mg/kg TMT to half the rats, reversal learning was assessed under varying conditions of delay and P(RFT). After recovery from the acute effects of TMT (1-2 weeks), treated rats reversed normally when no delay separated the CS+ and US; with delays of 2 to 4 s, they reversed less completely within a session than did controls. Changing P(RFT) did not affect reversal learning in either group, but reduced response rates similarly in both groups. Morphological damage was quantified by measuring the length of the remaining pyramidal cell line in sections of dorsal hippocampus. The degree of behavioral impairment correlated significantly with hippocampal damage only at nonzero CS(+)-US delays. These results indicate that TMT impaired ability of rats to integrate temporal relationships between stimulus events, and are consistent with theories of hippocampal mediation of temporal associations.

Animals

T-maze discrimination and reversal learning after unilateral temporal or frontal lobe lesions in man.

The interpretation of conditional discrimination and reversal learning as acquisition of declarative knowledge suggests that subjects with temporal lobe/hippocampal lesions are likely to be impaired on such tasks. Patients with unilateral left or right temporal lobectomy (and small hippocampal excisions) and patients with unilateral frontal lobe resections were compared with healthy controls on a discrimination reversal task, embedded in a computer game modelled on T-maze tasks traditionally used in animal experiments. The right temporal group showed a deficit in acquiring an initial conditional discrimination, and the frontal group tended to display a marginal impairment in discrimination reversal. These findings are compared with results from animal studies in terms of the mechanisms underlying reversal learning.

Adult

Beneficial effect of chronic treatment with Org 2766 and alpha-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area.

The effects of chronic treatment with the ACTH-(4-9) analogue Org 2766, alpha-MSH, and gamma 2-MSH were studied on T-maze reversal learning and on behavior assessed on the basis of open-field and other gross behavioral activities, grasping responses, inspection of various reflexes and electrical footshock sensitivity of rats with parafascicular lesions or sham-lesions. Repeated administration of Org 2766 and alpha-MSH to parafascicular area-lesioned rats resulted in functional recovery of impaired T-maze reversal learning. The structurally related neuropeptide gamma 2-MSH was without any effect. The alpha-MSH effect did not depend on time after lesioning as treatments during the first or second post-operative week were equally effective. Chronic peptide treatments did not change disturbed motor functions of parafascicular-lesioned rats, as measured by open-field activity, other gross behavioral activities and grasping responses. Since acute peptide treatments did not affect the impaired reversal learning performance of lesioned rats, the beneficial effect of Org 2766 and alpha-MSH could not be explained as a short-term effect on attention and motivation. It was more likely to be an accelerated recovery of cognitive function as a result of long-term neurotropic influences.

Adrenocorticotropic Hormone

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

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

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

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

Origins of anthropoid intelligence. III. Role of prefrontal system in delayed-alternation and spatial-reversal learning in a prosimian (Galago senegalensis).

A species of prosimian (bush baby, Galago senegalensis) was tested on delayed-alternation and spatial-reversal learning before and after ablation of prefrontal cortex. The results show that normal performance on the two behavioral tasks depend on different subdivisions of the MD-prefrontal system. Delayed alternation is disrupted by prefrontal lesions which cause degeneration in the lateral division of MD while spatial-reversal learning is disrupted by lesions causing degeneration of the medial division of MD. Therefore, the bush baby prefrontal system can be subdivided either on behavioral or anatomical grounds into at least two chief parts. Because of several similarities in the MD-prefrontal system of bush baby and monkey despite their remote common ancestry, it can be concluded that the differentiation of the MD-prefrontal system into distinct divisions and the involvement of this system in delayed alternation and spatial reversal are features probably as old as the order Primates itself. It can be further concluded that the further evolution of the anthropoid variety of prefrontal system beyond this common primate stage probably depended on selective pressure on abilities other than those measured here.

Animals

Verbalization of appropriate and inappropriate cues in discrimination reversal learning by moderately mentally retarded children.

Effects of verbalization on discrimination reversal learning for moderately mentally retarded children were examined under three training conditions. Predicted results indicated that verbalization of both appropriate and inappropriate cues within relevant dimension significantly facilitated reversal shift performance, as compared to verbalization of only appropriate cues or non-verbalization. Results were interpreted to be due to the fact that verbalization of both appropriate and inappropriate cues actually served to utilize attentional or verbal mediators in terms of combining appropriate with inappropriate cues within relevant stimulus dimension.

Adolescent

Arginine vasopressin facilitates reversal learning in albino, but not hooded rats.

Male Holtzman albino and Long-Evans hooded rats were administered one microgram of arginine vasopressin (AVP) or a placebo each day after the acquisition trials of a visual white-black discrimination. Animals were then trained in the reversal of the discrimination. Performance was assessed by the number of trials to criterion during acquisition and reversal. Treatment with AVP resulted in significantly fewer trials to criterion during reversal learning in Holtzman albino rats, but did not influence reversal learning in Long-Evans hooded rats. These results provide evidence that AVP may have differential actions on memory processes in different strains of rats.

Animals

Effects of perinatal PCB exposure on discrimination-reversal learning in monkeys.

Monkeys exposed to PCB mixtures during gestation and lactation were tested on two-choice discrimination-reversal learning (DR). In Experiment 1, offspring of mothers fed 1.0 ppm Aroclor 1248, and offspring born 1.5 years after maternal exposure to 2.5 ppm Aroclor 1248 ended did not differ from controls on spatial, color or shape DR problems. In Experiment 2, offspring of mothers fed 0.25 or 1.0 ppm Aroclor 1016 and offspring born 3 years after maternal exposure to 2.5 ppm Aroclor 1248 ended were tested on the same spatial, color and shape problems, but a spatial problem with color and shape as irrelevant cues was inserted after the initial spatial problem. Performance of the high dose Aroclor 1016 offspring was impaired on the initial spatial problem, and facilitated on the shape problem. Performance of the Aroclor 1248 postexposure offspring was facilitated on the shape problem. This apparently facilitatory effect may represent a failure of PCB-exposed monkeys to learn the irrelevancy of the shape cue when it was initially presented.

Adipose Tissue

Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.

Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were compared with controls for spatial, auditory, and olfactory serial reversal learning (SRL); spatial matching to sample (MTS); auditory go-no-go discrimination; and open-field exploration. PTD rats made more errors reaching criterion for SRL in all modalities but showed normal transfer effects between problems. PTD rats were also impaired in learning the go-no-go and MTS tasks and showed consistent alterations in exploratory activity. It is argued that the PTD rat, like human Korsakoff patients, have impairments of learning and memory (but spared capacity for reference memory) that extend across sensory modalities. Postmortem analyses showed normal indices of cortical cholinergic, noradrenergic, dopaminergic, and serotonergic function and consistent bilateral lesions of the thalamus, which were centered on the internal medullary lamina, and the medial mammillary nucleus.

Animals

Effects of context manipulation on memory and reversal learning in rats with hippocampal lesions.

In Experiment 1, groups of hippocampal and control rats learned a simultaneous discrimination habit and were subsequently tested for its retention under variable contextual conditions. All groups recalled the discrimination response to an equally high level when testing conditions were constant throughout, but the hippocampal group showed impaired memory when contextual stimuli at recall testing did not conform to those of original learning. Experiment 2 indicated that the hippocampal impairment was not simply the result of introducing novel stimuli. In Experimental 3, animals were administered a reversal learning task with contextual stimuli varied between the two tests. The typically observed impairment of hippocampal animals on this task was reduced by contrasting contextual conditions. The data are seen to support a contex-tetrieval interpretation of hippocampal function.

Animals

Reversal learning in pigeons: effects of selective lesions of the Wulst.

The effects of bilateral lesions of individual laminae of the Wulst on reversal-learning performance in pigeons were evaluated. After surgery, the birds were trained to perform a simultaneous color discrimination. Once successful discrimination was achieved, the positive and negative stimuli were reversed, and the birds were again trained to criterion. Twenty such reversals were carried out. A multiple regression analysis indicated that those components of the Wulst that were critical for increasing the numbers of errors on each reversal were the laminae that receive the thalamofugal visual projections, that is, the nucleus intercalatus of the hyperstriatum accessorium and the hyperstriatum dorsale. Lesions in the other laminae of the Wulst (the hyperstriatum accessorium and the hyperstriatum intercalatus superior) had no effect on errors. There was no evidence of an increase in either perseverative errors or position habits in the birds with lesions, which suggested that the reversal deficits were not likely to be due to perseveration, attentional impairment, or inappropriate processing of spatial information. The deficit may have been produced by excessive interference between learning in a given session and learning in previous sessions.

Animals

Effects of partial prefrontal lesions in dogs on go-no go avoidance reflex differentiation and reversal learning.

The effects of prefrontal medial or lateral lesions on the retention of avoidance go – no go click-tone differentiation in dogs were studied. The acquisition of the differentiation was influenced by the quality of the stimuli since more errors were performed to the click CS(-) than to the tone CS(-). Neither medial nor lateral lesions exerted any effect on retention of the differentiation. Similarly, as during original differentiation training, the quality of the stimuli had an effect on reversal learning in normal dogs. Such an effect was markedly reduced in dogs with prefrontal lesions and more strongly in those Ss which received lateral lesions. The results were discussed relative to data obtained from cats trained under similar conditions. The dogs showed better responding on positive trials while performance in cats was better on negative trials. The stimulus quality effect was more pronounced in dogs during negative, and in cats during positive trials.

Animals