Reversal learning facilitated by a single injection of lysergic acid diethylamide (LSD 25) in the rat.
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Serial discrimination-reversal learning with and without errors by the California sea lion.
A sea lion under water performed virtually without errors on a series of three form-discrimination reversals. Significant training requirements were the combining of a previously well-established size cue preference with the nonpreferred form cue, followed by the gradual reduction of the size cue until it was completely eliminated. Orienting responses reached a peak and then decreased during progressive-dimensional-change training, suggesting critical stages in the transition of attention from the size dimension to the form dimension. Further experimentation revealed that intensive training during these critical stages obviated the need to reduce very gradually the size cue. Without special training sea lions make perseverative errors on a series of form-discrimination reversals. "Emotional" or nontest-oriented behavior was associated only with the occurrence of successive errors.
Animals↗
Selective deficits in reversal learning after neostriatum caudolaterale lesions in pigeons: possible behavioral equivalencies to the mammalian prefrontal system.
The neostriatum caudolaterale (NCL) of birds is thought to be equivalent to the mammalian prefrontal cortex (PFC) due to its dense dopaminergic innervation, its associative structure, and its importance for cognitive tasks which are known to be affected in mammals with prefrontal lesions. The aim of the present study was to analyze the functional importance of the NCL and its main thalamic afferent structure, the n. dorsolateralis posterior thalami (DLP), in reversal and go/no-go tasks, two behavioral procedures which are often used to assess mammalian prefrontal functions. Using a multiple regression analysis in which structure-specific lesion extents are correlated with different postoperative behavioral measures, the specific contribution of the relevant structures were differentiated from the neighbouring areas CDL (area corticoidea dorsolateralis) and NC (neostriatum caudale). The analyses showed a highly significant contribution of the NCL to reversal but not to go/no-go or to visual discrimination performance, while all other structures under analysis had no impact on any behavioral measure. These results underline the specific contribution of the pigeons' NCL on a subset of cognitive tasks which are known to be affected by prefrontal lesions in mammals.
Animals↗
Effects of septal lesion on go, no-go differentiation and reversal learning in rats.
Experiments were done on 24 Sprague-Dawley male albino rats. Acquisition of go, no-go differentiation and its reversal were compared between normal and septal animals. Rats were trained in Skinner boxes on a 30-s VI food reinforcement schedule. Differentiation sessions consisted of periods with flashing and steady light on, randomly distributed. In half the subjects of each group reinforcement was available only during the flashing light (CS+ periods) while during the steady light no reinforcement was delivered (CS- periods). For the remaining subjects the allocation of stimuli as CS+ or CS- was reversed. During reversal training the signalling properties of the stimuli were reversed. The experiments confirmed that there is lesion-induced increment in base-line response rate. During differentiation training septal damage had no significant effect on the proportion of total responses emitted during CS-, although it increased the overall rate of CS- responding when the flashing light was used as CS-. During reversal training when the flashing light was used as CS- septal animals both responded at a higher rate during CS-, and emitted a higher proportion of their responses during CS-, relative to controls. There were no lesion effects on CS- responding when the steady light was used as CS-. Thus the septal deficit appeared when the to-be-extinguished habit was fairly strong and only under conditions of greater stimulus generalization. These results indicate that septal effects depend on a variety of experimental factors determining performance in any given test situation, among which stimulus intensity dynamism is one of particular importance.
Analysis of Variance↗
Olfactory discrimination, reversal learning, and stimulus control in rats.
Rats were trained to discriminate lights, tones, or odors and then given a series of discrimination reversals. Only rats trained with odors showed positive transfer on the first reversal and acquisition of a reversal set. Other experiments demonstrated that rats preferentially attend to odors when presented in compound with lights or tones; that odors exert more discriminative control than tones in tests using compound stimuli of competing sign; and that after pretraining on the positive stimulus, acquisition of an odor but not a light discrimination occurs with virtually no errors. These results demonstrate the importance of stimulus modality in the establishment of stimulus control and the need for more careful analysis of stimulus factors in cross-species comparisons of learning ability.
Animals↗
Cingulate cortical and anterior thalamic neuronal correlates of reversal learning in rabbits.
Unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training following differential conditioning of a locomotory (wheel rotation) avoidance response. The positive and negative conditional stimuli (CS+ and CS-) were pure tones (1 kHz and 8 kHz), and the unconditional stimulus was footshock (1.5 mA). During the first session, activity appropriate to the original task (i.e., a greater neuronal response to the CS- than to the CS+) occurred in the deep cortical laminae (V and VI), but the superficial laminae (I-IV) manifested the original discrimination in certain records and the reverse discrimination in others. All discriminative effects diminished during subsequent sessions except the short-latency (25-msec) deep laminar original discrimination, which persisted throughout reversal training. Activity of the AV nucleus underwent gradual transition, in parallel with the behavior, from the original to the reverse discrimination. Arousal-producing footshocks given after behavioral reversal educed the original and reverse discriminations in the deep and superficial laminae, respectively. These data are interpreted to indicate the role of cingulate cortex and anterior thalamus for encoding the associative significance of the conditional stimuli.
Animals↗
The effects of prenatal cocaine exposure on reversal learning using a simple visual discrimination task in rhesus monkeys.
The purpose of this research was to determine if adult animals that were exposed to cocaine prenatally would be able to adapt to changes in the rules of reinforcement for a simple discrimination task. Treatment groups included 0.0, 1.0, and 3.0 mg cocaine/kg/day and an escalating-dose group that began treatment at 3.0 mg cocaine/kg/day, after which the dose was increased by 0.5 mg cocaine/kg/day every 2 weeks throughout the pregnancy. All animals performed a color and position discrimination task for food reinforcers for approximately 6 years before the present study. For this task, subjects were presented with colored stimuli that determined the correctness of subsequent position choices: left for red or yellow and right for blue or green. At 7 years of age, the rules for obtaining reinforcement were reversed. Animals exposed to all doses of cocaine showed impaired reversal performance. Further, animals exposed to the escalating doses of cocaine continued to show this impairment for over 285 sessions (about 21/2 years). The number of sessions required by subjects to master these contingency changes indicated that, using a task with which they have an extensive history, cocaine-exposed animals have greater difficulty in adapting to important changes in their environment.
Age Factors↗
Reversal learning in Parkinson's disease depends on medication status and outcome valence.
We investigated the role of dopamine in distinct forms of reversal shifting by comparing two groups of patients with mild Parkinson's disease (PD), one ON and one OFF their normal dopaminergic medication. In accordance with our previous work, patients ON medication exhibited impaired reversal shifting relative to patients OFF medication. The present results extend previous studies by showing that the medication-induced deficit on reversal shifting was restricted to conditions where reversals were signaled by unexpected punishment. By contrast, patients ON medication performed as well as patients OFF medication and controls when the reversal was signaled by unexpected reward. The medication-induced deficit was particularly pronounced in patients on the dopamine D3 receptor agonist pramipexole. These data indicate that dopaminergic medication in PD impairs reversal shifting depending on the motivational valence of unexpected outcomes.
Aged↗
Teratology, survival, and reversal learning after fetal irradiation of mice by 2450-MHz microwave energy.
In the first of two factorially designed studies, 80 primigravid mice of the C3H-HeJ strain were subjected to 2450-MHz sinusoidally modulated microwave radiation or to sham radiation (with or without an accompanying injection of 5 mg of cortisone as a teratological marker) on the 11th, 12th, 13th or 14th day of gestation. The radiation treatment consisted of a single intense dosing of microwave energy (38 mW/g for 600 sec.= 22.8 J/g) in a multi-mode cavity. On the 19th day of gestation fetuses were taken via Caesarean section and were observed for gross structural abnormalities. While radiation of dams failed reliably to increase the incidence of fetal mortality or morbidity above that of controls, the dams treated with cortisone gave birth to reliably greater numbers of stillborn and deformed fetuses. In the second experiment and during their 14th day of gestation 60 primigravid mice received the radiation of sham-radiation treatment, half with, half without, the accompanying injection of cortisone. A virtually complete failure to survive to weaning characterized the pups born of the sham-radiated cortisone-treated group of dams, but the incidence of cortisone-induced mortality was reliably reduced in pups whose dams were also radiated by microwave energy. Pups sampled from all but the depleted group were observed later as young adults for competency in mastering a series of reversal habits in a water maze. No differences in maze performances were observed in the mice as a function of their placement in the control or the radiation condition, but offspring of cortisone-treated, radiated dams made reliably more errors. Careful measurement of elevations of colonic temperatures of radiated dams shortly after treatment with cortisone revealed an averaged deltaT that is close to that observed in a comparably radiated volume of water of equivalent mass. If the finding has generality beyond the gravid mouse-it, that is, cortisone effectively and reversibly renders the mammal ectothermic-an important advance in biological dosimetry of non-ionizing radiation may be at hand.
Abnormalities, Drug-Induced↗
Serial reversal learning of position discrimination in developing rats.
The current study established a procedure to evaluate the capability of rats on postnatal days (PND) 21, 26, and 30 to perform a spatial serial reversal task using a T-maze. Training consisted of an acquisition session followed by a series of six reversal sessions. To examine the role of proactive interference in the serial reversal effect, the point of reversal was manipulated so that it occurred at the start of each session (between-sessions) or the midpoint of each session (within-sessions). Performance was initially impaired during the first reversal but improved dramatically across the series. Reversal between-sessions enhanced this serial reversal effect in comparison to reversal within-sessions. Experiment 1 showed that rats of all ages learned the between-sessions serial reversal task at a comparable rate. However, on the within-sessions task, PND21 rats were impaired relative to the PND26 and 30 rats, which did not differ. Experiment 2 revealed that the addition of a tactile cue that is correlated with each phase of reversal eliminated age and task differences in serial reversal performance. These findings suggest that higher-order cognitive processes underlying serial reversal are present during the weanling period, but there is some improvement with age under conditions involving high memory interference and/or difficulty in detecting the transition between reversal phases.
Age Factors↗
Reversal learning and forgetting in bird and fish.
Pigeons and goldfish were trained in red-green discrimination in daily sessions, with the rewarded color changed every 2 days. Improvement in the performance of the pigeons could be traced to decrements in retention from each day to the next. The goldfish showed no improvement and no decrements in retention. The results suggest that progressive improvement in habit reversal is a product of proactive interference, and that the absence of improvement in the fish is due, not to the lack of some higher-order process which operates to produce improvement in higher vertebrates, but to a difference in learning-retention mechanisms.
Animals↗
Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.
Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.
Adult↗
Executive system dysfunction in the aged monkey: spatial and object reversal learning.
As part of the effort to characterize age-related cognitive changes in executive system function in a nonhuman primate model of human aging, the performance of seven rhesus monkeys, 20 to 28 years of age, was compared to that of five young adult monkeys, 6 to 11 years of age, on spatial and object reversal tasks. No differences in performance were found between the two groups in the initial learning of either task. On spatial reversals, aged monkeys were impaired relative to young adults, but there was no difference in overall performance between the groups on object reversals. Central to this article, a perseverative tendency was noted in the aged group on both spatial and object reversal tasks. Changes in executive system dysfunction may represent an important aspect of age-related cognitive decline.
Age Factors↗
A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.
Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.
Analysis of Variance↗
Associative encoding in posterior piriform cortex during odor discrimination and reversal learning.
Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex and basolateral amygdala (ABL). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. We recently reported that neurons in anterior piriform cortex (APC) in rats exhibited significant plasticity in their responses to odor cues during associative learning. Here, we have repeated this study, recording from neurons in posterior piriform cortex (PPC), a region of piriform cortex that receives much stronger input from ABL. If associative encoding in piriform cortex is driven by inputs from ABL, then we should see more plasticity in PPC neurons than we observed in APC. Consistent with this hypothesis, we found that PPC neurons were highly associative and appeared to be somewhat more likely than neurons recorded in APC to alter their responses to the odor cues after reversal of the odor-outcome associations in the task. Further, odor-selective PPC populations exhibited markedly different firing patterns based on the valence of the odor cue. These results suggest associative encoding in piriform cortex is represented in a topographical fashion, reflecting the stronger and more specific input from olfactory bulb concerning the sensory features of odors in anterior regions and stronger input from ABL concerning the meaning of odors in posterior regions.
Amygdala↗
Acute delta9-tetrahydrocannabinol-induced deficits in reversal learning: neural correlates of affective inflexibility.
Despite concerns surrounding the possible adverse effects of marijuana on complex cognitive function, the processes contributing to the observed cognitive deficits are unclear, as are the causal relationships between these impairments and marijuana exposure. In particular, marijuana-related deficits in cognitive flexibility may affect the social functioning of the individual and may contribute to continued marijuana use. We therefore examined the ability of rats to perform affective and attentional shifts following acute administration of Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive marijuana constituent. Administration of 1 mg/kg THC produced marked impairments in the ability to reverse previously relevant associations between stimulus features and reward presentation, while the ability to transfer attentional set between dimensional stimulus properties was unaffected. Concurrent in situ hybridization analysis of regional c-fos and ngfi-b expression highlighted areas of the prefrontal cortex and striatum that were recruited in response to both THC administration and task performance. Furthermore, the alterations in mRNA expression in the orbitofrontal cortex and striatum were associated with the ability to perform the reversal discriminations. These findings suggest that marijuana use may produce inelasticity in updating affective associations between stimuli and reinforcement value, and that this effect may arise through dysregulation of orbitofrontal and striatal circuitry.
Affect↗
Post-trial administration of H1 histamine receptor blocker improves appetitive reversal learning and memory in goldfish, Carassius auratus.
Based on the hypothesis that neuronal histamine exerts an inhibitory influence on learning and reinforcement, goldfish were tested for post-trial effects of the H1 receptor blocker chlorpheniramine (CPA) on learning the location of a food source in one of two compartments, one black the other white, with a feeder located in each compartment. Testing was carried out over 6 days. On the training day a food pellet was placed into the feeder of one of the compartments. After consumption of the food the fish were injected i.p. with either vehicle or CPA either immediately after training or 3 h later. Twenty-four-hours later, food was placed in the same compartment and the time to begin feeding was recorded. On the next day the location of the food pellet was reversed, and testing was continued for 4 days. On the first test day the time to begin feeding was significantly longer for the vehicle injected fish as compared with those injected with CPA. The vehicle group also took longer to begin feeding than the CPA group on the first reversal test day. The results of the 3-h delay groups indicated no significant differences between vehicle and drug for any experimental session. These results suggest that post-trial blockade of the H1 histamine receptor can affect appetitive learning in goldfish either by improving long-term memory consolidation and/or by the additive reinforcing effects of CPA (known from previous studies) on behavior.
Animals↗
Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that has been shown to alter spatial and visual learning following developmental exposure. The current study examined the effects of gestational and lactational exposure to TCDD on spatial and visual discrimination/reversal learning (spatial and visual RL) in rats using two-lever operant testing chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1 microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One male and one female from each litter were tested beginning at 100 days of age. For spatial RL, animals were reinforced for pressing the lever associated with the correct spatial location (either left or right). For visual RL, the animals were reinforced for pressing the lever associated with the correct visual stimulus (either the illuminated or nonilluminated cuelight). After reaching 85% correct for two consecutive days, the opposite spatial location or visual cue was reinforced. Five reversals were conducted for spatial RL, and two reversals for visual RL. For spatial RL, there were no differences between the TCDD-exposed and control rats in total number of errors committed. However, an in-depth analysis of errors in four different phases of the learning process revealed that TCDD-exposed rats made more errors early in learning when they were just beginning to learn the new reinforcement contingencies. The importance of this increase in errors during the initial stage of learning is unclear, given that there was no increase in overall errors to criterion. For visual RL, there was a reduction in errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed females exhibited a reduction in errors on the second reversal. Subsequent response pattern analyses revealed that the facilitation in performance was due to a more rapid transition through the early phase of learning. Why males were improved on OL and females were not until the second reversal is unknown, but the different patterns could reflect differences in learning style in male and female rats. In keeping with previous research, the results of the current study underscore the fact that (1) alterations in cognitive function observed following early TCDD exposure are very subtle and (2) under some conditions, learning is actually facilitated, rather than impaired, in TCDD-exposed animals.
Analysis of Variance↗