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Inferotemporal-frontal Disconnection: The Uncinate Fascicle and Visual Associative Learning in Monkeys.

We report a series of six experiments in which we examined the behavioural effects of disconnecting the inferior temporal cortex from the prefrontal cortex in cynomolgus monkeys by sectioning the direct cortico-cortical pathway between them, the uncinate fascicle. In experiment 1, monkeys with bilateral section of the uncinate fascicle showed a marked deficit in learning visuomotor conditional problems. Experiments 2 and 3 demonstrated that this deficit was not the result of a mild motor impairment, nor of a visual discrimination impairment. However, experiment 4 showed that the impairment extended to visual - visual conditional learning. In contrast, following bilateral section of the uncinate fascicle monkeys were unimpaired at two other tasks of visual associative learning: a reward - visual associative task (experiment 5), in which the presence or absence of a food reward served as a cue to the correct choice between two visual stimuli, and a time - visual associative task (experiment 6), in which the cue to the correct choice was the length of the intertrial interval. Thus, animals with uncinate fascicle section showed no impairment in learning to choose between visual stimuli based on their differential association with food reward or other non-visual cues, but were unable to learn to choose between visual stimuli based on their differential association with another visual stimulus. They were equally unable to choose between two motor responses on the basis of the visual cue.

Journal Article↗

Effects of learning contexts on implicit and explicit learning.

Two parallel tasks involving rule learning were identified in Experiment 1A and were used to assess implicit and explicit learning. In both tasks, subjects had to input numbers in order to reach the target values of outputs. The relationship between inputs and outputs was either simple (in the simple task) or complex (in the complex task), and the way in which target values were presented could be in the form of either numbers (in the simple task) or lines (in the complex task). Experiment 1B examined the validity of the explicit measure in the complex task. Experiments 2-4 investigated the interaction between learning contexts and the simple/complex learning tasks. Verbalization and instructions to search for the rules facilitated the simple-task learning and hurt or have no effect on the complex-task learning. In the observational-learning condition, no learning occurred for the simple task, and the complex task learning was impaired. These results suggest that the complex task and simple task involve two distinct learning systems. Other implications are also discussed.

Adolescent↗

[Stress-induced blood protein and blood lipid changes and their dependence on learning and conditioning].

Rats were subjected to two kinds of stress and consequent changes in blood protein and lipids were investigated. Furthermore, an attempt was made to ascertain whether or not increases or decreases in these blood parameters were reproducible by conditioning. In the first experiment animals were subjected to stress in a modified running wheel (Noble Collip drum). A series of 10 conditional stimuli (light-sound combined) was delivered together with the stress-producing stimulus. After the first exposure to stress a relative alpha1-globulin increase was observed. After 10 stress exposures the hitherto neutral stimulus alone produced a conditioned increase in the alpha1-globulin fraction. The gamma-globulin values were decreased after the first exposure to stress, but increased after 10 stress exposures. This increase could also be conditioned. In the second experiment "white noise" stress was used (110 dB). The conditional stimulus was light. After short exposure to the stress-inducing stimulus, the gamma-globulins showed a slight drop and remained thus during the whole experiment. The analysis of blood lipids showed increased stress values for alpha-lipoprotiens and reduced values for beta-fractions. Cholesterol and triglycerides reacted like the beta-lipoproteins. The total blood lipid content was, however, increased. The conditioned increase in alpha-lipoproteins and total lipids was statisticallysignigicant. It is noteworthy that the conditioned alpha-lipoprotein levels shoeed significant differences between experimental and control groups. The conditioned stress increased the levels of cholesterol and triglycerides, whereas under real stress conditions decreases were found. Research on "conditioned stress" could beof improtance in regard to clinical aspects of coronary heart disease.

Animals↗

NMDA receptor antagonist MK-801 blocks learning of conditioned stimulus-unconditioned stimulus contiguity but not fear of conditioned stimulus in goldfish (Carassius auratus L.).

The blockade of learning of Pavlovian fear conditioning by the N-methyl-D-aspartic acid (NMDA)-receptor antagonist MK-801 was examined in 166 goldfish. In previously untrained fish, MK-801 blocked learning of a light-off or a tone conditioned stimulus (CS) paired with an electrical shock unconditioned stimulus (US). Pretraining on the light-off CS did not affect the rate of learning of the tone CS but protected the tone learning from disruption by MK-801. Switching from the light-off to the tone CS changed the identity of the CS but not its temporal contiguity with the US. Pretraining consisting of pseudoconditioning of the light-off CS did not protect subsequent tone learning from blockade by MK-801. Thus, the NMDA receptor functions are necessary for learning related to the temporal contiguity of the CS and US but not to the identity of the CS as a cue to the occurrence of the fearful effects of the US.

Acoustic Stimulation↗

Reduced after-hyperpolarization in rat piriform cortex pyramidal neurons is associated with increased learning capability during operant conditioning.

Learning-related cellular modifications were studied in the rat piriform cortex. Water-deprived rats were divided to three groups: 'trained' rats were trained in a four-arm maze to discriminate positive cues in pairs of odours, 'control' rats were 'pseudo-trained' by random water rewarding, and 'naive' rats were water-deprived only. In one experimental paradigm, the trained group was exposed to extensive training with rats learning to discriminate between 35 and 50 pairs of odours. Piriform cortex pyramidal neurons from 'trained', 'control' and 'naive' rats did not differ in their passive membrane properties and single spike characteristics. However, the after-hyperpolarizations (AHPs) that follow six-spike trains were reduced after 'extensive training' by 43% and 36% compared with 'control' and 'naive', respectively. This effect was not observed in the piriform cortex of another group of rats, in which hyperexcitability was induced by chemical kindling. In another experimental paradigm rats were trained only until they demonstrated 'rule learning', usually after discriminating between one and two pairs of odours ('mild training'). In this experiment, a smaller, yet significant, reduction (20%) in AHPs was observed. AHP reduction was apparent in most of the sampled neurons. AHP remained reduced up to 3 days after the last training session. 5 days or more after the last training session, AHP amplitude recovered to pre-training value and did not differ between 'trained' rats and the others. Accordingly, training suspension for 5 days or more resulted in slower learning of novel odours. We suggest that increased neuronal excitability, manifested as reduced AHP, is related to the ability of the cortical network to enter a 'learning mode' which creates favourable conditions for enhanced learning capability.

Animals↗

The role of prefrontal cortex in object-in-place learning in monkeys.

Previous ablation studies in monkeys suggest that prefrontal cortex is involved in a wide range of learning and memory tasks. However, monkeys with crossed unilateral lesions of frontal and temporal cortex are unimpaired at concurrent object-reward association learning but are impaired at conditional learning and the implementation of memory-based performance rules. We trained seven monkeys preoperatively on an associative learning task that required them to associate objects embedded in unique complex scenes with reward. Three monkeys then had crossed unilateral lesions of frontal and inferior temporal cortex and the remaining monkeys had bilateral prefrontal cortex ablation. Both groups were severely impaired postoperatively. These results show that both bilateral prefrontal cortex ablation and frontal-temporal disconnection impair associative learning for objects embedded in scenes. The results provide evidence that the function of frontal-temporal interactions in memory is not limited to conditional learning tasks and memory-dependent performance rules. We propose that rapid object-in-place learning requires the interaction of frontal cortex with inferotemporal cortex because visual object and contextual information which is captured over multiple saccades must be processed as a unique complex event that is extended in time. The present results suggest a role for frontal-temporal interaction in the integration of visual information over time.

Animals↗

Nonconscious associative learning: Pavlovian conditioning of skin conductance responses to masked fear-relevant facial stimuli.

We examined the possibility of nonconscious associative learning in a context of skin conductance conditioning, using emotional facial expressions as stimuli. In the first experiment, subjects were conditioned to a backwardly masked angry face that was followed by electric shock, with a masked happy face as the nonreinforced stimulus. In spite of the effectively masked conditioned stimuli, differential conditioned skin conductance responses were observed in a subsequent nonmasked extinction phase. This effect could not be attributed to differential sensitization or pseudo-conditioning. In the second experiment, the differential responding during extinction was replicated with angry but not with happy faces as conditioned stimuli. It was concluded that with fear-relevant facial expressions as the conditioned stimulus, associative learning was possible even in conditions where the subjects remained unaware of the conditioned stimulus and its relationship to the unconditioned stimulus.

Adult↗

Conditional associative learning of spatial and object information in children with attention deficit/hyperactivity disorder.

The present study assessed frontostriatal mediated memory functions in children with ADHD (N=12) and healthy control participants (N=12) using two tests of conditional associative learning (i.e., object and spatial) that shared similar stimulus-response association structures but that differed in terms of the demands placed upon strategic processes. Children with ADHD displayed normal performance on the object learning task but were impaired on the spatial learning task that placed greater demands on internally derived strategic processes. Secondary analyses further indicated that this strategic processing impairment cannot be attributed specifically to perseverative or working memory errors but rather appears to be related to a more general inability to maintain a high degree of consistency in responding across trials. Although the results of this study must be interpreted in light of the small sample sizes, they suggest that ADHD does not produce a basic deficit in acquiring stimulus-response associations previously shown to be associated with basal ganglia dysfunction. Rather, these findings suggest that the impaired conditional associative learning performance of children with ADHD is attributable to deficits in strategic processes previously been found to be dependent upon the integrity of the prefrontal cortex.

Association Learning↗

Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study.

Catecholamines, including dopamine and norepinephrine, are the principal neurotransmitters that mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are implicated in some neurologic and neuropsychiatric disorders. Recent mouse molecular genetic approaches provide genetic evidence for an important role of catecholamines in brain functions. In this paper, I describe the phenotype of mutant mice with impairments in dopamine or norepinephrine biosynthesis. Mice defective in dopamine biosynthesis exhibit severe motor dysfunctions characterized by a reduction in spontaneous locomotion and cataleptic behavior, and defects in drug-induced hyperactivity at the juvenile stage. They also exhibit defects in the acquisition of conditioned learning dependent on tone stimulus. These results indicate that dopamine is essential for motor control and emotional learning during postnatal development, possibly through nigrostriatal and mesolimbic neuronal pathways. On the other hand, mice carrying the mutation in the gene encoding tyrosine hydroxylase (the rate-limiting enzyme of catecholamine biosynthesis) display a reduction in norepinephrine biosynthesis. This leads to deficits in latent learning and long-term memory formation of different conditioned learning paradigms. The results indicate that norepinephrine is essential for the consolidation process of long-term memory, suggesting that norepinephrine may control the neuronal activity in the cerebral cortex or amygdala to maintain the memory process of conditioned learning.

Animals↗

Effect of acetyl-L-carnitine on conditioned reflex learning rate and retention in laboratory animals.

The aim of the study was to evaluate the effects of acetyl-L-carnitine on learning and/or memory processes in laboratory animals. In the water maze test, acetyl-L-carnitine, given intraperitoneally at doses ranging from 0.3 to 100 mg/kg, improved performances in both mice and rats. In the latter the drug also proved active when administered orally in the 3-100 mg/kg dosage range. In the pole climbing test in the rat, acetyl-L-carnitine at doses ranging from 0.03 to 10 mg/kg i.p. increased the conditioned reflex learning rate. In the passive avoidance test in the rat, significant increases in retention were observed after treatment with acetyl-L-carnitine at doses ranging from 1 to 30 mg/kg i.p. In the passive avoidance plus electroconvulsive shock test in the mouse, acetyl-L-carnitine antagonized amnesia at doses ranging from 0.1 to 3 mg/kg i.p.

Acetylcarnitine↗

Role of the hippocampal system in conditional motor learning: mapping antecedents to action.

Macaque monkeys can learn arbitrary mappings between stimuli and spatially directed actions (often termed conditional motor learning), and, after the development of a strong learning set, can do so in just a few trials. Ablation studies have shown that the hippocampus plus subjacent cortex is necessary for this rapid and highly flexible type of learning. We consider evidence that the arbitrary mapping function of the hippocampal system may be more general and fundamental than currently accepted and what limitations there may be, if any, on the information that it can map. Removal of the hippocampal system yields a pattern of deficits and preserved abilities that correlates remarkably closely with that found in human global amnesics, such as patient H.M., on a variety of declarative memory tasks. Thus, the rapid acquisition of arbitrary visuomotor mappings may represent an example of declarative memory in nonhuman primates.

Animals↗

Effects of lesions to the hippocampus or the fornix on allocentric conditional associative learning in rats.

Rats with lesions of the fornix, the hippocampus, or normal control animals were trained on a visual-spatial conditional associative learning task in which they had to learn to go to a particular location based on the presence of a specific visual cue; the rats approached the cues from different directions. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals. The performance of the hippocampal rats was significantly impaired as compared with the control group. Both the fornix and the hippocampal animals were significantly impaired on a spatial working memory task, the eight-arm radial maze. These findings suggest that, under certain conditions, a functional dissociation exists between the effects of damage to the fornix or the hippocampus and that the fornix may be only selectively involved in spatial learning and memory.

Animals↗

The impairment of learning of conditioned avoidance response in rats after 6-hydroxydopamine.

Intraventricular injection of 250 mug of 6-hydroxydopamine, twice in two days apart caused a complete abolition of learning of conditioned avoidance response (CAR) in rats. L-DOPA in a dose of 100 mg/kg and then in a dose of 200 mg/kg 1. p. injected during several days did not restore the learning of CAR. This indicates that intact catecholaminergic neurons are essential for the learning of CAR. We suggest that different brain mechanisms are involved in learning and maintaining gross locomotor behavior.

Animals↗

The effect of social learning on a conditioned avoidance response of rats treated prenatally with aluminum lactate.

Aluminum (Al) has been proven to be a behavioral teratogenic agent in a number of experimental studies. Prenatal exposures to Al lactate have been shown to cause cognitive deficits in a variety of species. The present experiment was carried out on SPRD rat pups treated prenatally with Al lactate to determine whether observational conditioning (social learning) would reverse the impairment in learning described previously following such treatment. A conditioned avoidance response was used as an observational learning task. The results provide evidence that Al-treated pups are capable of social learning (i.e., the performance of the avoidance response improved as a result that Al-treated learning); however, the response latency of the avoidance response was not different in these animals from those that were not exposed to such facilitation, suggesting that additional factors are involved in the effects of prenatal aluminum intoxication on cognitive processes.

Aluminum Compounds↗

Conditional discrimination learning in the pigeon.

Four pigeons received conditional discrimination training in which reinforcement contingencies were related to specific combinations of color and form, but were unrelated to either color or form considered separately. During discrete-trial training, each response in the presence of two of four color-form displays produced reinforcement and terminated the trial; responding to the other two displays was never reinforced, and each such response prolonged the particular trial on which it occurred. Subsequently, the subjects received multiple-schedule training in which responding to either of the displays previously associated with reinforcement was now reinforced on a variable-interval schedule, and extinction was the schedule again correlated with the other two displays. After differential responding to the stimuli was clearly evident, intensity of the combination displays was changed in subsequent training sessions. Complex stimulus control was generally maintained across variation in intensity, although there were temporary disruptions in performance associated with onset of some of the intensity changes. Finally, a component-stimulus test revealed considerably more responding to the forms than to the colors.

Journal Article↗

Are people with mild cognitive impairment aware of the benefits of errorless learning?

Mild cognitive impairment (MCI) has been described as a memory deficit in the absence of other cognitive dysfunction. It can be thought of as a pre-clinical dementia. Memory impairment in this group is not as severe as in early dementia and thus learning is still possible. We were interested to see if errorless learning, a widely used rehabilitation technique, was of benefit to people with MCI. Since it has been shown that successful rehabilitation is somewhat contingent on awareness of function, we were also interested to see if people with MCI were aware of the benefits of errorless learning. The present study employed an errorless learning procedure on 16 people with MCI and 16 older adult controls to learn two lists of 10 words in errorless and errorful learning conditions. We adopted a metacognitive approach measuring people's memory monitoring through judgements of learning (JOLs) a prediction of future memory performance. The results revealed errorless learning is an effective memory rehabilitation tool for people with MCI, with significant increases in recall performance for both groups relative to errorful learning. Most interestingly participants were aware of the benefits of errorless learning in their JOLs. MCI participants and controls both had significantly higher JOLs for words studied under errorless learning conditions. The learning performance in MCI and theories of metacognitive awareness are discussed.

Aged↗