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Can amnesic patients learn without awareness? New evidence comparing deterministic and probabilistic sequence learning.

Can associative learning take place without awareness? We explore this issue in a sequence learning paradigm with amnesic and control participants, who were simply asked to react to one of four possible stimuli on each trial. Unknown to them, successive stimuli occurred in a sequence. We manipulated the extent to which stimuli followed the sequence in a deterministic manner (noiseless condition) or only probabilistically so (noisy condition). Through this paradigm, we aimed at addressing two central issues: first, we asked whether sequence learning takes place in either condition with amnesic patients. Second, we asked whether this learning takes place without awareness. To answer this second question, participants were asked to perform a subsequent sequence generation task under inclusion and exclusion conditions, as well as a recognition task. Reaction times results show that amnesic patients learned the sequence only in the deterministic condition. However, they failed to be able to reproduce the sequence in the generation task. In contrast, we found learning for both sequence structures in control participants, but only control participants exposed to a deterministic sequence were successful in performing the generation task, thus suggesting that the acquired knowledge can be used consciously in this condition. Neither amnesic nor control participants showed correct old/new judgments in the recognition task. The results strengthen the claim that implicit learning is at least partly spared in amnesia, and the role of contextual information available for learning is discussed.

Adult↗

The effects of estradiol on avoidance learning in ovariectomized adult rats.

The present study examined the effects of ovariectomy and subsequent estradiol replacement on learning in young adult rats using a set of instrumental avoidance paradigms differing in the nature and extent of prior experience in the learning context. Thus, one group of animals was placed directly into avoidance learning (AV). A second group was trained on an appetitive task first, and then transferred into the aversive context (AP-AV). The third group was exposed to the training context without any specific appetitive response requirement, and then required to learn an active avoidance response (Context-AV). We found that estradiol (OVX+E) impaired avoidance acquisition in all cases relative ovariectomized controls (OVX). In contrast, while avoidance learning is improved following appetitive training or context exposure in both OVX+E and OVX animals, the OVX+E animals profit to a greater extent from the appetitive or context experience than do the OVX controls. We suggest that this difference may be due to enhanced attentional processes or improved hippocampal processing of contextual factors. Thus, estradiol negatively influences simple associative avoidance learning in ovariectomized rats, but appears to promote positive transfer.

Animals↗

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity.

RATIONALE: Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine. OBJECTIVES: To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine. METHODS: Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined. RESULTS: Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS. CONCLUSIONS: Given that fluoxetine and rECS share antidepressant properties, but differ in their effects on learning and memory, we propose that the common effects on dentate connectivity and synaptic plasticity described here are more likely to relate to affective rather than cognitive function. This result is consistent with other experiments showing that a reduction in dentate connectivity correlates with stress susceptibility in animals.

Animals↗

Marr's theory of the neocortex as a self-organizing neural network.

Marr's proposal for the functioning of the neocortex (Marr, 1970) is the least known of his various theories for specific neural circuitries. He suggested that the neocortex learns by self-organization to extract the structure from the patterns of activity incident upon it. He proposed a feedforward neural network in which the connections to the output cells (identified with the pyramidal cells of the neocortex) are modified by a mechanism of competitive learning. It was intended that each output cell comes to be selective for the input patterns from a different class and is able to respond to new patterns from the same class that have not been seen before. The learning rule that Marr proposed was underspecified, but a logical extension of the basic idea results in a synaptic learning rule in which the total amount of synaptic strength of the connections from each input ("presynaptic") cell is kept at a constant level. In contrast, conventional competitive learning involves rules of the "postsynaptic" type. The network learns by exploiting the structure that Marr assumed to exist within the ensemble of input patterns. For this case, analysis is possible that extends that carried out by Marr, which was restricted to the binary classification task. This analysis is presented here, together with results from computer simulations of different types of competitive learning mechanisms. The presynaptic mechanism is best known in the computational neuroscience literature. In neural network applications, it may be a more suitable mechanism of competitive learning than those normally considered.

Algorithms↗

Modest neuropsychological deficits caused by reduced noradrenaline metabolism in mice heterozygous for a mutated tyrosine hydroxylase gene.

Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines that are considered to be involved in a variety of neuropsychiatric functions. Here, we report behavioral and neuropsychological deficits in mice carrying a single mutated allele of the TH gene in which TH activity in tissues is reduced to approximately 40% of the wild-type activity. In the mice heterozygous for the TH mutation, noradrenaline accumulation in brain regions was moderately decreased to 73-80% of the wild-type value. Measurement of extracellular noradrenaline level in the frontal cortex by the microdialysis technique showed a reduction in high K(+)-evoked noradrenaline release in the mutants. The mutant mice displayed impairment in the water-finding task associated with latent learning performance. They also exhibited mild impairment in long-term memory formation in three distinct forms of associative learning, including active avoidance, cued fear conditioning, and conditioned taste aversion. These deficits were restored by the drug-induced stimulation of noradrenergic activity. In contrast, the spatial learning and hippocampal long-term potentiation were normal in the mutants. These results provide genetic evidence that the central noradrenaline system plays an important role in memory formation, particularly in the long-term memory of conditioned learning.

Animals↗

The neuroethology of cognitive maps: contributions from research on the hippocampus and homing pigeon navigation.

The rich ethological tradition that characterizes the homing behavior of pigeons offers an excellent opportunity to examine the importance of the hippocampal formation for the regulation of spatial cognitive mechanisms. The present review summarizes both anatomical and behavioral data obtained in researches on the pigeon hippocampal formation that have been performed over the last 12 years. Pathway connection studies and investigations on the neurochemical organization of the avian hippocampal formation show that this structure shares many similarities with the mammalian hippocampus and provide the basis for structural as well as functional homology. The initial research on the role of the hippocampal formation in the homing behavior showed that this brain structure is likely to be involved in phenomena of spatial cognition. Therefore, the homing behavior of pigeons has been extensively used as an experimental model to investigate the role of the hippocampal formation in spatial cognition related to a naturally occurring behavior. These studies have revealed that the hippocampal formation plays a fundamental role in the learning of a navigational map based on atmospheric odors, but it doesn't seem to be involved in the operation of such a map. In contrast, both the learning and the operation of a navigational map based on the recognition of familiar landmarks require a functional hippocampal formation. Further investigations indicated that these functions of the hippocampal formation are mediated by its involvement in the use of the sun compass, and suggested that the hippocampal formation plays a fundamental role in a cognitive process in which the sun compass is specifically used to learn about the location of stimuli in space. The studies reviewed in the present paper have provided a considerable amount of experimental data both on the anatomical/neurochemical organization of the avian hippocampal formation and on the role played by this brain structure in spatial cognition. The future development of these researches will need to consider the contribution to hippocampal function of specific transmitter systems that are involved in hippocampal circuitry. In particular, the afferent cholinergic system and some of the peptidergic systems intrinsic to the hippocampal formation deserve particular attention in view of their possible involvement in the acquisition and/or operation of spatial cognitive abilities by homing pigeons.

Animals↗

Comparison of two intracranial self-stimulation (ICSS) paradigms in C57BL/6 mice: head-dipping and place-learning.

A variety of intracranial self-stimulation (ICSS) paradigms have been utilized for investigations of reward. Among them, nose-poking and spatial-preference paradigms are known to be relatively more resistant to the effects of drug-induced motor-deficits in rat studies, although these two ICSS paradigms have not been directly compared in previous studies. In the present study, head-dipping and place-learning (forms of nose-poking and spatial-preference tasks, respectively) paradigms with lateral hypothalamus stimulation were systematically analyzed using C57BL/6 mice in the presence and absence of two motor-deficit-inducing drugs: tolperisone and harmaline. Rapid acquisition and rapid extinction patterns of ICSS responding were observed in the head-dipping and place-learning paradigms. In contrast to these pre-drug similarities in responding, dramatic differences were noted after drug administration. Tolperisone significantly reduced head-dipping but not place-learning ICSS responding. Similarly, reduction of ICSS responding after harmaline was more pronounced in the head-dipping task. Therefore, the place-learning paradigm may be superior for the assessment of reward values under motor-deficit-inducing conditions in C57BL/6 mice. The relative benefits and disadvantages of both ICSS paradigms are discussed. Combinations of complementary ICSS paradigms using mice may be useful for further investigations of the molecular bases of reward.

Animals↗

Detection in fixed and random noise in foveal and parafoveal vision explained by template learning.

Foveal and parafoveal contrast detection thresholds for Gabor and checkerboard targets were measured in white noise by means of a two-interval forced-choice paradigm. Two white-noise conditions were used: fixed and twin. In the fixed noise condition a single noise sample was presented in both intervals of all the trials. In the twin noise condition the same noise sample was used in the two intervals of a trial, but a new sample was generated for each trial. Fixed noise conditions usually resulted in lower thresholds than twin noise. Template learning models are presented that attribute this advantage of fixed over twin noise either to fixed memory templates' reducing uncertainty by incorporation of the noise or to the introduction, by the learning process itself, of more variability in the twin noise condition. Quantitative predictions of the template learning process show that it contributes to the accelerating nonlinear increase in performance with signal amplitude at low signal-to-noise ratios.

Artifacts↗

Selective learning in children after traumatic brain injury: a preliminary study.

Selective learning (SL) is the ability to select items to learn from among other items. It requires the use of the executive processes of metacognitive control and working memory, which are considered to be mediated by the frontal cortex and its circuitry. We studied the efficiency with which verbal items of greater value are selectively learned from among items varying in value in 14 children ages 8-15 years who had sustained severe traumatic brain injury (TBI) and in 39 typically developing age-matched children. We hypothesized that children with TBI would be disproportionately compromised in selective learning efficiency in contrast to memory span when compared to normally developing children. The results supported our hypothesis, as children with TBI performed significantly worse than controls on a measure of selective learning efficiency, but the two groups performed similarly on a measure of word recall within the same task. Furthermore, the effect of TBI on performance was demonstrated to take place at the time of encoding, rather than at retrieval.

Adolescent↗

Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans.

Much evidence suggests that lesions of the prefrontal cortex (PFC) produce marked impairments in the ability of subjects to shift cognitive set, as exemplified by performance of the Wisconsin Card Sorting Test (WCST). However, studies with humans and experimental primates have suggested that damage to different regions of PFC induce dissociable impairments in two forms of shift learning implicit in the WCST (that is, extradimensional (ED) shift learning and reversal shift learning), with similar deficits also being apparent after damage to basal ganglia structures, especially the caudate nucleus. In this study, we used the same visual discrimination learning paradigm over multidimensional stimuli, and the H215O positron emission tomography (PET) technique, to examine regional cerebral blood flow (rCBF) changes associated with these subcomponent processes of the WCST. In three conditions, subjects were scanned while acquiring visual discriminations involving either (i) the same stimulus dimension as preceding discriminations (intradimensional (ID) shifts); (ii) different stimulus dimensions from previous discriminations (ED shifts) or (iii) reversed stimulus-reward contingencies (reversal shifts). Additionally, subjects were scanned while responding to already learnt discriminations ('performance baseline'). ED shift learning, relative to ID shift learning, produced activations in prefrontal regions, including left anterior PFC and right dorsolateral PFC (BA 10 and 9⁄46). By contrast, reversal learning, relative to ID shift learning, produced activations of the left caudate nucleus. Additionally, compared to reversal and ID shift learning, ED shift learning was associated with relative deactivations in occipito-temporal pathways (for example, BA 17 and 37). These results confirm that, in the context of visual discrimination learning over multidimensional stimuli, the control of an acquired attentional bias or'set', and the control of previously acquired stimulus-reinforcement associations, activate distinct cortical and subcortical neural stations. Moreover, we propose that the PFC may contribute to the control of attentional-set by modulating attentional processes mediated by occipito-temporal pathways.

Adult↗

Medial prefrontal and subcortical mechanisms underlying the acquisition of motor and cognitive action sequences in humans.

The anterior medial prefrontal cortex (AMPC) in humans is involved in affect and in regulating goal-directed behaviors. The precise function of the AMPC, however, is poorly understood. Using magnetic resonance imaging, we found that bilateral regions in the AMPC were selectively recruited to compute the reliability of subjects' expectations that developed when subjects were learning sequences of cognitive tasks. In contrast, regions similarly recruited in learning sequences of motor acts were found in the ventral striatum. Our results show that beyond the execution of motor acts, the AMPC is selectively engaged in computing the relevance of cognitive goals that subjects intend to achieve. This indicates that the fronto-striatal circuit, including the ventral striatum and AMPC, subserves hierarchically distinct evaluative processes mediating the human ability to build behavioral plans, ranging from motor to cognitive action plans.

Adult↗

Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.

Aged↗

Attitudes of general practitioners to caring for people with learning disability.

BACKGROUND: The views of general practitioners on their increasing role in caring for people with learning disability in the community are not known. AIM: A study was carried out to assess the views of general practitioners with regard to providing routine care, organizing health promotion and specific health checks for people with learning disability and the role of specialists. METHOD: A postal questionnaire was sent to all 242 general practitioners in Gwent, south Wales. Participants had to mark their level of agreement with 20 attitude statements regarding learning disability. RESULTS: A total of 126 general practitioners (52%) responded. Respondents generally agreed that general practitioners were responsible for the medical care of people with learning disability. Respondents tended to be opposed to providing regular structured health promotion for people with learning disability, such as annual health checks and assessing hearing and eyesight. Specialist services were generally valued by respondents. CONCLUSION: General practitioners largely accepted their role as primary health care providers for people with learning disability. In contrast, their role as providers of health promotion for this patient group was not generally accepted. Further research into the appropriateness and opportunity costs of health screening for people with learning disability is needed.

Attitude of Health Personnel↗

Inhibitory learning tests of conditioned stimulus associability in rats with lesions of the amygdala central nucleus.

Normal rats showed faster inhibitory learning about a light conditioned stimulus (CS) if it had previously been an inconsistent predictor of a tone CS than if it had been a consistent predictor of the tone. In contrast, the inhibitory learning of rats with ibotenic acid lesions of the amygdala central nucleus (CN) was unaffected by the prior predictive value of the light. These results support claims that the CN is critical to surprise-induced enhancement of attentional processing of CSs.

Acoustic Stimulation↗

A computational study of cross-situational techniques for learning word-to-meaning mappings.

This paper presents a computational study of part of the lexical-acquisition task faced by children, namely the acquisition of word-to-meaning mappings. It first approximates this task as a formal mathematical problem. It then presents an implemented algorithm for solving this problem, illustrating its operation on a small example. This algorithm offers one precise interpretation of the intuitive notions of cross-situational learning and the principle of contrast applied between words in an utterance. It robustly learns a homonymous lexicon despite noisy multi-word input, in the presence of referential uncertainty, with no prior knowledge that is specific to the language being learned. Computational simulations demonstrate the robustness of this algorithm and illustrate how algorithms based on cross-situational learning and the principle of contrast might be able to solve lexical-acquisition problems of the size faced by children, under weak, worst-case assumptions about the type and quantity of data available.

Algorithms↗

On the differential nature of implicit and explicit memory.

In this article, we report two experiments that provide further evidence concerning the differential nature of implicit and explicit memory. In Experiment 1, subjects first undertook a sentence-verification task. While carrying out this task, half of the subjects were also required to carry out a secondary processing task involving tone monitoring. Twenty-four hours later, the subjects' memory for target items in the sentence-verification task was tested explicitly by means of a recognition task and implicitly by examining the extent to which the items primed fragment completion. Recognition performance was significantly impaired by the imposition of secondary processing demands during the original learning phase. In contrast, fragment completion was completely unaffected by this additional processing, even though substantial priming was observed. In Experiment 2, we examined whether priming in fragment completion is influenced by the nature of repetition during initial learning. Subjects studied a list of target items that were each repeated twice. Half the items were repeated immediately (lag 0) and half were repeated after six intervening items (lag 6). Memory for the items was assessed by recognition and by priming in fragment completion. Recognition was affected by lag, with lag 6 items being recognized better than lag 0 items. However, although significant priming was obtained, the extent of this priming was uninfluenced by lag. These data indicate two additional dimensions along which implicit and explicit memory differ and, furthermore, they support recent conceptualizations of processing differences underlying these two forms of memory.

Adult↗

Primary and secondary memory: multistore versus process models of memory.

Healy, et al. recently distinguished between recency and "penultimate" effects when contrasting recall performance. They argued that the penultimate effect was significantly different from the typical recency effect, which point was taken as support for distinguishing between primary and secondary memory systems. The current study adapted the Healy, et al. methodology to control for the occurrence of intentional learning strategies. 40 participants were asked to recall the names of 42 U.S. Presidents by their term in office (secondary memory) or in a pseudorandom order (primary memory); the recency and penultimate effects were observed for each condition. With intentional learning controlled for, contrast analyses yielded a pattern of performance similar to that observed by Healy, et al.

Adolescent↗

Exploring bias in the Protein Data Bank using contrast classifiers.

In this study we analyzed the bias existing in the Protein Data Bank (PDB) using the novel contrast classifier approach. We trained an ensemble of neural network classifiers, called a contrast classifier, to learn the distributional differences between non-redundant sequence subsets of PDB and SWISS-PROT. Assuming that SWISS-PROT is a representative of the sequence diversity in nature while the PDB is a biased sample, output of the contrast classifier can be used to measure whether the properties of a given sequence or its region are underrepresented in PDB. We applied the contrast classifier to SWISS-PROT sequences to analyze the bias in PDB towards different functional protein properties. The results showed that transmembrane, signal, disordered, and low complexity regions are significantly underrepresented in PDB, while disulfide bonds, metal binding sites, and sites involved in enzyme activity are overrepresented. Additionally, hydroxylation and phosphorylation posttranslational modification sites were found to be underrepresented while acetylation sites were significantly overrepresented. These results suggest the potential usefulness of contrast classifiers in the selection of target proteins for structural characterization experiments.

Bias↗