Entorhinal but Not Hippocampal or Subicular Lesions Disrupt Latent Inhibition in Rats

Latent inhibition (LI) is the deficit of conditioning resulting from repeated nonreinforced preexposure to a conditioned stimulus before its pairing with an unconditioned stimulus. There are cumulative data showing that large lesions of the hippocampal formation disrupt LI. However, the effects of selective lesions of the different components of the hippocampal formation have never been directly addressed in the same study and conditioning paradigm. The first experiment of the present study aimed at investigating the effects of excitotoxic lesions of the hippocampus, subiculum, or entorhinal cortex on LI in an "off-baseline"-conditioned emotional response procedure. Hippocampus or subiculum lesions had no effect on either LI or conditioning. In contrast, entorhinal cortex lesions disrupted LI without modifying conditioning. In Experiment 2, locomotor activity in a novel environment was assessed in the same rats. Whereas lesions of hippocampus increased locomotor activity, lesions of the subiculum or the entorhinal cortex were devoid of effect. Although both LI and habituation to novel environmental cues are thought to involve interactions between the hippocampal formation and the mesolimbic pathway, these results indicate a functional dissociation between the hippocampus and the entorhinal cortex.     

A Grammatical Specific Language Impairment in Children: An Autosomal Dominant Inheritance?

The aim of this study is to provide further characterization of a subgroup of so-called “Grammatical specific language-impaired (SLI)” children. The Grammatical SLI children have a persistent and disproportionate impairment in grammatical comprehension and expression of language. Previous research has indicated that their language impairment may be characterized by a domain-specific and modular language deficit. This study provides an initial investigation as to whether there is a genetic basis underlying their disorder as has been found for other forms of SLI and for SLI in general. The incidence of familial aggregation of language impairment was investigated in 12 Grammatical SLI children (aged 9:3 to 12:10). A familial language impairment (LI) history was classified as positive if one or more of the probands' relatives had a history of a speech/language or reading/writing problem which required speech therapy or any other form of remedial help. Case history information provided an initial indication that the Grammatical SLI children had a significantly higher incidence of a positive familial LI history than could be expected by chance. A questionnaire provided evidence of a positive LI history in the first-degree relatives of the SLI probands and 49 normally developing control probands. The SLI probands had a clearly and significantly higher incidence of a positive familial LI history than the control probands (77.8 vs. 28.5%, respectively). The results are consistent with a genetic basis underlying Grammatical SLI. The pattern of impairment in the SLI probands' relatives is consistent with an autosomal dominant genetic inheritance. In contrast to the control probands, the SLI probands' impaired relatives did not show a male gender bias. Thus, the gene does not appear to be sex-linked. The data indicate that further research is warranted to investigate the nature of the LI in the relatives of the Grammatical SLI probands and the genetic characteristics of this subgroup. The implications for the biological, domain-specific, and modular bases to language are discussed.     

Contextual Control of Latent Inhibition by the Reinforcer

Three experiments examined the contextual control of latent inhibition (LI) by the unconditioned stimulus (US) using a within-subjects conditioned suppression procedure with rats. The effect of reducing the context change produced by the introduction of the shock US was investigated by presenting this US during preexposure to the conditioned stimulus (CS). Although limited CS preexposure in the absence of the US had no impact on subsequent conditioning, preexposure in the presence of the shock retarded both excitatory and inhibitory conditioning. We conclude that the introduction of the US during the conditioning phase of a normal LI experiment can produce a contextual change that reduces the observed magnitude of LI.     

Latent inhibition of US signal value.

Three experiments with rats examined the effects of preexposure to an unconditioned stimulus (US; a single food pellet) on the subsequent ability of that US to effectively signal the delivery of three food pellets during a US-US conditioning procedure. In Experiment 1, latent inhibition (LI) rats showed attenuated conditioning, compared to control (C) rats, when a single food pellet, delivered 10 minutes into a session, was followed by three additional pellets. In preexposure, one pellet had been delivered 10 minutes into each session (in group LI), or placed into the magazine at the beginning of each session (in group C). Experiment 2 showed that this effect was evident when the conditions of preexposure matched those of conditioning for group C, and Experiment 3 showed that the difference between groups LI and C was not a product of context conditioning, or latent inhibition to the noise of the feeder in group LI. Implications of these results for theories of latent inhibition are considered.     

A Comparison of Latent Inhibition and Learned Irrelevance Pre-Exposure Effects in Rabbit and Human Eyeblink Conditioning

The learning of an association between a CS and a US can be retarded by unreinforced presentations of the CS alone (termed latent inhibition or LI) or by un-correlated presentations of the CS and US (termed learned irrelevance or LIRR). In rabbit eyeblink conditioning, there have been some recent failures to replicate LI. LIRR has been hypothesized as producing a stronger retardation effect than LI based on both empirical studies and computational models. In the work presented here, we examined the relative strength of LI and LIRR in eyeblink conditioning in rabbits and humans. In both species, a number of preexposure trials sufficient to produce LIRR failed to produce LI (Experiments 1 & 3). Doubling the number of CS pre-exposures did produce LI in rabbits (Experiment 2), but not in humans (Experiment 4). LI was demonstrated in humans only after manipulations including an increased inter-trial interval or ITI (Experiment 5). Overall, it appears that LIRR is a more easily producible pre-exposure retardation effect than LI for eyeblink conditioning in both rabbits and humans. Several theoretical mechanisms for LI including the conditioned attention theory, stimulus compression, novelty, and the switching theory are discussed as possible explanations for the differences between LIRR and LI. Overall, future work involving testing the neural substrates of pre-exposure effects may benefit from the use of LIRR rather than LI.     

Loss of latent inhibition in conditioned taste aversion following exposure to a novel flavour before test

Killcross, Kiernan, Dwyer, andWestbrook (1998b) observed that latent inhibition(LI) of contextual fear was attenuated if animals received post-conditioning exposure to a novel context similar to the pre-exposure context. Six experiments used a conditioned taste aversion (CTA) procedure to examine this effect. Experiments 1A-1C demonstrated that LI of CTA was attenuated by a similar post-conditioning manipulation, establishing the generality of previous findings. Experiment 2A manipulated the taste elements to which animals were exposed after conditioning, revealing that exposure to a common element X, present at pre-exposure and conditioning, was not responsible for loss of LI. Experiment 2B manipulated test solution and showed that loss of LI depended on the presence of the full pre-exposed cue AX at test. These two results are contrary to predictions derived from the Dickinson-Burke (Dickinson & Burke, 1996) theory of retrospective revaluation or comparator theory (Miller & Matzel, 1988), and they support recent findings suggesting that retrospective effects may occur by several mechanisms. Experiment 3 showed that a novel element B had to be present during post-conditioning exposure for an attenuation of LI to be observed. Implications for the loss of LI following aretention interval between conditioning and test and retrieval-failure theories of LI are discussed.     

A comparison of latent inhibition and learned irrelevance pre-exposure effects in rabbit and human eyeblink conditioning

The learning of an association between a CS and a US can be retarded by unreinforced presentations of the CS alone (termed latent inhibition or LI) or by un-correlated presentations of the CS and US (termed learned irrelevance or LIRR). In rabbit eyeblink conditioning, there have been some recent failures to replicate LI. LIRR has been hypothesized as producing a stronger retardation effect than LI based on both empirical studies and computational models. In the work presented here, we examined the relative strength of LI and LIRR in eyeblink conditioning in rabbits and humans. In both species, a number of pre-exposure trials sufficient to produce LIRR failed to produce LI (Experiments 1 & 3). Doubling the number of CS pre-exposures did produce LI in rabbits (Experiment 2), but not in humans (Experiment 4). LI was demonstrated in humans only after manipulations including an increased inter-trial interval or ITI (Experiment 5). Overall, it appears that LIRR is a more easily producible pre-exposure retardation effect than LI for eyeblink conditioning in both rabbits and humans. Several theoretical mechanisms for LI including the conditioned attention theory, stimulus compression, novelty, and the switching theory are discussed as possible explanations for the differences between LIRR and LI. Overall, future work involving testing the neural substrates of pre-exposure effects may benefit from the use of LIRR rather than LI.     

Differential effects of personality traits related to the P-ImpUSS dimension on latent inhibition in healthy female subjects

An experiment was performed to investigate the effects of various personality traits (psychoticism, impulsiveness, sensation seeking) with substantial loadings on the P-ImpUSS dimension on latent inhibition (LI). LI refers to the finding that performance on a learning task is poorer for a preexposed irrelevant stimulus than for a novel stimulus. Forty-eight female subjects were tested by a rule-learning task that has been shown to reliably produce differential LI effects in low and high psychosis-prone normals. Results suggest that, besides psychoticism, the sensation seeking subfactor disinhibition is negatively associated with LI. Furthermore, stepwise regression analysis revealed that combining individual psychoticism and disinhibition scores results in a significant increase in explained variance of LI. These findings are discussed in terms of a relationship between distinct P-ImpUSS-related aspects of personality and LI.     

Examining the costs and benefits of inhibition in memory retrieval

Inhibitory control is thought to serve an adaptive function in controlling behavior, with individual differences predicting variation in numerous cognitive functions. However, inhibition is more properly construed as inducing both benefits and costs to performance. Benefits arise at the point when inhibition prevents expression of an unwanted or contextually inappropriate response; costs arise later, when access to the inhibited representation is required by other processes. Here we illustrate how failure to consider both the costs and benefits of inhibition has generated confusion in the literature on individual differences in cognitive control. Using retrieval-induced forgetting as a model case, we illustrate this by showing that changing the way that retrieval-induced forgetting is measured to allow greater expression of the benefits of inhibition together with the costs can reduce and even reverse the theoretically predicted correlation between motor and memory inhibition. Specifically, we show that when the final test in a retrieval-induced forgetting procedure employs item-specific cues (i.e., category-plus-stem cued recall and item-recognition) that better isolate the lingering costs of inhibition, better motor response inhibition (faster stop-signal reaction times) predicts greater retrieval-induced forgetting. In striking contrast, when the final test is less well controlled, allowing both the costs and benefits of inhibition to contribute, motor response inhibition has the opposite relationship with retrieval-induced forgetting. These findings underscore the importance of considering the correlated costs and benefits problem when studying individual differences in inhibitory control. More generally, they suggest that a shared inhibition mechanism may underlie people’s ability to control memories and actions.     

Stress affects the selection of relevant from irrelevant stimuli

Two experiments were used to examine the effects of stress on latent inhibition (LI; poorer learning with a previously exposed irrelevant stimulus rather than a novel stimulus). In Experiment 1, stress was induced in college students by threatening participants' self-esteem with a difficult number series completion test that was related to intelligence. In Experiment 2, the participants were job seekers who were either informed or not that the LI test was part of the selection process. In both experiments, LI was attenuated in high- as compared with low-stressed participants. The results suggest that stress and/or anxiety impairs the inhibition of irrelevant-preexposed stimuli. Implications for understanding the impaired selective attentional processes in schizophrenia and schizotypy are discussed.     

Human latent inhibition and the density of predictive relationships in the context in which the target stimulus occurs

In two experiments, participants were exposed to a listing of actions performed by a fictitious Mr. X, over three days of his life. For most of his actions an outcome was described, but some were not followed by any outcome. On Day 3, Mr. X performed an action (the target action) that was followed by a novel outcome. For participants in the control condition, the target action that preceded the appearance of this outcome was also novel; for participants in the latent inhibition (LI) condition, Mr. X had performed the target action on repeated occasions during Days 2 and 3, without it producing any outcome. All the participants were tested on their ability to retrieve the action performed by Mr. X prior to the target outcome. In Experiment 1, retrieval of the target action (indicating a less effective target action–outcome association) was poorer in the LI than in the control condition. In Experiment 2, reducing the proportion (the density) of nontarget actions that brought outcomes during initial training was found to reduce the size of the LI effect. These results are predicted by the account of LI put forward previously [Hall, G., & Rodríguez, G. (2010). Associative and nonassociative processes in latent inhibition: An elaboration of the Pearce-Hall model. In R. E. Lubow & I. Weiner (Eds.), Latent inhibition: Data, theories, and applications to schizophrenia (pp. 114–136). Cambridge, England: Cambridge University Press]. A high density of predictive relationships ensures strong activation of the expectancy that some outcome will occur when the target action is first presented; this facilitates the formation of a target action–no-event association during training in the LI condition, thus enhancing the LI effect.     

Human latent inhibition: Problems with the stimulus exposure effect

Latent inhibition (LI) is a startlingly simple effect in which preexposure of a stimulus without consequence retards subsequent responding to a stimulus–consequence relation. The effect was first demonstrated with Pavlovian conditioning in animals and was later suggested to be a marker of human psychopathology such as schizophrenia. Individual differences in LI has supported the continued use of animal models to understand human mental health. In this review, we ask whether there is sufficient evidence to support the continued application of LI from animal models to human psychopathology because of the weak evidence for LI in humans. There is considerable variability in the methods used to assess LI, sustaining different theoretical accounts of the effects observed, which differ from the accepted accounts of LI as demonstrated in animals. The review shows that although there have been many experiments testing human LI, none provide the necessary experimental controls to support the conclusion that retarded responding is caused simply by preexposure to a stimulus, as has been demonstrated with animal models. Establishing this conflict, we set out a framework for future research.     

Comprehension and expression of affect in language-impaired children

Eight children with developmental language impairment (LI) and eight age-, sex-, socioeconomic-status-, and I.Q.-matched controls were given tests of comprehension and expression of affective intent in spoken language and through facial expression. The LI children performed significantly more poorly than did controls in both comprehension and spontaneous expression of vocal affect. On tasks involving emotional facial expression, the opposite results were observed: The LI children were more dramatic in their expression of facial affect than were the controls. Children with language impairment appear to have a deficit in affective comprehension and expression that is modality-specific, i.e., limited to vocal affect. The heightened range of affective facial expression that they demonstrate may be a compensatory mechanism to offset their difficulties with vocal affect.This work was supported by grant 12-203 from the March of Dimes Birth Defects Foundation, and by NINDS grant NS22343 for the Center for the Study of the Neurological Basis of Language.     

Latent inhibition and compound conditioning: a reply to Holmes and Harris (2009)

Schmajuk, Lam, and Gray (SLG, 1996) presented a neural network model of classical conditioning that addresses the multiple properties of latent inhibition (LI). According to the model, LI is the result of the decreased attention to the target stimulus during preexposure and testing. Recently, Holmes and Harris (2009) suggested that, although the model was able to describe their experimental results showing that LI to a preexposed stimulus disappears with extended compound conditioning, it could not describe the fact that LI is not affected by a delay following compound conditioning. However, computer simulations demonstrate that the SLG model describes and explains both results. Because the model also explains both the deleterious and the facilitating effects on LI of a delay following simple conditioning, the SLG model seems unique in explaining the complete range of reported effects of temporal delays on LI as well as most of the properties of LI.     

Decreased latent inhibition is associated with increased creative achievement in high-functioning individuals

Reductions in latent inhibition (LI), the capacity to screen from conscious awareness stimuli previously experienced as irrelevant, have been generally associated with the tendency towards psychosis. However, "failure" to screen out previously irrelevant stimuli might also hypothetically contribute to original thinking, particularly in combination with high IQ. Meta-analysis of two studies, conducted on youthful high-IQ samples. demonstrated that high lifetime creative achievers had significantly lower LI scores than low creative achievers (r(effect size) = .31, p = .0003, one-tailed). Eminent creative achievers (participants under 21 years who reported unusually high scores in a single domain of creative achievement) were 7 times more likely to have low rather than high LI scores, chi2 (1, N = 25) = 10.69, phi = .47. p = .003.     

TRANSFER BETWEEN PICTURE NAMING AND TRANSLATION:

Abstract— A transfer paradigm was used to investigate the relationship between picture naming and translation English- Spanish bilinguals first named pictures and subsequently translated words in both their first (LI) and second (U) languages Some words in the translation task were repetitions of concepts that had previously been named as pictures Whereas picture naming produced reliable transfer to translation from LI to L2, It produced no transfer to translation from L2 to LI The results support the claim that connections in bilingual memory are asymmetric Translation is conceptually mediated from LI to L2 but lexically mediated from L2 to LI     

Context dependent latent inhibition in adult humans

Learning the association between one stimulus (a condition stimulus, CS) and another (unconditioned stimulus, US) can be impaired by prior exposure to the CS alone—latent inhibition (LI). Current theories attempting to elucidate the cognitive deficit in schizophrenia have used the abolition of LI in schizophrenia as an indicator of attentional dysfunction. However, it has always been unclear if human and animal LI are measuring the same psychological processes. It is obviously important to clarify this relationship so that theoretical and experimental developments in the rat do not mislead the investigation of brain-behaviour relationships in schizophrenia. LI in the rat is strongly dependent upon context. Our aim was to examine the context specificity of LI in humans and specifically to: (1) investigate whether participants' belief that they are in a different context is sufficient to abolish LI, even though there is no physical change in the environment; (2) produce a context manipulation that is immune to alternative interpretation in terms of stimulus generalization decrement; and (3) investigate whether a "tonic" change of context reduces or abolishes human LI, thus complementing previous reports using a "phasic" change of context. In two experiments we manipulated context in either the real world or a virtual world, and showed that LI is abolished by a change of context in adult humans.     

Hippocampal alpha 5 subunit-containing GABA A receptors are involved in the development of the latent inhibition effect

Hippocampal GABA(A) receptors containing the alpha 5 subunit have been implicated in the modulation of hippocampal-dependent learning, presumably via their tonic inhibitory influence on hippocampal glutamatergic activity. Here, we examined the expression of latent inhibition (LI)--a form of selective learning that is sensitive to a number of manipulations targeted at the hippocampal formation, in alpha 5(H105R) mutant mice with reduced levels of hippocampal alpha 5-containing GABA(A) receptors. A single pre-exposure to the taste conditioned stimulus (CS) prior to the pairing of the same CS with LiCl-induced nausea was effective in reducing the conditioned aversion against the taste CS in wild-type mice--thus constituting the LI effect. LI was however distinctly absent in male alpha 5(H105R) mutant mice. Hence, a partial loss of hippocampal alpha 5 GABA(A) receptors is sufficient to alter one major form of selective learning, albeit this was not seen in the female. This observed phenotype suggests that specific activation of these extrasynaptic GABA(A) receptors may confer therapeutic potential against the failure to show selectivity in learning by human psychotic patients.     

Some determinants of latent inhibition in human predictive learning

The present experiments assessed the effects of different manipulations between cue preexposure and cue-outcome pairings on latent inhibition (LI) in a predictive learning task with human participants. To facilitate LI, preexposure and acquisition with the target cues took place while participants performed a secondary task. Presentation of neither the target cues nor the target outcome was anticipated based on the instructions. Experiment 1 demonstrated the LI effect in the new experimental preparation. Experiment 2 analyzed the impact on LI of different activities that participants performed during the interval between preexposure and acquisition. Experiment 3 assessed LI as a function of changes in the secondary task cues made between preexposure and acquisition, namely presenting novel cues and reversing the cue-outcome contingencies. All of the manipulations in Experiments 2 and 3 resulted in a decrease in LI. The attenuation of LI by these manipulations challenges most current theories of learning and is best accommodated by Conditioned Attention Theory (Lubow, Weiner, & Schnur, 1981).     

Disruption of latent inhibition to a contextual stimulus with systemic amphetamine

This experiment examined the effects of 0.5 and 1.5 mg/kg doses of amphetamine (AMP) in male Wistar rats, on conditioning to a contextual stimulus that for half the animals has been pre-exposed, in an appetitive conditioning procedure. Amphetamine was administered during both pre-exposure (3 days) and acquisition (15 days). Latent inhibition (LI, reduced conditioning in pre-exposed relative to non-pre-exposed rats) was seen in controls but not at either AMP dose. This abolition of LI was seen under AMP at two levels of responding in acquisition and confirmed in drug free extinction. It suggests that, like conditioning to discrete stimuli, conditioning to contextual stimuli is subject to LI and can be disrupted by AMP.