A demonstration of within-subjects latent inhibition in the human: limitations and advantages

Gray, Nicola S.; Snowden, Robert Jefferson; Peoples, Michelle; Hemsley, David R.; Gray, Jeffrey A.

doi:10.1016/s0166-4328(02)00181-x

Cited by 21 publications

(14 citation statements)

References 25 publications

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“…Similar to NP, the period of conditioning is shortened in schizophrenia patients 84 and schizotypes. 72 , 85 , 86 Successful inhibition is critical for complex cognitive functions such as WM, which has emerged as a potential endophenotype of schizophrenia. 87 This is based on studies reporting subtle WM impairment in individuals with genetic 88 , 89 and phenomenological 90 , 91 vulnerability to schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies

Koychev

Joyce²,

Barkus

et al. 2016

Transl Psychiatry

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The development of drugs to improve cognition in patients with schizophrenia is a major unmet clinical need. A number of promising compounds failed in recent clinical trials, a pattern linked to poor translation between preclinical and clinical stages of drug development. Seeking proof of efficacy in early Phase 1 studies in surrogate patient populations (for example, high schizotypy individuals where subtle cognitive impairment is present) has been suggested as a strategy to reduce attrition in the later stages of drug development. However, there is little agreement regarding the pattern of distribution of schizotypal features in the general population, creating uncertainty regarding the optimal control group that should be included in prospective trials. We aimed to address this question by comparing the performance of groups derived from the general population with low, average and high schizotypy scores over a range of cognitive and oculomotor tasks. We found that tasks dependent on frontal inhibitory mechanisms (N-Back working memory and anti-saccade oculomotor tasks), as well as a smooth-pursuit oculomotor task were sensitive to differences in the schizotypy phenotype. In these tasks the cognitive performance of ‘low schizotypes' was significantly different from ‘high schizotypes' with ‘average schizotypes' having an intermediate performance. These results indicate that for evaluating putative cognition enhancers for treating schizophrenia in early-drug development studies the maximum schizotypy effect would be achieved using a design that compares low and high schizotypes.

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Section: Discussionmentioning

confidence: 99%

Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies

Koychev

Joyce²,

Barkus

et al. 2016

Transl Psychiatry

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“…A well-replicated finding is that unmedicated schizophrenia patients with positive symptoms display reduced LI relative to healthy controls. 59 Converging evidence based on investigations using verbal tasks, 57 auditory tasks, 61 and visual search tasks 62 indicate that participants with higher scores on measures of positive schizotypy show a reduced LI effect. 60,61,63 Impairments in WM, the active storage, manipulation, and selection of responses to guide subsequent behavior, have emerged as one of the cardinal features of schizophrenia.…”

Section: Attention and Memorymentioning

confidence: 96%

“…59 Converging evidence based on investigations using verbal tasks, 57 auditory tasks, 61 and visual search tasks 62 indicate that participants with higher scores on measures of positive schizotypy show a reduced LI effect. 60,61,63 Impairments in WM, the active storage, manipulation, and selection of responses to guide subsequent behavior, have emerged as one of the cardinal features of schizophrenia. [64][65][66] Indeed, WM is considered a potential endophenotypic marker for the disorder.…”

Section: Attention and Memorymentioning

confidence: 96%

Cognition and Brain Function in Schizotypy: A Selective Review

Ettinger

Möhr

Gooding

et al. 2015

Schizophrenia Bulletin

212

184

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Schizotypy refers to a set of personality traits thought to reflect the subclinical expression of the signs and symptoms of schizophrenia. Here, we review the cognitive and brain functional profile associated with high questionnaire scores in schizotypy. We discuss empirical evidence from the domains of perception, attention, memory, imagery and representation, language, and motor control. Perceptual deficits occur early and across various modalities. While the neural mechanisms underlying visual impairments may be linked to magnocellular dysfunction, further effects may be seen downstream in higher cognitive functions. Cognitive deficits are observed in inhibitory control, selective and sustained attention, incidental learning, and memory. In concordance with the cognitive nature of many of the aberrations of schizotypy, higher levels of schizotypy are associated with enhanced vividness and better performance on tasks of mental rotation. Language deficits seem most pronounced in higher-level processes. Finally, higher levels of schizotypy are associated with reduced performance on oculomotor tasks, resembling the impairments seen in schizophrenia. Some of these deficits are accompanied by reduced brain activation, akin to the pattern of hypoactivations in schizophrenia spectrum individuals. We conclude that schizotypy is a construct with apparent phenomenological overlap with schizophrenia and stable interindividual differences that covary with performance on a wide range of perceptual, cognitive, and motor tasks known to be impaired in schizophrenia. The importance of these findings lies not only in providing a fine-grained neurocognitive characterization of a personality constellation known to be associated with real-life impairments, but also in generating hypotheses concerning the aetiology of schizophrenia.

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“…Further details of the eight more common protocols are summarized in Table 3 . The earliest of these protocols was the auditory task that was run, almost universally, as a between-subjects task (e.g., Allan et al, 1995 ; Baruch et al, 1988a , 1988b ; Braunstein-Bercovitz & Lubow 2004 ; Ginton et al, 1975 ; Gray, Snowden, Peoples, Hemsley & Gray, 2003 ; Kumari et al, 1999 ; Lubow, Weiner, Schlossberg, & Baruch, 1987 ; Lubow et al, 1992 ; Serra, Jones, Toone & Gray, 2001 ; Williams et al, 1996 ; Williams et al, 1998 ; Wuthrich & Bates, 2001 ), with the exception of two within-subjects designs (Gray, Pilowsky, Gray, & Kerwin, 1995 ; Gray et al, 2003 ). The visual task minimally adapted the auditory task and was widely used as a between-subjects test of LI (e.g., De La Casa, Ruiz, & Lubow, 1993 ; Gray et al, 2001 ; Gray et al, 2002 ; Lipp, 1999 ; Lipp, Siddle, & Arnold, 1994; Lubow et al, 1992 ; Rascle et al, 2001 ; Swerdlow et al, 1996 ; Zalstein-Orda et al, 1995 ).…”

Section: Overview For Tests Of Human LImentioning

confidence: 99%

Human latent inhibition: Problems with the stimulus exposure effect

2018

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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.

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A demonstration of within-subjects latent inhibition in the human: limitations and advantages

Cited by 21 publications

References 25 publications

Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies

Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies

Cognition and Brain Function in Schizotypy: A Selective Review

Human latent inhibition: Problems with the stimulus exposure effect

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