Nicotine is a cholinergic agonist with known pro-cognitive effects in the domains of alerting and orienting attention. However, its effects on attentional top-down functions such as response inhibition and interference control are less well characterised. Here, we investigated the effects of 7 mg transdermal nicotine on performance on a battery of response inhibition and interference control tasks. A sample of N = 44 healthy adult non-smokers performed antisaccade, stop signal, Stroop, go/no-go, flanker, shape matching and Simon tasks, as well as the attentional network test (ANT) and a continuous performance task (CPT). Nicotine was administered in a within-subjects, double-blind, placebo-controlled design, with order of drug administration counterbalanced. Relative to placebo, nicotine led to significantly shorter reaction times on a prosaccade task and on CPT hits but did not significantly improve inhibitory or interference control performance on any task. Instead, nicotine had a negative influence in increasing the interference effect on the Simon task. Nicotine did not alter inter-individual associations between reaction times on congruent trials and error rates on incongruent trials on any task. Finally, there were effects involving order of drug administration, suggesting practice effects but also beneficial nicotine effects when the compound was administered first. Overall, our findings support previous studies showing positive effects of nicotine on basic attentional functions but do not provide direct evidence for an improvement of top-down cognitive control through acute administration of nicotine at this dose in healthy non-smokers.

Model systems of psychosis, such as schizotypy or sleep deprivation, are valuable in informing our understanding of the etiology of the disorder and aiding the development of new treatments. Schizophrenia patients, high schizotypes, and sleep-deprived subjects are known to share deficits in oculomotor biomarkers. Here, we aimed to further validate the schizotypy and sleep deprivation models and investigated, for the first time, their interactive effects on smooth pursuit eye movements (SPEM), prosaccades, antisaccades, predictive saccades, and measures of psychotomimetic states, anxiety, depression, and stress. To do so, n = 19 controls and n = 17 high positive schizotypes were examined after both a normal sleep night and 24 h of sleep deprivation. Schizotypes displayed higher SPEM global position error, catch-up saccade amplitude, and increased psychotomimetic states. Sleep deprivation impaired SPEM, prosaccade, antisaccade, and predictive saccade performance and increased levels of psychotomimetic experiences. Additionally, sleep deprivation reduced SPEM gain in schizotypes but not controls. We conclude that oculomotor impairments are observed in relation to schizotypy and following sleep deprivation, supporting their utility as biomarkers in model systems of psychosis. The combination of these models with oculomotor biomarkers may be particularly fruitful in assisting the development of new antipsychotic or pro-cognitive drugs.

No abstract

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional; however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11,807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori-defined subscales (93% overlap, normalised mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff's Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff's Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three-factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype.

The antisaccade (AS) task is considered a prominent measure of inhibitory control, but it is still unclear which cognitive processes are used for successful performance of the task. Previous results have provided evidence for the involvement of several processes, including working memory (WM), inhibition and attention. Thus, the aim of this study was to explore, using a range of neuropsychological tests, which cognitive factors predict individual differences in AS performance. To do so, 143 healthy participants underwent a battery including tests measuring inhibition, working memory, cognitive flexibility, sustained attention, IQ and fluency. Hierarchical stepwise regression analyses were conducted to assess the association with AS performance. Performance on the Trail-Making-Test, version B (TMT-B), a test measuring flexibility, divided attention and WM, was found to significantly predict AS latency. Rapid Visual Information Processing (RVIP), used to assess sustained attention and WM, significantly predicted AS error rate. Other cognitive measures, however, did not significantly predict AS performance. Bayesian Model Averaging supported these conclusions and showed that non-significant predictors are unlikely to be associated with AS outcomes. Several explanations are provided for the associations of TMT-B and RVIP with AS performance; as the tests measure a range of different cognitive processes, interpretation of these results remains less clear. For a better understanding of the cognitive mechanisms underlying AS performance, future research should make use of a wider range of attention and WM tests.

Model systems of psychosis play an important role in pathophysiology and drug development research. Schizotypal individuals display similar cognitive impairments as schizophrenia patients in several domains. Therefore, schizotypy may be interpreted as a trait model system of psychosis. In addition, experimentally controlled sleep deprivation is a putative state psychosis model that evokes subclinical psychosis-like states. We aimed to further validate these model systems by examining them in relation to central cognitive biomarkers of schizophrenia. Most of all, we were interested in investigating, for the first time, effects of their combination on cognitive function. Healthy subjects with high (N = 17) or low (N = 19) levels of schizotypy performed a cognitive task battery after one night of normal sleep and after 24 h of sleep deprivation. Sleep deprivation impaired performance in the go/nogo and n-back tasks relative to the normal sleep control condition. No differences between groups or interactions of group with sleep condition were found. The role of sleep deprivation as a model of psychosis is thus supported to some extent by impairments in inhibitory control. However, classical measures of cognition may be less able to detect deficits in schizotypy, in line with evidence of more basic information processing dysfunctions in schizotypy.

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional, however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori defined subscales (93% overlap, normalized mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff’s Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff’s Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype.

No abstract