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Introduction: Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke., Methods: We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged ≥65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by the Modified Mini-Mental State Examination (3MSE) and executive function by the Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors., Results: Among 5,443 participants ≥65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95% CI: -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95% CI: 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95% CI: -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year [95% CI: 0.003, 0.33]), as did SI participants (additional 0.27 points/year [95% CI: 0.19, 0.35])., Conclusion: Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention., (© 2023 S. Karger AG, Basel.)

Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide over the past two decades, with death rates for men reported at twice the rate for women. Using a controlled, cross-sectional, age-matched (18-56 y) design to better understand the cognitive neuroscience of OUD, we evaluated the electroencephalographic (EEG) responses of male and female participants with OUD vs. age- and gender-matched non-OUD controls during a simple visual object recognition Go/No-Go task. Overall, women had significantly slower reaction times (RTs) than men. In addition, EEG N200 and P300 event-related potential (ERP) amplitudes for non-OUD controls were significantly larger for men, while their latencies were significantly shorter than for women. However, while N200 and P300 amplitudes were not significantly affected by OUD for either men or women in this task, latencies were also affected differentially in men vs. women with OUD. Accordingly, for both N200 and P300, male OUD participants exhibited longer latencies while female OUD participants exhibited shorter ones than in non-OUD controls. Additionally, robust oscillations were found in all participants during a feedback message associated with performance in the task. Although alpha and beta power during the feedback message were significantly greater for men than women overall, both alpha and beta oscillations exhibited significantly lower power in all participants with OUD. Taken together, these findings suggest important gender by OUD differences in cognitive processing and reflection of performance in this simple visual task.

Associated with gastritis, peptic-ulcer disease, and gastric carcinoma, Helicobacter pylori (H. pylori) also has been associated with decreased cognitive function and dementia. In this study, we used data from the UK Biobank to further examine associations between H. pylori seropositivity and serointensity and performance on several cognitive tasks in adults 40 to 70 years of age (M = 55.3, SD = 8.1). In these analyses, H. pylori seropositivity (i.e., either positive or negative for H. pylori) and serointensity (concentration of antibodies against H. pylori antigens) in adjusted models were associated with worse function on tasks of Numeric memory, Reasoning, and errors on the Pairs matching test but better function on the Tower rearrangement task. Together, these findings suggest that H. pylori seropositivity and serointensity might be associated with worse cognitive function in this age group., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Erickson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We analyzed, through a Pavlovian conditioning procedure in rats, the temporal pattern of behavior in appetitive and aversive conditions within subjects, and the difference in inferred temporal working memory functioning with the Gap paradigm. For both conditions, we paired a 60-s conditioned stimulus (CS: tone1 or tone2) with an unconditioned stimulus (US: shock or chocolate pellet) delivered 20s after CS onset. The analyses of mean response rate and individual-trial data were performed during Probe trials, consisting of CS alone, and trials in which gaps of different position or duration were inserted, to assess the effect of the temporal manipulation on behavior. The results showed: (1) An anticipatory peak time in the aversive condition but better accuracy in the appetitive condition, (2) constancy in the Weber fraction suggesting that the difference in peak time was under clock control, (3) a graded effect of gap parameters only in the aversive condition and (4) different gap effects between conditions when a gap was inserted early in the CS. These results highlight behavioral differences between aversive and appetitive conditions and suggest that the temporal working memory mechanism was not engaged in the same manner in each condition., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) have been associated with worse human cognitive function in children and middle-aged adults. In this study, we sought to determine the association between Toxocara seropositivity and serointensity determined by detection of IgG antibodies against the Toxocara antigen recombinant Tc-CTL-1 and cognitive function in older adults, including approximately 1,350 observations from the 2013-2014 National Health and Nutrition Examination Survey. Mean fluorescence intensity was used to quantify IgG antibodies against the Toxocara recombinant Tc-CTL-1 antigen, and respondents were considered positive at values greater than 23.1. In adjusted models from sample sizes ranging from 1,274 to 1,288 depending on the individual cognitive task, we found that Toxocara seropositivity was associated with worse performance on the animal-fluency task (b = -1.245, 95% CI: -2.392 to -0.099, P< 0.05) and the digit-symbol coding task (b = -5.159, 95% CI: -8.337 to -1.980, P< 0.001). Toxocara serointensity assessed using log-transformed mean fluorescence intensity as a continuous variable was associated with worse performance on the digit-symbol coding task (b = -1.880, 95% CI: -2.976 to -0.783, P < 0.001). There were no significant associations with tasks assessing memory. Further, age modified the association between Toxocara and cognitive function, although sex, educational attainment, and income did not. These findings suggest that Toxocara might be associated with deficits in executive function and processing speed in older U.S. adults, although additional research is required to better describe cognitive function in older adults who are seropositive for Toxocara spp.

Infecting much of the world's population, the herpesviridae virus cytomegalovirus has been associated with lower cognitive function in some but not all studies. In this study, we further investigate associations between cytomegalovirus and cognitive function in a community-based sample of adults aged 40 to 70 years (M = 55.3; SD = 8.1) from the United Kingdom. Adjusted multiple-regression modeling showed no significant associations between cytomegalovirus and performance on nine cognitive tasks. Further, in adjusted interaction models, age, sex, educational attainment, and income did not moderate associations between cytomegalovirus and cognitive function. In this community-based adult sample, cytomegalovirus was not associated with cognitive function., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Several viral, bacterial, and parasitic diseases have been associated with cognitive function and neuropsychiatric outcomes in humans, including human T-cell lymphotropic virus 1 (HTLV-1). In this study, we sought to further generalize previously reported associations of cognitive function and depression with HTLV-1 seropositivity and serointensity using a community-based sample of adults aged approximately 40 to 70 years (mean = 55.3 years) from the United Kingdom. In this sample, the results of adjusted linear regression models showed no associations of HTLV-1 seropositivity or serointensity with reasoning, pairs-matching, or reaction-time cognitive tasks or with depression. In addition, neither age, sex, educational attainment, nor income moderated associations of HTLV-1 seropositivity or serointensity with cognitive function or depression. In this middle-aged to older middle-aged adult community sample, HTLV-1 seropositivity and serointensity do not appear to be associated with reasoning, pairs-matching, and reaction-time tasks or with depression.

Introduction: Recent clinical trials are considering inclusion of more than just apolipoprotein E ( APOE ) ε4 genotype as a way of reducing variability in analysis of outcomes., Methods: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex-adjusted GenoRisk., Results: The elastic net model that included age, age x sex interaction, allelic APOE terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to APOE genotype alone and achieved an area under the curve of 0.747., Discussion: GenoRisk could improve the risk assessment of individuals identified for prevention studies., Competing Interests: Suzanne Hendrix, as the owner of Pentara, received support from Affirmative Diagnostics for the manuscript and received contract work from AC Immmune, Acumen, ADCS, ADDF, Affirmativ Dignpostics, Alector, Alkahest, Allergan, Alzheon, Amylyx, Apodemus, Athira, Avanir, Banner, Biogen, Biohaven, Cadent, Capricor, Cerecin, Cognito, Cognoptix, Cortexyme, Elusis, Green Valley, Grifols, Ionis, Janssen, Kyowa‐Kirin, Lexeo, LuMind, Lundbeck, NCRI, Nilvad, NovoNordisk, Nutricia, Photopharmics, PTCBio, Regenera, Retrotope, Richard Isaacson, Samus, Soleno, Spaulding, Suven, Takeda, Telocyte, Tetra Discovery, Toyama, United Neuroscience, Vaccinex, Vacinity, vTv Therapeutics, and WGU. Suzanne Hendrix has also received royalties from Wiley in the last 36 months; received honoraria for lectures, presentations, etc. from Biogen; received support in the last 36 months from Grifols and Nutricia for presentations and conference attendance; claims one patent pending Brown BL, Hedges DW, Hendrix SB (2014) Extracting A periodic Components from a Time Series Wave Data Set—Patent Pending with a filing date of October 16, 2013, Application Number PCT/US2013/065327; and participated in Alzheon, Cortexyme, and Janssen DSMB or Advisory Board in the last 36 months. Samuel P. Dickson received support from Pentara, which in turn received support from Affirmativ Diagnostics for the manuscript. S. B. Booth received support from Affirmative Diagnostics for the manuscript; received travel support from her employer for work events; ADX provides profit sharing incentives with additional salary which were broadly applied to any work performed for the company (including manuscript generation). J. S. K. Kauwe received support for the manuscript from Brigham Young university and has received honoraria from UH Hilo. B. L. Brown received support through the following grants: Measuring the Interactive Effects of COVID‐19 and Latent Infections on Patterns of cognitive Timing: A Middle‐Aged to Elderly Sample from the Utah Valley Community. Translational Medicine Award from the BYU Simmons Research Endowment ($31,300). This is an intramural grant from a research endowment within our university to my departmental research fund. Brown also claims one patent pending Brown BL, Hedges DW, Hendrix SB (2014) Extracting A periodic Components from a Time Series Wave Data Set—Patent Pending with a filing date of October 16, 2013, Application Number PCT/US2013/065327. Data used in this manuscript is publically available. Participant consent is not needed, and was obtained from investigators who ran each study. M. L. Hardy has received paid consulting fees to the LLC solely owned by ML Hardy from ixLayer, NW Pathology & Labs, Mt. Baker Imaging, PlumCare, ADx Healthcare, Architectural Elements; received travel support from her employer for work events; and was the past Volunteer Secretary for the Lets Pool Together and Hope Philantropies non‐profit boards. P. G. Ridge had received honoraria from University of Kansas Alzheimer's Disease Center for a seminar presentation. R. R. Fortna is a board member of Northwest Pathology and ADx Healthcare and is co‐owner and holds stock for ADx healthcare. J. Nicodemus Johnson has nothing to disclose., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Infecting approximately one-third of the world's population, the neurotropic protozoan Toxoplasma gondii has been associated with cognition and several neuropsychiatric diseases including schizophrenia and bipolar disorder. Findings have been mixed, however, about the relationship between Toxoplasma gondii and depression, with some studies reporting positive associations and others finding no associations. To further investigate the association between Toxoplasma gondii and depression, we used data from the UK Biobank and the National Health and Examination Survey (NHANES). Results from adjusted multiple-regression modeling showed no significant associations between Toxoplasma gondii and depression in either the UK Biobank or NHANES datasets. Further, we found no significant interactions between Toxoplasma gondii and age, sex, educational attainment, and income in either dataset that affected the association between Toxoplasma gondii and depression. These results from two community-based datasets suggest that in these samples, Toxoplasma gondii is not associated with depression. Differences between our findings and other findings showing an association between Toxoplasma gondii and depression could be due to several factors including differences in socioeconomic variables, differences in Toxoplasma gondii strain, and use of different covariates in statistical modeling.

The intracellular protozoal parasite Toxoplasma gondii has been associated with worsened cognitive function in animal models and in humans. Despite these associations, the mechanisms by which Toxoplasma gondii might affect cognitive function remain unknown, although Toxoplasma gondii does produce physiologically active intraneuronal cysts and appears to affect dopamine synthesis. Using data from the UK Biobank, we sought to determine whether Toxoplasma gondii is associated with decreased prefrontal, hippocampal, and thalamic gray-matter volumes and with decreased total gray-matter and total white-matter volumes in an adult community-based sample. The results from adjusted multivariable regression modelling showed no associations between Toxoplasma gondii and prefrontal, hippocampal, and thalamic brain gray-matter volumes. In contrast, natural-log transformed antibody levels against the Toxoplasma gondii p22 (b = -3960, 95-percent confidence interval, -6536 to -1383, p < .01) and sag1 (b = -4863, 95-percent confidence interval, -8301 to -1425, p < .01) antigens were associated with smaller total gray-matter volume, as was the mean of natural-log transformed p22 and sag1 titers (b = -6141, 95-percent confidence interval, -9886 to -2397, p < .01). There were no associations between any of the measures of Toxoplasma gondii and total white-matter volume. These findings suggest that Toxoplasma gondii might be associated with decreased total gray-matter in middle-aged and older middle-aged adults in a community-based sample from the United Kingdom., Competing Interests: The authors have declared that no competing interests exist.

The present study investigated the effects of selective food devaluation on performance in the temporal bisection procedure with rats. Differential outcomes (sucrose vs. grain pellets) were associated with correct responding for a short and a long duration in order to analyze the effects of a selective duration-specific food devaluation on the temporal bisection function. Selective prefeeding produced differential changes in proportion of responding, the p(long) function, and PSE. A more consistent impact was observed when the food associated with the long anchor duration was devalued than when the short anchor duration food was devalued. The results are discussed in relation to the bias as well as a choose-short effect., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Infecting approximately one-third of the world's human population, Toxoplasma gondii has been associated with cognitive function. Here, we sought to further characterize the association between Toxoplasma gondii and cognitive function in a community sample of adults aged approximately 40 to70 years. Using adjusted linear regression models, we found associations of Toxoplasma gondii seropositivity with worse reasoning (b = -.192, p < .05) and matrix pattern completion (b = -.681, p < .01), of higher anti-Toxoplasma gondii p22 antibody levels with worse reasoning (b = -.078, p < .01) and slower Trails (numeric) performance (b = 5.962, p < .05), of higher anti-Toxoplasma gondii sag1 levels with worse reasoning (b = -.081, p < .05) and worse matrix pattern completion (b = -.217, p < .05), and of higher mean of the anti-Toxoplasma gondii p22 and sag1 levels with worse reasoning (b = -.112, p < .05), slower Trails (numeric) performance (b = 9.195, p < .05), and worse matrix pattern completion (b = -.245, p < .05). Neither age nor educational attainment moderated associations between the measures of Toxoplasma gondii seropositivity or serointensity. Sex, however, moderated the association between the sag1 titer and digit-symbol substitution and the association between the mean of the p22 and sag1 levels and digit-symbol substitution, and income moderated the association between Toxoplasma gondii seropositivity and numeric memory and the association between the p22 level and symbol-digit substitution. Based on the available neuropsychological tasks in this study, Toxoplasma gondii seropositivity and serointensity were associated with some aspects of poorer executive function in adults., Competing Interests: The authors have declared that no competing interests exist.

Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Air pollution has been associated with cognitive function and brain volume. While most previous research has examined the association between air pollution and brain volume in cortical structures or total brain volume, less research has investigated associations between exposure to air pollution and subcortical structures, including the thalamus. Further, the few available previous studies investigating associations between air pollution and thalamic volume have shown mixed results., Methods: In this study, we evaluated the association between PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides and volume of the thalamus in adults using the UK Biobank resource, a large community-based sample, while adjusting for multiple covariates that could confound an association between air pollution and thalamic volume., Results: In adjusted models, the left but not right thalamus volume was significantly inversely associated with PM2.5-10, although there were no significant associations between PM2.5, PM10, nitrogen dioxide, and nitrogen oxides with either left or right thalamic volumes. In addition, interactions between age and PM2.5-10 and PM10 were inversely associated with thalamic volume, such that thalamic volume in older people appeared more vulnerable to the adverse effects of PM2.5-10 and PM10, and interactions between educational attainment and PM2.5, nitrogen dioxide, and nitrogen oxides and between self-rated health and PM2.5-10 were positively associated with thalamic volume, such that higher educational attainment and better self-rated health appeared protective against the adverse effects of air pollution on the thalamus., Conclusion: These findings suggest a possible association between thalamic volume and air pollution particularly in older people and in people with comparatively low educational attainment at levels of air pollution found in the United Kingdom., Competing Interests: The authors have declared that no competing interests exist.

Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air pollution-PM 2.5 , PM 2.5-10 , PM 10 , nitrogen dioxide, and nitrogen oxides-and total gray-matter and total white-matter volumes in multivariable regression models in a large sample of adults. We found significant inverse associations between PM 2.5 concentration and total white-matter volume and between PM 2.5 , PM 2.5-10 , PM 10 , nitrogen dioxide, and nitrogen oxide concentrations and total gray-matter volume in models adjusted for age, sex, body-mass index, self-assessment of overall health, frequency of alcohol use, smoking status, educational attainment, and income. These findings of pollutant-associated decreases in total gray-matter and total white-matter volumes are in the context of mean PM 2.5 concentrations near the upper limit of the World Health Organization's recommendations. Similarly, mean PM 10 concentrations were below the recommended upper limit, and nitrogen dioxide concentration was slightly above. Still, there are many areas in the world with much higher concentrations of these pollutants, which could be associated with larger effects. If replicated, these findings suggest that air pollution could be a risk factor for neurodegeneration.

Research on emotion often involves the use of emotion-evoking stimuli that are used to manipulate emotional state across groups or conditions. One standardized set of stimuli that has been used for this purpose is the International Affective Picture System (IAPS) [1]. The data described in this article were obtained over the course of two experiments in which the primary task was for participants to judge the presentation duration of six IAPS pictures in the temporal bisection task [2-4]. Each of these experiments contained three types of phases (rating, training, and testing). In rating phases, participants rated the IAPS pictures for evoked valence, arousal, and fear. In training phases, participants were trained to classify the presentation duration of green squares (Experiment 1) or IAPS pictures (Experiment 2) as either "short" or "long." In testing phases, participants were instructed to use what they had learned in the preceding training phases to classify the IAPS pictures as either "short" or "long." The findings related to these data were published in Grommet, Hemmes, and Brown [5], and the data are available in Mendeley Data, DOI: 10.17632/xx6zh6mmjw.1 [6]., (© 2019 The Authors.)

Background: The hippocampus is important for memory processing. Several neuropsychiatric diseases including Alzheimer's disease are associated with reduced hippocampal volume, and further the hippocampus appears vulnerable to environmental insult. Air pollution has been associated with cardiovascular disease, abnormal brain structure, and cognitive deficits., Objective: Because of hippocampal vulnerability to environmental insults and based on the association between exposure to air pollution and cognitive function and brain structure, we evaluated the association between exposure to toxins in air pollution and left and right hippocampal volume using brain-imaging and air-pollution data from the UK Biobank, a large community-based dataset., Methods: We used regression modelling to evaluate the association between exposure to nitrogen dioxide, nitrogen oxides, PM 2.5 , PM 2.5-10 , and PM 10. and left and right hippocampal volume controlling for age, sex, body-mass index, overall health, alcohol use, smoking, educational attainment, socioeconomic status, inverse distance from the nearest major road, and a measure of total brain volume., Results: In these models, PM 2.5 concentration was associated with smaller left hippocampal volume. None of the other measures of air pollution was associated with either left or right hippocampal volume, although interaction models provided some evidence that sex might moderate the relationship between air pollution and hippocampal volume. In adjusted models, age, sex, educational attainment, income, overall health, current smoking, alcohol intake, and body-mass index were associated with hippocampal volume., Conclusions: PM 2.5 at levels found in the United Kingdom was associated with smaller left hippocampal volume. Additional associations between several covariates and hippocampal volumes indicate that hippocampal volume might be associated with several potentially modifiable variables., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent research on the effects of fear on timing has focused on two accounts proposed by Scalar Expectancy Theory for why the durations of fear stimuli are overestimated in comparison to the durations of neutral stimuli. One possibility is that fear serves as an arouser that increases the speed of a hypothetical internal clock. The other possibility is that fear increases attention to time, which results in organisms' beginning to time fear-evoking stimuli sooner than they do neutral stimuli. In Experiment 1, we asked which of these two possibilities was the underlying mechanism of temporal overestimation of fear cues by presenting emotion-evoking pictures (fear-evoking vs. neutral) across multiple duration ranges in the temporal bisection task. Larger effects of fear were observed at the longest duration range in comparison to the shortest duration range, supporting the arousal hypothesis. Penney et al. 1998 and Penney et al., 2000 memory-mixing hypothesis proposes that overestimation is only possible in preparations that allow for recalled reference memories for stimulus durations to be mixed across conditions. Therefore, in Experiment 2, we manipulated whether or not fear and neutral cues were presented within the same session, a condition that may be necessary for memory mixing to occur. Fear cues were overestimated relative to neutral cues within the session in which fear and neutral cues were both presented, but no effect of emotion was observed between the two sessions in which fear and neutral cues were presented separately., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Infectious diseases might affect cognitive aging and dementia risk, possibly via neuroinflammation. Similarly, risk factors for cardiovascular and cerebrovascular diseases are associated with cognitive function and dementia. We hypothesized that cardiovascular risk factors moderate the association of exposure to infectious diseases with cognitive function., Methods: We studied 5662 participants aged 20 to 59 years from the third National Health and Nutrition Examination Survey (1988-1994) in the United States. We used linear regression to investigate whether the Framingham general cardiovascular risk index moderated the association of infection burden based on exposure to eight different infectious diseases with cognitive functioning as measured by the Symbol Digit Substitution, Serial Digit Learning, and Reaction Time tests., Results: The multiplicative interaction between the infection-burden index and the cardiovascular-risk index was associated with performance on the Symbol Digit Substitution (B = .019 [95% CI: .008, .031], p < .001) but not on the Serial Digit Learning (B = .034 [95% CI: -.025, .094]) or for Reaction Time (B = -.030 [95% CI: -.848, .787]). Participants with a lower cardiovascular risk appeared to be more resilient against the potential adverse effects of higher infection burden on the Symbol Digit Substitution task., Conclusions: Participants at zero risk for a cardiovascular event in the next 10 years had no differences in processing speed with increasing exposure to infectious disease, whereas participants with higher risk for a cardiovascular event had worse processing speed with increased exposure to infectious disease., Competing Interests: The authors have declared that no competing interests exist.

This study demonstrates that overtraining in temporal discrimination modifies temporal stimulus control in a bisection task and produces habitual responding, as evidenced through insensitivity to food devaluation. Rats were trained or overtrained in a 2- versus 8-sec temporal discrimination task, with each duration associated with a lever (left or right) and food (grain or sucrose). Overtraining produced a leftward shift in the bisection point. Devaluation treatment induced a differential loss of responding depending on stimulus duration (short versus long) and the level of training (training versus overtraining). The relationships between timing behavior and habitual behavior are discussed., (© 2018 Araiba et al.; Published by Cold Spring Harbor Laboratory Press.)

The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.

Huntington disease (HD) is an autosomal dominantly inherited, progressive neurodegenerative disorder which is accompanied by executive dysfunctions and emotional alteration. The aim of the present study was to assess the impact of emotion/stress on on-going highly demanding cognitive tasks, i.e., temporal processing, as a function of age in BACHD rats (a "full length" model of HD). Middle-aged (4-6 months) and old (10-12 months) rats were first trained on a 2 vs. 8-s temporal discrimination task, and then exposed to a series of bisection tests under normal and stressful (10 mild unpredictable foot-shocks) conditions. The animals were then trained on a peak interval task, in which reinforced fixed-interval (FI) 30-s trials were randomly intermixed with non-reinforced probe trials. After training, the effect of stress upon time perception was again assessed. Sensitivity to foot-shocks was also assessed independently. The results show effects of both age and genotype, with largely greater effects in old BACHD animals. The older BACHD animals had impaired learning in both tasks, but reached equivalent levels of performance as WT animals at the end of training in the temporal discrimination task, while remaining impaired in the peak interval task. Whereas sensitivity to foot-shock did not differ between BACHD and WT rats, delivery of foot-shocks during the test sessions had a disruptive impact on temporal behavior in WT animals, an effect which increased with age. In contrast, BACHD rats, independent of age, did not show any significant disruption under stress. In conclusion, BACHD rats showed a disruption in temporal learning in late symptomatic animals. Age-related modification in stress-induced impairment of temporal control of behavior was also observed, an effect which was greatly reduced in BACHD animals, thus confirming previous results suggesting reduced emotional reactivity in HD animals. The results suggest a staggered onset in cognitive and emotional alterations in HD, with emotional alteration being the earliest, possibly related to different time courses of degeneration in cortico-striatal and amygdala circuits.

Mood disorders are common mental illnesses. Among the factors associated with major depression are exposures to infectious diseases including hepatitis C, influenza, varicella-zoster, and herpes viruses. In this study, we sought to evaluate further associations between viral exposure and depression. From the US Center for Disease Control's National Health and Nutrition Examination Survey, we obtained data about depression status, antidepressant use, exposure to hepatitis A, hepatitis B, herpes simplex virus type 1, herpes simplex virus type 2, human immunodeficiency virus, and cytomegalovirus, and sociodemographic variables and evaluated associations between depression and viral exposure in adjusted multivariable models. Herpes simplex virus type 2 was associated with an increased risk of depression, whereas hepatitis A, hepatitis B, and herpes simplex virus type 1 were not. Higher cytomegalovirus antibody levels were associated with depression in subjects seropositive for cytomegalovirus. In conclusion, exposure to herpes simplex virus type 2 and possibly cytomegalovirus are associated with depression in an adult US sample., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function., Methods: We used data obtained from the 1999-2000 continuous National Health and Nutrition Examination Survey produced by the United States' Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III. We then tested for interactions between each of the folate-cycle factors and Helicobacter pylori in the prediction of cognitive function., Results: Although Helicobacter pylori seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not associated with performance on the digit symbol coding task, Helicobacter pylori seropositivity interacted with 5-methyltetrahydrofolate concentration to predict performance on the digit symbol coding task. The Helicobacter pylori seropositive group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate concentration decreased., Conclusion: The interaction between Helicobacter pylori seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might impair aspects of cognitive function.

Caused by the parasitic nematodes Toxocara canis and cati , toxocariasis in humans can result in covert toxocariasis, ocular toxocariasis, visceral larval migrans, and neurotoxocariasis. A common infection, toxocariasis exposure varies widely within and between countries, with a previous estimate of Toxocara seroprevalence using data from 1988 to 1994 in the United States of approximately 13%. Age, poverty, sex, educational attainment, ethnicity, and region have been associated with Toxocara seroprevalence. In this study, we sought to determine the seroprevalence of and factors associated with Toxocara seropositivity in the United States using data from the National Health and Nutrition Examination Survey from 2011 to 2014 to provide a more recent estimate of Toxocara seroprevalence in the United States. We found an overall Toxocara seroprevalence of 5.1%. Increasing age, male sex, low educational attainment, low income, and immigration status each was associated with Toxocara seropositivity. Mexican Americans had reduced odds of exposure. These findings show that exposure to Toxocara continues in the United States and that several demographic factors influence the risk of exposure.

Although highly heritable, adult height is also associated with numerous environmental factors, including exposure to infection. Particularly in developing regions of the world, infection burden appears to slow growth during childhood. Using a large database representative of the US population, we examined associations between adult height and leg length and an infection-burden index based on past exposure to Toxocara species, Toxoplasmosis gondii, cytomegalovirus, hepatitis A, hepatitis B, hepatitis C, herpes simplex virus 1, and herpes simplex virus 2. In models controlled for age, sex, educational attainment, socioeconomic status, and race-ethnicity, we found that the infection-burden index predicted height (β=-0.10 [95% CI: -0.15, -0.05], p .001<0.001) but not leg length (β=-0.04 [95% CI: -0.12, 0.04], p=0.357). Both sex and race-ethnicity moderated this association. In addition, exposures to Toxocara species, cytomegalovirus, and hepatitis A were each individually associated with reduced height and reduced leg length. While associations between growth and infection have been found principally in children in developing regions of the world, our findings suggest that the effects of infection on height may persist into adulthood even in developed nations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Toxoplasma gondii ( T. gondii ) is a microscopic, apicomplexan parasite that can infect muscle or neural tissue, including the brain, in humans. While T. gondii infection has been associated with changes in mood, behavior, and cognition, the mechanism remains unclear. Recent evidence suggests that T. gondii may harvest folate from host neural cells. Reduced folate availability is associated with an increased risk of neurodevelopmental disorders, neurodegenerative diseases, and cognitive decline. We hypothesized that impairment in cognitive functioning in subjects seropositive for T. gondii might be associated with a reduction of folate availability in neural cells. We analyzed data from the third National Health and Nutrition Examination Survey to determine the associations between T. gondii infection, multiple folate-cycle factors, and three tests of cognitive functioning in U.S. adults aged 20 to 59 years. In these analyses, T. gondii moderated the associations of folate, vitamin B-12, and homocysteine with performance on the Serial Digit Learning task, a measure of learning and memory, as well as the association of folate with reaction time. The results of this study suggest that T. gondii might affect brain levels of folate and/or vitamin B-12 enough to affect cognitive functioning., Competing Interests: The authors declare no conflict of interest.

The present study investigated how the value of the long anchor duration influences the bisection point (BP) in the temporal bisection procedure. The ratio similarity rule (Gibbon, 1981, On the form and location of the psychometric bisection function for time. Journal of Mathematical Psychology, 24(1), 58-87) hypothesizes that the location of the BP is determined by a ratio comparison between the short and long anchor durations. The Short/no short hypothesis (Machado and Keen, 2003, Temporal discrimination in a long operant chamber. Behavioural Processes, 62(1), 157-182) indicates that the location of the BP is influenced mainly by the short duration. Two experiments with pigeons manipulated the long anchor duration while fixing the short anchor duration in a series of anchor pairs. The results showed that the location of the BP depended on the initial training condition, a primacy effect. When the initial training condition used anchors of 3- vs. 9-s, a relatively strong influence of the long anchor duration was observed as predicted by the ratio similarity rule. On the other hand, when anchors were 3- vs. 27-s in the initial training condition, the effect of the long duration was relatively small, conforming more closely to the Short/no short hypothesis. Keypecking to the sample key during a trial, sample-cue responding, was also observed. The functions relating sample-cue responding to elapsed trial time also indicated the primacy effect., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Helicobacter pylori (H. pylori) infection is associated with cognitive deficits in humans, an association potentially mediated or moderated by folate concentration or inflammation., Materials and Methods: We used the National Health and Nutrition Examination Survey (NHANES) datasets to examine whether folate concentration or inflammation mediates or moderates the relationship between H. pylori and cognitive function. Models were performed using linear, Poisson, and zero-inflated Poisson regression, and we performed separate analyses for groups aged 20-59 and 60-90 years with sample sizes ranging from 700 to 1700., Results: We did not find evidence of mediation in either age group. In the 20- to 59-year group, interactions between H. pylori and ferritin (p values ranging from .004 to .039) were associated with worse processing speed, better working memory, and worse reaction time. Interactions between H. pylori and fibrinogen (p values ranging from .023 to .045), C-reactive protein (CRP) (p = .023), and the inflammatory index (p = .045) were associated with worse processing speed. In 60- to 90-year-olds, H. pylori interacted with ferritin and the inflammatory index to predict fewer mathematical errors (p values of .036 and .023). Interactions with folate (p values of .016 and .006) and C-reactive protein (p values ranging from <.001 to .048) were inconsistent in directionality., Conclusions: In this dataset, representative of the US population, inflammation and folate concentrations moderated but did not mediate the association between H. pylori seropositivity and cognition., (© 2016 John Wiley & Sons Ltd.)

Toxoplasma gondii (Nicolle et Manceaux, 1908) is an intracellular parasite that can cause ongoing latent infection persisting for the duration of a non-definitive host's life. Affecting approximately one-third of the world's population, latent toxoplasmosis has been associated with neuropsychological outcomes and a previous report suggested an association between latent toxoplasmosis and adult height. Given the large number of people with latent toxoplasmosis and its potential associations with human height, we sought to better understand the association between latent toxoplasmosis and human morphology by evaluating seropositivity for T. gondii and multiple body measures reported in the National Health and Nutrition Examination Survey III (NHANES III) and in the more recent continuous NHANES data sets from the United States Centers for Disease Control and Prevention for which data on T. gondii are available. In these analyses, latent toxoplasmosis was not associated with any of the body measures assessed in the NHANES datasets even after taking into account interactions between latent toxoplasmosis and testosterone suggesting that in these samples, latent toxoplasmosis is not associated with adult morphology including height.

We analyzed the temporal pattern of conditioned suppression of lever-pressing for food in rats conditioned with tone-shock pairings using either a 10 or 15s conditioned stimulus (CS)-unconditioned stimulus (US) interval with a CS duration that was three times the CS-US interval. The analysis of average suppression and of individual trials was performed during Probe CS-alone trials and when a short gap was inserted during the CS. The pattern of suppression followed the classical temporal rules: (1) scalar property, (2) a shift in peak suppression due to a gap, compatible with a Stop rule, (3) a three-state pattern of lever-pressing in individual trials, with abrupt start and stop of suppression. The peak of the average suppression curve, but not the middle time, was anticipatory to the programmed US time. The pattern of lever-pressing in individual trials unraveled two types of start of suppression behavior: a clock-based biphasic responding, with a burst of lever-pressing before suppression, and a non-clock based monophasic reduction of lever-pressing close to the CS onset. The non-clock based type of behavior may be responsible for the anticipatory peak time, and the biphasic pattern of lever-pressing may reflect the decision stage described in clock models., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The amygdalo-nigrostriatal (ANS) network plays an essential role in enhanced attention to significant events. Interval timing requires attention to temporal cues. We assessed rats having a disconnected ANS network, due to contralateral lesions of the medial central nucleus of the amygdala (CEm) and dopaminergic afferents to the lateral striatum, as compared to controls (sham and ipsilateral lesions of CEm and dopaminergic afferents to LS) in a temporal bisection task. ANS disconnection induced poorer temporal precision and increased response latencies to a short duration. The present results reveal a role of the ANS network in temporal processing., (© 2016 Es-seddiqi et al.; Published by Cold Spring Harbor Laboratory Press.)

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Alzheimer's disease accounts for 60% of all dementia. Numerous biomarkers have been developed that can help in making an early diagnosis. The P300 is an event-related potential that may be abnormal in Alzheimer's disease. Given the possible association between P300 amplitude and Alzheimer's disease and the need for biomarkers in early Alzheimer's disease, the main purpose of this meta-analysis and meta-regression was to characterize P300 amplitude in probable Alzheimer's disease compared to healthy controls. Using online search engines, we identified peer-reviewed articles containing amplitude measures for the P300 in response to a visual or auditory oddball stimulus in subjects with Alzheimer's disease and in a healthy control group and pooled effect sizes for differences in P300 amplitude between Alzheimer's disease and control groups to obtain summary effect sizes. We also used meta-regression to determine whether age, sex, educational attainment, or dementia severity affected the association between P300 amplitude and Alzheimer's disease. Twenty articles containing a total of 646 subjects met inclusion and exclusion criteria. The overall effect size from all electrode locations was 1.079 (95% confidence interval=0.745-1.412, P<.001). The pooled effect sizes for the Cz, Fz, and Pz locations were 1.226 (P<.001), 0.724 (P=.0007), and 1.430 (P<.001), respectively. Meta-regression showed an association between amplitude and educational attainment, but no association between amplitude and age, sex, and dementia severity. In conclusion, P300 amplitude is smaller in subjects with Alzheimer's disease than in healthy controls., (© EEG and Clinical Neuroscience Society (ECNS) 2014.)

The ascarid nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) may infect humans resulting in toxocariasis. A prior study associated species of Toxocara Stiles, 1905 with cognitive deficits in children. To determine if a similar association between toxocariasis and cognition exists in adults, we analysed a large dataset from the United States' Center for Disease Control's National Health and Nutrition Examination Survey. We used linear-regression and multivariate models to examine the association between toxocariasis as assessed by the presence of anti-Toxocara IgG antibodies and three measures of cognitive function - simple reaction time (SRT), symbol-digit substitution (SDS) and serial-digit learning (SDL) in 4 279 adults aged 21 to 59 years. Toxocara seroprevalence did not vary with age or blood-lead concentration but did vary with gender, ethnicity, educational attainment and poverty-to-income ratio. Controlling for gender, age, blood-lead concentration, educational attainment, ethnic background and the poverty-to-income ratio, we found that toxocariasis predicted worse performance on the SDS but not on the SRT or the SDL. Moreover, there were significant interactions between toxocariasis and age, gender and educational attainment. In conclusion, toxocariasis appears to be associated with decreased cognitive function. Interactions between toxocariasis and gender, age and educational attainment further suggest that certain groups may be more susceptible than others to the cognitive dysfunction associated with toxocariasis in adults.

Helicobacter pylori and latent toxoplasmosis are widespread diseases that have been associated with cognitive deficits and Alzheimer's disease. We sought to determine whether interactions between Helicobacter pylori and latent toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and general health predict cognitive function in young and middle-aged adults. To do so, we used multivariable regression and multivariate models to analyze data obtained from the United States' National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention, which can be weighted to represent the US population. In this sample, we found that 31.6 percent of women and 36.2 percent of men of the overall sample had IgG Antibodies against Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied with sociodemographic variables. There were no main effects for Helicobacter pylori or latent toxoplasmosis for any of the cognitive measures in models adjusting for age, sex, race-ethnicity, educational attainment, economic standing, and self-rated health predicting cognitive function. However, interactions between Helicobacter pylori and race-ethnicity, educational attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive function. People seropositive for both Helicobacter pylori and latent toxoplasmosis - both of which appear to be common in the general population - appear to be more susceptible to cognitive deficits than are people seropositive for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a synergistic effect between these two infectious diseases on cognition in young to middle-aged adults.

Cognitive function may be influenced by education, socioeconomic status, sex, and health status. Furthermore, aging interacts with these factors to influence cognition and dementia risk in late life. Factors that may increase or decrease successful cognitive aging are of critical importance, particularly if they are modifiable. The purpose of this study was to determine if economic status in late life is associated with cognition independent of socioeconomic status in early life. Cross-sectional demographic, socioeconomic, and cognitive function data were obtained in 2592 older adults (average age 71.6 years) from the Center for Disease Control's National Health and Nutrition Examination Survey (NHANES) and analyzed with linear regression modeling. Cognitive function, as measured with a test of processing speed, was significantly associated with poverty index scores after adjusting for educational attainment as an estimate of childhood socioeconomic status, ethnic background, age, health status, and sex (P < 0.001). Our findings suggest that current economic status is independently associated with cognitive function in adults over age 60 years.

The aim of this study was to investigate the temporal abilities of children treated by surgery for a malignant tumor in the cerebellum, both in the perception and the production of rhythm. Children with a diagnosed medulloblastoma and age-matched control children were tested in a rhythm discrimination task and a sensorimotor synchronization task. Their motor and cognitive capabilities were also assessed through a battery of age-adapted neuropsychological tests. The results did not show any significant difference in performance between groups for the discrimination task. On the contrary, children with cerebellar lesions produced longer and more variable inter-tap intervals (ITI) in their spontaneous motor tempo (SMT) than did the control children. However, the length and, to a lesser extent, the variability of their SMT decreased after a synchronization phase, when they had been instructed to tap in synchrony with a beep. During the synchronization task, the children with medulloblastoma succeeded to modify the length of their ITI in response to an auditory rhythm, although with better success when the inter-stimuli intervals (ISI) were shorter than when they were longer than the ITIs of their own SMT. Correlational analyses revealed that children's poorer synchronization performance was related to lower scores in neuropsychological tests assessing motor dexterity and processing speed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

Time perception is crucial to goal attainment in humans and other animals, and interval timing also guides fundamental animal behaviors. Accumulating evidence has made it clear that in associative learning, temporal relations between events are encoded, and a few studies suggest this temporal learning occurs very rapidly. Most of these studies, however, have used methodologies that do not permit investigating the emergence of this temporal learning. In the present study we monitored respiration, ultrasonic vocalization (USV) and freezing behavior in rats in order to perform fine-grain analysis of fear responses during odor fear conditioning. In this paradigm an initially neutral odor (the conditioned stimulus, CS) predicted the arrival of an aversive unconditioned stimulus (US, footshock) at a fixed 20-s time interval. We first investigated the development of a temporal pattern of responding related to CS-US interval duration. The data showed that during acquisition with odor-shock pairings, a temporal response pattern of respiration rate was observed. Changing the CS-US interval duration from 20-s to 30-s resulted in a shift of the temporal response pattern appropriate to the new duration thus demonstrating that the pattern reflected the learning of the CS-US interval. A temporal pattern was also observed during a retention test 24 h later for both respiration and freezing measures, suggesting that the animals had stored the interval duration in long-term memory. We then investigated the role of intra-amygdalar dopaminergic transmission in interval timing. For this purpose, the D1 dopaminergic receptors antagonist SCH23390 was infused in the basolateral amygdala before conditioning. This resulted in an alteration of timing behavior, as reflected in differential temporal patterns between groups observed in a 24 h retention test off drug. The present data suggest that D1 receptor dopaminergic transmission within the amygdala is involved in temporal processing.

Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.

The aim of the present study was to investigate temporal abilities in children treated by surgery for a malignant tumor in the cerebellum. Children with a diagnosed medulloblastoma and age-paired control children were given a temporal discrimination task (bisection task) and a temporal reproduction task with two duration ranges, one shorter than 1s and the other longer than 4s. The motor and cognitive capacities of these children were also assessed by a battery of age-adapted neuropsychological tests. The results did not show any significant difference in performance between the children with or without cerebellar lesions in the temporal discrimination task. It was only in the temporal reproduction task that the children with cerebellar lesions reproduced longer and more variable durations than the other children, but only for the short stimulus durations (≤ 1 s). In addition, a hierarchical regression analysis revealed that the best predictor of variance in temporal performance was a significantly lower processing speed in children with cerebellar lesions in comparison to their controls. These results indicated that the major cause of deficits in temporal judgments in children with cerebellar lesions was due to their inability to reproduce accurately short temporal intervals in association with low processing speed, rather than to a specific deficit in the perception of time., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

To monitor global representation in the psychiatric literature, we compared publication rates in the ten psychiatric journals with the highest impact factors in 1998 and 2008 by world regions. In both 1998 and 2008, North America, Northern Europe, Western Europe and Oceania produced the majority of psychiatric research papers published in these journals, despite representing only a small fraction of the world's population. This suggests that much of the world's population continues to be underrepresented in highly influential psychiatric journals.

Background: Certain risk factors for cognitive decline appear modifiable. A potentially modifiable marker of inflammation, C-reactive protein may be associated with cognitive deficits, although not all studies have found a relationship between C-reactive protein and cognitive ability. Further, few research papers have examined whether gender may affect any association between C-reactive protein and cognitive deficit., Methods: To better understand the association between C-reactive protein, cognitive deficit, and gender in elderly people, we meta-analyzed cross-sectional studies that reported cognitive ability assessed by the Mini-Mental State Examination or an equivalent measure, C-reactive protein concentrations, and gender., Results: While we identified no studies containing only male subjects, the two identified studies containing both female and male subjects (n = 2,525) showed an effect size for cognition of -0.1809 (95% confidence interval, -0.2652 to -0.0967, p = 0.000025) between high and low C-reactive-protein groups. In contrast, the two identified studies containing only female subjects (n = 1,754) showed an effect size for cognition of 0.0345 (95% confidence interval, -0.0594 to 0.1285, not significant)., Conclusions: In the context of a small number of source studies and lack of an all-male group, these results suggest that any association between C-reactive protein and cognitive deficits may be stronger in elderly men than in elderly women.

The present study investigated temporal perception in a Huntington disease transgenic rat model using a temporal bisection procedure. After initial discrimination training in which animals learned to press one lever after a 2-s tone duration, and the other lever after a 8-s tone duration for food reward, the bisection procedure was implemented in which intermediate durations with no available reinforcement were interspersed with trials with the anchor durations. Bisection tests were repeated in a longitudinal design from 4 to 8 months of age. The results showed that response latencies evolved from a monotonic step-function to an inverted U-shaped function with repeated testing, a precursor of non-responding on trials with intermediate durations. We inferred that temporal sensitivity and incentive motivation combined to control the transformation of the bisection task from a two-choice task at the outset of testing to a three-choice task with repeated testing. Changes in the structure of the task and/or continued training were accompanied by improvement in temporal sensitivity. In sum, the present data highlight the possible joint roles of temporal and non-temporal factors in the temporal bisection task, and suggested that non-temporal factors may compensate for deficits in temporal processing.

Effects of prior discrimination training on stimulus control by color and shape dimensions of compound stimuli were studied with college students. In Phase 1, single-stimulus discrimination training was conducted for two values of color and shape. Phase 2 discrimination training employed two 2-dimensional compound stimuli composed of the color and shape stimuli trained in Phase 1. For conflict-compound stimuli, the stimulus-response-consequence contingency was altered between phases for one stimulus dimension (target dimension), but not for the other, non-target, dimension. Level of congruence (100%, 25%, and 0%) of the contingency for the target dimension between phases was manipulated across groups. When each stimulus value was tested in Phase 3, level of Phase-2-consistent responding to the target dimension varied with level of Phase-1-to-Phase-2 congruence. In Experiment 2, training history for the non-target dimension was altered across three conditions: (a) Correlated with reinforcement, as in Experiment 1, (b) No-Training, or (c) Not-Correlated. Phase-2-consistent responding to the target cue in Phase 3 was lower under the latter conditions than under the Correlated condition, indicating that the non-target dimension modulated control by the target dimension, consistent with stimulus competition. The data suggest elemental, rather than configural processing of the compound stimuli during Phase 2., (Published by Elsevier B.V.)

Cognitive decline precedes motor symptoms in Huntington disease (HD). A transgenic rat model for HD carrying only 51 CAG repeats recapitulates the late-onset HD phenotype. Here, we assessed prefrontostriatal function in this model through both behavioral and electrophysiological assays. Behavioral examination consisted in a temporal bisection task within a supra-second range (2 vs.8 s), which is thought to involve prefrontostriatal networks. In two independent experiments, the behavioral analysis revealed poorer temporal sensitivity as early as 4 months of age, well before detection of overt motor deficits. At a later symptomatic age, animals were impaired in their temporal discriminative behavior. In vivo recording of field potentials in the dorsomedial striatum evoked by stimulation of the prelimbic cortex were studied in 4- to 5-month-old rats. Input/output curves, paired-pulse function, and plasticity induced by theta-burst stimulation (TBS) were assessed. Results showed an altered plasticity, with higher paired-pulse facilitation, enhanced short-term depression, as well as stronger long-term potentiation after TBS in homozygous transgenic rats. Results from the heterozygous animals mostly fell between wild-type and homozygous transgenic rats. Our results suggest that normal plasticity in prefrontostriatal circuits may be necessary for reliable and precise timing behavior. Furthermore, the present study provides the first behavioral and electrophysiological evidence of a presymptomatic alteration of prefrontostriatal processing in an animal model for Huntington disease and suggests that supra-second timing may be the earliest cognitive dysfunction in HD.

Previous research suggests that time judgments are a function of the affective properties of to-be-timed stimuli and that time judgments are longer for stimuli that are fear-inducing (e.g., Hare, 1963; Watts and Sharrock, 1984). The goals of the present study were twofold: to replicate the effect of a fear cue on time estimation, and to evaluate the mechanism underlying the effect. Seven stimulus durations in two different duration ranges (short: 250-1000 ms; long: 400-1600 ms) were employed in the bisection procedure. Adult human participants were exposed to two successive sessions, one each with the short and long range. Images from the International Affective Picture System (IAPS; Lang et al., 2008) that were rated on three scales including arousal and fear were presented as temporal stimuli. Three images that were rated high on fear and three rated low served as fear cues and neutral control images, respectively. Results indicated that for both ranges, judgments were longer for fear cues than for neutral images, and that the magnitude of the effect did not differ between ranges as measured by the bisection point. Application of scalar expectancy theory (SET; Gibbon, 1977; Church, 1984) to these results suggests that the fear effects were mediated by switch latency of an internal clock, rather than by clock speed., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The role of interpositus nuclei (IN) in timing in the sub-second range is well supported in eyeblink conditioning studies. Timing impairments shown in the seconds range in patients with intermediate cerebellar lesion, and known intermediate cerebellar cortex projection to IN raise the question of a possible involvement of IN in timing in the supra-second range as well. To address this question, we tested rats (Sprague-Dawley) given bilateral lesions of IN with Colchicine in a 2- vs. 8-s temporal discrimination task, followed by three daily sessions of a temporal bisection tests with five added intermediate non-reinforced durations. IN lesioned rats showed normal acquisition of the temporal discrimination, but a transient impairment of temporal sensitivity during the bisection tests. In addition, their response latencies suggested a different behavioral strategy from that of control animals. Our results indicate that the IN of the cerebellum may not be critically involved in temporal processing in the 2-8 s range, but may play a role in the cognitive processes that access temporal information in the mediation of choice behavior.

Three children diagnosed with pervasive developmental disabilities emitted a high rate of mands and a low-to-zero rate of appropriate play responses when the two responses were reinforced on concurrent Fixed Ratio 1 (FR1) schedules. When mands were reinforced on an FR10 schedule and play responses were concurrently reinforced on an FR1 schedule, play responses increased. Two participants' mands decreased from baseline levels but were maintained, and the third participant's mands increased. Implications of the use of choice procedures for clinical settings are discussed.