Background Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. Aim To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). Methods Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. Results The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 +/- 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 +/- 1.83, p = 0.03). There was no such effect in any of the other study groups. Conclusion In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.
Background: Intra-individual variability in reaction time (RT IIV) is considered to be an index of central nervous system functioning. Such variability is elevated in neurodegenerative diseases or following traumatic brain injury. It has also been suggested to increase with age in healthy ageing. Objectives: To investigate and quantify age differences in RT IIV in healthy ageing; to examine the effect of different tasks and procedures; to compare raw and mean-adjusted measures of RT IIV. Data Sources: Four electronic databases: PsycINFO, Medline, Web of Science and EMBASE, and hand searching of reference lists of relevant studies. Study Eligibility: English language journal articles, books or book chapters, containing quantitative empirical data on simple and/or choice RT IIV. Samples had to include younger (under 60 years) and older (60 years and above) human adults. Study Appraisal and Synthesis: Studies were evaluated in terms of sample representativeness and data treatment. Relevant data were extracted, using a specially-designed form, from the published report or obtained directly from the study authors. Age-group differences in raw and RT-mean-adjusted measures of simple and choice RT IIV were quantified using random effects meta-analyses. Results: Older adults (60+ years) had greater RT IIV than younger (20-39) and middle-aged (40-59) adults. Age effects were larger in choice RT tasks than in simple RT tasks. For all measures of RT IIV, effect sizes were larger for the comparisons between older and younger adults than between older and middle-aged adults, indicating that the age-related increases in RT IIV are not limited to old age. Effect sizes were also larger for raw than for RT-mean-adjusted RT IIV measures. Conclusions: RT IIV is greater among older adults. Some (but not all) of the age-related increases in RT IIV are accounted for by the increased RT means.
Processing of visual features related to objects and space relations occurs within separate cortical streams that interact with selective attention. Such separation has implications for cognitive development because the perception of 'what' and 'where' provide a neural foundation for the development of aspects of higher cognition. Thus, a small attentional bias in early development for attending to one aspect over the other might influence subsequent higher cognitive processing in tasks involving object recognition and space relations. We examined 134 men and women for evidence of an inherent sex-related bias for attending to basic perceptual features related to object discrimination versus object position. Each stimulus consisted of a circle located in one of 9 positions within a surrounding frame. Circles were one of three shades of blue or red. These stimuli were used in a match-to-sample paradigm where participants were required to match circles on the basis of color or spatial position. The first stimulus appeared in the center of the screen for 400 msec and the matching stimulus subsequently appeared for 400 msec oriented 5 degrees to the right or left of center. The same stimuli were used to test the perception of color and position, with order of testing counterbalanced across participants. Results showed significantly longer reaction times in females compared with males, with better accuracy to discriminate color when that color was tested before position. Males showed better accuracy when object position was tested before color discrimination. A second experiment employed the same procedure, but enhanced selective attention by adding an endogenous cue that predicted the right or left location for the appearance of the matching stimulus. This manipulation greatly attenuated the sex differences in reaction time and accuracy compared to Experiment 1, suggesting that the sex-related attentional biases are strongly coupled to bottom-up processing. Overall, the sex related attentional biases toward processing object characteristics versus object position location suggest a differential manifestation of biased competition between the weighted systems of dorsal and ventral stream processing. Results are discussed with how a developmental bias in the processing objects versus space relations may contribute to adult cognitive sex differences in humans and animals.
Objective Increased levels of reaction time variability (RTV) are characteristics of sustained attention deficits. The clinical significance of RTV has been widely recognized. However, the reliability of RTV measurements has not been widely studied. The present study aimed to assess the test-retest reliability of RTV conventional measurements, e.g., the standard deviation (SD), the coefficient of variation (CV), and a new measurement called the amplitude of low frequency fluctuation (ALFF) of RT. In addition, we aimed to assess differences and similarities of these measurements between different tasks. Method Thirty-seven healthy college students participated in 2 tasks, i.e., an Eriksen flanker task (EFT) and a simple reaction task (SRT), twice over a mean interval of 56 days. Conventional measurements of RTV including RT-SD and RT-CV were assessed first. Then the RT time series were converted into frequency domains, and RT-ALFF was further calculated for the whole frequency band (0.0023-0.167 Hz) and for a few sub-frequency bands including Slow-6(< 0.01 Hz), Slow-5 (0.01-0.027 Hz), Slow-4 (0.027-0.073 Hz), and Slow-3 (0.073-0.167 Hz). The test-retest reliability of these measurements was evaluated through intra-class correlation (ICC) tests. Differences and correlations between each EFT and SRT measurement were further examined during both visits. Results 1) The RT-ALFF of the Slow-5/4/3 and conventional measurements of RT-SD and RT-CV showed moderate to high levels of test-retest reliability. EFT RT-ALFF patterns generated slightly higher ICC values than SRT values in higher frequency bands (Slow-3), but SRT RT-ALFF values showed slightly higher ICC values than EFT values in lower frequency bands (Slow-5 and Slow-4). 2) RT-ALFF magnitudes in each sub-frequency band were greater for the SRT than those for the EFT. 3) The RT-ALFF in the Slow-4 of the EFT was found to be correlated with the RT-ALFF in the Slow-5 of the SRT for both two visits, but no consistently significant correlation was found between the same frequency bands. Conclusions These findings reveal good test-retest reliability for conventional measurements and for the RT-ALFF of RTV. The RT-ALFF presented frequency-dependent similarities across tasks. All of our results reveal the presence of different frequency structures between the two tasks, and thus the frequency-dependent characteristics of different tasks deserve more attention in future studies.
Using instructed-delay choice reaction time (RT) paradigms, many previous studies have shown that the motor system is transiently inhibited during response preparation: motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex are typically suppressed during the delay period. This effect has been observed in both selected and non-selected effectors, although MEP changes in selected effectors have been more inconsistent across task versions. Here, we compared changes in MEP amplitudes in three different variants of an instructed-delay choice RT task. All variants required participants to choose between left and right index finger movements but the responses were either provided "in the air" (Variant 1), on a regular keyboard (Variant 2), or on a response device designed to control from premature responses (Variant 3). The task variants also differed according to the visual layout (more concrete in Variant 3) and depending on whether participants received a feedback of their performance (absent in Variant 1). Behavior was globally comparable between the three variants of the task although the propensity to respond prematurely was highest in Variant 2 and lowest in Variant 3. MEPs elicited in a non-selected hand were similarly suppressed in the three variants of the task. However, significant differences emerged when considering MEPs elicited in the selected hand: these MEPs were suppressed in Variants 1 and 3 whereas they were often facilitated in Variant 2, especially in the right dominant hand. In conclusion, MEPs elicited in selected muscles seem to be more sensitive to small variations to the task design than those recorded in non-selected effectors, probably because they reflect a complex combination of inhibitory and facilitatory influences on the motor output system. Finally, the use of a standard keyboard seems to be particularly inappropriate because it encourages participants to respond promptly with no means to control for premature responses, probably increasing the relative amount of facilitatory influences at the time motor inhibition is probed.
The aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3-pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2- butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance. Conclusions: Breath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.
Background Falls among older adults is one of the major public health challenges facing the rapidly changing demography. The valid assessment of reaction time (RT) and other well-documented risk factors for falls are mainly restricted to specialized clinics due to the equipment needed. The Nintendo Wii Balance Board has the potential to be a multi-modal test and intervention instrument for these risk factors, however, reference data are lacking. Objective To provide RT reference data and to characterize the age-related changes in RT measured by the Nintendo Wii Balance Board. Method Healthy participants were recruited at various locations and their RT in hands and feet were tested by six assessors using the Nintendo Wii Balance Board. Reference data were analysed and presented in age-groups, while the age-related change in RT was tested and characterized with linear regression models. Results 354 participants between 20 and 99 years of age were tested. For both hands and feet, mean RT and its variation increased with age. There was a statistically significant non-linear increase in RT with age. The averaged difference between male and female was significant, with males being faster than females for both hands and feet. The averaged difference between dominant and non-dominant side was non-significant. Conclusion This study reported reference data with percentiles for a new promising method for reliably testing RT. The RT data were consistent with previously known effects of age and gender on RT.
Interaction between integral membrane proteins and the lipid-bilayer component of biological membranes is expected to mutually influence the proteins and the membrane. We present quantitative evidence of a manifestation of the lipid-protein interactions in liposomal membranes, reconstituted with actively pumping Na⁺, K⁺-ATPase, in terms of nonequilibrium shape fluctuations that contain a relaxation time, τ, which is robust and independent of the specific fluctuation modes of the membrane. In the case of pumping Na⁺-ions, analysis of the flicker-noise temporal correlation spectrum of the liposomes leads to τ = 0.5 s, comparing favorably with an intrinsic reaction-cycle time of about 0.4 s from enzymology.
Background: Social familiarity, which is based on the ability to recognise familiar conspecific individuals following prior association, may affect all major life activities of group-living animals such as foraging, reproduction and anti-predator behaviours. A scarcely experimentally tested explanation why social familiarity is beneficial for group-living animals is provided by limited attention theory. Limited attention theory postulates that focusing on a given task, such as inspection and assessment of unfamiliar group members, has cognitive and associated physiological and behavioural costs with respect to the attention paid to other tasks, such as anti-predator vigilance and response. Accordingly, we hypothesised that social familiarity enhances the anti-predator success of group-living predatory mites, Phytoseiulus persimilis, confronted with an intraguild predator, the predatory mite Amblyseius andersoni. Methodology/Principal Findings: We videotaped and analysed the response of two P. persimilis larvae, held in familiar or unfamiliar pairs, to attacks by a gravid A. andersoni female, using the behavioural analyses software EthoVision Pro (R). Familiar larvae were more frequently close together, reacted more quickly to predator attacks, survived more predator encounters and survived longer than unfamiliar larvae. Significance: In line with the predictions of limited attention theory, we suggest that social familiarity improves antipredator behaviours because it allows prey to shift attention to other tasks rather than group member assessment.
We review a series of key travelling front problems in reaction-diffusion systems with a time-delayed feedback, appearing in ecology, nonlinear optics and neurobiology. For each problem, we determine asymptotic approximations for the wave shape and its speed. Particular attention is devoted to their validity and all analytical solutions are compared to solutions obtained numerically. We also extend the work by Erneux et al. (Erneux et al. 2010 Phil. Trans. R. Soc. A 368, 483-493 (doi:10.1098/rsta.2009.0228)) by considering the case of a slowly propagating front subject to a weak delayed feedback. The delay may either speed up the front in the same direction or reverse its direction. This article is part of the theme issue 'Nonlinear dynamics of delay systems'.