Detecting variable responses in time-series using repeated measures ANOVA: Application to physiologic challenges.

We present an approach to analyzing physiologic timetrends recorded during a stimulus by comparing means at each time point using repeated measures analysis of variance (RMANOVA). The approach allows temporal patterns to be examined without an a priori model of expected timing or pattern of response. The approach was originally applied to signals recorded from functional magnetic resonance imaging (fMRI) volumes-of-interest (VOI) during a physiologic challenge, but we have used the same technique to analyze continuous recordings of other physiological signals such as heart rate, breathing rate, and pulse oximetry. For fMRI, the method serves as a complement to whole-brain voxel-based analyses, and is useful for detecting complex responses within pre-determined brain regions, or as a post-hoc analysis of regions of interest identified by whole-brain assessments. We illustrate an implementation of the technique in the statistical software packages R and SAS. VOI timetrends are extracted from conventionally preprocessed fMRI images. A timetrend of average signal intensity across the VOI during the scanning period is calculated for each subject. The values are scaled relative to baseline periods, and time points are binned. In SAS, the procedure PROC MIXED implements the RMANOVA in a single step. In R, we present one option for implementing RMANOVA with the mixed model function "lme". Model diagnostics, and predicted means and differences are best performed with additional libraries and commands in R; we present one example. The ensuing results allow determination of significant overall effects, and time-point specific within- and between-group responses relative to baseline. We illustrate the technique using fMRI data from two groups of subjects who underwent a respiratory challenge. RMANOVA allows insight into the timing of responses and response differences between groups, and so is suited to physiologic testing paradigms eliciting complex response patterns

Effects of go/no-go training on food-related action tendencies, liking and choice

Inhibitory control training effects on behaviour (e.g. ‘healthier’ food choices) can be driven by changes in affective evaluations of trained stimuli, and theoretical models indicate that changes in action tendencies may be a complementary mechanism. In this preregistered study, we investigated the effects of food-specific go/no-go training on action tendencies, liking and impulsive choices in healthy participants. In the training task, energy-dense foods were assigned to one of three conditions: 100% inhibition (no-go), 0% inhibition (go) or 50% inhibition (control). Automatic action tendencies and liking were measured pre- and post-training for each condition. We found that training did not lead to changes in approach bias towards trained foods (go and no-go relative to control), but we warrant caution in interpreting this finding as there are important limitations to consider for the employed approach–avoidance task. There was only anecdotal evidence for an effect on food liking, but there was evidence for contingency learning during training, and participants were on average less likely to choose a no-go food compared to a control food after training. We discuss these findings from both a methodological and theoretical standpoint and propose that the mechanisms of action behind training effects be investigated further

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Detecting variable responses in time-series using repeated measures ANOVA: Application to physiologic challenges.

We present an approach to analyzing physiologic timetrends recorded during a stimulus by comparing means at each time point using repeated measures analysis of variance (RMANOVA). The approach allows temporal patterns to be examined without an a priori model of expected timing or pattern of response. The approach was originally applied to signals recorded from functional magnetic resonance imaging (fMRI) volumes-of-interest (VOI) during a physiologic challenge, but we have used the same technique to analyze continuous recordings of other physiological signals such as heart rate, breathing rate, and pulse oximetry. For fMRI, the method serves as a complement to whole-brain voxel-based analyses, and is useful for detecting complex responses within pre-determined brain regions, or as a post-hoc analysis of regions of interest identified by whole-brain assessments. We illustrate an implementation of the technique in the statistical software packages R and SAS. VOI timetrends are extracted from conventionally preprocessed fMRI images. A timetrend of average signal intensity across the VOI during the scanning period is calculated for each subject. The values are scaled relative to baseline periods, and time points are binned. In SAS, the procedure PROC MIXED implements the RMANOVA in a single step. In R, we present one option for implementing RMANOVA with the mixed model function "lme". Model diagnostics, and predicted means and differences are best performed with additional libraries and commands in R; we present one example. The ensuing results allow determination of significant overall effects, and time-point specific within- and between-group responses relative to baseline. We illustrate the technique using fMRI data from two groups of subjects who underwent a respiratory challenge. RMANOVA allows insight into the timing of responses and response differences between groups, and so is suited to physiologic testing paradigms eliciting complex response patterns

Detecting variable responses in time-series using repeated measures ANOVA: Application to physiologic challenges [version 2; referees: 2 approved]

We present an approach to analyzing physiologic timetrends recorded during a stimulus by comparing means at each time point using repeated measures analysis of variance (RMANOVA). The approach allows temporal patterns to be examined without an a priori model of expected timing or pattern of response. The approach was originally applied to signals recorded from functional magnetic resonance imaging (fMRI) volumes-of-interest (VOI) during a physiologic challenge, but we have used the same technique to analyze continuous recordings of other physiological signals such as heart rate, breathing rate, and pulse oximetry. For fMRI, the method serves as a complement to whole-brain voxel-based analyses, and is useful for detecting complex responses within pre-determined brain regions, or as a post-hoc analysis of regions of interest identified by whole-brain assessments. We illustrate an implementation of the technique in the statistical software packages R and SAS. VOI timetrends are extracted from conventionally preprocessed fMRI images. A timetrend of average signal intensity across the VOI during the scanning period is calculated for each subject. The values are scaled relative to baseline periods, and time points are binned. In SAS, the procedure PROC MIXED implements the RMANOVA in a single step. In R, we present one option for implementing RMANOVA with the mixed model function “lme”. Model diagnostics, and predicted means and differences are best performed with additional libraries and commands in R; we present one example. The ensuing results allow determination of significant overall effects, and time-point specific within- and between-group responses relative to baseline. We illustrate the technique using fMRI data from two groups of subjects who underwent a respiratory challenge. RMANOVA allows insight into the timing of responses and response differences between groups, and so is suited to physiologic testing paradigms eliciting complex response patterns

Sex differences in insular cortex gyri responses to a brief static handgrip challenge

Abstract Background Cardiovascular disease varies between sexes, suggesting male-female autonomic control differences. Insular gyri help coordinate autonomic regulation and show a sex-dependent response to a sympathetic challenge. Methods We examined sex-related insular gyral responses to a short static handgrip exercise challenge eliciting parasympathetic withdrawal with functional magnetic resonance imaging (fMRI) during four 16-s challenges (80% maximum strength) in 23 healthy females (age; mean ± std 50 ± 8 years) and 40 males (46 ± 9 years). Heart rate (HR) and fMRI signals were compared with repeated measures ANOVA (P < 0.05). Additional analyses were performed with age and age interactions, as well as right-handed only subjects. Results Females showed higher resting HR than males, but smaller percent HR change increases to the challenges. All gyri showed fMRI patterns concurrent with an HR peak and decline to baseline. fMRI signals followed an anterior-posterior organization in both sexes, but lateralization varied by gyri and sex. All subjects showed greater signals in the anterior vs. posterior gyri (females 0.3%, males 0.15%). The middle gyri showed no lateralization in females but left-sided dominance in males (0.1%). The posterior gyri showed greater left than right activation in both sexes. The anterior-most gyri exhibited a prominent sex difference, with females showing a greater right-sided activation (0.2%) vs. males displaying a greater left-sided activation (0.15%). Age and handedness affected a minority of findings but did not alter the overall pattern of results. Conclusions The anterior insula plays a greater role in cardiovascular regulation than posterior areas during a predominantly parasympathetic withdrawal challenge, with opposite lateralization between sexes. In females, the left anterior-most gyrus responded distinctly from other regions than males. Those sex-specific structural and functional brain patterns may contribute over time to variations in cardiovascular disease between the sexes

Sex differences in insular cortex gyri responses to a brief static handgrip challenge.

BackgroundCardiovascular disease varies between sexes, suggesting male-female autonomic control differences. Insular gyri help coordinate autonomic regulation and show a sex-dependent response to a sympathetic challenge.MethodsWe examined sex-related insular gyral responses to a short static handgrip exercise challenge eliciting parasympathetic withdrawal with functional magnetic resonance imaging (fMRI) during four 16-s challenges (80% maximum strength) in 23 healthy females (age; mean ± std 50 ± 8&nbsp;years) and 40 males (46 ± 9&nbsp;years). Heart rate (HR) and fMRI signals were compared with repeated measures ANOVA (P &lt; 0.05). Additional analyses were performed with age and age interactions, as well as right-handed only subjects.ResultsFemales showed higher resting HR than males, but smaller percent HR change increases to the challenges. All gyri showed fMRI patterns concurrent with an HR peak and decline to baseline. fMRI signals followed an anterior-posterior organization in both sexes, but lateralization varied by gyri and sex. All subjects showed greater signals in the anterior vs. posterior gyri (females 0.3%, males 0.15%). The middle gyri showed no lateralization in females but left-sided dominance in males (0.1%). The posterior gyri showed greater left than right activation in both sexes. The anterior-most gyri exhibited&nbsp;a prominent sex difference, with females showing a greater right-sided activation (0.2%) vs. males displaying a greater left-sided activation (0.15%). Age and handedness affected a minority of findings but did not alter the overall pattern of results.ConclusionsThe anterior insula plays a greater role in cardiovascular regulation than posterior areas during a predominantly parasympathetic withdrawal challenge, with opposite lateralization between sexes. In females, the left anterior-most gyrus responded distinctly from other regions than males. Those sex-specific structural and functional brain patterns may&nbsp;contribute over time to variations in cardiovascular disease between the sexes