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

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 563
Author(s):  
Paul M. Macey ◽  
Philip J. Schluter ◽  
Katherine E. Macey ◽  
Ronald M. Harper
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
A Priori ◽  
Brain Regions ◽  
Single Step ◽  
Response Patterns ◽  
Whole Brain ◽  
Average Signal Intensity ◽  
Respiratory Challenge ◽  
Time Point

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.

scholarly journals Detecting variable responses within fMRI time-series of volumes-of-interest using repeated measures ANOVA

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 563 ◽  
Author(s):  
Paul M. Macey ◽  
Philip J. Schluter ◽  
Katherine E. Macey ◽  
Ronald M. Harper
Keyword(s):  
Repeated Measures ◽  
A Priori ◽  
Brain Regions ◽  
Response Patterns ◽  
Whole Brain ◽  
Repeated Measures Analysis ◽  
Average Signal Intensity ◽  
Respiratory Challenge ◽  
Post Hoc

We present an approach to analyzing fMRI timetrends from volumes-of-interest (VOI) within and between subject groups using repeated measures analysis of variance (RMANOVA), which allows temporal patterns to be examined without an a priori model of expected timing or pattern of response. 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 package 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, imported into SAS, and the procedure PROC MIXED implements the RMANOVA. 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 fMRI paradigms eliciting complex response patterns.

Effective Connectivity During an Avoidance-Based Pavlovian-to-Instrumental Transfer Task

2021 ◽  
Author(s):  
Daniel Petrie ◽  
Sy-Miin Chow ◽  
Charles Geier
Keyword(s):  
Effective Connectivity ◽  
A Priori ◽  
Transfer Task ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Response Patterns ◽  
Multiple Model ◽  
Hemodynamic Response Function ◽  
Blood Oxygen Level ◽  
Psychological Phenomena

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25-32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Behaviorally, participants exhibited specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood-oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

scholarly journals Correlations in Social Neuroscience Aren't Voodoo: Commentary on Vul et al. (2009)

2009 ◽  
Vol 4 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Matthew D. Lieberman ◽  
Elliot T. Berkman ◽  
Tor D. Wager
Keyword(s):  
Individual Difference ◽  
Meta Analysis ◽  
Brain Regions ◽  
Single Step ◽  
Social Neuroscience ◽  
Regression Analyses ◽  
Step Method ◽  
Whole Brain ◽  
Multiple Tests ◽  
Post Hoc

Vul, Harris, Winkielman, and Pashler (2009) , (this issue) claim that many brain—personality correlations in fMRI studies are “likely … spurious” (p. 274), and “should not be believed” (p. 285). Several of their conclusions are incorrect. First, they incorrectly claim that whole-brain regressions use an invalid and “nonindependent” two-step inferential procedure, a determination based on a survey sent to researchers that only included nondiagnostic questions about the descriptive process of plotting one's data. We explain how whole-brain regressions are a valid single-step method of identifying brain regions that have reliable correlations with individual difference measures. Second, they claim that large correlations from whole-brain regression analyses may be the result of noise alone. We provide a simulation to demonstrate that typical fMRI sample sizes will only rarely produce large correlations in the absence of any true effect. Third, they claim that the reported correlations are inflated to the point of being “implausibly high.” Though biased post hoc correlation estimates are a well-known consequence of conducting multiple tests, Vul et al. make inaccurate assumptions when estimating the theoretical ceiling of such correlations. Moreover, their own “meta-analysis suggests that the magnitude of the bias is approximately .12—a rather modest bias.

scholarly journals Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 962-967
Author(s):  
Andrea V. Haas ◽  
Rene Baudrand ◽  
Rebecca M. Easly ◽  
Gillian R. Murray ◽  
Rhian M. Touyz ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Repeated Measures ◽  
Mixed Model ◽  
Risk Allele ◽  
A Priori ◽  
Antihypertensive Medications ◽  
Adrenal Hormones ◽  
High Sodium ◽  
Caveolin 1 ◽  
Statin Use

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin’s aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1–43.2) lower aldosterone level ( P =0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels ( P =0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant ( P =0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin’s aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.

scholarly journals Effective Connectivity during an Avoidance-Based Pavlovian-to-Instrumental Transfer Task

2021 ◽  
Vol 11 (11) ◽  
pp. 1472
Author(s):  
Daniel J. Petrie ◽  
Sy-Miin Chow ◽  
Charles F. Geier
Keyword(s):  
Effective Connectivity ◽  
A Priori ◽  
Transfer Task ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Response Patterns ◽  
Multiple Model ◽  
Hemodynamic Response Function ◽  
Blood Oxygen Level ◽  
Psychological Phenomena

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25–32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Participants exhibited behavior that was suggestive of specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood–oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

scholarly journals 64 Immunological, physiological, and behavioral responses to an experimentally-induced respiratory disease challenge in growing steers

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 41-42
Author(s):  
Lauren Wottlin ◽  
Gordon E Carstens ◽  
William E Pinchak ◽  
Kevin Washburn ◽  
Sarah Lawhon ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Repeated Measures ◽  
Fixed Effects ◽  
Mixed Model ◽  
Behavioral Responses ◽  
Immunological Response ◽  
Blood Oxygen Saturation ◽  
Rumen Temperature ◽  
Arterial Blood ◽  
Respiratory Challenge

Abstract Immunologic, physiologic, and behavioral responses to a combined viral-bacterial respiratory challenge were explored in beef steers (initial BW 293 kg). Steers (n = 24) were inoculated intranasally with bovine herpes virus-1 (2×108 PFU) and intratracheally with Mannheimia haemolytica (MH, 2.15×1010 CFU) on days -3 and 0, respectively, (n = 16; VB), or similarly inoculated with phosphate-buffered saline (n = 8; PBS). Venous and arterial blood were collected on -3, -1, 0, 2, 3, 5, 7, 10, and 14 relative to MH challenge for CBC, haptoglobin, and arterial blood oxygen saturation analysis. Continuously recorded variables included rumen temperature, activity, rumination, DMI, and feeding behavior. Data were analyzed with a repeated-measures mixed model (SAS 9.4) with fixed effects of day, inoculation, and the interaction. Bunk visit frequency and DMI were reduced (P < 0.01) in VB steers throughout the 14 d post-MH period compared to PBS steers. Rumination (days 1, 7) and activity (days 1, 2, 4–8, and 11–13) were reduced (P < 0.03) in VB steers vs PBS steers. Rumen temperature was elevated (P < 0.04) in VB steers until day 6 post MH inoculation. Neutrophil concentrations (days 2 and 3), platelets (days 7–14), fibrinogen (days 2–10), and haptoglobin (days 2–7) were elevated (P < 0.05) in VB vs PBS steers. Hematocrit was depressed (P < 0.05) in VB steers on days 3–10. The VB steers had decreased (P < 0.05) arterial SO2% and pO2 than PBS steers; however, the inoculation × day interaction was not significant. Results indicate that the experimental VB challenge substantially altered rumen temperature, DMI, feeding behavior, rumination and immunological response as expected. Arterial sO2% and pO2 concentrations were reduced minimally by VB challenge, indicating challenges in using blood gas to detect BRD in beef cattle.

Abstract W P382: Cognitive Outcome in SAMMPRIS: Medical Therapy vs. Stenting

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Alison P Smock ◽  
Tanya N Turan ◽  
George A Cotsonis ◽  
Michael J Lynn ◽  
Colin P Derdeyn ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Repeated Measures ◽  
Mixed Model ◽  
Cerebral Arteries ◽  
Cognitive Outcome ◽  
Chi Square ◽  
Treatment Groups ◽  
Angioplasty And Stenting ◽  
Time Point

Background: It has been hypothesized that revascularization of stenotic cerebral arteries may improve cognitive outcome by increasing cerebral perfusion. We sought to compare cognitive outcome in patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) vs. AMM alone in the SAMMPRIS Trial. Methods: In SAMMPRIS, 451 patients with recent TIA or stroke attributed to 70%-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients with stroke as the qualifying event who had a NIHSS indicating aphasia or neglect were excluded from these analyses. Patients with any ischemic stroke, cerebral infarct with temporary signs (CITS), or ICH during follow-up were excluded from subsequent follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition at baseline, 4 months, 12 months, and closeout (mean 3.05 years in AMM group and 3.12 years in PTAS group). Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t-tests and Chi-square tests. Differences in MoCA means from baseline to follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests. Results: As shown in the Figure, there were no significant differences between the treatment groups for mean MoCA at any time point. There were significant improvements in mean MoCA from baseline to 4 months, 12 months, and closeout in both groups. The percentage of patients with cognitive impairment in the AMM vs. PTAS groups were not significantly different at baseline (53 vs. 56%), 4 months (38 vs. 44%), 12 months (42 vs. 40%), and closeout (43 vs. 39%). Conclusions: Revascularization did not provide any additional cognitive benefit over AMM alone in SAMMPRIS even after excluding patients who had cerebral infarction or ICH during follow-up.

scholarly journals Is There Benefit from Stenting on Cognitive Function in Intracranial Atherosclerosis?

2016 ◽  
Vol 43 (1-2) ◽  
pp. 31-35 ◽  
Author(s):  
Tanya N. Turan ◽  
Alison Smock ◽  
George Cotsonis ◽  
David Bachman ◽  
Sami Al Kasab ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Repeated Measures ◽  
Mixed Model ◽  
Cerebral Arteries ◽  
Arterial Stenosis ◽  
Cerebrovascular Event ◽  
Treatment Groups ◽  
Cognition Impairment ◽  
Time Point

Background: Revascularization of stenotic cerebral arteries is hypothesized to improve cognition by increasing cerebral perfusion. Aims: We compared cognition impairment among patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) versus AMM alone in the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) Trial. Methods: In SAMMPRIS, 451 patients with recent transient ischemic attack or stroke attributed to 70-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients who had stroke as the qualifying event with National Institutes of Health Stroke Scale indicating aphasia or neglect were excluded from these analyses. Patients with a cerebrovascular event (ischemic stroke, cerebral infarct with temporary signs or intracranial hemorrhage) during follow-up were excluded from follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t tests and chi-square tests. Differences in MoCA mean at baseline and follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests. Results: There were no significant differences between the treatment groups for mean MoCA at any time point. Mean MoCA scores improved in both groups. The percentage of patients with cognitive impairment in the AMM versus PTAS groups was not significantly different at any time point. Conclusions: Revascularization with PTAS showed no improvement in cognitive impairment over AMM alone among patients who did not have recurrent cerebrovascular events during follow-up.

Effects of Aging on the Subcortical Encoding of Stop Consonants

2020 ◽  
Vol 29 (3) ◽  
pp. 391-403
Author(s):  
Dania Rishiq ◽  
Ashley Harkrider ◽  
Cary Springer ◽  
Mark Hedrick
Keyword(s):  
Older Adults ◽  
Repeated Measures ◽  
Mixed Model ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Aging Effects ◽  
Formant Frequency ◽  
Place Of Articulation ◽  
Second Formant ◽  
Effects Of Aging

Purpose The main purpose of this study was to evaluate aging effects on the predominantly subcortical (brainstem) encoding of the second-formant frequency transition, an essential acoustic cue for perceiving place of articulation. Method Synthetic consonant–vowel syllables varying in second-formant onset frequency (i.e., /ba/, /da/, and /ga/ stimuli) were used to elicit speech-evoked auditory brainstem responses (speech-ABRs) in 16 young adults ( M age = 21 years) and 11 older adults ( M age = 59 years). Repeated-measures mixed-model analyses of variance were performed on the latencies and amplitudes of the speech-ABR peaks. Fixed factors were phoneme (repeated measures on three levels: /b/ vs. /d/ vs. /g/) and age (two levels: young vs. older). Results Speech-ABR differences were observed between the two groups (young vs. older adults). Specifically, older listeners showed generalized amplitude reductions for onset and major peaks. Significant Phoneme × Group interactions were not observed. Conclusions Results showed aging effects in speech-ABR amplitudes that may reflect diminished subcortical encoding of consonants in older listeners. These aging effects were not phoneme dependent as observed using the statistical methods of this study.

Power of Modified Brown-Forsythe and Mixed-Model Approaches in Split-Plot Designs

Methodology ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Pablo Livacic-Rojas ◽  
Guillermo Vallejo ◽  
Paula Fernández ◽  
Ellián Tuero-Herrero
Keyword(s):  
Repeated Measures ◽  
Statistical Power ◽  
Mixed Model ◽  
Covariance Structure ◽  
Simulation Method ◽  
Future Research ◽  
Repeated Measures Design ◽  
Fixed And Random Effects ◽  
Split Plot ◽  
High Level

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.

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