Computational protocol: Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study

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Protocol publication

[…] Whole-brain fMRI activation was modeled as the contrast of temperature stimuli (those temperatures perceived as producing warmth versus mild pain versus moderate pain against a fixed baseline). We also modeled the period required for the thermal probe to ramp up to target temperature and to ramp down from target temperatures. Because individual temperature threshold precepts were measured, ramp up and ramp down periods and individual temperature percepts were modeled as covariates of no interest in the general linear model (GLM). These resulting subject-specific contrast maps were used in higher-level analyses for between-group comparisons and within-group analysis in SPM8 to compare noxious pain (mild and moderate) versus innocuous warmth. These analyses generated an activation map of t-statistics that were used to identify brain regions indicating statistically significant between-group (male versus female) activation differences. To account for multiple comparisons, statistical thresholds for these higher-level analyses were corrected using the intrinsic smoothness of the data [] and Monte Carlo simulations in 3dClustSim (http://afni.nimh.nih.gov/pub/dist/doc/program_help/3dClustSim.html) at 10,000 iterations to produce family wise error corrected data (p ≤ 0.05) based on whole-brain analysis with a cluster size of 1659 voxels for significance. After generating whole-brain statistically significant clusters, peak MNI coordinates were identified in pain regions of interest (ROIs) within those clusters. Using Marsbar [], we created 3-mm spheres around select peak coordinates in pain processing regions and extracted the average signal for each ROI activated in males and females for each contrast/condition to use in analyses of the association of psychophysical reports with brain activation.Demographic and standardized sample characteristics were non-normally distributed and summarized using median and 25th to 75th inter-quartile ranges (IQR; continuous data) and Ns (percentages; categorical data). Medians and IQR were also used to summarize the psychophysical and ROI percent signal change data. Mann-Whitney tests were used to test for sex differences in the self-reported temperature and unpleasantness ratings at each of the pain sensory levels, as well as difference in the amount of change in those self-reports between pain levels. Associations of psychophysics (temperature intensity and unpleasantness) changes with respective contrast signal change values in ROIs associated with pain were assessed using linear regression analyses. To match the signal change contrast conditions (e.g. mild versus warm), each analysis controlled for the temperature and unpleasantness ratings in the referent pain condition also (e.g. warm temperature or unpleasantness if the focus in on the mild versus warm signal change condition). Tests of differences between the groups in the strength of those regression coefficients were conducted using the z test for independent correlations. Because this study focuses on a subset of participants in an ongoing larger study and because it is a preliminary investigation of the phenomena, statistical powering for this specific study was not conducted, rather, the primary focus is on the effect sizes observed. Thus, effect indices (e.g., Cohen’s d and beta coefficients) are reported with respective statistical p values and if of sufficient magnitude to demonstrate promising potential for future research, may be interpreted even if the respective p value does not meet the statistical significance criteria. Those findings, of course, are interpreted with caution. For these same reasons, we did not use any type of correction to the alpha level used. Unless otherwise noted, p < 0.05 was used for determining statistical significance. […]

Pipeline specifications

Software tools SPM, AFNI
Application Functional magnetic resonance imaging
Organisms Homo sapiens