Computational protocol: Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

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Protocol publication

[…] Data analyses were conducted using FMRIB’s Software Library (FSL) ( [] and in-house Matlab (MathWorks, Natick, MA) programs. Functional brain images obtained from every animal were first preprocessed by extracting the skull and other non-brain regions using FMRIB’s brain extraction tool (BET, []), while motion correction was performed using FMRIB’s Linear Image Registration Tool (MCFLIRT, []) on each EPI volume. In addition, a spike detection algorithm was used to identify abrupt head motion. All imaging volumes were then spatially smoothed with a 2-mm full-width-half-maximum (FWHM) Gaussian spatial filter, and the time series at each voxel temporally filtered using a 0.01 Hz high-pass filter to remove low-frequency temporal noise and drift of fMRI data. Following these preprocessing steps, subject-level GLM analysis of fMRI data was carried out with FSL’s fMRI Expert Analysis Tool using FMRIB’s Improved Linear Model (FEAT FILM, []) with nonparametric estimation of time series autocorrelation to locally pre-whiten voxel-wise time series. To perform unbiased univariate linear regression analysis, nuisance regressors were prepared to exclude confounding explanatory variables (EVs) using six motion parameters derived from head movement (three translations and three rotations). Mean time-course signals extracted from ventricles and white matter were also included to regress out additional confounds related to physiological noises and the linear drift.For the group-level analyses, functional data of each animal were first co-registered to individual’s anatomical images with a 6 degree-of-freedom rigid body transformation. Subsequently, co-registration to a template monkey brain in MNI space (a standard created by Montreal Neurological Institute (MNI), []) was performed using FMRIB’s Linear Image Registration Tool (FLIRT, []) with a 12 degree-of-freedom affine transformation. The calculated transformation matrix parameters were then applied to the functional dataset to perform group-level analyses in MNI standard space. The absence of vehicle data for three of the animals meant that a fully factorial repeated measures analysis could not be completed. Consequently, group comparisons were conducted using a mixed-effects (FSL FLAME 1+2) paired t-test to determine the group mean of the differential BOLD responses to the 42°C stimulus pre- and post-capsaicin and pre- and post-vehicle separately (see supplementary material for a full factorial analysis from the five animals completing all procedures). The final group activation maps were thresholded at z > 2.3 with differences considered statistically significant at p < 0.02 [], in order to identify brain regions showing potentiated heat BOLD responses under capsaicin-induced hypersensitization.In addition, region-of-interest (ROI) analyses were performed using a standard monkey brain atlas []. Regional percentage BOLD signal changes were extracted using the same atlas from selected anatomical brain regions under each condition (42°C vs 35°C heat stimulus before and post-capsaicin or vehicle). The regions selected were based on previous publications [, , –], including vermis, cerebellum, anterior cingulate cortex, posterior cingulate cortex, insula, thalamus, primary and secondary somatosensory cortices and frontal cortex. The effects of capsaicin (versus vehicle) and regions were determined using repeated measures ANOVA implemented in SPSS (Statistics for Research & Analysis V21). […]

Pipeline specifications

Software tools BET, SPSS
Applications Miscellaneous, Magnetic resonance imaging, Functional magnetic resonance imaging
Organisms Macaca fascicularis, Homo sapiens
Diseases Monkey Diseases
Chemicals Capsaicin