title: Test-retest reliability of evoked heat stimulation BOLD fMRI.
abstract: To date, the blood oxygenated-level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique has enabled an objective and deeper understanding of pain processing mechanisms embedded within the human central nervous system (CNS). In order to further comprehend the benefits and limitations of BOLD fMRI in the context of pain as well as the corresponding subjective pain ratings, we evaluated the univariate response, test-retest reliability and confidence intervals (CIs) at the 95% level of both data types collected during evoked stimulation of 40°C (non-noxious), 44°C (mildly noxious) and a subject-specific temperature eliciting a 7/10 pain rating. The test-retest reliability between two scanning sessions was determined by calculating group-level interclass correlation coefficients (ICCs) and at the single-subject level. Across the three stimuli, we initially observed a graded response of increasing magnitude for both VAS (visual analog score) pain ratings and fMRI data. Test-retest reliability was observed to be highest for VAS pain ratings obtained during the 7/10 pain stimulation (ICC=0.938), while ICC values of pain fMRI data for a distribution of CNS structures ranged from 0.5 to 0.859 (p<0.05). Importantly, the upper and lower confidence interval CI bounds reported herein could be utilized in subsequent trials involving healthy volunteers to hypothesize the magnitude of effect required to overcome inherent variability of either VAS pain ratings or BOLD responses evoked during innocuous or noxious thermal stimulation.
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jaymin
authors.initials: J
authors.lastname: Upadhyay
authors.affiliation: Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Lemme
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Neuroscience Research, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bleakman
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Preclinial Research and Translational Medicine, Sunovion Inc., Marlborough, MA 01752, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Large
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Imaging, Merck Research Laboratories, West Point, PA 19486-0004</postal>, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Evelhoch
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Discovery Sciences, Biogen-Idec, Cambridge, MA 02142, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Borsook
authors.affiliation: Imaging Consortium for Drug Development, Boston, MA 02115, USA; Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lino.becerra@childrens.harvard.edu.
authors.forename: Lino
authors.initials: L
authors.lastname: Becerra
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply*; D016001:Confidence Intervals; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000209:etiology / Q000473:pathology*; D010147:Pain Measurement; D015203:Reproducibility of Results; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Evoked heat stimulation; Pain; Test–retest; fMRI