title: Optimizing and Interpreting Insular Functional Connectivity Maps Obtained During Acute Experimental Pain: The Effects of Global Signal and Task Paradigm Regression.
abstract: The insula is uniquely located between the temporal and parietal cortices, making it anatomically well-positioned to act as an integrating center between the sensory and affective domains for the processing of painful stimulation. This can be studied through resting-state functional connectivity (fcMRI) imaging; however, the lack of a clear methodology for the analysis of fcMRI complicates the interpretation of these data during acute pain. Detected connectivity changes may reflect actual alterations in low-frequency synchronous neuronal activity related to pain, may be due to changes in global cerebral blood flow or the superimposed task-induced neuronal activity. The primary goal of this study was to investigate the effects of global signal regression (GSR) and task paradigm regression (TPR) on the changes in functional connectivity of the left (contralateral) insula in healthy subjects at rest and during acute painful electric nerve stimulation of the right hand. The use of GSR reduced the size and statistical significance of connectivity clusters and created negative correlation coefficients for some connectivity clusters. TPR with cyclic stimulation gave task versus rest connectivity differences similar to those with a constant task, suggesting that analysis which includes TPR is more accurately reflective of low-frequency neuronal activity. Both GSR and TPR have been inconsistently applied to fcMRI analysis. Based on these results, investigators need to consider the impact GSR and TPR have on connectivity during task performance when attempting to synthesize the literature.
authors.affiliation: 1 Department of Anesthesiology, Center for Pain Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: James W
authors.initials: JW
authors.lastname: Ibinson
authors.affiliation: 2 Department of Anesthesiology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Vogt
authors.affiliation: 3 University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Taylor
authors.affiliation: 4 George Washington University School of Medicine and Health Sciences , Washington, District of Columbia.
authors.forename: Shiv B
authors.initials: SB
authors.lastname: Dua
authors.affiliation: 3 University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Becker
authors.affiliation: 5 Department of Radiology, Massachusetts General Hospital, Brigham and Women's Hospital , and Harvard Medical School, Boston, Massachusetts.
authors.forename: Marco
authors.initials: M
authors.lastname: Loggia
authors.affiliation: 1 Department of Anesthesiology, Center for Pain Research, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
mesh_terms: D000328:Adult; D001921:Brain / Q000502:physiology; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000502:physiology* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D012146:Rest / Q000502:physiology; D055815:Young Adult
keywords: blood oxygen level-dependent signal; electric nerve stimulation; functional connectivity MRI; global signal regression; pain; task paradigm regression