title: Regional brain signal variability: a novel indicator of pain sensitivity and coping.
abstract: Variability in blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. We tested the hypothesis that individual pain sensitivity and coping is reflected by regional fMRI BOLD signal variability within dynamic pain connectome-brain systems implicated in the pain experience. We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.
authors.affiliation: Division of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Anton
authors.initials: A
authors.lastname: Rogachov
authors.affiliation: Division of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Division of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Erpelding
authors.affiliation: Division of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Kasey S
authors.initials: KS
authors.lastname: Hemington
authors.affiliation: Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Crawley
authors.affiliation: Division of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.|Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Davis
mesh_terms: D000223:Adaptation, Psychological; D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D063132:Connectome; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000000981:diagnostic imaging; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000000981:diagnostic imaging; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation; D011601:Psychophysics; D011930:Reaction Time / Q000502:physiology; D012146:Rest; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D010100:Oxygen