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Regional brain signal variability: a novel indicator of pain sensitivity and coping

Rogachov, Anton; Cheng, Joshua C.; Erpelding, Nathalie; Hemington, Kasey S.; Crawley, Adrian P.; Davis, Karen D.

doi: 10.1097/j.pain.0000000000000665
Research Paper

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.

Supplemental Digital Content is Available in the Text.Regional brain signal variability is related to individual differences in pain sensitivity and pain-coping strategies.

aDivision of Brain, Imaging and Behaviour Systems, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada

bInstitute of Medical Science, University of Toronto, Toronto, ON, Canada

cJoint Department of Medical Imaging, University Health Network, Toronto, ON, Canada

dDepartment of Surgery, University of Toronto, Toronto, ON, Canada

Corresponding author. Address: Krembil Research Institute, Toronto Western Hospital, 399 Bathurst St, Room MP12-306, Toronto, ON M5T 2S8, Canada. Tel.: (416) 603-5662. E-mail address: (K.D. Davis).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received April 20, 2016

Received in revised form May 31, 2016

Accepted June 28, 2016

© 2016 International Association for the Study of Pain
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