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Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain

Tu, Yihenga,b; Jung, Minyounga; Gollub, Randy L.a; Napadow, Vitalyb; Gerber, Jessicab; Ortiz, Anaa; Lang, Courtneya; Mawla, Ishtiaqa; Shen, Weia; Chan, Suk-Takb; Wasan, Ajay D.c; Edwards, Robert R.d; Kaptchuk, Ted J.e; Rosen, Bruceb; Kong, Jiana,b,*

doi: 10.1097/j.pain.0000000000001507
Research Paper

Accumulating evidence has shown that complicated brain systems are involved in the development and maintenance of chronic low back pain (cLBP), but the association between brain functional changes and clinical outcomes remains unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to identify abnormal functional connectivity (FC) between the default mode, sensorimotor, salience, and central executive brain networks in cLBP and tested whether abnormal FCs are related to pain and comorbid symptoms. Fifty cLBP patients and 44 matched healthy controls (HCs) underwent an fMRI scan, from which brain networks were identified by independent component analysis. Multivariate pattern analysis, graph theory approaches, and correlation analyses were applied to find abnormal FCs that were associated with clinical symptoms. Findings were validated on a second cohort of 30 cLBP patients and 30 matched HCs. Results showed that the medial prefrontal cortex/rostral anterior cingulate cortex had abnormal FCs with brain regions within the default mode network and with other brain networks in cLBP patients. These altered FCs were also correlated with pain duration, pain severity, and pain interference. Finally, we found that resting-state FC could discriminate cLBP patients from HCs with 91% accuracy in the first cohort and 78% accuracy in the validation cohort. Our findings suggest that the medial prefrontal cortex/rostral anterior cingulate cortex may be an important hub for linking the default mode network with the other 3 networks in cLBP patients. Elucidating the altered FCs and their association with clinical outcomes will enhance our understanding of the pathophysiology of cLBP and may facilitate the development of pain management approaches.

Using functional imaging and multivariate pattern analysis, authors identified abnormal medial prefrontal cortex/rostral anterior cingulate cortex connectivity across multiple brain networks that were linked to chronic low back pain symptoms.

aDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

bDepartment of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

cDepartment of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, United States

dDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

eProgram of Placebo Studies and the Therapeutic Encounter, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Corresponding author. Address: Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA 02129, United States. Tel.: +1 617 286 9879. E-mail address: (J. Kong).

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 August 30, 2018

Received in revised form January 19, 2019

Accepted January 23, 2019

© 2019 International Association for the Study of Pain
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