title: Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA.
  
  
  METHODS
  24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity.
  
  
  RESULTS
  When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters.
  
  
  CONCLUSIONS
  Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Flodin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Martinsen
authors.affiliation: Department of Medicine, Rheumatology Unit, CMM, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: Reem
authors.initials: R
authors.lastname: Altawil
authors.affiliation: Department of Medicine, Rheumatology Unit, CMM, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Waldheim
authors.affiliation: Department of Medicine, Rheumatology Unit, CMM, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: Jon
authors.initials: J
authors.lastname: Lampa
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kosek
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Fransson
keywords: brain connectivity; fMRI; inflammation; joint; pain; resting-state; rheumatoid arthritis