title: Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study.
abstract: BACKGROUND
  Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3-15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain.
  
  
  OBJECTIVE
  The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain. The current study sought specifically to investigate IC-CC functional connectivity in TMD patients and healthy controls (HCs), both during resting state and during the application of a painful stimulus.
  
  
  METHODS
  Eight patients with TMD, and 8 age- and sex-matched HCs were enrolled in the present study. Functional magnetic resonance imaging data during resting state and during the performance of a pressure pain stimulus to the temple were acquired. Predefined seed regions were placed in the IC (anterior and posterior insular cortices) and the extracted signal was correlated with brain activity throughout the whole brain. Specifically, we were interested whether TMD patients and HCs would show differences in IC-CC connectivity, both during resting state and during the application of a painful stimulus to the face.
  
  
  RESULTS
  As a main finding, functional connectivity analyses revealed an increased functional connectivity between the left anterior IC and pregenual anterior cingulate cortex (ACC) in TMD patients, during both resting state and applied pressure pain. Within the patient group, there was a negative correlation between the anterior IC-ACC connectivity and clinical pain intensity as measured by a visual analog scale.
  
  
  CONCLUSIONS
  Since the pregenual region of the ACC is critically involved in antinociception, we hypothesize that an increase in anterior IC-ACC connectivity is indicative of an adaptation of the pain modulatory system early in the chronification process.
authors.affiliation: Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ichesco
authors.forename: Andres
authors.initials: A
authors.lastname: Quintero
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.forename: Scott
authors.initials: S
authors.lastname: Peltier
authors.forename: Pia M
authors.initials: PM
authors.lastname: Sundgren
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Gerstner
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmidt-Wilcke
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply* / Q000473:pathology; D005260:Female; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010147:Pain Measurement; D010812:Physical Stimulation / Q000009:adverse effects; D010865:Pilot Projects; D011312:Pressure / Q000009:adverse effects; D012146:Rest / Q000502:physiology; D018709:Statistics, Nonparametric; D013705:Temporomandibular Joint Disorders / Q000473:pathology*; D055815:Young Adult
chemical_list: D010100:Oxygen