Disturbed insular functional connectivity and its clinical implication in patients with complex regional pain syndrome

Jinsol Kim, Eun Namgung, Suji Lee, Eunji Ha, Haejin Hong, Yumi Song, Hyangwon Lee, Sohyun Oh, In Kyoon Lyoo, Sujung Yoon, Hyeonseok Jeong

Research output: Contribution to journalArticlepeer-review


Background: Complex regional pain syndrome (CRPS) is characterized by continued amplification of pain intensity. Given the pivotal roles of the insula in the perception and interpretation of pain, we examined insular functional connectivity and its associations with clinical characteristics in patients with CRPS. Methods: Twenty-one patients with CRPS and 49 healthy controls underwent resting-state functional magnetic resonance imaging. The seed-to-seed functional connectivity analysis was performed for the bilateral insulae and cognitive control regions including the dorsal anterior cingulate cortex (dACC) and bilateral dorsolateral prefrontal cortex (DLPFC) between the two groups. Correlations between altered functional connectivity and clinical characteristics were assessed in CRPS patients. Results: CRPS patients exhibited lower functional connectivity within the bilateral anterior insulae, between the insular and cognitive control regions (the bilateral anterior/posterior insulae-dACC; the right posterior insula-left DLPFC), as compared with healthy controls at false discovery rate-corrected p < 0.05. In CRPS patients, pain severity was associated negatively with the left–right anterior insular functional connectivity (r = −0.49, p = 0.03), yet positively with the left anterior insula-dACC functional connectivity (r = 0.51, p = 0.02). Conclusions: CRPS patients showed lower functional connectivity both within the bilateral anterior insulae and between the insular and cognitive control regions. The current findings may suggest pivotal roles of the insula in dysfunctional pain processing of CRPS patients.

Original languageEnglish
Article number103440
JournalNeuroImage: Clinical
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by Ministry of Science and ICT ( NRF-2020M3E5D9080555 ) and Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education ( NRF-2020R1A6A1A03043528 ).

Publisher Copyright:
© 2023


  • Complex regional pain syndrome
  • Insula, functional connectivity
  • Magnetic resonance imaging


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