title: Altered cognitive function of prefrontal cortex during error feedback in patients with irritable bowel syndrome, based on FMRI and dynamic causal modeling.
abstract: OBJECTIVE
  Patients with irritable bowel syndrome (IBS) have increased activity in the insula and reduced activation of the dorsolateral prefrontal cortex (DLPFC) in response to visceral stimulation. We investigated whether they have latent impairments in cognitive flexibility because of dysfunction in the DLPFC and insula and altered connectivity between brain regions.
  
  
  METHODS
  We analyzed data from 30 individuals with IBS (15 men; age, 21.7 ± 3.0 y) diagnosed based on Rome III criteria, along with 30 individuals matched for age, sex, and education level (controls). Event-related functional magnetic resonance imaging of the brain was performed to evaluate cognitive flexibility and was assessed by the Wisconsin Card Sorting Test, in which subjects are allowed to change choice criteria, defined as set-shifting in response to error feedback. Brain images were analyzed with statistical parametric mapping 5 and 8 software and dynamic causal modeling.
  
  
  RESULTS
  Subjects with IBS had significantly more Nelson perseverative errors (P < .05) and set-maintenance difficulties (P < .05) than controls. They also showed significantly decreased activity of the right DLPFC (Brodmann's area 9; P < .001) and right hippocampus (P < .001), and significantly increased activity of the left posterior insula (P < .001) at error feedback during set-shifting. Dynamic causal modeling analysis during set-shifting revealed significantly less connectivity from the DLPFC to pre-supplementary motor area in subjects with IBS, compared with controls (P = .012).
  
  
  CONCLUSIONS
  Individuals with IBS have latent impairments in cognitive flexibility as a result of altered activity of the DLPFC, insula, and hippocampus, and impaired connectivity between the DLPFC and pre-supplementary motor area.
authors: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Emiko
authors: E
authors: Aizawa
authors: Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
authors: Yasuhiro
authors: Y
authors: Sato
authors: Primate Research Institute, Kyoto University, Kyoto, Japan.
authors: Takanori
authors: T
authors: Kochiyama
authors: Department of Clinical Neuroscience, Yamagata University Graduate School of Medicine, Yamagata, Japan.
authors: Naohiro
authors: N
authors: Saito
authors: Sendai Nakae Hospital, Sendai, Japan.
authors: Masahiro
authors: M
authors: Izumiyama
authors: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Joe
authors: J
authors: Morishita
authors: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Motoyori
authors: M
authors: Kanazawa
authors: Department of Physiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Keisetsu
authors: K
authors: Shima
authors: Department of Physiology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hajime
authors: H
authors: Mushiake
authors: Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan; Department of Comprehensive Medicine, Tohoku University Hospital, Sendai, Japan.
authors: Michio
authors: M
authors: Hongo
authors: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan. Electronic address: sfukudo@med.tohoku.ac.jp.
authors: Shin
authors: S
authors: Fukudo
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000150:complications / Q000503:physiopathology*; D005246:Feedback; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D055815:Young Adult