title: Altered Cerebellar Activity in Visceral Pain-Related Fear Conditioning in Irritable Bowel Syndrome.
abstract: There is evidence to support a role of the cerebellum in emotional learning processes, which are demonstrably altered in patients with chronic pain. We tested if cerebellar activation is altered during visceral pain-related fear conditioning and extinction in irritable bowel syndrome (IBS). Cerebellar blood oxygenation level-dependent (BOLD) data from N = 17 IBS patients and N = 21 healthy controls, collected as part of a previous fMRI study, was reanalyzed utilizing an advanced normalizing method of the cerebellum. The differential fear conditioning paradigm consisted of acquisition, extinction, and reinstatement phases. During acquisition, two visual conditioned stimuli (CS) were presented either paired (CS+) or unpaired (CS-) with painful rectal distension as unconditioned stimulus (US). In the extinction phase, the CS+ and CS- were presented without US. For reinstatement, unpaired US presentations were followed by unpaired CS+ and CS- presentations. Group differences in cerebellar activation were analyzed for the contrasts CS+ > CS- and CS- > CS+. During acquisition, IBS patients revealed significantly enhanced cerebellar BOLD responses to pain-predictive (CS+) and safety (CS-) cues compared to controls (p < 0.05, family-wise error corrected). Increased activation was found in three main clusters, including the vermis (maximum in vermal lobule VI), intermediate cerebellum (maximum in lobule VIII), and the posterolateral cerebellar hemisphere (maximum in lobule VI). Areas overlapped for the contrasts CS+ > CS- and CS- > CS+. Group differences were most prominent in the contrast CS- > CS+. During extinction and reinstatement, no significant group differences were found. During visceral pain-related fear conditioning, IBS patients showed increased activations in circumscribed areas of the medial, intermediate, and lateral cerebellum. These areas are involved in autonomic, somatosensory, and cognitive functions and likely contribute to the different aspects of pain-related fear. The cerebellum contributes to altered pain-related fear learning in IBS.
authors: Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: J
authors: J
authors: Claassen
authors: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: F
authors: F
authors: Labrenz
authors: Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: T M
authors: TM
authors: Ernst
authors: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: A
authors: A
authors: Icenhour
authors: Integrative Gastroenterology, Clinic for Internal and Integrative Medicine, Kliniken Essen-Mitte, Essen, Germany.
authors: J
authors: J
authors: Langhorst
authors: Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: M
authors: M
authors: Forsting
authors: Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors: D
authors: D
authors: Timmann
authors: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. sigrid.elsenbruch@uk-essen.de.
authors: S
authors: S
authors: Elsenbruch
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological / Q000502:physiology; D001931:Brain Mapping; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000502:physiology; D010812:Physical Stimulation; D059265:Visceral Pain / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology
chemical_list: D010100:Oxygen
keywords: Anticipation; Cerebellum; Extinction; Fear conditioning; Irritable bowel syndrome; Visceral pain