Volume 145, Issue 6, Pages 1253-1261.e3 (December 2013) Impaired Emotional Learning and Involvement of the Corticotropin-Releasing Factor Signaling System in Patients With Irritable Bowel Syndrome  Jennifer S. Labus, Catherine S. Hubbard, Joshua Bueller, Bahar Ebrat, Kirsten Tillisch, Michelle Chen, Jean Stains, George E. Dukes, Dennis L. Kelleher, Bruce D. Naliboff, Michael Fanselow, Emeran A. Mayer  Gastroenterology  Volume 145, Issue 6, Pages 1253-1261.e3 (December 2013) DOI: 10.1053/j.gastro.2013.08.016 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Estimated means for SCR amplitude (microsiemens) and standard errors during acquisition, test, and extinction for PLA, 20 mg and 200 mg doses of the CRF-R1 antagonist (CRF-R1A) for IBS (blue) and HCs (red). Gastroenterology 2013 145, 1253-1261.e3DOI: (10.1053/j.gastro.2013.08.016) Copyright © 2013 AGA Institute Terms and Conditions

Figure 2 Brain regions showing greater BOLD responses to the cue during acquisition in HCs compared to IBS patients for the PLA condition. Whole-brain maps threshold at P < .001, uncorrected. Gastroenterology 2013 145, 1253-1261.e3DOI: (10.1053/j.gastro.2013.08.016) Copyright © 2013 AGA Institute Terms and Conditions

Figure 3 Brain regions showing greater BOLD responses to the cue during extinction in IBS patients compared with HCs during PLA condition. Whole-brain maps threshold at P < .001, uncorrected. Gastroenterology 2013 145, 1253-1261.e3DOI: (10.1053/j.gastro.2013.08.016) Copyright © 2013 AGA Institute Terms and Conditions

Supplementary Figure 1 Schematic illustrating experimental design (top) and the fear-conditioning paradigm (bottom). Top: Each subject received a single acute oral dose of PLA (0 mg), 20 mg of GW876008, or 200 mg of GW876008 in a randomized, double-blind manner across 3 separate study treatment (TX) visits (visit days 3−5), each separated by approximately 1 month. Bottom: fear-conditioning paradigm comprised of acquisition, 5 trials of a cue presentation (red light) always followed by an aversive abdominal stimulus (750 milliseconds); test phase, 10 trials in which the cue was followed by the aversive stimulus on only 50% of the trials; and extinction, 5 trials in which none of the cues were followed by an aversive stimulus. Each cue presentation lasted for 9 seconds in each phase and the inter-trial interval was 20.75 seconds. Gastroenterology 2013 145, 1253-1261.e3DOI: (10.1053/j.gastro.2013.08.016) Copyright © 2013 AGA Institute Terms and Conditions

Supplementary Figure 2 Activation map from threat of abdominal pain stimulus paradigm. This figure illustrates the response to the cue or threat of abdominal pain in a sample 19 female IBS patients not on placebo. The paradigm activates regions of the homeostatic afferent network, including the thalamus, insula, and midcingulate cortex (unpublished findings). Gastroenterology 2013 145, 1253-1261.e3DOI: (10.1053/j.gastro.2013.08.016) Copyright © 2013 AGA Institute Terms and Conditions