white matter tracts in nausea-susceptible individuals. Alternatively, repeated experience of motion sickness may, over time, yield microstructural alterations in these individuals. 312 Increased Regional Cerebral Type 1 Cannabinoid Receptor Availability in Functional Dyspepsia: A [18F]MK9470 PET Study Huynh Giao Ly, Jenny Ceccarini, Nathalie Weltens, Michel Koole, Lieselot Holvoet, Guy Bormans, Koen Van Laere, Jan F. Tack, Lukas Van Oudenhove INTRODUCTION: Functional dyspepsia (FD) is defined as the presence of chronic epigastric symptoms in the absence of underlying structural or biochemical abnormalities likely to explain them. These dyspeptic symptoms are often meal-related and disturbances in appetite regulation and food intake might lead to unexplained weight loss. FD patients are also characterized by abnormal regional cerebral activity in key areas of the ‘pain neuromatrix'. However, it is unknown which neurotransmitter mechanisms underlie these abnormalities. Endocannabinoids are involved in pain processing, regulation of gastrointestinal function and reward/food intake AIM: To compare the regional cerebral availability of the type 1 cannabinoid (CB1) receptor between FD patients and healthy controls. METHODS: 12 FD patients (mean age 29.4 ± 10.6, 11 women) with significant weight loss (mean 13.2 kg) and 12 age-, gender- and BMI-matched healthy controls participated in the study; psychiatric co-morbidity and intake of centrally acting medication or (recreational) drugs were exclusion criteria. Each subject underwent a 30 minute dynamic positron emission tomography scan consisting of 6 frames at 90 min postinjection of the CB1 receptor-selective radioligand [18F]MK9470. Parametric maps of CB1 receptor availability were constructed using modified standard uptake value (mSUV) values as estimate of receptor availability. These maps were spatially normalized to Montreal Neurological Institute space to allow whole-brain voxel- based analysis. A significance level of p height < 0.001 (uncorrected) was used to compare CB1 receptor availability between both groups. RESULTS: Significantly higher CB1 receptor availability was found in FD patients with local maxima in the following brain regions: anterior cingulate cortex (ACC, perigenual), caudate head, insular cortex (INS, anterior/mid, bilateral), orbitofrontal cortex (bilateral) and putamen (Table 1). The large cluster also included the amygdala, globus pallidus, hypothalamus, PAG and ventral striatum (nucleus accumbens) (Figure 1). CONCLUSION: We report the first study demonstrating a signific- antly higher CB1 receptor availability in regions involved in the regulation of visceral sensation (ant/mid INS, ACC and amygdala), and reward/food intake (hypothalamus and (ventral) striatum) in FD patients compared to controls. Whether this elevated receptor availability predisposes to or is a consequence of FD symptoms remains to be elucidated. However, within the patients group weight loss was not associated with receptor binding in any of the brain regions. These results may indicate that the abnormal brain activity in several of these regions previously demonstrated in FD may be due to abnormal functioning of the endocannabinoid system, identifying it as a potential novel target for treatment. Table1 S-71 AGA Abstracts 313 Gray Matter Morphometric Differences Associated With Clinical and Behavioral Phenotypes in IBS Patients and Healthy Controls Jennifer S. Labus, Zhiguo Jiang, Cody Ashe-McNalley, Florian Kurth, Jui-Yang Hong, Bahar Ebrat, Alen Zamanyan, Yonggang Shi, Alex Genco, Sam Hobel, Boris Gutman, Shantanu H. Joshi, Craig Schwartz, Paul Thompson, Ivo Dinov, Arthur W. Toga, Emeran A. Mayer Background.Alterations in gray matter density and voxel-based morphometry have been demonstrate in small and heterogeneous samples of patients with persistent pain syndromes, including irritable bowel syndrome(IBS).Aims.To examine group differences in regional gray matter volume and tensor based morphometry(TBM)in a large sample of female IBS patients and healthy controls(HCs), and to correlate these brain findings with clinical and behavioral measures.Methods. Structural brain images were obtained from 276 females(83 IBS, 193 HCs)from 14 studies conducted at UCLA. The LONI (UCLA Laboratory of Neuroimaging) pipeline was utilized for image preprocessing,volumetric analysis to produce mean gray matter for 13 regions of interests (ROIs), and tensor based morphometry yielding Jacobian determinant images indicating local volumetric expansion and compression. The general linear model was applied to test for group differences in regional gray matter and the Jacobian determinant images using SPM8 and SPSS19. All analyses controlled for age and total gray matter volume. We collected phenotyping data on catastrophizing (Coping Strategies Questionnaire), early life trauma (early life trauma inventory), state anxiety and depression (Hospital Anxiety and Depression scale), health status (Patient Health Questionnaire), trait anxiety scores (State Trait Anxiety Inventory) and IBS symptom severity and duration (Bowel Symptoms Questionnaire). Results. Volumetric analysis demonstrated several highly significant (5% false discovery rate) regional volume reductions in IBS patients compared to HCs including insula (INS), anterior cingulate cortex (ACC), hippocampus, parahippocampal gyrus, middle frontal gyrus, rectus gyrus and amygdala. Correlational analysis in IBS patients between non-imaging metadata and regional gray matter volumes indicated that volumetric decreases in left INS (r(75)=-.23, p=.04) and L rectus gyrus (r(73)=-.27, p=.02) were associ- ated with early life trauma. Volume reductions in R middle frontal gyrus (r(75)=-.25 p=.03) and R hippocampus (r(75)=-.25, p=.03) were associated with increased state anxiety, while reductions in L hippocampus volume were correlated with chronicity of IBS symptoms (r(73)=-.29, p=.012). Consistent with the volumetric analysis, TBM analysis revealed signific- ant (p<.05, family wise error) local differences between IBS and HCs bilaterally in multiple brain regions, including pregenual and subgenual ACC,INS subregions, thalamus,amygdal- a,hippocampus and parahippocampal gyrus, and nucleus accumbens. Conclusions. Two different analytical approaches in a large sample of female IBS and HC subjects yielded extensive regional reductions in grey matter volume associated with clinical phenotypes in the patient group compared to controls. Grant Support: K08 DK071626,R03 DK084169(JSL),P50 DK064539,R24 AT002681,R01 DK048351(EAM) 314 The Corticotropin Releasing Factor 1 Receptor (CRF-R1) Antagonist Gw876008 Differentially Modulates Brain Response During Acquisition and Extinction of Conditioned Fear in Irritable Bowel Syndrome (IBS) Patients and Healthy Control Subjects (HCS) Jennifer S. Labus, Catherine S. Hubbard, Michael S. Fanselow, Michelle P. Chen, Bahar Ebrat, Joshua A. Bueller, Kirsten Tillisch, Jean Stains, George E. Dukes, Dennis Kelleher, Bruce D. Naliboff, Emeran A. Mayer Background. Engagement of the central CRF/CRF-R1 signaling system is involved in the central coordination of the stress response, and in emotional learning. Alterations in this system have been implicated as a possible factor contributing to the pathophysiology of IBS. Conditioned fear responses to abdominal pain and discomfort are likely to play a role in IBS symptoms. Aim. To characterize the effect of the CRF-R1 antagonist on brain responses during acquisition and extinction of conditioned fear to an abdominal pain stimulus in female IBS patients and HCs. Experimental Paradigm. Brain response using functional mag- netic resonance imaging was measured during conditioning and extinction in a fear learning protocol in age-matched female IBS patients (n = 11) and HCs ( n =15) using a 2 group (IBS, HC) x 3 drug (placebo [PLA], 20 mg and 200 mg of GW876008) cross-over design. The fear conditioning and extinction learning protocol consisted of three phases: 1) Acquisition [5 trials of cue presentation (red light) followed by an aversive abdominal stimulation (electric AGA Abstracts