Su1961 Alterations in Cognitive Control Mechanisms During Selective Attention to Threatening Stimuli in Irritable Bowel Syndrome Patients Jui-Yang Hong, Emeran A. Mayer, Catherine S. Hubbard, Maunoo Lee, Suzanne R. Smith, Nuwanthi Heendeniya, Kirsten Tillisch, Bruce D. Naliboff, Jennifer S. Labus Background. Converging evidence suggests that increased attention to afferent signals from the gut plays an important role in the increased perceptual response to visceral stimuli reported in irritable bowel syndrome (IBS). We hypothesize that prefrontal circuitry control- ling attention to threat-related stimuli is less efficient in IBS patients compared to healthy controls (HCs). Aims. To quantify and compare the efficiency of cognitive control regions underlying selective attention to threat-related stimuli between IBS patients and HCs, using a GI symptom unrelated paradigm. Methods. We measured brain response (Siemens 3 Tesla Trio MRI scanner) in 32 females (16 IBS patients, 16 HCs) during administration of the house face matching task, a cognitive task developed and validated to test selective attention to threatening stimuli as well as index processing of task-irrelevant threat stimuli. Subjects were presented with pictures of pairs of houses and faces (fearful or neutral) arranged in a vertical or horizontal orientation around a central fixation cross. During the task subjects were asked to match either houses or faces.. SPM8 was employed to preprocess and analyze the imaging data using the general linear model and a region of interest analysis examining cognitive control and emotional arousal regions. Results were considered significant at p<.05, corrected using family wise error. Results. No significant group differences were observed for reaction time or accuracy on the house face matching task. However, when examining brain responses to viewing attended fearful versus attended neutral faces (AF-AN), IBS patients exhibited significantly greater brain activation compared with HCs in prefrontal control regions [dorso and ventrolateral prefrontal cortex (PFC), medial PFC] as well as in dorsal anterior insula (INS) and left anterior mid-cingulate cortex (MCC). Within group analysis indicated activations in these regions for IBS, but not for HCs, the latter showing deactivation of the ventrolateral PFC, left anterior INS and hippocampus. HCs also showed significant activation in the L middle and posterior INS. Conclusions. In response to an IBS symptom unrelated paradigm (attended fearful versus neutral faces), IBS show greater activity in prefrontal control regions [lPFC, medial PFC) as well as in dorsal anterior insula and left anterior mid-cingulate cortex. Results suggest greater recruitment of cognitive control mechanisms during presentation of emotionally salient or threat-related stimuli in IBS patients. Grants: K08 DK071626, R03 DK084169 (JSL),K23DK073451, R01 AT007137KT),T32 DK007180(CH),P50 DK064539, R24 AT002681, R01 DK048351(EAM) Su1962 IBS Patients Show Altered Behavioral and Functional Brain Responses During an Orienting Attention Task Catherine S. Hubbard, Emeran A. Mayer, Jui-Yang Hong, Bahar Ebrat, Suzanne R. Smith, Nuwanthi Heendeniya, Kirsten Tillisch, Jennifer S. Labus, Bruce D. Naliboff Background: Cognitive alterations in IBS subjects include inadequate activation of cortical networks involved in the modulation of pain and emotion, as well as altered attention to potentially aversive gastrointestinal stimuli. Attention refers to the selection of competing sensory information aimed to optimize current behavioral responses to specific stimuli relevant to an organism. Normalization of attention network alterations are associated with IBS symptom improvement. We test the hypothesis that central pain amplification in IBS is in part related to impaired brain mechanisms responsible for regulating attention.Aims: To quantify and compare the efficiency of brain networks, particularly those in the prefrontal cortex, that support alerting, orienting, and executive attention functions between IBS patients and healthy controls (HC).Methods: A standardized attention task, the attentional network task (ANT), was administered to 15 HC [mean age= 31(10.91)] and 14 IBS [mean age= 31(11.96)] patients during functional magnetic resonance imaging to test the efficiency of specific anatomical brain networks involved in alerting, orienting, and executive components of attention. All functional and structural brain imaging was conducted with a Siemens 3 Tesla Trio MRI scanner.SPM8 was used to preprocess and analyze the imaging data using the general linear model and a region of interest analysis examining attentional and emotional arousal regions. Results were considered significant at p<.05, corrected using family wise error. The pain catastrophizing scale was used to measure catastrophizing. Structural images were bias-corrected, segmented into gray matter, white matter and cerebrospinal fluid, and brought to MNI space. We then calculated mean gray matter for regions of interests using the LONI pipline environment. Correlational analyses were performed in SPSS v19.Results: IBS patients compared to HC showed more rapid orienting (significantly lower reaction time) (t(27)=2.36,p<.05) associated with lack of right lateral superior/inferior frontal gyrus (BA 44/6) and posterior mid cingulate cortex recruitment during the task (p<.001). Further- more, structural analysis indicated gray matter volume in the same lateral prefrontal region correlated negatively with orienting scores (r(29)= -.44., p<.01) and positively with catastro- phizing (r(29)= .44, p<.01). Conclusion: We have previously demonstrated attentional network alterations which correlate with IBS symptoms. Together the results suggests that IBS may have specific abnormalities in inhibitory control centers focused in the lateral prefrontal cortex, and these deficits may underlie higher levels of hypervigilance (i.e., symp- tom specific anxiety) seen in IBS. Grant Support: K08 DK071626, R03 DK084169 (JSL), T32 DK007180 (CH), R01 DK048351(EAM) Su1963 Cortical Thinning in Female Patients With Irritable Bowel Syndrome Zhiguo Jiang, Jennifer S. Labus, Cody Ashe-McNalley, Florian Kurth, Bahar Ebrat, Alen Zamanyan, Yonggang Shi, Alex Genco, Sam Hobel, Shantanu H. Joshi, Craig Schwartz, Paul Thompson, Ivo Dinov, Arthur W. Toga, Emeran A. Mayer Background: Regional changes in grey matter morphometry in brain regions (insular [INS] and anterior cingulate [ACC] cortices involved in the processing of homeostatic afferent signals, including pain have been reported in several persistent pain conditions, including IBS. However, sample sizes have been small and reported results in IBS are conflicting. S-547 AGA Abstracts Aims: 1) To examine cortical thickness differences between a large sample of female IBS and healthy control subjects (HCs) within automatically parcellated bilateral subregions of the INS (anterior, mid and posterior) and ACC. 2) To identify possible correlation of these morphological changes with clinical and behavioral parameters. Method: We collected T1- weighted structural magnetic resonance images from 222 age-matched female subjects (70 IBS and 155 HC). We used the LONI (Laboratory of Neuroimaging) pipeline software to preprocess the structural scans, reconstruct cortical surfaces (white matter and pial surfaces), calculate regional grey matter thickness using the Eikonal Fire equation in millimeters for each subject, and establish one-to-one correspondences across reconstructed brain surface vertices. Two sample t-tests (one tail) were performed to examine the difference in mean thickness within each region of interest (ROI) between IBS and HC while controlling the effect of age and total grey matter volume (GMV). Phenotyping data, including duration of the symptom, catastrophizing (Coping Stategies 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 Invent- ory) and IBS symptom severity and duration (Bowel Symptoms Questionnaire) was collected. The correlation between phenotype data and regional cortical thickness was calculated after removing the effects of age and GMV. Results: The surface ROI based analysis showed significant regional cortical thinning (P<0.05) in all six bilateral anterior, mid and posterior insula cortices and left subgenual sgACC in IBS compared with HC. There was a trend (P= 0.06) for cortical thinning in the right sgACC in IBS patients compared with HC. In IBS patients state anxiety was negatively correlated to the mean cortical thickness in right anterior INS (r=-28; P=0.02), whereas no such significant correlation was found in HC. Chronicity of IBS pain was also found to correlate negatively to the right mid-insula (r=-0.30; P=0.01). Conclusions: Cortical thinning in bilateral insula cortices and left sgACC are found in female patients with IBS. These cortical reductions might be associated with the elevated state anxiety level and the duration of the symptoms in IBS patients. Grant Support:P50 DK064539, R24 AT002681, R01 DK048351(EAM), K08 DK071626, R03 DK084169 (JSL) Su1964 Alterations in the Central Dopaminergic System in Patients With Functional Dyspepsia Breg Braak, Jan Booij, Tamira K. Klooker, Rene M. van den Wijngaard, Guy E. Boeckxstaens Introduction: Functional dyspepsia (FD) is a chronic condition characterized by upper abdominal symptoms without identifiable cause. While the serotonergic system is supposed to play a key factor in the regulation of gut physiology, the role of the dopaminergic system, which is important in the regulation of visceral pain and stress, is understudied. Therefore this study investigated the dopaminergic system and the relation with drinking capacity and symptoms in FD patients. Methods: FD (n=8, 63% female, 39±5 yr) and healthy volunteers (HV, n=20, 60% female; 31±3 yr) underwent [123I]IBZM single photon emission computed tomography (SPECT) to assess central dopamine D2 receptors (D2Rs). In addition, the effect of acute dopamine depletion obtained by an alpha-methyl-para-tyrosine (AMPT) challenge test was studied on maximal ingested volume and symptoms evoked by a nutrient drink test. Results: Compared to HV, FD patients had lower striatal binding potential of D2Rs (BPNP; average L+R; median+75th IQR) in the caudate nucleus (BPNP: FD: 1.19 + 0.1 vs. HV: 1.37 + 0.2, p=0.02), but not in the putamen (BPNP: FD: 0.95 + 0.1 vs. HV: 1.10 + 0.2, p=0.15). The drinking capacity was comparable between FD and HV (FD: 800 ml (200- 1600) vs. HV: 850 (350-1500), NS). Postprandial symptoms such as nausea, pain and bloating were more pronounced in FD compared to HV (p<0.05). In FD patients, the D2R BPNP of the caudate nucleus correlated with drinking capacity (r=0.756, p=0.03) whereas the D2R BPNP in the putamen showed a correlation with meal-evoked nausea (r=0.857, p=0.01). After acute dopamine depletion, the drinking capacity and the prolactine release was not different between FD (86 (59-130)) and HV (87 (30-185), NS). Conclusion: In FD patients we observed decreased striatal D2R BPNP of the caudate nucleus, which was correlated with drinking capacity, whereas the D2R BPNP of the putamen was correlated with meal-evoked nausea. In contrast, acute dopamine depletion did not affect drinking capacity and did not evoke symptoms in healthy subjects. These data suggest that chronic rather than acute alterations in the dopaminergic system may be involved in the pathogenesis of FD. Su1965 Corticotropin-Releasing Hormone is Associated With Exaggerated Brain Activity and Pituitary-Adrenal Response During Colorectal Distention in IBS Yukari Tanaka, Joe Morishita, Motoyori Kanazawa, Toyohiro Hamaguchi, Manabu Tashiro, Shin Fukudo Aim Corticotropin-releasing hormone (CRH) is a major mediator of stress response in the brain-gut axis. We previously reported that peptidergic modification of CRH receptors changes visceral sensorimotor function in patients with irritable bowel syndrome (IBS). However, evidence how CRH agonist changes human brain function was lacking. We reported that exogenous CRH accelerates regional brain activity during visceral stimulation like IBS in healthy subjects (Gastroenterology 2011;140:S57). We therefore hypothesized that patients with IBS have exaggerated brain activation to the distention after CRH injection. Methods Sixteen IBS males aged 22.3 ± 1.75 were enrolled and compared with 16 healthy males aged 22.8 ± 2.5. They were randomly allocated into the CRH injection group and saline injection (placebo) group. A barostat bag was inserted into the colorectum and was randomly inflated with sham (0 mmHg), mild (20 mmHg), or intense (40 mmHg) distention for 80s. CRH (2 μg/kg) or placebo was then injected and same distention protocol was repeated. Radioactive H 2 15 O saline was injected at bag inflation and then positron emission tomography was performed. Changes in regional cerebral blood flow were analyzed using statistical parametric mapping. To detect the CRH group and distention effect, the image with 40 mmHg with CRH in IBS was subtracted by that with placebo. It was then compared with that in healthy controls. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol were measured at each stimulation. Results In IBS, colorectal distention with 40 mmHg with CRH activated the right parahippocampal cortex, left orbitofrontal cortex, left insula, AGA Abstracts