Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurring abdominal pain associated with alterations in bowel habits. MD FTSJ2 in the thalamus internal capsule and coronal radiata projecting to sensory/motor regions suggestive of differential changes in axon/dendritic density in these regions. Sex differences in FA and MD were also observed in the patients but not in HCs. Probabilistic tractography confirmed a higher degree of connectivity in patients between the thalamus and pre-frontal cortex as well as the medial dorsal thalamic nuclei and anterior cingulate cortex and a lower degree of connectivity between the globus pallidus and thalamus. Together these results support the hypothesis that patients with chronically recurring visceral pain from IBS have long-term microstructural changes within the brain particular in regions associated with integration of sensory information and cortico thalamic modulation. Introduction Irritable bowel syndrome (IBS) is a common gastrointestinal disorder defined by symptoms of chronically recurring abdominal pain associated with alterations in bowel habits. Although the pathophysiology remains poorly understood there is general consensus that it reflects alterations in brain-gut interactions [51]. Many of the alterations reported in IBS patients and pre-clinical models are consistent with altered CNS processing and modulation of visceral information including central pain amplification [50] altered autonomic output [68] and alterations in cognitive and affective functioning [5; 47; 44]. However ongoing sensitization of primary visceral afferents generating persistently altered input into the central neuroaxis may also play a role in the observed CNS changes [51]. Based on these observations and analogous to reports in other persistent pain syndromes [7; 36; 28; 53] we hypothesized that behavioral alterations observed in IBS patients may be associated UMI-77 with long-term microstructural reorganization in UMI-77 the brain. This hypothesis is also supported by reports demonstrating regional alterations in gray [17; 63] and white matter [23] in smaller samples of IBS patients. Evidence for functional and structural brain changes in regions of the homeostatic afferent network including thalamus anterior cingulate cortex and insula subregions have been reported in IBS [67] and other persistent pain disorders [7]. Similar to the anterior insula the basal ganglia (BG) play a prominent role in integration of multiple sensory and non-sensory information [26; 56]. Numerous studies have implicated the BG in the modulation and interpretation of both acute and chronic pain [8; 15; 25; 24; 19] while multiple persistent pain disorders including IBS have shown altered functional responses in the BG in response to experimental stimuli [40; 10; UMI-77 65; 67]. Since multisensory integration is known to occur within the BG [26; 56] it is conceivable that the microstructure of the BG may be altered in chronic pain. Based on these observations we hypothesized that IBS patients may show microstructural alterations within regions of the homeostatic afferent network and the BG. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can elicit subvoxel microstructural information within tissues by measuring both the directionality and magnitude of water self-diffusion [9]. The average apparent diffusion coefficient (ADC or mean diffusivity MD) a measure of mean water mobility as well as the fractional UMI-77 anisotropy (FA) a scalar measure of relative diffusion anisotropy have been used as surrogate measures for microstructural integrity within the human brain. Recent DTI investigations involving a small number of patients have shown preliminary evidence for microstructural changes within sensory processing regions in patients with chronic pancreatitis [37] chronic back pain [20; 7] chronic pelvic pain [36] and chronic pain associated with IBS[23]. In the current study we aimed to determine if IBS patients show microstructural changes within the brain by comparing voxel-wise DTI measurements within white UMI-77 matter tracts and deep gray matter structures in a large sample of phenotyped IBS patients and HCs. Additionally we tested whether there were significant differences in the number of fiber tract connections between areas of the brain involved in pain processing between IBS and.