This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research team in the Division of Gastroenterology continues to study the brain-gut axis using functional magnetic resonance imaging (fMRI). The thrust of recent research has been directed at evaluating the interaction between the cerebral cortex and the gut during subliminal and perceived visceral stimulation. In the upper gut, studies of brain response to esophageal acid perfusion at various acid concentrations in healthy subjects and gastroesophageal reflux disease (GERD) patients has yielded new insights into the neural sensitivity hypothesized to be a contributing factor in the pathology of GERD. These studies were carried out in GERD patients that have undergone anti-reflux therapy. Future studies will be directed at evaluating the cortico-esophageal interaction in GERD patients that have not undergone therapy. Systematic study of the cortical response to unperceived and perceived lower gut stimulation in the form of rectal balloon distension has been directed at specifically evaluating the contribution of cortical sub-structures such as the cingulate gyrus and insular cortex. Using fMRI-scanning techniques designed to evaluate small spatial domains (on the order of a few millimeters), a fine-grained analysis of regional cortical activity has differentiated regions of the insula and cingulate gyrus activated during visceral as opposed to motor stimulation of the lower gut. Upcoming studies will apply these new techniques to patient populations, potentially utilizing the ongoing studies of fMRI cortical response to rectal distension in patients suffering from irritable bowel syndrome (IBS) as a platform for fMRI studies of targeted cortical structures. Analysis of the brain-gut axis in health and disease continues to be the focus of the functional magnetic resonance imaging (fMRI) research group in the Division of Gastroenterology and Hepatology. Recent work has been directed at the study of the brain-gut interaction during perceived and unperceived visceral stimulation of the upper gut primarily focusing on esophageal distension and acid exposure. Similar to our published work addressing the cerebral cortical activity associated with subliminal rectal stimulation, we have begun to systematically define the range of subliminal esophageal distension pressures that are associated with fMRI activity in the cortex. The subliminal domain of stimulation is particularly important in unraveling the parts of cortical activity resulting from visceral esophageal stimulation that are associated with perception from those parts of cortical activity that are related to purely neurogenic effects. This delineation of perception-related cortical processes from purely neural processes is vital to understanding the pathology of diseases such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD) and idiopathic functional esophageal disorders. Future experiments will focus on work already begun in populations of GERD and NERD patients to study the cortical activity associated with unperceived and perceived esophageal distension, as well as esophageal acidification. Using scanning techniques developed in our analysis of lower gut visceral sensation, fMRI activity of specific cortical sub-regions such as the insular cortex and cingulate gyrus during esophageal stimulation are being studied wherein the fMRI spatial resolution is on the scale of a few millimeters. These high spatial resolution studies will further define the interaction of functionally distinct cortical regions and give insight into the role these regions play in esophageal viscero-sensation.
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