Structural and Functional Alterations of the Brain’s Deep Grey Matter in Patients with Primary Biliary Cholangitis

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dc.contributor.advisorGoodyear, Bradley
dc.contributor.advisorMacQueen, Glenda
dc.contributor.authorMosher, Victoria
dc.contributor.committeememberSwain, Mark
dc.contributor.committeememberDunn, Jeffrey
dc.contributor.committeememberAddington, Jean
dc.date2018-06
dc.date.accessioned2018-01-22T23:54:19Z
dc.date.available2018-01-22T23:54:19Z
dc.date.issued2018-01-04
dc.description.abstractPrimary biliary cholangitis (PBC) is an autoimmune liver disease that results in the destruction of the intrahepatic bile ducts. If left untreated, PBC can progress to liver failure or death within 10-20 years. Treatment with ursodeoxycholic acid (UDCA) can delay disease progression, but it does not work in approximately one third of patients, and it has no impact on behavioural symptoms commonly reported by PBC patients, including itch, mood disturbances, fatigue and cognitive deficits. Despite the negative impact these symptoms have on quality of life and survival, little is known about how (or even if) symptoms may impact the brain. In this thesis, we used a selection of structural and functional magnetic resonance imaging techniques to determine the impact of PBC on the brain's deep grey matter regions. We found that the functional connections between deep grey matter regions and higher-order cognitive brain regions were increased in strength, suggesting that brain networks compensate in order to maintain homeostasis in response to the immune insult from the liver. Decreased volume was observed for the thalamus, the hippocampus and a number of hippocampal subfields. In addition, regions of the brain involved in interoception showed evidence of neuroinflammation in relation to disease and symptom severity. These structural findings suggest that some brain changes observed in PBC patients may be irreversible. For most of our findings, a complete clinical response to UDCA did not impact the functional or structural brain alterations observed, suggesting these changes may occur early on in disease progression. Overall, our findings suggest early intervention may be needed to halt changes in the brain resulting from immune-mediated insults The studies within this thesis provide a base of knowledge for how behavioural symptoms may impact the brain and offer suggestions on how future research can build upon these findings.en_US
dc.identifier.citationMosher, V. A. L. (2018) Structural and functional alterations of the brain’s deep grey matter in patients with primary biliary cholangitis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/5383
dc.identifier.urihttp://hdl.handle.net/1880/106302
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectfMRIen_US
dc.subjectMedical Imagingen_US
dc.subjectBrainen_US
dc.subjectMRIen_US
dc.subject.classificationNeuroscienceen_US
dc.titleStructural and Functional Alterations of the Brain’s Deep Grey Matter in Patients with Primary Biliary Cholangitisen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Medical Sciencesen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrue
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