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

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Primary 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.
fMRI, Medical Imaging, Brain, MRI
Mosher, 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