Towards a cognitive neurobiology of brain-gut axis disorders

dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.entireThesisEntire Thesis Restricted
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorDinan, Timothy G.en
dc.contributor.advisorCryan, John F.en
dc.contributor.advisorClarke, Gerarden
dc.contributor.authorKennedy, Paul J.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderUniversity College Corken
dc.description.abstractThe past two decades have seen substantial gains in our understanding of the complex processes underlying disturbed brain-gut communication in disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Despite a growing understanding of the neurobiology of brain-gut axis dysfunction, there is a relative paucity of investigations into how the various factors involved in dysregulating the brain-gut axis, including stress, immune activation and pain, could impact on fundamental brain processes such as cognitive performance. To this end, we proposed a cognitive neurobiology of brain-gut axis dysfunction and took a novel approach to examine how disturbed brain-gut interactions may manifest as altered cognitive performance in IBS and IBD, both cross-sectionally and prospectively. We have demonstrated that, disorders of the brain-gut axis are characterised by stable deficits in specific cognitive domains. Specifically, patients with IBS exhibit a consistent hippocampal mediated visuospatial memory impairment. In addition we have found evidence to suggest a similar visuospatial impairment in IBD. However, our most consistent finding within this population was that patients with Crohn’s disease exhibit impaired selective attention/ response inhibition on the classic Stroop interference test. These cognitive deficits may serve to perpetuate and sustain brain-gut axis dysfunction. Furthermore, this research has shed light on some of the underlying neurobiological mechanisms that may be mediating cognitive dysfunction in IBS. Our findings may have significant implications for the individual who suffers from a brain-gut axis disorder and may also inform future treatment strategies. Taken together, these findings can be incorporated into existing neurobiological models of brain-gut axis dysfunction, to develop a more comprehensive model accounting for the cognitive-neurobiology of brain-gut axis disorders. This has furthered our understanding of disease pathophysiology and may ultimately aid in both the diagnosis and treatment of these highly prevalent, but poorly understood disorders.en
dc.description.sponsorshipScience Foundation Ireland (SFI/12/RC/2273, 02/CE/B124 and 07/CE/B1368); Health Research Board (Health Research Awards HRA_POR/2011/23); University College Cork ( Strategic Research Fund)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.identifier.citationKennedy, J. P. 2014. Towards a cognitive neurobiology of brain-gut axis disorders. PhD Thesis, University College Cork.en
dc.publisherUniversity College Corken
dc.rights© 2014, Paul John Kennedyen
dc.subjectBrain-gut axisen
dc.subjectCrohn's diseaseen
dc.subjectUlcerative colitisen
dc.subjectAcute tryptophan depletionen
dc.subjectHPA axisen
dc.subjectIrritable bowel syndrome (IBS)en
dc.subjectInflammatory bowel diseaseen
dc.subjectTrier social stress testen
dc.titleTowards a cognitive neurobiology of brain-gut axis disordersen
dc.typeDoctoral thesisen
dc.type.qualificationnamePhD (Medicine and Health)en
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