Whitcroft, Katherine Lisa; (2025) Assessment of Human Olfaction: Investigations into Clinical Practice and Neuroanatomical Correlates of Dysfunction. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Olfaction augments daily life. It guides and enriches feeding behaviours, signals environmental hazards, and facilitates social communication. Olfactory dysfunction (OD) is common – affecting at least one in five adults. Additional to effects on nutrition and quality of life, OD is associated with important healthcare outcomes, including neurodegeneration and death. However, historical data suggest clinicians infrequently assess olfaction. When assessed, controversy remains regarding how this should be done. My thesis has two broad aims: in Theme A, to characterise current clinical assessment practice through interrogation of clinician and end-user populations; in Theme B, to explore new ways in which olfaction could be assessed, through investigation of potential neuroanatomical correlates of OD. In Theme A I gathered quantitative and semi-qualitative data from 465 clinicians and 576 end-users, from 17 and 33 countries respectively, providing the largest, most detailed analysis of current clinical practice and end-user preferences for assessment. These data suggest that most otorhinolaryngologists do not formally assess olfaction across different clinical scenarios. End-users prioritise tests of orthonasal identification and specialist assessment. Many patients are unhappy with the standard of assessment received, with issues relating to the emergent themes of ‘knowledge’, ‘rigour’, ‘attitudes’ and ‘healthcare systems’. In Theme B I provide the first multimodal longitudinal evidence of functionally significant structural plasticity within the central olfactory networks in association with improved olfactory function. In patients undergoing FESS for CRS, structural changes were observed within the hippocampus, parahippocampus, anterior cingulate cortex, orbitofrontal cortex, insula and temporal poles. Increased functional activity was demonstrated within the latter four regions. Functionally significant structural plasticity was replicated in these four regions in patients with non-CRS OD undergoing functional septorhinoplasty. Together, this work provides more robust evidence for these regions as neuroanatomical correlates of general OD than existing cross-sectional data. Interestingly, bidirectional changes in grey matter volume were observed.

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