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Physiological Phenotyping of Fronto-temporal Lobar Degenerations

Fletcher, PD; (2016) Physiological Phenotyping of Fronto-temporal Lobar Degenerations. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Fronto-temporal lobe degenerations encompass a spectrum of neurodegenerative diseases underpinned by pathological protein deposition. The study of these diseases is of considerable interest, both from a neurobiological perspective of brain organization in health and disease, and in order to develop novel biomarkers. However, the translation of the effects of abnormal protein to clinical syndrome is far from clear and whilst the current classification systems provide a framework upon which to base evaluations, they do not capture the full spectrum of the complexity of these disease entities. Recently there has been a shift in collective thinking towards describing brain functions in terms of the activity of inter-connected neuronal ‘networks’ rather than as the discrete functional areas, networks that underlie core physiological processing systems. There are symptoms in FTD that, whilst not the most prominent, may speak to derangement of these physiological systems, systems involved in processes such as salience, hedonic and emotion appraisal. Here I propose that using a physiological approach to examine these symptoms may allow insight into the real time in-vivo physiological effects of proteinopathies upon dynamic neuronal systems. Five studies are presented investigating FTD in relation to AD and healthy older adults. In experiment 1 behaviours suggestive of abnormalities of pain and temperature perception are investigated to both better characterize the nature of these symptoms and investigate underlying neuroanatomical correlates. In experiment 2, 3 and 4 the physiological effects, as measured by pupillometry, of manipulations of three levels of salience cues are examined and in the final experiment the effects of hedonic and emotion processing from sound and music are explored. Taken together these experiments provide insight into disordered physiological processing in these diseases and offer new metrics for a physiological approach to the assessment of these patients.

Type: Thesis (Doctoral)
Title: Physiological Phenotyping of Fronto-temporal Lobar Degenerations
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/1505756
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