Clark, CN; (2016) Social Signal Decoding in Frontotemporal Lobar Degeneration. Doctoral thesis , UCL (University College London).

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Abstract

Frontotemporal lobar degeneration (FTLD) is associated with progressive social cognitive impairment. Currently a comprehensive pathophysiological model allowing disease effects to be understood and anticipated at the level of the whole brain is lacking. In this thesis I explored candidate cognitive operations underpinning complex behaviours in patients with the canonical syndromes of FTLD; behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD). I correlated behavioural deficits with brain network disintegration using the structural magnetic resonance imaging (MRI) technique, voxel based morphometry (VBM). I created synthetic scenes to manipulate congruity across semantic and emotional domains (Chapter 3) and showed deficits across both patient groups. The deficits have grey matter correlates in prefronto-parieto-temporo-insular network and a temporo-insulo-striatal network. I used music as a non-verbal syntactic probe to investigate reward anticipation and valuation (Chapter 4) and demonstrated dissociable deficits across dementias. Performance was associated with grey matter in a distributed network including anterior temporal cortex and orbitofrontal cortex (OFC), previously implicated in computing diverse rewards. I created a novel neuropsychological test of humorous intent (Chapter 5) to model incongruity processing. bvFTD demonstrates a particular difficulty decoding novel humorous situations while SD produces a more general deficit of humour detection. Humour detection accuracy was associated with temporoparietal junction (TPJ) and anterior superior temporal cortical volume which are hubs for processing incongruity and semantic associations. To assess the relevance of these findings (Chapter 5) to daily life behaviour I explored humour preferences across dementias (Chapter 6). Altered sense of humour is particularly salient in bvFTD and SD, but also frequent in AD and may predate more typical symptoms. In conclusion, impairment in incongruity processing and reward allocation was shown across paradigms. The neuroanatomical networks underpinning these processes overlapped with areas known to be targeted by FTLD. These processes have implications for our understanding of the social dysfunction that defines bvFTD.

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