Hardy, Christopher John Donald; (2017) Mechanisms of auditory signal decoding in the progressive aphasias. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The primary progressive aphasias (PPA) are a diverse group of neurodegenerative disorders that selectively target brain networks mediating language. The pathophysiology of PPA remains poorly understood, but emerging evidence suggests that deficits in auditory processing accompany and may precede language symptoms in these patients. In four studies, I have probed the pathophysiology of auditory signal decoding in patient cohorts representing all major PPA syndromes – nonfluent variant PPA (nfvPPA), semantic variant PPA (svPPA), and logopenic variant PPA (lvPPA) – in relation to healthy age-matched controls. In my first experiment, I presented sequences of spoken syllables manipulated for temporal regularity, spectrotemporal structure and entropy. I used voxel-based morphometry to define critical brain substrates for the processing of these attributes, identifying correlates of behavioural performance within a cortico-subcortical network extending beyond canonical language areas. In my second experiment, I used activation functional magnetic resonance imaging (fMRI) with the same stimuli. I identified network signatures of particular signal attributes: nfvPPA was associated with reduced activity in anterior cingulate for processing temporal irregularity; lvPPA with reduced activation of posterior superior temporal cortex for processing spectrotemporal structure; and svPPA with reduced activation of caudate and anterior cingulate for processing signal entropy. In my third experiment, I manipulated the auditory feedback via which participants heard their own voices during speech production. Healthy control participants spoke significantly less fluently under delayed auditory feedback, but patients with nfvPPA and lvPPA were affected significantly less. In my final experiment, I probed residual capacity for dynamic auditory signal processing and perceptual learning in PPA, using sinewave speech. Patients with nfvPPA and lvPPA showed severely attenuated learning to the degraded stimuli, while patients with svPPA showed intact early perceptual processing, but deficient integration of semantic knowledge. Together, these experiments represent the most concerted and comprehensive attempt to date to define the pathophysiology of auditory signal decoding in PPA.

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