Abstract

BackgroundNon-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA.MethodsWe studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters—temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)—in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images.ResultsRelative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen.ConclusionsOur findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development.

Highlights

  • Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined

  • On the test of temporal regularity processing, the Non-fluent variant primary progressive aphasia (nfvPPA) group performed significantly worse than the healthy control group (p = 0.03) whereas the performance of the Semantic variant primary progressive aphasia (svPPA) group did not differ significantly from controls (p = 0.07)

  • We have demonstrated behavioural and neuroanatomical correlates of the defective analysis of generic speech signal attributes in two canonical PPA syndromes

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Summary

Introduction

Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. We addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. Hardy et al Alzheimer's Research & Therapy (2017) 9:53 characteristically presents with vocabulary loss and impaired word comprehension associated with asymmetric anterior temporal lobe atrophy Consistent with these syndromic profiles, nfvPPA is associated with more prominent deficits of early perceptual auditory analysis including impaired temporal (rhythm) perception, while svPPA is associated with auditory associative deficits and impaired sound meaning [4,5,6, 9,10,11,12,13].

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