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MECHANISMS of VOICE PROCESSING in DEMENTIA Julia MECHANISMS OF VOICE PROCESSING IN DEMENTIA A Thesis presented for the degree of Doctor of Philosophy in Neuropsychology by Julia Catherine Hailstone The Dementia Research Centre Institute of Neurology UCL 2012 1 Declaration I, Julia Hailstone confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. All participants gave informed consent and all experimental work was carried out with the approval of the University College London Hospitals’ Research Ethics Committee, in accordance with the guidelines established by the Declaration of Helsinki. _____________________ Julia C Hailstone Date 2 Abstract Perception of nonverbal vocal information is essential in our daily lives. Patients with degenerative dementias commonly have difficulty with such aspects of vocal communication; however voice processing has seldom been studied in these diseases. This thesis comprises a series of linked studies of voice processing in canonical dementias: Alzheimer’s disease, behavioural variant frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. A series of neuropsychological tests were developed to examine perceptual and semantic stages of voice processing and to assess two aspects of accent processing: comprehension of foreign accented speech and recognition of regional and foreign accents; patient performance was referenced to healthy control subjects. Neuroanatomical associations of voice processing performance were assessed using voxel based morphometry. Following a symptom-led approach, a syndrome of progressive associative phonagnosia was characterised in two detailed case studies. Following a disease-led approach, this work was extended systematically to cohorts of patients representing the target diseases and assessing voice processing in relation to other aspects of person recognition (faces and names). This work provided evidence for separable profiles of voice processing impairment in different diseases: associative deficits were particularly severe in semantic dementia, whilst perceptual deficits showed relative specificity for Alzheimer’s disease. Neuroanatomical associations were identified for voice recognition in the right temporal pole and anterior fusiform gyrus, and for voice discrimination in the right inferior parietal lobe. The final phase of this work addressed the neuropsychological and neuroanatomical basis of accent processing, as an important dimension of nonverbal vocal analysis that is not dependent on voice identity. This work provides evidence for impaired processing of accents in progressive nonfluent aphasia and Alzheimer’s with neuroanatomical associations in the anterior and superior temporal lobe. The thesis contributes new information about voice processing in the degenerative dementias and furthers our understanding of the mechanisms of human voice analysis. 3 Division of labour for experimental work The experimental work described in this thesis was conducted by the author in collaboration with researchers at the Dementia Research Centre and affiliated institutions. Substantial contributions made by others are detailed below, and other contributions are credited in the acknowledgements. Chapter 3 (Study 1) Experimental design of voice tests: author, Jason Warren, Sebastian Crutch Experimental design of size test: author, Martin Vestergaard and Roy Patterson Construction and piloting of tests: author Data collection: author Data analysis: author in consultation with Jonathan Bartlett Writing the published paper: author and Jason Warren Chapters 4 & 5 (Studies 2 and 3) Experimental design: author, Jason Warren and Sebastian Crutch Construction and piloting of tests: author Experimental data collection: author Background neuropsychological data collection: author, Jo Goll and Aisling Buckley Data analysis: author in consultation with Jonathan Bartlett VBM image processing: author in consultation with Jo Goll VBM analyses: author in consultation with Gerard Ridgway Writing the published papers: author and Jason Warren 4 Acknowledgements Thanks must first be expressed to my supervisors: Jason who has provided an encyclopaedic knowledge of the field and has been a major source of inspiration for the work, and to Sebastian who provided neuropsychological expertise and moral support which have been invaluable to the work and to my professional development. Together they have been a tireless source of help and support and have steered my PhD to completion. I am also indebted to two important contributors to this work: Jonathan Bartlett for continual statistical advice and Ged Ridgway for masterful consultation on VBM analyses. My deepest thanks go to the patients and control participants without whom this work would not have been possible, and Professors Martin Rossor and Nick Fox for overseeing the clinical care of the patients involved. I am grateful to Dr Doris-Eva Bamiou for assistance with audiometric assessments, Dr John Stevens for assistance in interpretation of brain images and Professor Warrington for helpful discussion. I thank members of the admin team at the Dementia Research Centre: Suzie Barker, Anne Parnell, Ayesha Khatun and Carolyn Anderson who assisted in the logistics of patient recruitment and research visits. I am grateful to Johanna Goll, Manja Lehmann and Susie Henley for their support with VBM and general comradery. I am indebted to all the DRC members and friends that been guinea pigs for pilot neuropsychological tests and/or have allowed me to record their voice for tests in this Thesis: Adam Reid, Rick Merrick, Francesca Silman, Josephine Davies, Harry Lee and Sophie Coulombeau, Laila Ahsan, Shona Clegg, Anne Parnell, Jane Douglas, Claire Bloomfield and Mary Keilty. I am also grateful to Marina Tyndall, Tessa Mellow, Katie Piwnica-Worms, Keri Sills, Kate Butler and Kerry Fernhead for recording non- British accent samples and to staff at the British Library for their help sourcing voice recordings. Lastly I would like to thank Pete, Laila and my family for their kindness and support throughout this demanding process. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an Alzheimer’s Research UK Co-ordinating Centre. This work was funded by the Wellcome Trust and by the UK Medical Research Council. 5 Contents Declaration ..................................................................................................................................................2 Abstract .......................................................................................................................................................3 Division of labour for experimental work...................................................................................................4 Acknowledgements .....................................................................................................................................5 Contents ......................................................................................................................................................6 Figures presented in this Thesis ................................................................................................................ 11 Tables presented in this Thesis ................................................................................................................. 12 Abbreviations presented in this Thesis ..................................................................................................... 13 1. General Introduction ............................................................................................................................ 14 1.1. Overview ...................................................................................................................................... 14 1.2. Background: perception of paralinguistic information in voices .................................................. 16 1.2.1. Segregation of linguistic and paralinguistic processing streams ................................................... 16 1.2.2. Voice production: shaping of the vocal auditory signal ............................................................... 19 1.2.3. Paralinguistic perceptual characteristics of voices........................................................................ 20 1.3. Neuropsychological and neuroanatomical framework for assessing voice processing ................ 22 1.4. Familiar voice processing: cognitive, neuropsychological and neuroanatomical mechanisms .... 22 1.4.1. Familiar voice recognition in healthy volunteers .......................................................................... 22 1.4.2. Disorders of familiar voice recognition: phonagnosia .................................................................. 24 1.4.3. Functional imaging of voice recognition in healthy controls ....................................................... 27 1.5. Non-native accent processing: cognitive, neuroanatomical and neuropsychological mechanisms ...................................................................................................................................................... 32 1.5.1. Non-native accent processing in healthy controls ........................................................................ 32 1.5.2. Neuropsychology of accent processing .......................................................................................
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