auditory scene analysis in alzheimer's disease

233 Pages·2016·3.72 MB·English

by  Hannah Golden

AUDITORY SCENE ANALYSIS IN
ALZHEIMER’S DISEASE

A thesis submitted to University College London
for the Degree of Doctor of Philosophy

Hannah Golden

Dementia Research Centre
Institute of Neurology
UCL

2015
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DECLARATION

I, Hannah Louise Golden, 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 (Appendix 4).

_________________________________________________________
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ABSTRACT

This thesis explores the behavioural and neuroanatomical picture of
Auditory Scene Analysis (ASA) in Alzheimer’s disease (AD). Central
auditory dysfunction is an understudied symptom of AD and there has
been little connection between the neuropathological profile of the
disease, its relationship to generic ASA functions, and real-world listening
situations. Utilising novel neuropsychological batteries alongside
structural and functional imaging techniques, this thesis aims to bridge
this gap through investigations of auditory spatial, speech in noise, and
(as a specialised auditory scene) music processing.

Spatial location discrimination and motion detection of sounds was
impaired in both typical AD and posterior cortical atrophy; this was
associated with atrophy in right inferior parietal and posterior medial
regions. A functional imaging investigation of auditory spatial processing
in typical AD revealed abnormalities in posterior medial cortical areas
when sounds were changing in location. Functional imaging of an
everyday auditory scenario (hearing one’s own name over background
babble) highlighted alteration in a right inferior parietal region. Novel
neuropsychological tasks assessing components of musical ‘scenes’ found
that global aspects of pitch pattern processing were impaired in both the
typical and language variant of AD while local aspects were preserved;
both global and local forms of temporal processing were also intact.
These patients also exhibited diminished tonality perception and musical
stream segregation based on familiar templates.

These investigations delineate reduced ASA capacity in a number of
components that make up everyday auditory scenes. This has real world
implications for both typical AD and its rarer phenotypes. Furthermore,
ASA dysfunction may inform us about network breakdown, network
function, and sources of phenotypic similarity in AD.
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ACKNOWLEDGEMENTS

Firstly I would like to thank the research volunteers and their carers who
gave so much of their time, effort and good humour participating in my
studies.

I am indebted to my supervisors Jason Warren and Sebastian Crutch who
were a tireless source of support, guidance and knowledge. Their
generosity in both time and expertise has been invaluable. There are a
large number of colleagues at the Dementia Research Centre who
enabled my research to go ahead: Jenny Nicholas who generously
provided her unparalleled statistical abilities; Jen Agustus, Jo Goll and
Colin Mahoney who kindly and patiently assisted with imaging analysis;
Chris Hardy for his helpful comments and proof reading of this thesis;
consultant clinicians who allowed me to recruit from their clinics (Martin
Rossor, Nick Fox, Cath Mummery, Jon Schott, Alberto Cifelli and Gill
Livingston); psychologists who provided both moral and practical support
(Laura Downey, Keir Yong, Tim Shakespeare, Kirsty Macpherson, Felix
Woodward, Susie Henley, Miriam Cohen, Amelia Carton); the admin team
(Suzie Barker, Anne Parnell, Stuart Luscombe, Carolyn Andersen, Ayesha
Khatun); Stuart Rosen, Steve Nevard and Andrea Halpern for assistance
with stimuli; to so many others at the Dementia Research Centre for their
various forms of support (Camilla Clark, Phil Fletcher, Lorna Harper,
Mandy Haines, Katy Judd, Ian Malone, Shona Clegg, Laila Ahsan, Manja
Lehmann, Dave Thomas, Catherine Slattery, Ross Paterson, Alex Foulkes,
Liz Gordon, Emily Manning, Jane Douglas, Gill Barley, Claire Bloomfield)
and the radiographers at both the Wellcome Trust Centre for
Neuroimaging and the National Hospital for Neurology and Neurosurgery
for their assistance with neuroimaging.

I would like especially to thank Ryan and my parents, whose
encouragement and patience saw me through this demanding process; I
don’t think I could have done this without you! Finally to Molly and
Alfred, I dedicate this to you.

This work was supported by an Alzheimer’s Research UK PhD studentship
Jason Warren is supported by a Wellcome Trust Senior Clinical Fellowship.
This work was supported by the NIHR Queen Square Dementia Biomedical
Research Unit. This work was undertaken at University College London
Hospital/University College London which received a proportion of
funding from the Department of Health’s NIHR Biomedical Research
Centres funding scheme.

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TABLE OF CONTENTS

DECLARATION ................................................................................................ 2
ABSTRACT ...................................................................................................... 3
ACKNOWLEDGEMENTS ................................................................................... 4
TABLE OF CONTENTS ...................................................................................... 5
TABLE OF FIGURES.......................................................................................... 9
TABLE OF TABLES ......................................................................................... 10
ABBREVIATIONS ........................................................................................... 11
1 GENERAL INTRODUCTION ..................................................................... 12
1.1 Diagnosis of typical AD .......................................................................... 13
1.2 Phenotypic variability in AD .................................................................. 14
1.3 Neuroanatomical characteristics of AD ................................................ 15
1.4 DMN function ........................................................................................ 18
1.5 DMN and the neuropsychological profile of AD ................................... 20
1.5.1 PMC: memory and visuospatial impairment in AD ....................... 20
1.5.2 Temporoparietal cortex: executive, attentional, working memory,
lexical access and visuospatial deficits in AD ............................................... 22
1.5.3 AD neuropsychological deficits and ASA ....................................... 23
1.6 Central auditory processing: mechanisms and anatomy ...................... 23
1.6.1 Cortical auditory processing pathways ......................................... 24
1.6.2 Conceptualisations of ASA ............................................................ 26
1.6.3 The role of attention ..................................................................... 27
1.6.4 Schema based processing ............................................................. 28
1.6.5 Auditory spatial processing ........................................................... 29
1.6.6 Specialized applications of auditory scene analysis ...................... 30
1.6.6.1 Speech ....................................................................................... 30
1.6.6.2 Music ......................................................................................... 31
1.6.7 DMN regions involved in ASA processing ..................................... 32
1.7 A review of auditory processing in AD .................................................. 35
1.7.1 Peripheral hearing in AD ............................................................... 35
1.7.2 Neuropsychological aspects of central auditory function in AD ... 36
1.7.3 Music processing in AD ................................................................. 41
1.7.4 Neuroanatomical aspects of central auditory function in AD ...... 42
1.7.5 Electrophysiological studies of central auditory function in AD ... 43
1.8 DMN and ASA in AD .............................................................................. 45
1.9 Thesis aims and outline ......................................................................... 48
2 METHODS OVERVIEW........................................................................... 50
2.1 Participants ........................................................................................... 50
2.1.1 Typical AD patients ....................................................................... 51
2.1.2 PCA patients .................................................................................. 51
2.1.3 lvPPA patients ............................................................................... 52
2.1.4 naPPA patients .............................................................................. 52
2.1.5 Healthy control participants ......................................................... 52
2.2 Peripheral audiometry assessment ...................................................... 52
2.3 Pitch discrimination musical screening task ......................................... 53
2.4 Musical background questionnaire....................................................... 53
2.5 Neuropsychological assessment ........................................................... 54
2.6 Generation and presentation of auditory stimuli ................................. 55
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2.6.1 Spatial sound generation .............................................................. 55
2.7 Image acquisition .................................................................................. 57
2.7.1 Structural MRI ............................................................................... 57
2.7.2 Functional MRI .............................................................................. 57
2.8 Image preprocessing ............................................................................. 58
2.8.1 Structural MRI ............................................................................... 59
2.8.2 Functional MRI .............................................................................. 59
2.8.3 Study specific mean image............................................................ 59
2.8.4 Small volume generation .............................................................. 60
2.9 Statistical analysis ................................................................................. 60
2.9.1 Demographic, neuropsychological and peripheral audiometry
analysis ………………………………………………………………………………………………….60
2.9.2 Behavioural analysis ...................................................................... 61
2.9.3 Brain imaging analysis ................................................................... 61
2.9.3.1 VBM ........................................................................................... 62
2.9.3.2 Functional imaging .................................................................... 62
2.9.3.3 Correction for multiple comparisons ........................................ 63
3 AUDITORY SPATIAL PROCESSING IN AD: A NEUROPSYCHOLOGICAL AND
STRUCTURAL NEUROANATOMICAL INVESTIGATION ...................................... 64
3.1 Introduction .......................................................................................... 64
3.2 Hypotheses ........................................................................................... 65
3.3 Methods ................................................................................................ 66
3.3.1 Participants ................................................................................... 66
3.3.2 Background neuropsychometry .................................................... 68
3.3.3 General structure of experimental battery................................... 68
3.3.4 Externalised versus non-externalised sound discrimination ........ 70
3.3.5 Moving versus stationary sound discrimination ........................... 71
3.3.6 Stationary sound position discrimination ..................................... 71
3.3.7 Auditory control tasks ................................................................... 72
3.3.8 Visual spatial control tasks ............................................................ 72
3.3.9 Procedure ...................................................................................... 73
3.3.10 Behavioural analysis ...................................................................... 74
3.3.11 VBM analysis ................................................................................. 75
3.4 Results ................................................................................................... 76
3.4.1 Demographics, neuropsychology and peripheral audiometry ..... 76
3.4.2 Auditory spatial tasks .................................................................... 77
3.4.3 Auditory control tasks ................................................................... 81
3.4.4 Visual spatial control tasks ............................................................ 81
3.4.5 Correlations between parameters ................................................ 81
3.4.6 Effect of perceptual parameter .................................................... 84
3.4.7 Neuroanatomical associations ...................................................... 86
3.5 Discussion.............................................................................................. 90
4 AUDITORY SPATIAL PROCESSING IN AD: AN FMRI INVESTIGATION ........ 95
4.1 Introduction .......................................................................................... 95
4.2 Hypotheses ........................................................................................... 96
4.3 Methods ................................................................................................ 97
4.3.1 Participants ................................................................................... 97
4.3.2 Experimental design and stimuli ................................................... 98
4.3.3 Procedure .................................................................................... 100
4.3.3.1 Stimulus presentation and brain image acquisition ............... 100
4.3.3.2 Post-scan behavioural task ..................................................... 100
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4.3.4 fMRI analysis ............................................................................... 101
4.3.5 VBM analysis ............................................................................... 103
4.3.6 Analysis of behavioural data ....................................................... 103
4.4 Results ................................................................................................. 104
4.4.1 Demographic, neuropsychological and peripheral audiometry
characteristics ............................................................................................ 104
4.4.2 Post-scan behavioural task ......................................................... 106
4.4.3 Structural neuroanatomy ............................................................ 106
4.4.4 Functional neuroanatomy ........................................................... 107
4.5 Discussion............................................................................................ 115
5 AUDITORY MASKING IN AD: AN FMRI INVESTIGATION ........................ 121
5.1 Introduction ........................................................................................ 121
5.2 Hypotheses ......................................................................................... 122
5.3 Methods .............................................................................................. 123
5.3.1 Participants ................................................................................. 123
5.3.2 Experimental design and stimuli ................................................. 125
5.3.3 Procedure .................................................................................... 127
5.3.3.1 Stimulus presentation ............................................................. 127
5.3.3.2 Post-scan behavioural task ..................................................... 127
5.3.4 fMRI analysis ............................................................................... 129
5.3.5 Voxel-based morphometry analysis............................................ 131
5.3.6 Behavioural analysis .................................................................... 131
5.4 Results ................................................................................................. 131
5.4.1 Demographic, neuropsychological and peripheral audiometry
characteristics ............................................................................................ 131
5.4.2 Post-scan behavioural task ......................................................... 132
5.4.3 Structural neuroanatomy ............................................................ 132
5.4.4 Functional neuroanatomy ........................................................... 133
5.5 Discussion............................................................................................ 141
6 ASSESSING PITCH, TEMPORAL, STREAMING AND KEY FUNCTIONS AS
‘MUSICAL SCENE’ ELEMENTS IN AD: A NEUROPSYCHOLOGICAL INVESTIGATION
148
6.1 Introduction ........................................................................................ 148
6.1.1 Pitch and melody perception ...................................................... 148
6.1.2 Key perception ............................................................................ 150
6.1.3 Rhythm and metre perception ................................................... 151
6.1.4 Musical streaming ....................................................................... 152
6.1.5 Designing a dementia-specific musical scene battery ................ 153
6.2 Hypotheses ......................................................................................... 155
6.3 Methods .............................................................................................. 155
6.3.1 Participants ................................................................................. 155
6.3.2 General structure of experimental battery................................. 160
6.3.3 Local-global pitch deviance detection ........................................ 160
6.3.3.1 Main task ................................................................................. 160
6.3.3.2 Easy version............................................................................. 161
6.3.4 Key deviance detection ............................................................... 162
6.3.5 Local-global temporal deviance detection .................................. 162
6.3.6 Timbre deviance detection control ............................................. 163
6.3.7 Embedded tune detection .......................................................... 163
6.3.7.1 Tune recognition control ........................................................ 164
6.3.8 Behavioural analysis .................................................................... 165
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6.3.8.1 Deviance detection tasks ........................................................ 165
6.3.8.1.1 Pitch deviance detection .................................................. 166
6.3.8.1.2 Key deviance detection ..................................................... 166
6.3.8.1.3 Temporal deviance detection ........................................... 166
6.3.8.1.4 Timbre control task ........................................................... 166
6.3.8.1.5 Embedded tunes ............................................................... 166
6.4 Results ................................................................................................. 167
6.4.1 Demographic, neuropsychological and peripheral audiometry
characteristics ............................................................................................ 167
6.4.2 Local-global pitch deviance detection ........................................ 168
6.4.2.1 Easy version............................................................................. 169
6.4.3 Key deviance detection ............................................................... 170
6.4.4 Local-global temporal deviance detection .................................. 171
6.4.5 Timbre deviance detection control ............................................. 172
6.4.6 Embedded tune detection .......................................................... 173
6.4.6.1 Recognition task ...................................................................... 173
6.4.6.2 Main task ................................................................................. 174
6.5 Discussion............................................................................................ 176
7 GENERAL DISCUSSION ........................................................................ 184
7.1 Summary of findings ........................................................................... 184
7.2 ASA and neural networks in AD .......................................................... 185
7.3 ASA processing in AD phenotypic variants ......................................... 188
7.4 Top down and executive factors ......................................................... 190
7.5 Can ASA aid diagnosis of AD? ............................................................. 190
7.6 ASA and naturalistic listening situations in AD ................................... 191
7.7 Limitations .......................................................................................... 192
7.8 Future directions ................................................................................. 193
REFERENCES ............................................................................................... 194
APPENDICES ............................................................................................... 229
Appendix 1: Participation of individual typical AD patients by study ............ 229
Appendix 2: Items used in the musical experience questionnaire ................. 230
Appendix 3: Items used in the embedded tunes task .................................... 231
Appendix 4: Division of Labour ....................................................................... 232
Appendix 5: Publications ................................................................................ 233
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TABLE OF FIGURES

Figure 1.1 – Schematic representation of the DMN, AD pathology and atrophy
progression. .......................................................................................................... 17
Figure 1.2 – Schematic representation of auditory processing streams .............. 25
Figure 1.3 – Schematic representation of neuroanatomical regions involved in
both ASA and DMN ............................................................................................... 47
Figure 3.1 – Schematic representation of experimental battery ......................... 70
Figure 3.2 – Verbal instructions and visual aids used in experimental auditory
tests ....................................................................................................................... 74
Figure 3.3 – Individual raw scores for each experimental task ............................ 80
Figure 3.4 – Group mean d prime scores .............................................................. 85
Figure 3.5 – Grey matter associations with auditory spatial task performance ... 88
Figure 4.1 – Schematic representation of all conditions ...................................... 99
Figure 4.2 – Post-scan behavioural task visual guide ......................................... 101
Figure 4.3 – Small volumes used for analysis of functional data ........................ 103
Figure 4.4 – Atrophy map of the AD group compared to healthy controls ........ 106
Figure 4.5 – Functional neuroanatomy of auditory stimulation ......................... 108
Figure 4.6 – Functional neuroanatomical data: within-group contrasts ............ 111
Figure 4.7 – Functional neuroanatomical data: between-group contrasts ........ 112
Figure 5.1 – Schematic representation of fMRI stimulus conditions .................. 127
Figure 5.2 – Visual guide shown to participants in post-scan behavioural testing
............................................................................................................................ 129
Figure 5.3 – Small volumes used for analysis of functional data ........................ 130
Figure 5.4 – Atrophy map of the AD group compared to healthy controls ........ 133
Figure 5.5 – Functional neuroanatomy of auditory stimulation ......................... 134
Figure 5.6 – Functional neuroanatomical data – within group contrasts ........... 136
Figure 5.7 – Functional neuroanatomical data – between group contrasts....... 138
Figure 6.1 – Schematic representation of musical task stimuli .......................... 164
Figure 6.2 – Individual corrected-detection-scores for local-global pitch deviance
detection ............................................................................................................. 170
Figure 6.3 – Individual corrected-detection-scores for key deviance detection 171
Figure 6.4 – Individual corrected-detection-scores for local-global temporal
deviance detection ............................................................................................. 172
Figure 6.5 – Individual corrected-detection-scores for timbre deviance detection
control ................................................................................................................. 173
Figure 6.6 – Individual proportion correct scores for embedded tune detection
............................................................................................................................ 174
Figure 7.1 - Schematic representation of proposed associations between DMN
and ASA in AD: integration with findings of current investigations ................... 188
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TABLE OF TABLES

Table 1.1 – Summary of behavioural studies investigating aspects of ASA in AD
............................................................................................................................. .39
Table 2.1 – Participant assignment to each generic HRTF .................................... 57
Table 3.1 – General demographic, clinical and neuropsychological data for
participant groups ................................................................................................. 67
Table 3.2 – Summary of group performance on experimental tasks ................... 78
Table 3.3 – Summary of performance correlations (Spearman’s rho) between
experimental tasks and relevant general neuropsychological functions ............. 83
Table 3.4 – Summary of neuroanatomical associations for experimental auditory
spatial tasks in the patient groups ........................................................................ 89
Table 4.1 – Demographic and post-scan behavioural task data ........................... 97
Table 4.2 – Neuropsychological profile of experimental groups ........................ 105
Table 4.3 – Summary of AD group regional grey matter atrophy ...................... 107
Table 4.4 – Summary of fMRI data for experimental contrasts of interest in
participant groups. .............................................................................................. 113
Table 5.1 – General demographic, clinical, neuropsychological and behavioural
data for participant groups ................................................................................. 124
Table 5.2 – Summary of AD group regional grey matter atrophy ...................... 133
Table 5.3 – Summary of fMRI data for experimental contrasts of interest in
participant groups. .............................................................................................. 139
Table 6.1 – General demographic, clinical and neuropsychological profiles ...... 157
Table 6.2 – Summary of group level performance for each experimental task . 175
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