Characterising Amygdala Activation During Emotion Processing in a Sub-Clinical Anxiety Cohort ...

322 Pages·2016·2.93 MB·English

by  Jess Fielding

Characterising Amygdala Activation During Emotion Processing
in a Sub-Clinical Anxiety Cohort

by

Jessica Lucy Fielding

Submitted in fulfilment for the Degree of Doctor of Philosophy

Brain and Behaviour Research Group
School of Psychology
Faculty of Health and Medical Sciences
University Of Surrey
March 2016
Supervisors: Professor Annette Sterr, Dr Philip Dean

© Jessica Lucy Fielding 2016
Abstract
Emotions play a pivotal role in guiding our behaviour within society and our environment. In
particular, emotions enable interpersonal social interactions through non-verbal
communication that may be below conscious awareness. However, when there is some
disruption to normal emotional processing, such as in anxiety disorders, quality of life of the
individual can be severely disrupted. Anxiety disorders account for nearly a quarter of all
mental health diagnoses, however the aetiology and underpinning neural correlates of anxiety
are still not fully understood. This thesis sought to investigate the neurobiological
mechanisms of emotion processing, specifically in the amygdala, in a healthy sub-clinical
cohort. Six different studies are presented using quantitative methodology to explore
amygdala activation and connectivity during emotion processing, and structural differences,
as modulated by gender and sub-clinical anxiety. Overall results reveal a modulating effect of
sub-clinical anxiety on amygdala habituation, fronto-amygdala connectivity (at rest and
during emotion processing) and neural structure. In addition, results presented in this thesis
suggest that there may be an attentional component to characteristic hyper-responsivity of the
amygdala during emotion processing seen in clinical anxiety patients that should be
incorporated into future models of maladaptive emotion. Furthermore, various different
chapters in this thesis present evidence that the left amygdala appears to be more specialised
for responses to more socially salient stimuli and the right amygdala appears to be more
responsive to threat related stimuli indicating that key theoretical models of emotion (the dual
processing model, and the salience detection model) should be integrated into one cohesive
model of emotion processing. In addition to these theoretical implications, results
demonstrating the modulating effect of anxiety and gender presented in this thesis suggest
that research on emotion should account for individual differences as a matter of standard
practice. This thesis also supports the use of resting state -functional magnetic resonance
imaging (fMRI) as a low cost, valid alternative, to task based fMRI within the study of
anxiety. Finally, results suggest that investigation of structural differences in sub-clinical
populations, and the use of analytical methods such machine learning classification
techniques, could aid the development of diagnostic tools that can track disease progression
and identify individuals at risk of developing anxiety disorders. The possibility of identifying
such neural biomarkers will allow research to look for therapeutic treatments and
interventions, which could prevent individuals from transitioning from sub-clinical anxiety to
chronic anxiety disorders.
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Acknowledgements
I would like to thank my supervisors for their help and guidance throughout this PhD. In
particular, I would like to give special recognition to Dr Phil Dean for his time, feedback and
tolerance during the running, analysis and in particular the writing of this research. With his
continued support, guidance, and unwavering motivation, he has made this experience, and
my time, at the University of Surrey rewarding.

I would also like to thank my collaborators Professor Joao Sato and Dr Gilson Vieira for their
help and advice on data pre-processing and subsequent analysis, and my colleague Ari
Lingeswaren for his support during acquisition of the data. In addition, I would like to thank
the University of Surrey for the first three years of funding for my PhD, without this financial
assistance, I would not have been able to start this research endeavour.

Amongst my fellow postgraduates in the Department of Psychology, I would like to give
special thanks to Helen Brunger, Yasemin Hirst and Kay Moakes whom I have known for
many years and have provided enduring friendship and positive words of encouragement
even when times have been stressful. In addition, I would like to thank my colleagues and
friends with whom I have shared an office over the years; Barbara Berger, Sarah Campbell,
Brendan Richards, Ben Toovey and Nicola Johnstone, as well as our honorary office
members Lewis Dunne, Lauren Marsh and Anna Whittle. Thank you all for being such
fantastic friends and great support throughout this PhD, and in particular thank you for
making lunch times so enjoyable. I wish you all the very best in your own research
undertakings. I wish to also thank my friends outside of academia for all their understanding
and consideration when I have had work late and change plans, and in particular to Siddhi
Lukha and Nina Sellars who have been there for me when I’ve needed you most.

I wish to thank my parents, Nigel Fielding and Jane Fielding, for their unconditional love and
support. Thank you for your patience, advice (and financial support) throughout this PhD and
for always answering the phone no matter what the time. Finally, I would like to thank my
partner, Richard Muir, for your love and understanding throughout this PhD. I am grateful for
your continued support, words of encouragement and conviction in my ability.
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Declaration of originality

This thesis and the work to which it refers are the results of my own efforts. Any ideas, data,
images or text resulting from the work of others (whether published or unpublished) are fully
identified as such within the work and attributed to their originator in the text, bibliography or
in footnotes. This thesis has not been submitted in whole or in part for any other academic
degree or professional qualification. I agree that the University has the right to submit my
work to the plagiarism detection service TurnitinUK for originality checks. Whether or not
drafts have been so-assessed, the University reserves the right to require an electronic version
of the final document (as submitted) for assessment as above.

Signature: ____________

Date: ______________17.03.16 _________________________

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Table of Contents

Chapter 1: Literature Review .................................................................................................................. 1
1. Overview ......................................................................................................................................... 1
1.1 Introduction: Why is emotion research important? ....................................................................... 3
1.1.1 What are emotions? ................................................................................................................ 4
1.1.2 Psychophysiological Models of Emotion............................................................................... 5
1.2 Physiological and psychological measurement of emotion .......................................................... 9
1.2.1 Generating an emotion: stimuli ............................................................................................ 10
1.2.2 Measuring the emotion: Response ....................................................................................... 14
1.2.3 Summary .............................................................................................................................. 16
1.3 Measurement of emotion in the brain ......................................................................................... 17
1.3.1 Animal models ..................................................................................................................... 17
1.3.2 Research in human participants ........................................................................................... 19
1.4 The biology of emotion ............................................................................................................... 25
1.4.1 Neuropsychological models of emotion ............................................................................... 25
1.4.2 Biological Circuitry of Emotion .......................................................................................... 28
1.5 The Amygdala ............................................................................................................................. 39
1.5.1 Models of direct amygdala activation .................................................................................. 41
1.5.2 Dual Route of Fear ............................................................................................................... 42
1.5.3 What are the key characteristics of the amygdala? .............................................................. 45
1.5.4 Resting state analyses of amygdala connectivity ................................................................. 54
1.6 Anxiety, abnormal anxiety and emotional disorders................................................................... 54
1.6.1 Behavioural Inhibition System (BIS)/ Behavioural Approach System (BAS) models of
anxiety disorders ........................................................................................................................... 56
1.6.2 Putative Neurocognitive Correlates of BIS/BAS ................................................................. 56
1.6.3 Neural Basis for Anxiety Disorders ..................................................................................... 59
1.7 Chapter Summary ....................................................................................................................... 60
Chapter 2: Research Aims .................................................................................................................... 62
2.1 Aims of thesis ............................................................................................................................. 62
2.2 Plan of thesis ............................................................................................................................... 62
Chapter 3: Method ................................................................................................................................ 65
3.1 Overview ..................................................................................................................................... 65
3.1.1 Recruitment Overview ......................................................................................................... 65
3.1.2 Study Design Overview ....................................................................................................... 65
3.1.3 Behavioural Materials and measures ................................................................................... 66
3.3.4 The Mood Online Experience Survey: MOOX ................................................................... 73
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3.3.5 Experimental Phase .............................................................................................................. 77
Chapter 4: Study 1 ................................................................................................................................ 87
4.1 Chapter overview ........................................................................................................................ 87
4.2 Introduction ................................................................................................................................. 87
4.3 Aims ............................................................................................................................................ 91
4.4 Method ........................................................................................................................................ 91
4.4.1 Study design and recruitment ............................................................................................... 91
4.4.2 Participants ........................................................................................................................... 92
4.4.3 Measures .............................................................................................................................. 92
4.4.4 Analytic Strategy.................................................................................................................. 93
4.5 Results ......................................................................................................................................... 94
4.5.1 Descriptive Statistics ............................................................................................................ 94
4.5.2 Overall participation likelihood for performance measure and neuroimaging tasks ........... 95
4.5.3 Willingness to participate in specific study designs ............................................................ 98
4.6 Discussion ................................................................................................................................. 103
4.6.1 Implications and limitations ............................................................................................... 107
4.7 Conclusion ................................................................................................................................ 109
Chapter 5: Study 2 .............................................................................................................................. 110
5.1 Chapter Overview ..................................................................................................................... 110
5.2 Introduction ............................................................................................................................... 110
5.3 Aims .......................................................................................................................................... 113
5.4 Method ...................................................................................................................................... 114
5.4.1 Design ................................................................................................................................ 114
5.4.2 Participants ......................................................................................................................... 114
5.4.3 Procedure ........................................................................................................................... 115
5.4.4 fMRI Acquisition and pre-processing ................................................................................ 115
5.4.5. ROI Extraction .................................................................................................................. 116
5.5 Results ....................................................................................................................................... 117
5.5.1 Demographic Data Analysis .............................................................................................. 117
5.5.2 Functional imaging data ..................................................................................................... 118
5.6 Summary of Results .................................................................................................................. 125
5.7 Discussion ................................................................................................................................. 126
5.8. Implications.............................................................................................................................. 132
5.9 Limitations ................................................................................................................................ 134
5.10 Conclusions ............................................................................................................................. 136
Chapter 6: Study 3 .............................................................................................................................. 138
6.1 Chapter Overview ..................................................................................................................... 138
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6.2 Introduction ............................................................................................................................... 138
6.3 Aims .......................................................................................................................................... 141
6.4 Method ...................................................................................................................................... 142
6.4.1 PPI Analysis ....................................................................................................................... 142
6.5 Results ....................................................................................................................................... 145
6.5.1 Descriptive statistics .......................................................................................................... 145
6.5.2 Overall PPI analysis ........................................................................................................... 145
6.5.3. Amygdala ROI analysis .................................................................................................... 150
6.5.4. Fusiform Gyrus ROI analysis ........................................................................................... 156
6.5.5 Summary ............................................................................................................................ 161
6.6 Discussion ................................................................................................................................. 162
6.6.1 Fronto-amygdala connectivity ........................................................................................... 163
6.6.2 Fronto-Fusiform gyrus connectivity .................................................................................. 167
6.6.3 Emotion processing and functional specialisation ............................................................. 169
6.6.4 Individual differences ........................................................................................................ 170
6.6.4.1 Gender ............................................................................................................................. 170
6.6.4.2 Anxiety ............................................................................................................................. 173
6.6.4.3 Summary of individual differences .................................................................................. 174
6.7 Limitations and implications ..................................................................................................... 174
6.8 Conclusion ................................................................................................................................ 176
Chapter 7: Study 4 .............................................................................................................................. 178
7.1 Chapter Overview ..................................................................................................................... 178
7.2 Introduction ............................................................................................................................... 178
7.3 Aims .......................................................................................................................................... 181
7.4 Method ...................................................................................................................................... 181
7.4.1 Data from first level GLM and PPI .................................................................................... 181
7.4.2 Support vector machines and maximum uncertainty linear discrimination analysis ......... 182
7.4.3 Classification and Brain Mapping ...................................................................................... 183
7.5 Results ....................................................................................................................................... 184
7.6 Discussion ................................................................................................................................. 186
7.7 Limitations and implications ..................................................................................................... 191
7.8 Conclusion ................................................................................................................................ 192
Chapter 8: Study 5 .............................................................................................................................. 193
8.1 Overview ................................................................................................................................... 193
8.2 Introduction ............................................................................................................................... 193
8.3 Aims .......................................................................................................................................... 195
8.4 Method ...................................................................................................................................... 196
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8.4.1 Participants ......................................................................................................................... 196
8.4.2 MRI Acquisition ................................................................................................................ 197
8.4.3 Volumetric Data ................................................................................................................. 197
8.4.4 Statistical Analysis: Freesurfer .......................................................................................... 198
8.4.5 Statistical Analysis: ROI Extraction .................................................................................. 198
8.5 Results ....................................................................................................................................... 199
8.5.1 Descriptive Statistics .......................................................................................................... 199
8.5.3 Volumetric results: Freesurfer ........................................................................................... 199
8.5.4 Volumetric results: ROI analysis ....................................................................................... 199
8.6 Discussion ................................................................................................................................. 202
8.6.1 Comparison to previous literature using STAI .................................................................. 203
8.6.2 Sub-clinical anxiety related structural differences when using HADS .............................. 204
8.7 Implications............................................................................................................................... 207
8.8 Limitations ................................................................................................................................ 209
8.9 Conclusions ............................................................................................................................... 210
Chapter 9: Study 6 .............................................................................................................................. 211
9.1 Overview ................................................................................................................................... 211
9.2 Introduction ............................................................................................................................... 211
9.3 Aims .......................................................................................................................................... 214
9.4 Methods..................................................................................................................................... 214
9.4.1 Participants ......................................................................................................................... 214
9.4.2 Procedure ........................................................................................................................... 215
9.4.3 Pre-processing .................................................................................................................... 215
9.4.4 Study A: Whole amygdala resting state ............................................................................. 215
9.4.5 Study B: Parcellated amygdala resting state ...................................................................... 217
9.5 Results ....................................................................................................................................... 219
9.5.1 Study A: Whole amygdala resting state ............................................................................. 219
9.5.2 Study B: Parcellated amygdala resting state ...................................................................... 229
9.5.3 Summary ............................................................................................................................ 239
9.6 Discussion ................................................................................................................................. 241
9.6.1 Resting amygdala connectivity .......................................................................................... 241
9.6.2 Modulation by anxiety ....................................................................................................... 246
9.6.3 Modulation by gender ........................................................................................................ 249
9.7 Limitations ................................................................................................................................ 250
9.8 Conclusion ................................................................................................................................ 252
Chapter 10: Discussion ....................................................................................................................... 254
10.1 Overview of aims .................................................................................................................... 254
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10.2 Summary of results by study ................................................................................................... 254
10.3 Implications of results ............................................................................................................. 257
10.3.1 Theoretical Implications .................................................................................................. 257
10.3.2 Methodological Implications ........................................................................................... 261
10.3.3 Practical Implications ....................................................................................................... 262
10.4 Methodological limitations ..................................................................................................... 265
10.5 Conclusion .............................................................................................................................. 267
References ........................................................................................................................................... 269
Appendices .......................................................................................................................................... 305
Appendix A ..................................................................................................................................... 305

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List of Tables
Chapter 4 Mood Online Experience Survey (MOOX)
Table 4.1 Percentage breakdown of demographic information across all 95
participants, and within each demographic (by anxiety group or gender).
Table 4.2 Cross tabulation results (count) for overall group results 96
Table 4.3 Percentage of participates who would not participate in each study by 98
anxiety group. ‘N.S.’ denotes non-significant (p>0.05) relationships
between high and low anxiety participants
Table 4.4 Percentage of participates who would not participate in each study by 99
gender group. ‘N.S.’ denotes non-significant (p>0.05) relationships between
male and female participants
Table 4.5 Inferential results of the three-way cross tabulations of 102
gender/age/English as a first language by anxiety group by different study
design types.

Chapter 5: General Linear Model
Table 5.1 Table showing different Contrasts that were considered in the second 116
level regression
Table 5.2 Overview of descriptive results for the male and female participants and 117
the age/ hospital anxiety and depression ranges, mean scores and standard
deviations

Chapter 6: PsychoPhysiological Interaction
Table 6.1 Main effect and interaction results of the two-way ANOVA looking at 151
connectivity between four regions of interest (ACC, dmPFC, vmPFC and
Precuneus) and bilateral amygdala as modulated by the valence condition
and the seed ROI hemisphere (left or right amygdala).
Table 6.2 Main effect and interaction results of the mixed ANOVA with gender as 153
a between groups variable looking at connectivity between four regions of
interest (ACC, dmPFC, vmPFC and Precuneus) and bilateral amygdala as
modulated by the valence condition and the seed ROI hemisphere (left or
right amygdala).
Table 6.3 Main effect and interaction results of the mixed ANOVA with anxiety as 155
a between groups variable looking at connectivity between four regions of
interest (ACC, dmPFC, vmPFC and Precuneus) and bilateral amygdala as
modulated by the valence condition and the seed ROI hemisphere (left or
right amygdala).
Table 6.4 Main effect and interaction results of the two- ANOVAs looking at 156
connectivity between four regions of interest (ACC, dmPFC, vmPFC and
Precuneus) and bilateral fusiform gyrus as modulated by the valence
condition and the seed ROI hemisphere (left or right amygdala).
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