[PDF] Adiel Mallik PhD Thesis Neurochemical and Social Aspects of Music

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Neurochemical and Social Aspects of Music

Adiel Mallik

Integrated Program in Neuroscience, McGill University

July 2019

A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Doctor of Philosophy in Neuroscience

© Adiel Mallik, 2019

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Table of Contents

Table of Contents ............................................................................................................................ 2

List of Tables .................................................................................................................................... 4

List of Figures .................................................................................................................................. 5

Abstract ............................................................................................................................................ 6

Résumé ............................................................................................................................................. 8

Preface ............................................................................................................................................ 11

Manuscript-based thesis ........................................................................................................... 11

Contribution of authors ........................................................................................................... 11

Chapter 1: Music, Emotion, Neurochemical Mechanisms and Theory of Mind: An Integrated Review

......................................................................................................................................................... 13

1.1 Introduction ........................................................................................................................ 13

1.2 Music, Emotion and Neurological Correlates ............................................................. 14

1.5: Reading, Music and Theory of Mind ............................................................................... 35

1.6: Review of Theory of Mind Assessment Techniques ...................................................... 45

1.7: Rationale and Objectives for Research ........................................................................... 61

Chapter 2: Anhedonia to music and μ-opioids: Evidence from administration of naltrexone63

2.1: Abstract .............................................................................................................................. 64

2.2: Introduction ....................................................................................................................... 64

2.3: Materials and Methods ..................................................................................................... 68

2.3.1: Participants ................................................................................................................. 68

2.3.2: Design ......................................................................................................................... 69

2.3.3: Procedure .................................................................................................................... 70

2.3.4: Pharmacological agent .............................................................................................. 71

2.3.5: Musical stimuli ........................................................................................................... 72

2.3.6: Food stimuli ................................................................................................................ 75

2.3.7: Physiological measurements ..................................................................................... 76

2.3.8: Data analysis ............................................................................................................... 76

2.4: Results ................................................................................................................................ 78

2.5: Discussion ........................................................................................................................... 85

2.6: Supplementary Information ............................................................................................. 93

2.6.1: Participant selection and screening .......................................................................... 93

2.6.2: Sample size and justification ..................................................................................... 95

2.6.3: Data Analysis .............................................................................................................. 95

2.6.4: Choice of naltrexone over naloxone ......................................................................... 96

2.7: Supplementary results ....................................................................................................... 97

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2.7.1: Physiological measures: pleasure and neutral music difference of electromyograms of

corrugator muscles ............................................................................................................... 97

2.7.2: Behavioural measures: changes in state trait anxiety inventory (STAI) and profile of

mood states (POMS) after placebo/naltrexone treatment ............................................... 99

2.7.3: Physiological measures: changes in differences between post-placebo/drug and pre-

placebo/drug for BVPA, RR, EMG ZYG and EMG COR. ......................................... 100

Chapter 3: The Effect of Music on Theory of Mind ................................................................ 102

3.1: Abstract ............................................................................................................................ 103

3.2: Introduction ..................................................................................................................... 105

3.3: Experiment One: The Effect of Music Listening on Theory of Mind ........................ 113

3.3.1: Materials and Methods ............................................................................................ 113

3.3.2: Results ....................................................................................................................... 116

3.3.3: Discussion ................................................................................................................. 118

3.3.4: Conclusion ................................................................................................................ 122

3.4: Experiment Two: The Effect of Sensorimotor Engaging Musical Stimuli on Theory of Mind

(Yoni Test) .............................................................................................................................. 122

3.4.1: Materials and Methods ............................................................................................ 122

3.4.2: Results ....................................................................................................................... 124

3.4.3: Discussion ................................................................................................................. 131

3.4.4: Conclusion ................................................................................................................ 136

3.5: Experiment Three: The Effect of Sensorimotor Engaging Musical Stimuli on Theory of Mind

(Director Task and Yoni Test) .............................................................................................. 137

3.5.1: Materials and Methods ............................................................................................ 137

3.5.2: Results ....................................................................................................................... 138

3.5.3: Discussion ................................................................................................................. 145

3.5.4: Conclusion ................................................................................................................ 150

3.5.5 Financial Disclosure Statement ............................................................................... 151

Chapter 4: Contributions to Knowledge and Future Directions ............................................ 152

4.1: Contributions From Study 1: Anhedonia to music and μ-opioids: Evidence from

administration of naltrexone ................................................................................................. 152

4.2: Implications of Study 1 .................................................................................................... 153

4.3: Future Work for Study 1 ................................................................................................. 153

4.4: Contributions From Study 2: The Effect of Music on Theory of Mind (ToM) ......... 154

4.5: Implications for Study 2 .................................................................................................. 157

4.6: Future Work for Study 2 ................................................................................................. 159

4.7: Overall Conclusions and Implications ........................................................................... 161

References .................................................................................................................................... 163

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List of Tables

Table 1: Power analysis of the effect of music on the RMET at a power of 0.80 ................................. 118

Table 2: Power analysis of first and second order cognitive Yoni test scores. Total sample size for

both groups was calculated at a power of 0.80 ......................................................................................... 127

Table 3: Power analysis of first and second order affective Yoni test scores. Total sample size for both

groups was calculated at a power of 0.80 .................................................................................................. 129

Table 4: Power Analysis of Director Task Accuracy (α = 0.05, power = 0.80) ................................... 140

Table 5: Power Analysis of Director Task Response Time (α = 0.05, power = 0.80) ........................ 142

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List of Figures

Figure 1: Limbic circuitry, red arrows show glutamatergic pathways, black arrows show GABAergic

pathways and blue arrows show dopaminergic pathways (Pierce & Kumaresan, 2006). ....................... 29

Figure 2: Yoni test assessing ToM by calculating the number of correct responses (Adjeroud et al.,

2015). ............................................................................................................................................................. 49

Figure 3: Director task instructions and trial types (Dumontheil et al., 2010a). .................................... 51

Figure 4: Sample displays of trial conditions and perspectives of modified Director task, testing for

effects of selective attention (Rubio-Fernández, 2017). ........................................................................... 55

Figure 5: Opioid blockade (naltrexone condition (NTX) caused a decrease in (a) zygomatic and (b)

corrugator muscle activity in both music conditions (* denotes p < 0.05, *** denotes p < 0.001). .... 80

Figure 6: Effects of opioid blockade (naltrexone condition, NTX). NTX caused a decrease in self- report measures of pleasure for pleasurable music (p < 0.05) but not neutral music, (p = 0.12) or

food (p = 0.48). ............................................................................................................................................ 82

Figure 7: Effects of opioid blockade (naltrexone condition, NTX) on (a) blood volume pulse

amplitude, (b) respiratory rate and (c) heart rate. .................................................................................... 84

Figure 8: Chemical structures of a) Naloxone and b) Naltrexone (NTX). ............................................. 97

Figure 9: Opioid blockade (naltrexone condition, NTX) caused a decrease in the difference between

pleasurable and neutral music in the corrugator electromyogram (p < 0.05). ....................................... 98

Figure 10: Opioid blockade showed no significant changes in a) State-Trait Anxiety Inventory (STAI)

or in any of the b) Profile of Mood States (POMS) components. ........................................................... 99

Figure 11: Opioid blockade showed no significant changes in differences between pre and post

placebo/drug baselines in a) BVPA, b) RR, c) EMG ZYG, d) EMG COR. ....................................... 101

Figure 12: The effect of music listening on the reading the mind in the eyes test (RMET). There were

no significant differences between any of the experimental groups. ..................................................... 117

Figure 13: A) First order and B) Second order cognitive Yoni test scores (* denotes p < 0.05 by

Fisher Randomization Test (2000 iterations)). ....................................................................................... 125

Figure 14: A) First order and B) Second order affective ToM Yoni test scores (* denotes p < 0.05 by

Fisher Randomization Test (2000 iterations)). ....................................................................................... 126

Figure 15: Director task accuracy (mean % error) for Reading, Rock Band and Frets on Fire

treatment groups (*** denotes p < 0.001). .............................................................................................. 139

Figure 16: Director task response time for Reading, Rock Band and Frets on Fire treatment groups.

...................................................................................................................................................................... 141

Figure 17: Second order affective Yoni trial scores immediately after Rock Band treatment versus 11

minutes after Rock Band treatment (* denotes p < 0.05) ..................................................................... 144

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Abstract

This thesis investigates the neurochemical and social impacts of music and music-related activities with two primary objectives: 1) to determine whether the opioid neurochemical system is implicated in mediating positive and negative valence emotional responses to music and 2) to investigate whether music or music- related activities impact social cognition skills as measured by performance on theory of mind (ToM) tests. Chapter 1 presents an integrated literature review covering music, emotion, neurochemistry of musical reward, and ToM. Chapter 2 examines the role of the opioid system in mediating the emotional responses to music. In this published paper, an opioid receptor antagonist (naltrexone) was used in a double-blind placebo-controlled crossover design. The results showed that the opioid system mediates pleasurable as well as positive and negative emotional valence reactions to music. Chapter 3 explored how music impacts social cognition in healthy adults as measured by ToM tests, involving three experiments. The first experiment examined whether listening to musical excerpts eliciting different emotions (happy, sad, mysterious) impacts affective ToM performance as measured by the reading the mind in the eyes test (RMET) compared to a control group that read a non-fiction excerpt. The results showed no significant difference between any of treatment groups suggesting that music listening does not impact affective ToM. The second experiment examined whether playing a sensorimotor engaging musical videogame 7 (Rock Band) improves ToM as measured by the Yoni test compared to other treatment groups, reading a non-fiction excerpt, listening to music, watching music videos and playing Tetris. The Rock Band group scored higher than the reading and music listening groups in the most difficult trial type and difficulty level (affective, 2 nd order). But the results for the other trial types and difficulty levels were mixed. The third experiment explored whether playing Rock Band impacts the perspective- taking component of ToM as measured by the Director task compared to groups reading a non-fiction excerpt and playing a game called Frets on Fire (similar to Guitar Hero) on a laptop computer. Results showed no significant difference between any of the treatment groups in the Director experimental trials. The outcome of the thesis makes three novel, original contributions: first, I found that the opioid system mediates both positive and negative emotional responses to music; second, music listening alone does not impact ToM performance; third, musically sensorimotor engaging videogames such as Rock Band may improve affective ToM but not cognitive ToM or the perspective-taking component of ToM. However, Rock Band's positive impact on affective ToM needs to be substantiated by further studies. 8

Résumé

Cette thèse étudie les impacts neurochimiques et sociaux de la musique et des activités liées à la musique avec deux objectifs principaux : 1) déterminer si le système neurochimique opioïde est impliqué de la médiation des réponses émotionnelles de valence positive et négative à la musique et 2) déterminer si la musique les activités ont un impact sur les aptitudes cognitives sociales mesurées par la performance aux tests de théorie de l'esprit (ToM). Le chapitre 1 présente une revue de littérature intégrée couvrant la musique, les émotions, la neurochimie de la récompense musicale et ToM. Le chapitre 2 examine le rôle du système opioïde dans la médiation des réponses émotionnelles à la musique. Un antagoniste des récepteurs opioïdes (naltrexone) a été utilisé dans un croisement à double insu contrôlé par placebo. Les résultats ont montré que le système opioïde permettait des réactions de valence émotionnelle positives et négatives à la musique. Le chapitre 3 a examiné l'impact de la musique sur la cognition sociale chez des adultes en bonne santé, mesuré à l'aide de tests ToM et comprenant trois expériences. La première expérience visait à déterminer si l'écoute d'extraits musicaux suscitant différentes émotions (heureuse, triste, mystérieuse) avait une incidence sur les performances affectives de la ToM, telles que mesurées par le test de lecture de l'esprit dans les yeux (RMET) par rapport à un groupe témoin lisant un extrait de non-fiction. Les résultats n'ont montré aucune différence significative entre les groupes de traitement suggérant que l'écoute de musique n'a pas d'impact sur la 9 ToM affective. La seconde expérience visait à déterminer si la lecture d'un jeu vidéo musical interactif (Rock Band) améliorait ToM, mesurée par le test de Yoni par rapport à d'autres groupes de traitement, lisant un extrait de non-fiction, écoutant de la musique, visionnant des vidéos musicales et jouant Tetris. Le groupe Rock Band a obtenu des scores plus élevés que les groupes de lecture et d'écoute de musique dans le type d'essai et le niveau de difficulté les plus difficiles (affectif, 2e ordre). Mais les résultats pour les autres types d'essais et les niveaux de difficulté

étaient mitigés. La troisième expérience visait à déterminer si le fait de jouer Rock

Band avait un impact sur la prise de perspective de ToM, mesurée par la tâche du réalisateur par rapport aux groupes qui lisaient un extrait de non-fiction et jouaient un jeu appelé Frets on Fire (similaire à Guitar Hero) sur un ordinateur portable. Les résultats n'ont montré aucune différence significative entre les groupes de traitement dans les essais expérimentaux avec Director. Le résultat de la thèse a apporté trois contributions originales : premièrement, le système opioïde assure la médiation des réactions émotionnelles tant positives que négatives à la musique ; deuxièmement, l'écoute de musique à elle seule n'a pas d'impact sur les performances de ToM ; Troisièmement, les jeux vidéo interactifs tels que Rock Band peut améliorer la ToM affective, mais non la ToM cognitive ou la composante de prise de perspective de ToM. Cependant, l'impact positif de Rock Band sur ToM affectif doit être corroboré par d'autres études. 10

Acknowledgements

It would not have been possible for me to present the work in this thesis without the help and support of many outstanding colleagues and friends. Firstly, I would like to tha nk my supe rvisor Pro fessor Daniel Levitin fo r giving me the opportunity to undertake this incredible scientific journey and guiding my growth as a scientist while encouraging my scientific independence. I would also like to thank my graduate committee members, Professors Marc Pell, Jorge Armony, Stephen McAdams who provided me with valuable comments and suggestions on my research over the years. I would also like to thank Professor Eve-Marie Quintin for her valuable advice and for allowing me to use the laptop in her lab for data collection in the Chapter 3, Experiment Three of this thesis. I also would like to thank my undergraduate research assistants, Tabea Haas- Heger, Frank Zhang and Yueyang Li for assisting me in recruitin g and testing participants and perform ing literature reviews. I would also like to thank Karle Philip Zamor for his valuable technical assistance as well as Lindsay Fleming for her help with recruiting undergraduate research assistants. I would like to thank my friends Wisit Chan tawarang and D r. Ayokunle Olanrewaju for their friendship and support over the years. Last but not least, I would like to than k my pare nts Professor Azim and Dr. Mary Mallik for th eir continuous support and encouragement through this challenging journey and taking the time to read and comment on manuscript drafts and drafts of this thesis. 11

Preface

Manuscript-based thesis

McGill University allows a manuscript-based alternative to the traditional thesis format: a collection of publishable manuscripts formatted to satisfy the thesis guidelines. The present thesis conforms to this style and consists of two "content" chapters of original research in journal submission form as well as all other standard thesis requirements, including an abstract, table of contents, introduction, conclusion, and reference section. Chapter 2 has been published in Scientific Reports (Mallik, Chanda, & Levitin, 2017). Chapter 3 will be submitted to

Psychomusicology.

Note that all references for all four chapters are listed in a bibliography at the end of this thesis. In accordance with McGill University Graduate Thesis Guidelines, a detailedquotesdbs_dbs25.pdfusesText_31

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