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The Development of Evidence Based Music Therapy with Disorders of Consciousness

Dissertation submitted for the degree of Doctor of Philosophy

Department of Communication and Psychology

Aalborg University, Denmark 2014

Julian O'Kelly

Supervisors

Associate Professor Wendy Magee

Professor Hanne Mette Ochsner Ridder

J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014

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Declaration

I confirm that this thesis and the research it presents has not previously, in part or in its entirety, been submitted for examination at an academic institution of higher education in Denmark or abroad. Except where otherwise indicated, this thesis is my own work.

27th November 2013………………………………………………………………………....................Date Julian O’Kelly


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Research Environment

The research detailed in this thesis was funded primarily through a three year full time PhD

Mobility Fellowship from the Doctoral School of the Humanities within the Department of

Psychology and Communication at Aalborg University. Additional funding was provided by

the Royal Hospital for Neuro-disability and the Music Therapy Charity.

The study was undertaken at the Royal Hospital for Neuro-disability, a large specialist unit

providing rehabilitation and long-term care for individuals with acquired brain injuries and

neuro-degenerative conditions, with dedicated education and research departments. The

hospital was founded in 1854, and is the oldest independent hospital and medical charity in

the UK. The author was seconded from the post of Head of Music Therapy to undertake this

research.

Acknowledgements

Many individuals were indispensable in terms of the support they gave to ensure the

completion of this project. Firstly, the biggest thank you must go to all the carers who gave

approval for their loved ones to participate in the study as patient subjects, the patients

themselves, and the healthy volunteers who gave their time to provide healthy comparison

data.

Conducting research in a clinical setting necessarily involves negotiation and good

communication with multi-disciplinary colleagues. In particular, the music therapists,

occupational therapists, and nurses working with the patients recruited to the study deserve

heartfelt thanks for co-operating with me as I scheduled sessions and sought information

about patients.

The study benefited from technical assistance offered by several individuals.

Neurophysiologist Dr Leon James gave invaluable support in EEG electrode placement

methods and the use of MATLAB software. Dr Ramaswamy Palaniappan provided software

support and on-going advice in the use of bespoke MATLAB programmes to analyse the

neurophysiological measures used in the study. Professor Jӧrg Fachner brought to the study

advice born of his many years of experience in applying EEG methods to music therapy


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research. Finally Jana Tamborin volunteered her time as the study’s independent observer

for behavioural data.

The study’s primary supervisor, Associate Professor Wendy Magee gave many hours of

patient supervision and guidance throughout the study. Her experience as a clinician, author

and researcher in the field of neuro-disability meant that the study benefited immeasurably

from her support. At Aalborg, Professor Hanne Mette Ochsner Ridder provided on-going

supervision and guidance in relation to the various protocols involved in the fellowship

scheme, for which I am immensely grateful. At my workplace and site of the research, line

manager Dr Sophie Duport gave a consistently high level of support, advice and

encouragement. At the final stages of submission Jan Brooman and Catherine Hazell also

deserve thanks for their contribution in proof reading and Stine Lindahl Jacobson for

translating the thesis abstract into Danish.

In terms of acknowledgements, it is essential to highlight that the existence of the PhD

Mobility Fellowship, and hence this study, is in great part a result of the late Tony Wigram’s

pioneering and tireless support of music therapy both at Aalborg and internationally.

Finally, this work has in many ways been made possible by the love and encouragement of

my partner Joanne, and has been in many ways inspired by my daughter Evie, born during

the data collection for this thesis.


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Abstract

By improving arousal and awareness for those with disorders of consciousness (DOC),

music therapy may contribute to the assessment of whether individuals are in vegetative

states (VS) or minimally conscious states (MCS). However, supporting evidence is lacking.

The purpose of this thesis is to address a primary research question: can music therapy

effect neurophysiological and behavioural changes suggesting arousal and awareness to

contribute to the assessment of patients with DOC?

The thesis comprises three peer reviewed papers. The first explores relevant music therapy

and neuroscience literature, highlighting how interdisciplinary dialogue is mutually beneficial.

The second asks: what do concurrent music therapy and global assessments reveal about

DOC patients’ responsiveness to auditory and musical stimuli? An audit compared 42 music

therapy assessments (MATADOC) with concurrent multimodal assessments (SMART) using

standardised measures for each. Statistical analysis highlighted that whilst MATADOC has

higher sensitivity within auditory and visual domains, SMART has higher sensitivity in the

motor domain. Findings support the use of the music therapy assessment in contributing to

the understanding of a patient’s level of awareness.

The third paper addresses further questions: what information will a neurophysiological and

behavioural examination of DOC and healthy responses to music therapy and other auditory

stimuli reveal in relation to (i) contrasting responses across and within healthy, MCS and VS

cohorts, and (ii) comparison with standardised behavioural assessments? A multiple baseline

within-subjects study compared electroencephalogram (EEG), cardio-respiratory and

behavioural responses of 20 healthy, 12 VS and 9 MCS subjects to music therapy (live

preferred music and improvised music entrained to respiration), pre-recorded disliked music,

white noise and silence. Post-hoc ANOVA tests indicated that preferred music produced the

widest range of significant responses (p ≤ 0.05) across healthy subjects, particularly for

respiration rate and EEG amplitude. Significant EEG amplitude peaks were found in frontal

areas in MCS and VS cohorts (p ≤ 0.05) in response to music therapy, suggesting increased

arousal. These cortical responses may also indicate selective attention. Furthermore,

behavioural data showed significantly increased blink rates for preferred music in VS patients

(p = 0.029).


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In conclusion, this thesis has developed our understanding of the role of music therapy with

DOC. Neurophysiological and behavioural evidence indicates that music therapy improves

arousal and awareness, providing empirical support for its role in optimising the conditions

needed for assessment and rehabilitation. Further research is indicated exploring how these

effects may be harnessed to improve clinical outcomes for DOC patients.

Dansk Abstract

Ved at forbedre arousal og bevidsthed (awareness) hos mennesker med

bevidsthedsforstyrrelser (Disorders of Consiousness; DOC), kan musikterapi bidrage til at

vurdere om patienter befinder sig i vegetative (VS) eller minimalt bevidste tilstande (MCS).

Der mangler dog understøttende dokumentation for dette. Formålet med denne afhandling er

formuleret i det primære forskningsspørgsmål: Kan musikterapi medvirke til

neurofysiologiske og adfærdsmæssige ændringer, hvorved arousal og bevidsthed kan

bidrage til assessment af patienter med bevidsthedsforstyrrelser?

Afhandlingen består af tre peer-reviewed artikler. Den første udforsker relevant

musikterapiteoretisk og neurologisk videnskabelig litteratur, og fremhæver hvordan

tværfaglig dialog er til gensidig gavn. I den næste artikel stilles spørgsmålet: Hvad kan

sammenlignelige musikterapeutiske og globale assessment-redskaber afsløre om DOC-

patientens reaktioner på auditive og musikalske stimuli? Ved hjælp af standardiserede

målinger blev 42 musikterapi-assessment-vurderinger (Music Therapy Assessment Tool for

Disorders of Consciousness; MATADOC) sammenlignet med multimodale assessment-

vurderinger ('Sensory Modality Assessment and Rehabilitation Technique; SMART). Den

statistiske analyse viste, at mens MATADOC har højere følsomhed i forhold til auditive og

visuelle domæner, så har SMART højere følsomhed inden for det motoriske domæne.

Resultaterne understøtter brug af musikterapeutisk assessment som et bidrag til forståelsen

af patienters bevidsthedstilstande.

Den tredje artikel omhandler yderligere delspørgsmål: Hvilke oplysninger vil en

neurofysiologisk og adfærdsmæssig undersøgelse af bevidsthedsforstyrrelser samt raske

personers reaktioner på musikterapi og andre auditive stimuli afsløre i forbindelse med (I)

kontrasterende respons mellem raske, MCS- og VS-deltagere, og (II) sammenligning med

standardiserede adfærdsassessment-vurderinger? En multiple baseline within-subject

undersøgelse sammenlignede elektroencefalogram (EEG) , kardio-respiratoriske- og

adfærdsmæssige reaktioner på 20 raske, 12 VS- og 9 MCS-deltagere som fik musikterapi


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(live-spillet foretrukket musik og improviseret musik tilpasset deres vejrtrækning), som lyttede

til indspillet ikke-foretrukket musik, hvid støj og stilhed. Post-hoc ANOVA-analyser viste, at

der ved foretrukket musik var den største grad af signifikante responser (p ≤ 0,05) blandt

raske forsøgspersoner, især for åndedrætsfrekvens og EEG-signaler. Signifikante udsving i

EEG-målingerne blev fundet i frontale områder hos MCS- og VS-deltagerne (p ≤ 0,05) som

reaktion på musikterapi, hvilket tyder på øget arousal. Disse kortikale reaktioner kan også

indikere selektiv opmærksomhed. Desuden viste adfærdsmæssige data signifikant flere blink

ved foretrukket musik hos VS-patienter (p = 0,029).

Det kan konkluderes, at denne afhandling har udviklet vores forståelse af musikterapiens

rolle hos mennesker med bevidsthedsforstyrrelser. Neurofysiologiske og adfærdsmæssige

data indikerer, at musikterapi forbedrer arousal og bevidsthed, hvilket giver empirisk belæg

for musikterapiens rolle med henblik på at optimere de nødvendige betingelser for

assessment og rehabilitering. Videre forskning bør undersøge hvordan disse virkninger kan

udnyttes til at forbedre de kliniske resultater for patienter med bevidsthedsforstyrrelser.


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Contents

Research Environment.....................................................................................................................ii

Acknowledgements..........................................................................................................................ii

Abstract...........................................................................................................................................iv

Dansk Abstract.................................................................................................................................v

List of Publications...........................................................................................................................1

PhD Thesis Papers..........................................................................................................................1

Peer Reviewed PhD Related Conference Presentations...........................................................1

Other PhD Related Presentations.................................................................................................2

Table of Abbreviations Used............................................................................................................4

1. Introduction..................................................................................................................................5

2. Theoretical Framework................................................................................................................7

2.1 Neuro-rehabilitation...................................................................................................................7

2.2 Evidence Based Medicine........................................................................................................7

2.3 Physical Rehabilitation Medicine............................................................................................8

2.4 Music Therapy...........................................................................................................................9

2.5 Consciousness..........................................................................................................................9

2.5.1 The Humanist Perspective..............................................................................................10

2.5.2 The Behavioural/Pragmatic Perspective.......................................................................10

2.5.3 Consciousness and Disorders of Consciousness.......................................................11

2.5.4 Arousal..............................................................................................................................12

2.5.5 Awareness........................................................................................................................15

2.5.6 Awareness or Consciousness?......................................................................................15

2.6 Diagnostic Criteria...................................................................................................................17

2.6.1 Coma.................................................................................................................................17

2.6.2 Locked-in Syndrome........................................................................................................17

2.6.3 Vegetative State (VS)......................................................................................................18

2.6.4 Minimally Conscious State (MCS).................................................................................21

2.7 Assessment of DOC...............................................................................................................23

2.7.1 Music Therapy and DOC Assessment..........................................................................23

2.7.2 Neuroimaging and DOC Assessment...........................................................................25

2.7.3 Behavioural Assessment of DOC..................................................................................26


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2.8 Sensory Stimulation and Regulation....................................................................................27

2.8.1 Sensory Stimulation.........................................................................................................28

2.8.2 Sensory Regulation.........................................................................................................29

2.8.3 Neuroplasticity..................................................................................................................31

3. Aims of the Thesis.....................................................................................................................32

3.1 Research questions................................................................................................................32

4. Overall Research Design...........................................................................................................33

5. Methodology..............................................................................................................................35

5.1 Search Strategy.......................................................................................................................35

5.2 Recruitment..............................................................................................................................35

5.2.1 Ethical Considerations.....................................................................................................37

5.3 Data Collection........................................................................................................................38

5.3.1 Materials............................................................................................................................38

5.3.2 Procedures and Protocol................................................................................................38

5.4 Data Analysis...........................................................................................................................40

6. Overview of Results for Paper III...............................................................................................42

6.1 Results from Healthy Data.....................................................................................................42

6.2 Results from Patient Data......................................................................................................43

7. Summary and Background of Papers........................................................................................44

7.1 Paper I......................................................................................................................................44

7.2 Paper II.....................................................................................................................................45

7.3 Paper III....................................................................................................................................46

8. Discussion..................................................................................................................................48

8.1 Sub Question 2........................................................................................................................48

8.2 Sub question 3a......................................................................................................................50

8.2.1 Healthy Neurophysiological Responses.......................................................................50

8.2.2 Patient Behavioural Responses.....................................................................................52

8.2.3 Patient Neurophysiological Responses........................................................................53

8.3 Sub question 3b......................................................................................................................57

8.4 Primary Research Question...................................................................................................59

8.5 Limitations................................................................................................................................60

9. Conclusions...............................................................................................................................62

10. Summary.................................................................................................................................64


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Reference List................................................................................................................................74

Appendix I......................................................................................................................................89

Appendix 2.....................................................................................................................................91

Appendix 3a...................................................................................................................................96

Appendix 3b...................................................................................................................................97

Appendix 3c...................................................................................................................................98

Thesis Papers I, II & III.................................................................................................................100

Note on Publications and Copyright.............................................................................................100

Paper I...........................................................................................................................................101

Paper II..........................................................................................................................................104

Paper III.........................................................................................................................................106

Figures

Figure 1: Relationship between Arousal and Consciousness................................................14

Figure 2: Study Protocol.........................................................................................................40

Figure 3: Healthy Respiration Rates and Beats per Minute Compared.................................51

Tables

Table 1: Significant Change in Patient Physiological Measures……………………………….56


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List of Publications

PhD Thesis Papers Paper I: O'Kelly, J., & Magee, W.L. (2013). Music therapy with disorders of consciousness

and neuroscience: the need for dialogue. Nordic Journal of Music Therapy. 22(2), 93-106.

doi: 10.1080/08098131.2012.709269

Paper II: O'Kelly, J., & Magee, W.L. (2013). The complementary role of music therapy in the

detection of awareness in disorders of consciousness: an audit of concurrent SMART and

MATADOC assessments. Neuropsychological Rehabilitation, 23(2), 287-298.

doi:10.1080/09602011.2012.753395

Paper III: O'Kelly J., Magee, W.L. James, L., Palaniappan, R., Taborin, J., & Fachner, J.

(2013). Neurophysiological and behavioural responses to music therapy in vegetative and

minimally conscious states. Frontiers in Human Neuroscience. 7:884. doi:

10.3389/fnhum.2013.00884

Papers I, II and III cannot be provided in full in the online version of this thesis due to

copyright restrictions, however details for downloading each paper, including the free open

access copy of Paper III are provided on pages 101-105 of this thesis The level and nature of

the co-authors contributions to each of the main PhD publications is detailed in Appendices

3a-c.

Peer Reviewed PhD Related Conference Presentations O'Kelly, J., Magee, W.L., James, L., Palaniappan, R., Taborin, J., & Fachner, J. (2013,

August). The development of evidence based music therapy for disorders of consciousness:

Comparing healthy neurophysiological responses to individuals in vegetative and minimally

conscious states. In M. Schutz, & F Russo, (Eds), Programme and Abstracts, Biennial

meeting of the Society for Music Perception and Cognition. Paper presented at the meeting

of the Society for Music Perception and Cognition (p. 104), Toronto, Canada: Ryerson

University.

Moore, K., Hanson-Abromeit, D., Magee, W.L., & O’Kelly, J. (2013, August). The theory,

practice, and measurement of music therapy: Developing evidence from diverse practice. In

M. Schutz, & F. Russo, F (Eds), Programme and Abstracts, Biennial Meeting of the Society


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for Music Perception and Cognition. Paper presented at the meeting of the Society for Music

Perception and Cognition August 8-11 (p. 104). Toronto, Canada: Ryerson University.

O'Kelly, J., Magee, W.L., James, L., Palaniappan, R., Taborin, J., & Fachner, J. (2013).

Music therapy applications for promoting arousal and emotional responses in those with

disorders of consciousness. Preliminary analysis of a neurophysiological and behavioural

study. In G. Luck, & O. Brabant, Programme and Abstracts, 3rd International Conference on

Music and Emotion. Paper presented at the 3rd International Conference on Music and

Emotion (p. 31). Jyväskylä, Finland: University Press, University of Jyväskylä.

O'Kelly, J1. (2013, June). A neurophysiological study of receptive music therapy with healthy

adults and individuals with disorders of consciousness: Implications for practice. Paper

presented at the Music Therapy Advances in Neuro-disability, Royal Hospital for Neuro-

disability, London.

O'Kelly J., Magee, W.L., James, L., Palaniappan, R., & Fachner, J. (2013, April). The

development of evidence based music therapy in the assessment and rehabilitation of those

with disorders of consciousness. Poster presented at the British Festival of Neuroscience,

Barbican, London.

O'Kelly, J., Magee, W.L., Palaniappan, R., & James, L. (2012). Preferred music and

entrained improvisation: A neurophysiological study. In K. Brabant, J. Johansson & J.

Fachner, (Eds.), Programme and Abstracts, 7th Nordic Music Therapy Congress. Paper

presented at the 7th Nordic Music Therapy Congress, Music Therapy Models, Methods and

Techniques (p. 34). Jyväskylä, Finland: University Press, University of Jyväskylä.

Other PhD Related Presentations O'Kelly, J. (2013, November) Music therapy with neurodisabilities and disorders of

consciousness: discoveries, challenges and opportunities. Paper presented at the University

of Roehampton Psychology Research Seminars. University of Roehampton, London.

O'Kelly, J., & Magee, W.L. (2013, June). Music therapy advances in neuro-disability:

International perspectives. Paper presented at the Royal Hospital for Neuro-disability Open

Lecture. Royal Hospital for Neurodisability, London.

1 Plenary speaker, Chair of Scientific Committee and conference organiser


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O'Kelly, J. (2012, November). Music therapy with disorders of consciousness: The search for

evidence. Paper presented at the International Symposium on Music Therapy and Disorders

of Consciousness, Elizabeth Seton Paediatric Center. Yonkers, New York.

O'Kelly, J. (2012, September). Music therapy applications for enhancing social relationships

for those with complex disabilities. Paper presented at Heading Forward Tyne and Wear

NHS Trust one day Conference, Newcastle.


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Table of Abbreviations Used

Analysis of Variance ANOVA

Autonomic Nervous System ANS

Ascending Reticular Activating System ARAS

Baseline Silence BLS

Coma Recovery Scale-Revised CRS-R

Disliked music DM

Disorder of Consciousness DOC

Electroencephalogram EEG

Entrained improvisation EI

Event Related Potential ERP

Evidence Based Medicine EBM

Functional Magnetic Resonance Imaging fMRI

Glasgow Coma Scale GCS

Heart rate HR

Heart rate variability HRV

Hi frequency HF

Liked/preferred music LM

Low Frequency LF

Music Therapy Assessment Tool for Awareness in Disorders of

Consciousness

MATADOC

Minimally Conscious State MCS

Physical Rehabilitation Medicine PRM

Positron Emission Tomography PET

Respiration rate RR

Royal Hospital for Neuro-disability RHN

Root mean square of successive differences RMSSD

Sensory Modality Assessment and Rehabilitation Technique SMART

Skin Conductance Level SCL

Spearman Rho rs

Traumatic Brain Injury TBI

Vegetative State VS

The Wessex Head Injury Matrix WHIM


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White noise WN

1. Introduction

In the care of those with disorders of consciousness (DOC), diagnosis, misdiagnosis and

treatment are critically important issues for clinicians, family members and of course the

individuals with DOC themselves (Andrews 2005). Assessment of awareness and

rehabilitation treatments are often confounded by ambiguous responses resulting from

fluctuating arousal levels, perceptual and motor impairments (Majerus, Bruno, Schnakers,

Giacino & Laureys, 2009). These issues are particularly critical for the nature and level of

care patients receive. In my experience of working within the UK healthcare system the

differences in treatment paths for those with a diagnosis of vegetative state (VS) who retain

sleep-wake cycles but lack awareness, and minimally conscious states (MCS), where some

form of awareness is observed, are significant. Individuals assessed as MCS may be entitled

to a high level of multidisciplinary input aimed at optimising their rehabilitation potential,

however for VS diagnoses, high dependency and a lack of adaptive capacity preclude such

input.

My case load as a music therapist over the last 13 years has included both ‘unresponsive’

palliative patients in the final stages of dying, and those with DOC who provide the focus of

this thesis. In both cases I have witnessed individuals appearing to be more responsive to

others and their environment when I performed their preferred music. This has led me to

question how and why music should be effective in engaging with these individuals where

other stimuli appear less effective. Music therapists have made claims with regard to

‘reaching’ or ‘contacting’ those with DOC (e.g., Aldridge, Gustorff, & Hannlich, 1990, Gustorff,

1995, 2002; Herkenrath, 2005). However, existing studies are based on small numbers, and

lack control measures or randomisation (e.g., Aldridge, Gustorff, & Hannlich, 1990; Ghiozzi,

2005). Thus, robust evidence-based explanations of why music therapy might be effective

are lacking, as are investigations as to which techniques might be most effective.


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Whilst my personal experience, the literature, and media stories2 involving music awakening

those in coma or DOC are compelling, there are no rigorous studies to counter the argument

that these ‘miraculous’ responses might simply be co-incidental, part of the patient’s natural

recovery, or unrelated to the nature of the music presented to them. It is also hard to avoid

the impression that music therapy is sometimes called upon here in a rather ad-hoc fashion,

with a type of ‘last resort’ rationale.

This study aims to systematically address the lack of evidence base underpinning music

therapy with those with DOC through a series of investigations within an evidence-based

framework.

2 A Google search using the terms 'music' 'coma' and 'recovery' produced 130,000 hits, with a wide range of newspaper articles reporting cases of individual 'brought out ' of coma through listening to their favourite music. Items such as a recent UK Guardian newspaper article “Robin Gibb stuns doctors by waking from coma” (Michaels 2012) rarely report any scientific explanation for such occurrences.


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2. Theoretical Framework

To contextualise the research reported in this thesis, it is important to outline the main

theoretical and professional models which inform the research environment of the study. The

following sections will outline concepts directly relating to DOC care such as ‘neuro-

rehabilitation’, and detail the most pertinent aspects of wider concepts such as

consciousness in relation to music therapy practice with DOC.

2.1 Neuro-rehabilitation The material for this thesis was collected from patients and staff within a neuro-rehabilitation

unit in the UK. Neuro-rehabilitation has been defined as: "an active and dynamic process by

which a disabled person is helped to acquire knowledge and skills in order to maximise

physical, psychological and social function" (Barnes, 1999, p. 929). In neuro-rehabilitation,

dynamic aspects of care are emphasised, as are the active involvement of the individual with

impairment, the family, multi-disciplinary teams and social services in the rehabilitation

process (Barnes, 1999). Two primary conceptual frameworks inform clinical work in neuro-

rehabilitation – ‘Evidence-Based Medicine’ (EBM), and the more eclectic approach of

‘Physical Rehabilitation Medicine’ (PRM).

2.2 Evidence Based Medicine EBM is defined by Sackett, Rosenberg, Haynes, and Richardson as “the conscientious,

explicit, and judicious use of current best evidence in making decisions about the care of

individual patients” (1996, p. 71). EBM bases practices primarily on evidence that purports to

separate science from other activities, such as those based on unsystematic or intuitive

methods (Kuhn, 1996).The framework broadly conforms to a positivist, epistemological

approach, which places importance on clinical interventions based on the latest rigorous

clinical research, ranking systematic reviews and randomised control trials at the top of a

hierarchy of evidence, followed by ‘lesser forms’ of evidence such as case studies (Sackett

et al., 1996).

Ruud (2005) outlines some of the core characteristics of the positivist, EBM approach which

may be advantageous for exploring and communicating about music therapy in the

EBM/PRM environment. For example, he details one of the important characteristics of

‘empirical positivism’ as reductionism whereby complex or generalizing statements such as ‘x

patient became more aroused’ need to be traced to more basic and objective observations


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such as ‘x’s heart rate increased by ‘y’ amount indicating an increase in arousal’. In this

sense, the descriptor ‘reductionist’ need not be seen as pejorative, more as an important

requirement for music therapy research and practice in this field, where communicating

meaningfully about clinical issues to a wider multidisciplinary audience is of paramount

importance.

Aside from clinical considerations, for modern neuro-rehabilitation providers, the importance

of basing clinical work on the best available evidence may be crucial in terms of receiving

funding from regional government agencies and referring general practices, who in the UK

make spending decisions partly based on the evidence-based rigour of care providers.

2.3 Physical Rehabilitation MedicineIn relation to neuro-disability, EBM has limitations in terms of its emphasis on randomized

control trials which, whilst ideally suited to pharmacological studies, are difficult to apply to

neuro-rehabilitation interventions. Such interventions are often ‘relearning’ techniques led by

a range of clinicians, sometimes collaboratively, in different settings (Homberg, 2005). In its

reliance on evidence from clinical trials and objective measures, EBM has also been

criticised by the phenomenological movement as ignoring the legitimate and important

aspects of the patient’s self-understanding and experience of illness (Goldenberg, 2006).

Similarly, Aldridge (1991) points out how the scientific foundations of modern medicine

ignore aspects of spirituality and notions of healing valued by patients and religious

traditions.

The Physical Rehabilitation Model (PRM) addresses some of the limitations of EBM by

acknowledging the complexity of disability, the interaction of one’s disability with personal

factors and the environment, and the need for interdisciplinary input to address this

complexity effectively (Stucki & Melvin, 2007). PRM has been defined as:

..the medical specialty that, based on the assessment of functioning and including the

diagnosis and treatment of health conditions, performs, applies and co-ordinates biomedical

and engineering and a wide range of other interventions with the goal of optimising

functioning of people experiencing or likely to experience disability. (Stucki & Melvin, 2007

p. 288)


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The role of the patient themselves is core to most rehabilitation models. Aims of interventions

need to be to be informed by a joint decision-making approach, thus patient-centeredness is

an important prerequisite of PRM (Gutenbrunner, Meyer, Melvin, & Stucki, 2011). However,

translating this philosophy to the care of those with DOC naturally poses challenges, given

the profound communication impairments typical with this population. Similarly PRM-

interventions may focus on aspects of quality of life, e.g., improvement in functions or

perception of wellbeing (Gutenbrunner et al., 2011). With DOC patients, who lack capacity

and communication skills, treatment decisions aimed at improving quality of life can only be

based on observable behaviours and symptoms, such as spasticity and excess saliva, and

measured by their success in addressing these symptoms, whereupon clinicians can only

make subjective assumptions regarding quality of life.

2.4 Music TherapyThere are a variety of music therapy definitions reflecting the range of perspectives existing

internationally. One authoritative definition from a neuro-rehabilitation framework proposed

by Magee is: "..a clinical intervention that can be defined as the planned and intentional use

of music to meet an individual’s social, psychological, physical and spiritual needs within an

evolving therapeutic relationship." (2002, p. 179). Whilst this definition does not exclude

social or spiritual concerns, it highlights the ‘planned and intentional’ use of the ‘intervention’

of music therapy. In other words, the definition can be seen as eclectic, through the inclusion

of evidence based thinking, without disregarding the holistic approach to patient care, where

interpersonal phenomena are acknowledged as core to effective practice.

A survey of all the literature on music therapy in neuro-rehabilitation as a whole is beyond the

scope of this thesis however; a comprehensive literature review of the field is available

elsewhere by Gilbertson (2005). Both the following section and Paper I will focus on a

discussion of the key music therapy approaches and rationales for music therapy with DOC.

2.5 ConsciousnessThere exists a wide range of contrasting epistemological and ontological perspectives as to

the nature of consciousness. However, given the focus of this thesis, it is appropriate to

focus on perspectives informing the music therapy literature, rather than an expansive outline

of the many philosophical and historical debates in this field. Here, the primary approaches

one finds may be summarised as 'humanist/music centred' and 'behavioural/pragmatic'.

These approaches are outlined below, and in more detail in Paper I of this thesis.


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2.5.1 The Humanist PerspectiveIn relation to music therapy with DOC, the humanist perspective postulates an elementary

consciousness common to all DOC, which Herkenwrath contrasts with more bio-medical

perspectives:

..are statements on orientation potentials, cortical processing of perception and adequate

reactions enough for a comprehensive description of human existence? The spirit, the self,

the ego of a man is more than neuronal activity, and human consciousness is so manifold

that it cannot be reduced to the functionality of the brain nerves. (2005, p. 158)

Core to humanist thinking is the concept of 'dualism', which refers to the two entities of the

mind ‘res cogitans’, or non-extended and thinking and, 'res entensa’, or relating to the body,

extended and physical (Descartes, 1641, translated in Descartes 1985). Dualist thinking

poses one of the enigmas of the study of consciousness which continues to be debated,

termed the ‘mind – brain’ problem. Essentially, the ‘problem’ centres on the difficulty we have

in relating the non-physical subjective phenomena of the mind to the objective physical

contents of the brain.

It is often challenging to explain in words what happens in music therapy, which to a great

extent comprises non-verbal phenomena such as musical and feeling states - an issue

described as the 'music therapist’s dilemma' (Ansdell, 1996, p.5). Furthermore, and

depending on one's personal or theoretical perspective, one may readily accept the

possibility of spiritual phenomena separate from the purely physical world, especially in

relation to 'peak' musical experiences. However, with perhaps the exception of palliative

settings, clinical or research discussions using dualist, metaphysical or humanist concepts

such as 'soul' or 'spirit' do not sit comfortably within an EBM/PRM framework.

2.5.2 The Behavioural/Pragmatic PerspectiveWith the rise of behaviourism in science, and the EBM framework which pervades modern

health care delivery, dualistic theory has largely been marginalised in favour of the view that

consciousness should be defined by brain function, mirrored by the structure of a set of

neural processes, and consequently, DOC by the lack of these functions and processes. This

thinking, variously referred to as ’positivist’, ’reductionist’, ‘materialist’ or ‘physicalist’, is

outlined in formalised approaches developed by behavioural psychologists Watson and

Skinner from the early 20th century onwards. Watson stressed the primacy of the relationship

between cognitive input and behavioural output over inner or subjective experiences,


11

providing the primary focus for a more scientific, psychological model of consciousness

(1913).

Through reviewing the literature, the term 'Behavioural/Pragmatic' was considered

appropriate to denote the shared perspective of the 'non humanist' music therapy literature in

this field. The term was given in view of the language and focus of the literature in which

EBM, behavioural concepts and pragmatic considerations inform the work, and a more

biomedical concept of consciousness is tacitly implied. For example, authors frequently

discuss music therapy practice in relation to 'interventions', 'operant conditioning techniques’,

or 'behavioural assessment', and other terms readily accepted within an EBM frame of

reference (e.g., Baker & Tamplin, 2006; Boyle & Greer, 1984; Boyle, 1994; Daveson, Magee,

Crewe, Beaumont, & Kenealy, 2007; Magee, 2005).

Within the neuroscience and neuro-psychological literature, we find the term consciousness

used in reference to a range of function and concepts, from basic processes such as

perception and attention, to less concrete concepts such as 'hope' or 'desire'. Three

meanings of consciousness have been delineated by Zeman:

(i) Consciousness as the waking state – comprising our ability to perceive, and interact with,

the environment purposefully

(ii) Consciousness as experience - the qualitative, subjective phenomena of experience

(iii) Consciousness as mind, or mental states with propositional content relating to hopes,

fears, and beliefs (2001, pp. 1265-6).

The first of these meanings will frame the majority of discussions of consciousness in this

thesis. This is not to deny all those with DOC the capacity for subjective experiences, hopes

or fears, as will be discussed in the following sections. However, given the complexity of

disability found with DOC, such concepts, often predicated on speech or movement for their

expression, challenge authentic representation by current assessment and research

methods.

2.5.3 Consciousness and Disorders of ConsciousnessOne of the first definitions of consciousness one may glean from a biomedical perspective is

found in lectures of the pioneering psychologist/physician and philosopher William James.

James described consciousness as predicated upon 'awareness of the self and the


12

environment' (James, 1902, cited in Hirschberg & Giacino, 2011, p. 774). Eighty years later,

Posner and Plum used virtually the same definition in their landmark publication 'The

diagnosis of stupor and coma’ as: “the state of awareness of the self and the environment”

(1982, p. 1). However, they also developed the concept of consciousness as comprising two

core characteristics: arousal (used synonymously with 'wakefulness’ in the literature) and

awareness, on which the differential diagnoses of MCS and VS hinge. In addition they

proposed the term 'persistent vegetative state' (PVS) to refer to a condition of wakefulness

without awareness. Over two decades later, the Multi-Society Task Force on PVS provided

greater clarification on the relationship between awareness and arousal, i.e., that

wakefulness may exist without awareness, but not the converse, and that VS represented a

wakeful state, but with a complete inability to experience or have awareness of the

environment (1994).

Evolving from the basic definition of Posner and Plum (1982), a definition of consciousness

which seems implicit in current DOC clinical work and research is provided by Giacino:

“consciousness refers to three basic elements: wakefulness, the capacity to detect and

perceptually encode interoceptive and exteroceptive stimuli, and the capacity to formulate

goal-directed behaviour” (1997, p.106). This definition informs the way consciousness is

clinically assessed with DOC, which usually comprises behavioural observation of a patient's

ability to perceive the external world and interact with it, through evaluation of voluntary,

purposeful, consistent and sustained responses to stimuli across the senses i.e., responses

to visual, auditory and tactile stimuli (Majerus, Gill-Thwaites, Andrews.K, & Laureys, 2005).

Observable behaviours such as 'goal-directed behaviour' are amenable to standardised

behavioural assessment, using a range of assessment tools detailed further on.

The differential diagnoses of VS and MCS will be outlined in detail later; however, before

appreciating current clinical practice in DOC assessment, it is useful to explore the range of

current thinking on consciousness, arousal and awareness in this field.

2.5.4 ArousalIn the medical model, the level of consciousness may be also described as the level of

arousal (Laureys, 2005), which is determined by the level of functioning in the sub-cortical

arousal systems in the brainstem, midbrain and thalamus, evidenced most clearly by the

opening of the eyes. Work in the 1940’s by Moruzzi and Magoun first highlighted the

involvement of a structure in the brainstem known as the ‘ascending reticular activating

system’ (ARAS), residing in part of the upper brain stem, in our sleep-wake cycles and


13

arousal levels. The ARAS was delineated as responsible for the transmission and modulation

of nerve impulses from the sense organs to areas of the brain such as the thalamus,

hypothalamus, and cortex (Moruzzi & Magoun, 1995). Our understanding of the ARAS has

progressed from a monolithic system limited to the ’reticular’ nuclei in the brain stem, to an

extended model where activating structures extend as far as the spinal cord, forebrain, and

cerebral hemisphere (Robbins, 1997, Zeman, 2001). It is also noteworthy that the ARAS is

implicated in a range of behaviour beyond wakefulness, such as mood, motivation, attention,

learning, memory and movement (Robbins, 1997).

Primitive arousal function is believed to provide the foundations for all motivated behavioural

responses, cognitive functions, and emotional expression (Pfaff, Ribeiro, Matthews, & Kow,

2008), and may be considered as a state of readiness to act, comprising responses to the

environment such as predictable reflexive reactions to stimuli (Cohen, 1993). However,

because of the multidimensional nature of arousal, it is a challenging construct to analyse

empirically (Robbins, 1997).

Parallel to our understanding of the ARAS has been the developing knowledge of

electrophysiological correlates of arousal, as measured from the scalp using

electroencephalogram (EEG) methods. As early as 1929, Hans Berger, the pioneer of EEG

recording, distinguished two different electrophysiological rhythms of wakefulness: ‘alpha’ at

8-13 Hz, which represented ‘passive EEG’ and ‘beta’ or ‘active EEG’ at 13 Hz <, which is

representative of 'mental exertion' (Berger, 1929, cited in Zeman, 2001). We are now aware

of additional rhythms including ‘theta’ (4-7 Hz) and ‘delta’ at 3.5 < Hz, which when

topographically widespread at higher amplitudes indicate reduced arousal in adults (Zeman,

2001). More details on EEG methods relevant to DOC research may be found in the

introduction and methods section of Paper III of this thesis (p. 3). With the addition of

positron emission tomography (PET) analysis, we are also able to differentiate different

levels of global cerebral glucose metabolism in these states. For example, deep sleep is

accompanied by a 20% fall in metabolism, particularly in the rostral brain stem, thalamus,

prefrontal and cingulate cortex (Hofle et al., 1997).

Arousal occurs across a continuum including none (i.e., coma, brain death), vegetative and

minimal, through to alert wakefulness (Demertzi, Laureys, & Boly, 2009). Individuals in coma

and DOC may be considered as being in a state of ‘hypoarousal', where the level of arousal

is insufficient to process incoming stimuli, and the brain is unable to distinguish relevant from

irrelevant information (Heilman, Schwartz, & Watson, 1978; Testa Flaada, 2011). A useful


14

graphical representation of the role of arousal in different DOC and levels of consciousness

is provided by Laureys (2005):

Figure 1: Relationship between Arousal and Consciousness

Reproduced from Laureys (2005) with permission

It is noteworthy that the relationship between arousal and consciousness is not a simple

linear one, i.e., increases in arousal do not necessarily equate to increased levels of

consciousness. Studies with healthy individuals have shown how in some circumstances,

increased arousal may cause a decrease in attention (Easterbrook, 1959; Cohen, 1993).

Baker draws our attention to traumatic brain injury (TBI) patients experiencing post-traumatic

amnesia, who may experience over-arousal (hyper-arousal), where an oversensitive filtering

system may reject both relevant and irrelevant information relating to stimuli (2001). Whilst

the relationship between arousal and awareness and attention with DOC has not yet been

fully established, it is likely there are optimal relationships between the components which

may be influenced by internal and external stimuli, or the lack thereof. This will be discussed

further on in relation to sensory stimulation programmes with DOC.


15

2.5.5 Awareness Arousal is considered as the essential pre-requisite for the second condition, awareness,

which has been related to the contents of consciousness (Giacino & Whyte, 2005).

Awareness has been described as comprising all subjective perceptions, feelings and

thoughts (Posner, 2008). It is considered by mainstream neuroscience as dependent upon

the functional capacity of the cerebral cortex to facilitate perceptual experiences (e.g.,

perceiving colours), bodily sensations in response to stimuli, moods (e.g., tiredness,

boredom) and phenomenal aspects with emotional reactions akin to 'self-awareness’ such as

regret or joy (Demertzi et al., 2009; Haugeland, 1985; Majerus et al., 2005). However, there

exists some debate as to the relationship between awareness, self-awareness and

consciousness, as the following section details.

2.5.6 Awareness or Consciousness?Providing a consensus definition of awareness is challenging, due to its synonymous use

with ‘consciousness’, which also lacks consensus definition in the literature (Aspen

Neurobehavioral Conference Workgroup, 1996). Moreover, a debate focuses on whether one

takes the view that to hear, see and feel, or otherwise experience something, denotes

consciousness, or if a more sophisticated self-awareness of these sensations is necessary.

Some authors suggest there is separation between the concepts of awareness and

consciousness. For example Tulving (1993) proposed consciousness as referring to the

basic ability to detect sensory events and the capacity for subjective experience, whereas

awareness included the specific utilisation of subjective experience through the interpretation

of perceptions, and directed acts defining the subjective experience. It seems the gradation

between consciousness and awareness is incorporated in the definition of consciousness by

Giacino noted previously, i.e., "wakefulness, the capacity to detect and perceptually encode

interoceptive and exteroceptive stimuli, and the capacity to formulate goal-directed

behaviour" (1997, p.106).

The above conceptual differences naturally have implications for how behaviours and

neurophysiolgical responses of VS patients to environmental and other stimuli are

interpreted. Added to this, there exists a range of opinions as to how much of the cerebral

cortex is required for awareness, self-awareness, and, by implication, consciousness to

function.

An argument for acknowledging consciousness at the basic level of sensing is proposed by

Merker (2007) in a review of studies supporting this view. He cites animal and human studies

which have utilised local brain stimulation of sub-cortical regions by means of depth


16

electrodes to find ‘coherent' behavioural responses such as orienting or defensive

behaviours occurring, despite the lack of higher-cortical connectivity (e.g., Brandao,

Anseloni, Pandossio, de Araujo, & Castilho, 1999; Holstege & Georgiadis, 2004; Schuller &

Radtke-Schuller, 1990). Merker also highlights the case of children born with

hydranencephaly, often caused by a stroke of the foetal brain, where areas including the

cerebral cortex, thalamus and basal ganglia are massively compromised, leaving skull

cavities filled with cerebrospinal fluid. Despite the absence of the network of cortical

connections an integrated model of consciousness would imply, there appeared a variety of

behaviours which he felt could only be described as conscious in these individuals. For

example, from spending time with hydroencephalitic children, and reviewing 26,000 emails

from family carers, Merker could report that the children were able to "show responsiveness

to their surroundings in the form of emotional or orienting reactions to environmental events,

most readily to sounds", "express pleasure by smiling and laughter", and "show preferences

for certain situations and stimuli over others, such as a specific familiar toy, tune, or video

program" (2007, p. 79).

It is apparent from mainstream neuroscience and neurology literature that the above, more

primal, level of functioning is not universally accepted as denoting consciousness. For

example Damasio (2010) believes consciousness only begins when the “self comes to mind”.

He might segregate the behaviour described by Merker as indicative of the ‘protoself’, the

first necessary stage in the functioning of full consciousness in humans. He describes the

‘protoself’ as involved in "the generation of primordial feelings, the elementary feelings of

existence", which needs two higher states to develop into full consciousness. These states

comprise the ‘core self’, which "unfolds in a sequence of images that describe an object

engaging the protoself including its primordial feelings", and the "autobiographical self

defined in terms of biographical knowledge pertaining to the past as well as the anticipated

future" (2007, pp. 22-23).

From a contemporary neuro-scientific perspective, consciousness has been described by

Laureys and Schiff as an "emergent property of the collective behaviour of widespread

frontoparietal network connectivity modulated by specific forebrain circuit mechanisms"

(2012, p.478). Modern cerebral activation studies using positron emission tomography (PET)

and functional magnetic resonance imaging (fMRI) are providing us with important

information regarding consciousness. Through studies of patients in VS we are able to see

how the connectivity has broken down between areas of the brain which were normally


17

interconnected, particularly between the primary cortical areas and multimodal associated

areas e.g., the pre-motor and prefrontal areas (Laureys, Owen, & Schiff, 2004).

In summary, consciousness, as it is conceptualised in current DOC research and clinical

literature, is considered to comprise arousal, which relates to the level of consciousness, and

awareness, which relates to the contents of consciousness. Whilst arousal is a

multidimensional concept with no agreed unitary measure, the mainstream clinical concept of

consciousness requires evidence of functional, goal directed, behaviour. However,

consciousness is a concept with a range of perspectives in relation to its nature in DOC and

relationship with awareness and self awareness. These conceptual issues are important to

bear in mind in relation to consensus DOC diagnostic criteria detailed in the following

sections.

2.6 Diagnostic Criteria

2.6.1 ComaComa may be considered as the total loss of consciousness, where there is a “total absence

of awareness of self and environment even when externally stimulated” (Posner & Plum,

1982), and where patients do not open their eyes, obey commands or utter any

understandable words (Ponsford, Sloan, & Snow, 2013). This study will not feature work with

patients in coma, although there does exist a tradition of music therapy input with individuals

described as in ‘coma’ (e.g., Aldridge et al., 1990; Ghiozzi, 2005; Gustorff, 1995; Gustorff,

2002; Tamplin, 2000). As discussed in Paper I, it is not always clear from the literature

whether subjects are actually in VS or MCS or coma as defined here.

2.6.2 Locked-in Syndrome As with coma, this study will not detail work with 'locked-in' patients, who also fall outside the

boundaries of DOC. The syndrome, typically caused by lesions in the lower brain and brain

stem known as the ventral pontines, is characterised by quadriplegia and anarthria, but with

a preservation of full consciousness and cognitive skills, including an awareness of self and

one’s impairments. Communication may be facilitated via vertical eye movements and

blinking (Leon-Carrion, Van, Dominguez-Morales, & Perez-Santamaria, 2002; Smith &

Delargy, 2005). Given the focus of this study, it is noteworthy that locked in syndrome may

be erroneously assessed as VS, due to the lack of behavioural responses to the environment

common to both conditions. Because of the range of challenges to accurate assessment of


18

awareness, the time taken to diagnose, and thus to differentiate the condition from VS, may

take from an average of 2.5 months to 4-6 years in the extreme (Majerus et al., 2005).

2.6.3 Vegetative State (VS)VS may be differentiated from coma primarily by the complete lack of arousal function in the

latter, and the partial or full preservation of sleep-wake cycles, autonomic and brain stem

function, and sub-cortical reflexes found in VS. Current medical diagnoses of VS and MCS

are guided by the nosological criteria agreed by the Aspen Neurobehavioural Conference

Workgroup set up to address the inconsistent and even contradictory literature in the field

(1996). The Workgroup, or 'Multi-Society Task Force’, comprised international experts from

bioethics, neurology, neuro-psychology, neurosurgery, nursing, physical medicine and

rehabilitation, who reviewed and discussed the literature on DOC in relation to their clinical

experience, reaching consensus statements regarding the diagnosis and prognosis of the

conditions. The definition of VS provided by the group is: “a condition in which awareness of

self and the environment is presumed to be absent and there is an inability to interact with

others, although the capacity for spontaneous or stimulus-induced arousal (i.e., wakefulness)

is preserved” (p. 7).

Further diagnostic criteria agreed by the Task Force included:

No evidence of sustained, reproducible, purposeful, or voluntary behavioural

responses to visual, auditory, tactile, or noxious stimuli;

No evidence of language comprehension or expression;

Intermittent wakefulness manifested by the preservation of sleep-wake cycles;

Sufficiently preserved hypothalamic and brainstem autonomic functions to permit

survival with medical and nursing care.

The poorest prognosis in VS has been observed for those with post traumatic VS, in

particular those with non-traumatic etiologies (Georgiopoulos et al., 2010). Where individuals

have been assessed as in VS for more than one year, a further classification of ‘persistent

vegetative state’ (PVS) has been used widely, given the perceived low probability of the

recovery of consciousness after this period. However, the use of the prefix 'persistent' or

'permanent' with VS is not currently advocated, as this depiction of the condition suggests


19

irreversibility. Instead, a description of the cause and length of time is recommended (i.e.,

‘traumatic VS for 4 months’) (Giacino et al., 1997).

The ‘irreversibility’ of PVS has been challenged by the evidence of unexpected recovery and

the purported effects of various interventions. For example, recent studies illustrate the

possibility of late recovery after four months (Andrews, 1993) or one year (Childs & Mercer,

1996), where patients have received cranioplasty and long-term rehabilitation programmes

(Sancisi et al., 2009), or received intrathecal baclofen administration (Sara et al., 2007).

Furthermore, where patients diagnosed as PVS have been given electrophysiological

monitoring (Faran et al., 2006), or more sophisticated brain scanning interventions such as

fMRI (Monti et al., 2010; Owen et al., 2007; Owen, Schiff, & Laureys, 2009), evidence of

consciousness has been indicated, contradicting the findings of purely behavioural

assessments.

The neuropathology of VS has been explored through both post mortem and scanning

techniques. A post mortem study by Adams, Graham and Jennet (2000) of 49 patients who

were in VS due to acute brain insult, revealed 71% had a structure of diffuse axonal injury,

where the thalamus was abnormal in 28 of these cases, with abnormal thalamus in 96% of

cases surviving over three months, a finding supported by a later study by Jennett, Adams,

Murray and Graham, (2001). Laureys, Owen, & Schiff (2004) reviewed studies of cerebral

metabolism in VS to conclude overall cortical metabolism is 40–50% of the normal range of

values.

Laureys, Perrin, Schnakers, Boly and Majerus’ review of functional connectivity studies

highlighted the existence of residual cortical activity in VS patients, but suggested this was

normally restricted to a 'low-level' without 'higher-order' integration, which they considered as

necessary for conscious perception (2005, p. 727). Contrasting levels of sophistication

between MCS and VS are particularly noted for auditory processing. However, more positive

suggestions as to the sophistication of cortical processing in VS are available, for example

studies point to isolated fragments of intact behavioural responses (Schiff et al., 2002),

semantic processing, learning processes (Kotchoubey, 2005, 2006) and a range of

contrasting 'arousal profiles' observable in response to multi-modal stimulation

(Wilson, Brock, Powell, Thwaites & Elliott, 1996). More details on these contrasting views

are provided in Paper I (pp. 95-97).


20

There is a lack of consensus as to whether patients in VS experience pain. In studying

responses to noxious stimuli (electrical stimulation of the median nerve), Boly et al. echo

Laureys et al. (2005) in regard to a 'disconnection' for pain perception, where: "functional

connectivity analysis showed extended functional disconnections between primary

somatosensory cortex and fronto-parietal association cortices in VS patients compared to

controls" (2005, p. 287). However, Kassubek et al. found a “residual cortical pain processing

matrix” in seven PVS patients of hypoxic origin, which might point to some pain perception,

although in the absence of behavioural evidence the authors admit this can only be a

hypothetical interpretation (2003, p. 91). Further support for the possibility of pain perception

(alongside other high level processing) in some patients diagnosed as in VS may be drawn

from Celesia’s recent review of neuroimaging studies of nociceptive or emotional affective

stimuli. The study reported 35% of VS research subjects had activation of primary sensory

cortices and higher-order associative areas, and 5% activation of cortical regions associated

with mental imagery or high-level language stimuli such as decoding ambiguous phrases

(2013).

Panksepp, Fuchs, Abella Garcia and Lesiak, (2007) suggest a distinction between ‘affective

consciousness’ and ‘cognitive consciousness’ (p. 7) may be observed in those in those they

describe as PVS, noting how these patients may have preserved mechanisms of thirst and

hunger. They suggest that instinctual emotional reactions, or pain ‘reflexes’ observed in PVS

patients may represent some form of ‘mentality’, with or without cognitive awareness. Using

a functional evolutionary perspective, and resonating with Merker’s observations noted

previously, Panksepp et al. believe evidence of ‘primary–process affective states’ may be

observed in the activation of medial and ventral brain regions associated with ancient

affective forms of consciousness, established before organisms were afforded the capacity

for reflection on one’s experiences. By extension, they afford the possibility that VS patients

are capable of experiencing forms of suffering.

The heterogeneity of pathology in VS should guide us in resisting any generalised

statements on pain, or indeed other types of processing, be they perceptual, emotional or

cognitive. This, coupled with the previously noted likelihood of misdiagnosis, and potential

for late recovery in VS patients, illustrates the need for an open mind on their capacity for

sensory perception, and consequently the wider field of cognition, awareness and

consciousness. This sentiment is perhaps tacitly supported by the lack of the term

‘consciousness’ in authoritative definitions of VS (Multi Society Task Force, 1994; Aspen

Neurobehavioral Conference Workgroup, 1996). Given the subtlety of behavioural indications


21

of awareness, and the complexity of the condition, skilled and frequently prolonged

assessment by multidisciplinary teams capable of closely monitoring VS patients’ medical

needs, and being watchful for any signs of awareness, is crucial (Andrews 2005). Repeated

and reliable assessment and longer term follow-up by individuals with inter-disciplinary skills

is also advised (Wilson, Harpur, Watson, & Morrow, 2002). Giacino et al. (2002) recommend

the use of a range of different assessment tools to elicit responses with a range of different

stimuli, which is supported by the findings of Paper II (pp. 293-297). Most importantly, VS

patients require a high quality of nursing care to prevent avoidable complications such as

pressure wounds and infections in their dependent state.

2.6.4 Minimally Conscious State (MCS)The Aspen Workgroup defined MCS as: “a condition of severely altered consciousness in

which minimal but definite behavioural evidence of self or environmental awareness is

demonstrated” (1996, p. 13). In contrast to coma and VS diagnosis, those in MCS display

behavioural signs of awareness, which, though often inconsistent, may be differentiated from

reflex or spontaneous behaviours. The definition, first formally published by Giacino et al.

(2002), evolved from the previous classification of ‘minimally responsive state’ (American

Congress of Rehabilitation Medicine, 1995) as it was considered this term did not sufficiently

differentiate the population from those in VS. The description of the condition by the Aspen

Workgroup details a diagnosis which must include evidence of one or more of the following

behaviours:

Simple command following;

Gestured or verbal yes/no responses;

Intelligible verbalisation;

Movements or affective behaviours that occur in contingent relation to environmental

stimuli and are not attributable to reflexive activity. Any of the following examples

provides sufficient evidence for contingent behavioural responses:

I. Episodes of crying, smiling, or laughing in response to the linguistic content of

comments or questions;

II. Vocalizations or gestures that occur in direct response to the linguistic content of

questions;

III. Reaching for objects that demonstrates a clear relationship between object location

and direction of reach;


22

IV. Touching or holding objects in a manner that accommodates the size and shape of

the object;

V. Pursuit eye movement or sustained fixation that occurs in direct response to moving

or salient stimuli;

VI. Ambulation or wheelchair propulsion with avoidance of environmental obstacles

(Aspen Neurobehavioral Conference Workgroup 1996, p. 14)

Although in MCS some cognitive ability is evident, patients are similar to those in VS with

regard to their inability to take part in meaningful activities of daily living. In contrast,

however, the evidence of awareness and cognitive ability in MCS indicates the need for

interdisciplinary rehabilitation. These efforts tend to be directed towards enhancing adaptive

learning and stimulating axonal growth and neuro-plasticity (Lancioni et al., 2010; Schiff,

2005). However, despite a wide range of interventions currently utilised in this endeavour,

there is little evidence yet to show any treatments which can improve functional outcomes

(Giacino & Whyte, 2005).

In terms of neuro-pathology, the previously noted study by Jennet et al. (2001) found diffuse

axonal injury slightly less common in MCS than VS patients (42%:50%), and thalamic lesions

significantly less common in MCS compared to VS (50%:80%). Laureys et al. (2004) also

report a greater spread of cortical activation to stimuli in MCS compared to VS. Significantly,

in relation to the focus of this study, the authors found that auditory stimuli with emotional

valence (infant cries and the patient's own name) stimulated widespread activation compared

to meaningless noise, to a level comparable to healthy controls. Analysis of cortical

electrophysiological data from EEG recording also highlighted cognitive potentials showing

preserved auditory (P300) responses to the patient's own name.

As with VS, there exists considerable heterogeneity within MCS, leading Bruno,

Vanhaudenhuyse, Thibaut, Moonen, and Laureys to establish criteria for the 'grey areas'

between VS and MCS, with the categories of 'MCS+' where behaviours such as command

following and verbal and gestural yes/no responses exist, and 'MCS -' where less

sophisticated responses occur, such as visual pursuit or contingent behaviours to emotional

stimuli e.g., smiling when presented with appropriate stimuli (2011). MCS is described as

transitioning into higher levels of consciousness once the individual is consistently able to

reliably and consistently participate in interactive communication such as verbalisation,

yes/no signals, or functional object use requiring the discrimination and appropriate use of at

least two common articles (e.g., a comb or mug) (Giacino & Whyte, 2005).


23

2.7 Assessment of DOCThe differential diagnoses of VS and MCS have significant implications on the nature of on-

going care a patient receives, with the potential for the ’warehousing of patients’ (Fins, Schiff,

& Foley, 2007) when no rehabilitative capacity is assumed. Distinguishing between VS and

MCS is crucial for decisions regarding treatment, prognosis, resource allocation and medico-

legal judgments (Andrews, 1998; Giacino et al., 2002). Fortunately, the field of assessment

and diagnosis is evolving as a result of the developments in brain scanning, and the on-going

refinement of behavioural assessment tools guiding assessment, diagnosis and treatment.

2.7.1 Music Therapy and DOC AssessmentMusic has played an important role in every culture since antiquity, and a relationship

between music and medicine has been postulated to date back to Palaeolithic times (West,

2000). More recently (as will be detailed further on), an assessment tool to support DOC

diagnosis and guide the clinical work of music therapists has been developed and

standardised known as the ‘Music Therapy Assessment Tool for Awareness in Disorders of

Consciousness ’ or 'MATADOC' (Magee, Siegert, Lenton-Smith, Daveson, & Taylor, 2013).

However, as Paper I details (p. 95), despite its documented use for over thirty years, there

exists very little empirical evidence to directly support music therapy in assessment or

rehabilitation work with DOC. Indeed, it is precisely this lack of evidence which has provided

the impetus and motivation for this thesis. Thus, the rationale for using music and music

therapy in the assessment of DOC is explored in Paper I (pp. 98-99), with new evidence to

support music therapy in this field provided in Papers II and III.

In the context of discussing other means of assessment with DOC, and to understand why

music should be any more effective than other stimuli in supporting DOC assessment, a brief

survey of some of the relevant research into human processing of music is useful here.

Beyond stimulating the auditory pathway, music has been shown to influence physiological

states in terms of affecting cerebral blood flow (Bernardi, Porta, & Sleight, 2006; Blood &

Zatorre, 2001; Evers, Dannert, Rodding, Rotter, & Ringelstein,1999) and inducing

psychophysiological responses such as: changes in blood pressure (Bernardi et al., 2006;

Khalfa et al., 2008; Krumhansl, 1997) , heart rate (Bernardi et al., 2006; Blood & Zatorre,

2001; Khalfa et al., 2008; Krumhansl, 1997; Roy, Mailhot, Gosselin, Paquette, & Peretz,

2009), respiration rate changes (Bernardi et al., 2006; Blood & Zatorre, 2001; Khalfa et al.,

2008; Krumhansl, 1997), and electrodermal responses (Koelsch, 2005; Krumhansl, 1997).


24

There is some debate as to what extent responses of the autonomic nervous system (ANS)

to music are unconsciously entrained to the tempo of music listened to, or are more related

to conscious functioning, i.e., emotional responses, particularly in relation to respiration rate

(RR). A range of papers implicate RR increases with unconscious entrainment to musical

tempo, or the 'bottom up' process of 'tempo entrainment' (Bernardi et al., 2006; Etzel,

Johnsen, Dickerson, Tranel, & Adolphs, 2006; Gomez & Danuser, 2007; Khalfa et al., 2008).

In contrast, RR increases have been related to more cortically mediated, emotional, or 'top

down' processes. Salimpoor, Benovoy, Longo, Cooperstock, and Zatorre (2009) studied ANS

responses in 217 individuals to music rated as pleasurable by the subjects. After accounting

for musical structural elements such as tempo, the authors were able to attribute increases in

skin conductance level, heart rate (HR) and RR more to 'top down' processes associated

with pleasurable and rewarding experiences.

In relation to DOC assessment, ANS responses to musical stimuli may provide crucial

prognostic information. For example, Wijnen, Heutink, van Boxtel, Eilander, and de Gelder

(2006) illustrated that heightened sympathetic, or arousal responses to multimodal

stimulation correspond to the recovery of consciousness in DOC. Furthermore, Riganello,

Candelieri, Quintieri, Conforti, and Dolce (2010) have identified a frequency parameter of

heart rate variability, namely the ‘normalised low frequency’, which may correspond to

residual emotional reactions to music (symphonic compositions of varying complexity)

through comparison with responses of healthy controls.

Listening to music causes widespread cortical activity in limbic and paralimbic cerebral

structures thought to be involved in reward/motivation, emotion, and arousal, such as the

amygdala, orbitofrontal cortex, ventral striatum, hippocampus, parahippocampal gyrus,

temporal poles, insula midbrain and ventral medial prefrontal cortex (Blood & Zatorre, 2001;

Koelsch, 2005). Studies have also suggested that music provides positive influences on

cognitive functioning (Rickard, Toukhsati, & Field, 2005), particularly in the elderly

(Mammarella, Fairfield, & Cornoldi, 2007). The positive effect induced by ‘happy music’ may

increase semantic access and the breadth of attentional selection in healthy individuals

(Rowe, Hirsh, & Anderson, 2007), and decrease visual neglect in neurological patients (Soto

et al., 2009). Neocortical responses to music may also activate higher functions such as

sensory perception, motor commands, conscious thought and language (Koelsch, 2005;

Peretz, 2002). In relation to music and DOC assessment, Jones, Vaz Pato, Sprague, Stokes

and Haque (2000) found preservation of auditory evoked potentials relating to complex tones

could establish discriminative hearing in patients with severe brain injury, whose ability to


25

communicate was negated by severe motor disability, although the authors felt this

insufficient to suggest conscious awareness on its own.

In summary, the non-verbal, emotionally powerful and personal qualities of music, combined

with its ability to activate widespread cortical activity indicate music therapy may provide a

unique contribution to assessment of DOC. This contribution may be made possible by the

ability of certain musical stimuli to support arousal to optimise conditions for assessment of

awareness, and the potential of music to elicit intact emotional, memory or other processing

through its dynamic effects. However, as Paper I details, there is a need to support the

clinical applications of music therapy assessment and rehabilitation for those with DOC with

more empirical, scientific research drawing on recent advances in 'music neuroscience' and

neuroimaging technologies.

2.7.2 Neuroimaging and DOC Assessment The lack of defining pathological markers of VS or MCS poses various challenges for

clinicians. Clinical assessment must be informed by presenting behaviour and clinical history.

Herein lies a core factor contributing to misdiagnosis rates, i.e., the fallibility of clinicians in

determining whether behavioural responses, often inconsistent, incomplete or unclear,

represent conscious or unconscious behaviour (Coleman, Bekinschtein, Monti, Owen, &

Pickard, 2009; Gill-Thwaites & Munday, 1997). Behavioural responses to commands are

frequently masked by brain damage causing expressive or receptive aphasia (Majerus et al.,

2009), or combinations of brain and physical injury limiting patients’ motor responses.

Reflexive responses to stimuli such as sudden noise may also contribute to misdiagnosis

(Magee, 2007). For these reasons multimodal approaches are advocated by leading

authorities in the field, where magnetoencephalography (MEG), EEG, positron emission

tomography (PET) and functional magnetic resonance imaging (fMRI) methods may reveal

activation of brain regions indicative of conscious, cognitive processing and volition in

relation to verbal commands, or selective attention in 'odd ball' experiments.

Detailing the plethora of studies using neuroimaging methods to reveal conscious behaviours

with DOC is beyond the scope of this thesis (for reviews see Laureys & Schiff, 2012 &

Celesia, 2013). A study by Monti et al. is typical, which revealed the case of an individual

able to display evidence of imagining playing tennis and walking round her house, through

activation of the supplementary motor area similar to healthy levels. This led the authors to

claim we may detect covert wilful or voluntary responses, without the need for observation of

behavioural responses such as speech or movement (2010).


26

The interpretation of neuro-imaging data in this way is not without its critics. For example, by

exploring the underlying assumptions of several fMRI active and passive paradigm studies,

Nachev and Hacker suggest the claims of detecting ‘covert consciousness’ in such a

manner, is: “not supported by the extant data because it relies on critical assumptions,

obscured by conceptual unclarities, that are either untested or untestable” (2010, p. 68). The

authors list a range of inconsistencies in studies claiming to reveal covert consciousness

using fMRI paradigms. For example, they suggest that many studies are guilty of “affirming

the consequent” by assuming contrasting neural activity seen concurrently with different

commands ('imagine playing tennis' versus 'walking round your house') in both healthy and

PVS subjects, should necessarily directly relate to distinct corresponding relationships. They

point out that the converse, i.e., that all neural activity in a certain area must relate directly to

the same mental activity, has not been demonstrated by the authors, and that brain

activation may simply represent automatic responses to the presented narrative. Turner-

Stokes et al. also point out that as many as one in five healthy individuals are unable to

generate fMRI activity on motor imagery tasks, which questions the validity of assumptions

made regarding 'negative' results in such studies. Furthermore they highlight that fMRI

methods require that patients are able to lie still, and are without metallic implants such as

shunts, limiting their applicability to significant numbers of DOC patients (2012).

2.7.3 Behavioural Assessment of DOCThe principal tools used in the behavioural assessment of DOC include the Coma Recovery

Scale-Revised (CRS-R) (Giacino & Kalmar, 2006), the Sensory Modality Assessment and

Rehabilitation Technique (SMART) (Gill-Thwaites, 1997; Gill-Thwaites & Munday, 2004), the

Western Neuro Sensory Stimulation Profile (WNSSP) (Ansell & Keenan, 1989), the Wessex

Head Injury Matrix (WHIM) (Shiel et al., 2000) and the Glasgow Coma Scale (GCS)

(Teasdale & Jennett,1974).

A recent systematic review of behavioural assessment scales used with DOC concluded that

the CRS-R performed best in terms of content validity and inclusiveness of the Aspen

Workgroup criteria for DOC (1996), and was to be used with ‘minor reservations’ of the

authors, with the SMART and WHIM receiving a verdict of use with ‘moderate reservations’

(Seel et al., 2010). Given the contrasting strengths of the tools, and heterogeneity of the

DOC population it is recommended that a combination of different tools should be used in

assessment (Giacino et al., 2002).


27

A detailed account of each of these tools is beyond the remit of this paper; however SMART,

the CRS-R and the recently standardised ‘Music Therapy Assessment Tool for Awareness in

Disorders of Consciousness ’ or 'MATADOC' (Magee et al., 2013) will receive further

attention in the three papers of this thesis. A core component of assessment scales used

with DOC such as the SMART, WNSSP and MATADOC is the use of sensory stimulation to

promote contingent behavioural responses indicative of awareness. Sensory stimulation has

also been adopted in DOC rehabilitation, but with limited success to date, as the following

sections detail.

2.8 Sensory Stimulation and Regulation The brain processes sensory information using a complex network of systems which we are

still learning about. In simple terms, the core areas involved are (i) the ARAS, (ii) the

thalamus and (iii) the frontal cortex (Wood, 1991). Stimuli modulated in these areas may elicit

behavioural responses to an individual's environment, which may indicate that the individual

can perceive and start processing external stimuli. Interventions using stimuli in this way may

also enhance the recovery process by optimising the patient’s receptivity to rehabilitation

input. Treatments designed for accelerating recovery from coma or DOC have been

categorised as: pharmaceutical, physical management interventions, deep brain stimulation,

hyperbaric oxygen therapy and sensory stimulation or regulation (Giacino, & Whyte 2005).

Patients’ responses to these interventions may be crucial in identifying those with the

potential for adaptive behaviour capable of facilitating communication and other functional

gains. The use of music and music therapy with DOC may be viewed as related to wider

approaches advocating either sensory stimulation or sensory regulation to aid diagnosis or

raise levels of consciousness to promote adaptive behaviour to optimise rehabilitation

potential.

Sensory stimulation and regulation interventions have evolved due to the value placed by

health care providers on the importance of encouraging the transition from coma to more

aroused DOC as soon as possible. In 2000, Tamplin reviewed the extant literature in this

area to summarise the three reasons for this rationale:

(i) medical: the longer and more deep a coma, the poorer prognosis for the patient

(ii) humanitarian: early awakening from coma may ameliorate anxiety levels for both patient

and family


28

(iii) economic: those in coma require more financial resources (2000, p. 39)

To contextualise the use of music therapy with DOC it will be useful to summarise the

different approaches of sensory stimulation and sensory regulation, as various concepts

relevant to music therapy have evolved alongside the development of these approaches. A

shorter summary of these approaches may be found in Paper I, p. 95.

2.8.1 Sensory StimulationAnecdotal accounts of patients recovering from coma after exposure to familiar objects and

relatives’ voices led to the more systematic use of stimulation to aid this process either

continuously (e.g., with TV or radio), in the environment (e.g., with relatives’ pictures and

familiar objects), or intermittently with tactile, visual or meaningful auditory stimulation. One

rationale for this approach was provided by LeWinn and Dimancescu (1978), who highlighted

both the negative effects on brain activity of sensory deprivation, and positive effects of

enriched environments, drawing on work by Galbraith Jennert and Raismanon synaptic

innervations in rats (1978). The argument followed that the more environmental stimulation

one provided patients with, the greater their potential for recovery. This logic provides an

early example of clinicians attempting to encourage neuroplasticity, a concept which will be

discussed later in the thesis.

The logic of the sensory stimulation approach was adopted in a study on ‘coma arousal’ by

Doman, Dimancescu, Wilkinson and Pelligra (1993), who utilised ‘intense multisensory

stimulation’ hourly for 15-20 minutes. Although his treatment group (n: 200) had 69 patients

making a ‘good’ (n: 37) or ‘moderate’ (n: 32) recovery compared to the age/sex matched

control group where no patients recovered, the findings are questionable given the

differential size of the control group (n: 33). A similar study by Mitchell, Bradley, Welch and

Britton (1990), trained family members to provide daily 'vigorous' multimodal sensory

stimulation at regular intervals, recording that for those in the intervention group (n: 12)

duration of coma was significantly shorter than for controls (n: 12). Again, given the size of

the samples, this conclusion needs to be viewed with caution.

2.8.2 Sensory RegulationWood (1991) provides a compelling and influential critique of sensory stimulation

programmes based on major flaws he observed in their rationale. He noted through clinical

experience how patients exposed to “an undifferentiated bombardment of sensory

information” lost the ability to process information through a process of habituation to


29

background noise (p. 404). Wood proposed a new approach of ‘sensory regulation’ which

focused on optimising appropriate conditions for awareness rather than simply increasing

arousal in the hope of recovering consciousness, noting that standard assessment tools

focus on measures of awareness, rather than arousal. Rather than adopting sensory

stimulation for the purposes of activating the ARAS to arouse the cortex, he argued for

greater sensitivity and focus on achieving the appropriate level of arousal to maintain what

Luria (1979), described as 'cortical tone' predating the mechanism now ascribed for

supporting 'sustained attention' by Warm, Parasuraman, and Matthews (2008).

Posner has further developed a conceptualisation of attention as comprising three networks

involved in (i) functions of obtaining and maintaining the alert state (alerting network), (ii)

orienting to sensory events (orienting or posterior network), and (iii) regulating thoughts and

behaviours (executive, or anterior network) (2008; Posner & Petersen, 1990). The alerting

network is particularly relevant to DOC and the concept of sensory regulation, comprising

two processes: (i) tonic, or the sustained activation over time, and (ii) phasic, or the non-

specific activation caused by a warning signal prior to a target of attention (Callejas,

Lupianez, Funes, & Tudela, 2005). In a series of experiments, Callejas et al. (2005) have

indicated that the relationships between these networks dictate the nature and efficiency of

attention, indicating, for example, that the alerting network enhances the orienting network by

increasing its speed of functioning, but the alerting network may also inhibit the executive

network.

As noted previously, it is likely that there is an optimum level of arousal to facilitate

awareness and attention, and that ‘over stimulation’ or ‘over arousal’ may prove

counterproductive in maintaining awareness. A landmark paper by Yerkes and Dobson

(1908) postulated that medium levels of arousal are associated with optimal performance,

where the relationship between arousal and behavioural performance is curvilinear, (e.g., an

inverted ‘U’ shape depending on the difficulty of the task). In this relationship, the upward

part of the inverted U represents the energizing effect of arousal, and the downward part is

explained by negative effects of arousal (or stress) on cognitive processes like attention,

memory, and problem-solving. However, whilst there has been further research exploring

examples, mechanisms, and explanatory models of this relationship (e.g., Calabrese, 2008a;

Calabrese, 2008b; Diamond, Campbell, Park, Halonen, & Zoladz, 2007) a definitive

explanation of the correlation has not been established, and it is unclear how relevant these

models are for DOC given the level and heterogeneity of cortical damage found in this

population. Interestingly for this study, musically induced arousal in individuals with visual


30

neglect has been shown to enhance attention, in terms of facilitating decision-level

processes (Soto et al., 2009).

Wood encouraged clinicians to be aware of habituation where responses might decrease

following stimulus repetition (Thompson & Spencer, 1966, as cited in Wood, 1991) when

using sensory stimulation with DOC. He observed studies illustrating how patients’ rate of

stimulus recognition decreased under prolonged stimulation, and that background activity

can habituate neural responses away from selective attention (Mackworth, 1968 cited in

Wood, 1991).

Wood concluded that clinicians should consider all interventions, be they personal care, or

passive range of movement exercises, as stimuli. In order for interventions to target vigilance

and attention he advocated that: “the delivery of any stimuli needs to be carefully regulated in

terms of its intensity, frequency, inter-stimulus intervals, duration and target to noise levels”

(1991, p.408).

Whilst most of the studies cited by Wood (1991) were based on healthy subjects, there has

been little subsequent research with DOC to counter the logic of sensory regulation, which is

referred to frequently in guidelines for the care of DOC patients (e.g., Gray, 2000; Lombardi,

Taricco, De Tanti, Telaro, & Liberati, 2002; Wilson, Powell, Brock, & Thwaites, 1996;

Tamplin, 2000). However, this remains a poorly understood field. In 2002, efficacy studies of

sensory stimulation and regulation interventions were evaluated in a Cochrane systematic

review, which concluded that they were of poor methodological quality, and the range of

outcome measures precluded the possibility of quantitative meta-analysis. Only three studies

met the inclusion criteria of the review, none of which “provided useful and valid results on

the outcomes of clinical relevance” (Lombardi et al., 2002, p. 264). This conclusion is echoed

by a literature review by Meyer et al. (2010), which only found strong evidence for

pharmaceutical intervention in promoting arousal from coma. Meyer et al. did however

provide some support for the other interventions reviewed (including music therapy),

concluding that they “showed promise in some aspect of arousal” (p. 722), and warranted

further investigation.

2.8.3 NeuroplasticityAs indicated previously in the early studies informing the sensory stimulation approach, our

evolving understanding of neuroplasticity provides a rationale for the use of sensory

stimulation, and ‘enriched environments’ in the rehabilitation of DOC. There is a growing

understanding of how the brain is capable of re-organisation and self-modification following


31

neurological trauma (Johansson & Grabowski, 1994; Mateer & Kerns, 2000; Stein, 2009).

There are also indications that environment and stimulation programmes may play a role in

promoting plasticity for DOC from animal studies. For example, Johansson (1996) found

enhanced functional behaviour in rats with focal brain ischemic damage, when provided with

enriched sensory environments. This evidence has been cited in the music therapy literature

in support of input with TBI (Baker & Roth, 2004; O'Callaghan, 1999). In the music

neuroscience and psychology fields, studies are lacking with DOC. However Särkomo et al.

(2008) has provided evidence to support music listening to enhance cognitive recovery and

mood after middle cerebral artery, and Soto et al. (2009) found that preferred music may

decrease visual neglect. In another study, Schlaug, Maechina and Norton (2008) used fMRI

methods to reveal that improvements in speech for stroke patients following melodic

intonation therapy were matched with improvements in functional connectivity in the

sensorimotor and premotor cortices.


32

3. Aims of the Thesis

The overall aim of this thesis is to develop the evidence base for the use of music therapy in

the assessment of those with DOC. This is important as evidence is currently lacking to

guide appropriate interventions with this population. The thesis addresses this aim in three

publications which comprise: Paper I, an exploration of the DOC music therapy and relevant

neuroscience literature to establish the rationale for the thesis; Paper II, an audit of

concurrent musical and global behavioural assessment records to improve our

understanding of the role of music therapy in DOC assessment; and Paper III, a behavioural

and neurophysiological study exploring the responses of healthy volunteers and those with

DOC to a range of music therapy and other auditory stimuli.

3.1 Research questionsThe primary research question for this study is:

1. Can music therapy treatment effect physiological and behavioural changes suggesting

arousal and awareness to contribute to diagnosis in assessment of patients with DOC?

(Papers II and III)

In order to answer this question, a series of sub-questions will be addressed:

2. Specifically what do concurrent music therapy and multimodal assessments reveal about

DOC patients in relation to their responsiveness to auditory and musical stimuli? (Paper II)

3. What information will a combined behavioural and neuro-physiological examination of VS,

MCS and healthy individuals presented with different music therapy treatments reveal in

relation to:

a) the differing effects of the treatments within and between individuals

and diagnostic groups i.e., healthy volunteers, VS, MCS (Paper III)

b) DOC patients and their assessment through means of standardised behavioural

assessments alone? (Paper III)


33

4. Overall Research Design

A scientific, empirical approach was adopted when designing this research, as it is both

timely and appropriate for the clinical practice of music therapy with DOC. In clinical settings,

DOC patients are unable to communicate their experience of music therapy in any way other

than through subtle behavioural changes. Therefore the use of alternative research

frameworks, such as qualitative, phenomenological approaches, would be primarily limited to

the experience of the clinician and/or observers, and their subjective perception of the

participants’ experience. In this field, focused, empirical evidence is required, given the

limited range and coverage of the literature noted in Paper I, and the demand for more

scientific evidence within today’s economic climate.

To answer the research questions and aims of this thesis, an appropriate overarching

research design was constructed, informed by the Medical Research Council’s (MRC)

guidelines on ‘developing and evaluating complex interventions' (Craig et al., 2008). The

MRC advocates a circular strategy to structure enquiries focused on multi-dimensional or

complex areas such as music therapy interventions. Given the time scale afforded the study,

and the lack of empirical evidence in this field, appropriate aspects of the first two stages of

this process were selected to form the basis of the research namely 'identifying the evidence

base' (development) and 'testing procedures' (feasibility and piloting).

In addition to the MRC recommendations, the overall design of the study was informed by

Robson (2011), who advocates a ‘combined strategy design’ for small scale research

projects where there is little in the way of evidence base or coherent theory to support the

use of an intervention or service. Here, an initial flexible design stage of exploratory purpose

is advocated for gathering empirical data to reveal likely ‘bankers’ or processes involved in

the situation under investigation. The findings of this type of research are envisaged as

contributing to a further stage of research advocated by Robson, where a more ‘fixed’

research design might comprise more focused research questions. Similarly, the studies

contained in this thesis have been designed to explore a range of responses related to

arousal and awareness in order to refine our understanding of music therapy practice in

assessment and rehabilitation with DOC. It is envisaged that results obtained in this fashion

may contribute to future fixed design research, which might focus on those responses or

measures seen as most clinically important.


34

With the recommendations from these authoritative sources in mind, a flexible, exploratory

research design was constructed in three phases as follows:

Phase One: review the relevant literature within the fields of music therapy, DOC and

neuroscience to identify the evidence base and contextualise the research components of

the thesis.

Phase Two: explore and compare archived data from music therapy and multimodal

assessments in an audit study to understand what music therapy assessment contributes to

clinical practice in this field from a purely behavioural perspective.

Phase Three: building on the findings of the audit, this phase aimed to underpin clinical

assessment practice with evidence based enquiry into the neurophysiological and

behavioural responses elicited by music therapy. This phase used a single subject design

with a randomized order of conditions that alternated contrasting auditory stimuli. Results

may inform future research exploring the utility of music therapy in rehabilitation with DOC,

where activities promoting arousal, neuroplasticity and awareness responses play important

roles in improving clinical outcomes.


35

5. Methodology

The three papers contained in this thesis comprise the three phases of the study design

listed in the previous section. Whilst the methodologies for the audit and

neurophysiological/behavioural studies are reported in Papers II and III respectively, this

section will elaborate on methodological elements not detailed in the papers, in particular the

search strategy informing the thesis as a whole, and fuller details of the methodology

adopted in the final study detailed in Paper III. Such a level of detail was not afforded within

the space constraints of the publications, but is useful to present here in order to provide the

reader with a comprehensive outline of the methods adopted. Readers are directed to Paper

II (pp. 290-291) for the methodology of the audit study.

5.1 Search StrategyTo develop an understanding of the extant evidence base for music therapy assessment and

rehabilitation with DOC, a literature search was conducted using the main electronic

database search engines (PubMed, PsychINFO, AMED, CINAHL, EMBASE, Scopus and

Springerlink). The terms ‘music’, ‘music therapy’, ‘music AND therapy’, ‘sensory AND

stimulation’, music therapy AND assessment OR rehabilitation in combination with ’head

injury’, ‘brain damage’, ‘coma’, ‘vegetative’ ,’minimally conscious’, ‘minimally responsive’, ‘low

awareness state’, and ’disorders of consciousness’ were selected for the search.

Given the relatively recent establishment of DOC nomenclature, in particular the discrete

diagnosis of MCS, it was unsurprising that only a handful of publications using consistent

terminology relating to music therapy were elicited. With a lack of empirical research which

might form the basis of a systematic literature review or meta-analysis, the decision was

made to produce an introductory paper (Paper I) to highlight this issue. This introductory

paper also drew on the wider literature base found on DOC to inform and establish the

rationale for the research components of the thesis found in Papers II and III.

5.2 RecruitmentA pragmatic a priori decision to recruit 20 healthy volunteers, 10 VS and 10 MCS patients

was made, balancing the need for as large a sample size as possible with both the time

constraints of the PhD study, and rates of admissions at the hospital. An extra patient was

recruited prior to data analysis to cover the eventuality of any missing or corrupted data

within the measures.


36

To provide healthy comparison data, volunteers were recruited from staff at the investigator’s

work place detailed in the Research Environment section of this thesis. Volunteers were

recruited via an email sent to all staff outlining the nature of the research and the experiment

they would be involved in. Inclusion criteria comprised all male and female staff members

responding to the email. Exclusion criteria comprised individuals with known hearing

impairment or a high level of musical proficiency. Musical proficiency was defined as

pertaining to those who had received musical training to an advanced level and/or currently

worked on a regular basis performing music. The literature indicates that those with musical

expertise may display different responses to stimuli in EEG measures compared to non-

musical subjects (e.g., Bhattacharya & Petsche, 2005; Ott, Stier, Herrmann, & Jäncke,

2013), and so this exclusion criteria was chosen to avoid the data being skewed.

Furthermore, Altenmüller, Schürmann, Lim and Parlitz (2002) indicate that compared to

males, females produce greater valence related responses to musical stimuli in terms of

lateralised EEG power increases (i.e., positive emotional responses with left temporal

activation, negative with more right fronto-temporal activation). Consequently, an attempt

was made to recruit equal numbers of both genders to provide further skewing of the data in

this manner.

Patients were recruited from two specialist DOC assessment and rehabilitation units within

the hospital. Inclusion criteria comprised medically stable patients, who were undergoing

assessment for diagnosis of awareness using SMART (Gill-Thwaites & Munday 2004; Gill-

Thwaites 1997) and MATADOC (Magee et al., 2013) assessments, or had completed these

assessments within four weeks of the research session with a diagnostic outcome of VS or

MCS. This time period was chosen in order to eliminate as far as possible patients who might

have improved or deteriorated in their clinical status since their behavioural assessment and

diagnosis. Patients were excluded with incomplete SMART or MATADOC assessments, who

were medically unstable, or who had a known hearing impairment. Two patients were

excluded from data collection due to their SMART and MATADOC assessments indicating

that they were at a level of functioning higher than MCS.

Patients were recruited further to completion of (i) a mental capacity assessment by the

investigator and a clinician working closely with the patient (ii) written approval from the

patient’s hospital physician further to reading an information sheet detailing the study, and

(iii) written approval by a consultee (i.e., their named next of kin and/or first contact for the

hospital), further to reading an information sheet. The mental capacity assessment and

consultee information sheet are provided in this thesis as Appendix 1 and 2.


37

Conducting research with individuals who lack capacity necessarily involves a host of ethical

considerations. The following section elaborates on these considerations as they applied to

patients successfully recruited to the study.

5.2.1 Ethical Considerations This study conforms to the Mental Capacity Act Code of Practice for Research (Andrews,

Duport, Haynes & Gale, 2005), the World Medical Association Declaration of Helsinki (2004),

and received ethical approval from both RHN and the appropriate UK regulatory body (East

London NHS Research Ethics Committee). However, given the sensitive nature of work with

this population, it is important to detail the ethical considerations specific to this research.

Patients with DOC usually have seating tolerance difficulties whereby their immobility puts

them at risk of developing pressure ulcers (also known as ‘bedsores’). By the time DOC

patients at RHN have received a full SMART assessment, they usually have a 2-3 hour

seating tolerance. Patients’ timetables were carefully considered to ensure that when

combined with other treatments booked that day, the experiment would not exceed the

patients’ seating tolerance. As an experienced member of staff at the RHN, the investigator

was also aware of the patients’ personal care schedules, usual treatment regimes and the

staff involved. Experimental sessions were scheduled in liaison with appropriate staff

members to cause minimal disruption to the patients’ care.

As well as a lack of data regarding the positive effects of music therapy with this population,

there is a lack of data regarding contra-indications of musical or non-musical sound. As

detailed previously, clinical practice of sensory regulation with DOC, recommends that: "the

delivery of any stimuli needs to be carefully regulated in terms of its intensity, frequency,

inter-stimulus intervals, duration and target to noise levels" (Wood, 1991, p. 408). In

designing the research protocol, the investigator was mindful of these recommendations.

As part of the research session, one of the musical methods presented to patients was pre-

recorded music disliked by patients (according to their closest carers). This method was

incorporated as the overriding aim of any assessment with DOC is to ascertain awareness.

To facilitate awareness interventions are required that increase arousal levels. As it is

unclear which music methods might be best at assisting this process, this novel ‘nociceptive’

method was introduced in addition to standard music therapy methods. This addition is in line

with the established use of nociceptive stimuli in assessment protocols designed to increase

and regulate arousal levels and awareness such as those found in SMART (Gill-Thwaites,

1997; Gill-Thwaites & Munday, 2004). SMART incorporates the use of loud sound, bright


38

light and pleasant and unpleasant smelling solutions as stimuli. Whilst causing momentary

discomfort, noxious stimuli are deemed essential to the assessment process. Similarly,

disliked music might be successful in stimulating an awareness response, including reactions

such as crying. By ascertaining awareness in a patient where awareness is unknown, the

therapeutic benefits to informing the long term treatment for the patient were considered as

over-riding the negative aspects of any short-term discomfort caused.

5.3 Data Collection

5.3.1 MaterialsData for healthy and patient subjects was collected in a quiet treatment room within the

specialist unit of the hospital. All unnecessary electric devices were removed or switched off

to avoid contaminating the EEG and ECG data, and the room was free from interruptions.

Fig. 2 provides a graphical overview of the first half of a typical research session protocol for

illustrative purposes. Specific details of materials are reported in the following sections on

procedure and protocol.

5.3.2 Procedures and ProtocolA multiple baseline within subjects protocol which was chosen to provide data on a range of

contrasting music therapy, and non-music therapy auditory stimuli, in order to ascertain

whether music therapy was able to elicit any responses distinct from other stimuli across

cohorts. Stimuli were chosen for their distinct qualities in relation to saliency, musical and

non–musical characteristics. Five minutes’ baseline silence (BLS) was followed by the

presentation of the four contrasting stimuli which will each be described in turn.

Music therapy stimuli comprised of two conditions:

(i) Liked Music (LM)

Live performance by the investigator, a trained music therapist and professional musician, of

the patient’s preferred song music. This method is advocated within the MATADOC

assessment for promoting arousal and awareness in DOC patients by eliciting intact

emotional and long term memory responses.


39

(ii) Entrained Improvisation (EI)

Live performance by the investigator of a simple improvised vocal melody, featuring the

repeated phrase 'Hello (patient’s name) .....hello to music' with a basic supporting

accompaniment entrained to respiration. This method replicates a technique used in the

MATADOC (Magee et al., 2013) and is also advocated in the humanist/music centred

literature detailed in Paper I. The technique is designed to promote arousal and awareness

responses in DOC patients in a manner tailored to the patients’ physiological state and

limited capacity for processing auditory stimuli.

Non music therapy stimuli comprised pre-recorded stimuli produced via audio speakers

attached to a laptop with digital audio files of:

(i) Disliked Music (DM)

Recordings of music disliked by patients by original artists. DM was included to provide any

evidence of nociceptive or discriminatory responses indicative of awareness, as detailed

previously in section 5.2.1. Audio recordings were chosen in preference to live performance,

to ensure the stimulus remained true to its original format, thus avoiding the potential for the

investigator to 'dilute' the disliked aspect of the stimulus through their performance style.

(ii) White Noise (WN), as a non-musical auditory control.

Information about personal music preferences for the LM and DM conditions were obtained

at the recruitment stage from consultees in the case of patients, and directly from healthy

subjects. LM and EI were performed using a Yamaha NP31 digital electric piano using the

option of battery power to minimise electrical artifacts in the EEG data.

Volume was maintained within a 50-70 Db range for all stimuli using a Tecpal 331 sound

level meter. The sound source location was kept constant by placing speakers for the DM

and WN either side of the piano from which LM and EI were performed. Healthy subjects

were instructed to close their eyes half way into each stimulus presentation to provide both

eyes open and closed data for direct comparison with patient data in both states

Data were recorded using a XLTEC 50 channel video EEG and neurophysiological data

acquisition system with a piezoelectric respiratory belt, and analysed using Mathworks

MATLAB, SPSS (Ver20) and BrainVision Analyzer 2 (BVA) software. Nineteen channels of

EEG data were obtained using a common average montage and 10:20 electrode

configuration. Due to the presence of craniotomies amongst patients, free electrode


40

placement was adopted in preference to skull caps. The investigator conducted the electrode

placement himself, with assistance and training from the hospital neurophysiologist (Dr Leon

James). Electrocardiogram (ECG) data were collected on the XLTEC system for heart rate

(HR) and its variability (HRV) via two chest electrodes together with respiration data collected

via the piezoelectric respiratory belt. The process of attaching electrodes and other devices

took between 30 and 45 minutes.

For the patient cohorts, commands from the auditory function scale of the CRS R (Giacino, J

& Kalmar, K., 2006) were presented after each stimulus to observe for signs of awareness

which might be considered as related to the arousal or other effects of prior stimuli.To control

for order effects, the order of stimuli was randomised, with order series placed in opaque

sealed envelopes with envelopes selected by an independent observer for each participant.

Figure 2: Study Protocol

5.4 Data AnalysisRaw EEG data extracted from the XLTEC system in EDF format for analysis in BVA and

MATLAB, with sampling at 512 Hz. In BVA, data was filtered to a hi/low cut off bandpass

filter at 0.5 and 30 Hz, to focus on data within the delta to beta frequency range. Independent

Component Analysis was performed by the investigator in BVA to remove artifacts, followed

by Fast Fourier Transformation to produce the frequency spectrum, or amplitude as a

function of frequency, for each electrode. Data were segmented to 2 second units and


41

pooled into 21 different electrode configurations to represent different brain regions, e.g.,

occipital region: O1 & O2 [see Paper III appendix table 1 for details (p. 15)]. The first five

seconds of the healthy cohort ‘eyes closed’ EEG data was excluded from analysis due to the

high level of blink and muscle artefact during the transition from open to closed eyes.

Raw ECG and respiration data was extracted from the XLTEC system in EDF format and

analysed in MATLAB using bespoke software designed by a signal processing expert (Dr

Ramaswamy Palaniappan) for deriving HR, HRV, respiration rate and variance data. On-

going training and support was provided during this process by Dr James, BVA Scientific

Support and Dr Palaniappan.

After exporting to SPSS, one way repeated measures ANOVA analysis with Bonferroni

corrections was applied to data. For healthy subjects all data were pooled to provide

indicators of healthy responses across measures using ANOVA's around means. Post hoc F

statistics were obtained using simple contrasts in relation to BLS to indicate the strength of

association of positive or negative change for individual stimuli in contributing to overall

ANOVA significance and F statistic levels.

Given the clinical and neuro-pathological heterogeneity of those with DOC, within-subject

statistical analyses were conducted using segmented data that produced individual ANOVAs

for the case material provided in Paper III.

Behavioural data using video recordings of patient sessions were analysed by a trained

volunteer, who was blinded by removing audio from recordings. 10 second segments were

scored for a range of behaviours using a graded system from Wilson, Powell, Brock, and

Thwaites (1996) from 'eyes shut and no body movement' to 'engaged in activity' (e.g.,

scratching). Any additional behaviours such as blinking and mouth movement were also

documented.


42

6. Overview of Results for Paper III

As with the previous methodology section, whilst results are reported in Papers II and III, it is

helpful here to provide an overview of the diverse range of results obtained in the second

study (Paper III). The results of the audit study (Paper II) require less elaboration, derived as

they were from standardised behavioural assessment forms alone rather than the range of

measures adopted in Paper III. For these results, the reader is directed to Paper II (pp. 291-

296) and the summary of Paper II in this thesis.

6.1 Results from Healthy DataFurther to trailing the data collection methods on 3 healthy volunteers, data was obtained

and analysed for 20 healthy volunteers: 13 female (aged 24-52 years, mean 34 yrs, SD 12.5)

and 7 males (aged 29-59 mean 41 SD 11), to provide comparison data for the patient

cohorts. Missing EEG data for one female subject resulted from a corrupted signal. For

healthy and patient data, the principal statistical test applied to all measures was the one way

repeated measures ANOVA with Bonferroni corrections, appropriate to the repeated

measures design of the study.

The ANOVA tests on physiological data revealed significant3 overall change within

(i) respiration rate [ANOVA F(4, 56) = 5.8, p = 0.001], where LM produced the largest post

hoc contrast with baseline silence [F(1, 14) = 35.7, p < 0.001].

(ii) respiration variance, or peak to peak variance [F(4,56) = 4.1, p = 0.006] where WN

provided the largest increase4 [F(1,14) = 11.5, p = 0.005].

For the EEG data, the ANOVA tests for each pooled area revealed clear significance for

changes in mean amplitude across delta (δ), theta (θ), alpha (α) and beta (β) bandwidths in

most areas, particularly in frontal and temporal regions, but less so for parietal, central,

posterior and occipital regions. Post hoc contrasts with BLS highlighted the dominant

contribution of LM to significant ANOVA results in the R frontal region with peak increases in

β [F(1, 685) =100, p < 0.001] and α [F(1, 685) = 50.2, p < 0.001]. Significant amplitude

3 Significance henceforth denoted by p ≤ 0.054 'increases' and 'decreases' henceforth in relation to post hoc ANOVA contrasts with BLS


43

differences for θ in the frontal midline (FMT) region were particularly noteworthy, where a

contrast between DM decreases and LM increases was most marked compared to other

regions and bandwidths [see Paper III, fig 2 (p. 7)]. For more details on amplitude changes

within each bandwidth in frontal, temporal and left/right hemisphere regions, the reader is

directed to Paper III, fig 1 and table 2 (pp. 5-6).

6.2 Results from Patient DataAll patient data were pooled for observation of trends in patient responses. The results were

heterogeneous as expected, particularly for physiological measures, however notable

exceptions were found within behavioural and EEG data. In VS behavioural data, pooled eye

blink rate data reached significance [F(2.3,13.9) = 3.6, p = 0.019], with a peak for the LM

post hoc contrast with baseline silence [F(1,11) = 8.2, p = 0.029]. Fig. 4 in Paper III (p. 7)

provides a graphical representation of this data. Similar non-significant trends were observed

for LM in eye and mouth movement and 'eyes open no body movement' measures. Whilst

stimuli producing peak EEG amplitudes in different regions varied between VS patients,

mean FMT increased significantly for LM in half (n: 6) of cases where ANOVA's were

significant. Pooled MCS FMT data also peaked significantly in 4 cases (44%). It is also

noteworthy that frontal α peaked for LM in 3 VS and 4 MCS subjects, where overall ANOVAs

were significant between p = 0.05 - 0.0001, which contributed to the significant finding for

frontal α across the MCS cohort [F(4, 1850.1) = 36.5, p < 0.001] with a peak for LM [post hoc

contrast F(1, 809) = 50.6, p < 0.001]. This finding is illustrated in fig. 5 (p. 7) of Paper III.


44

7. Summary and Background of Papers

The main sections of this thesis comprise three peer reviewed papers designed to address

the research questions detailed previously. The following provides a summary of the content

and background for each paper.

7.1 Paper I

Music therapy with disorders of consciousness and neuroscience: the need for dialogue

Paper I was designed to provide the rationale for the studies reported in thesis. A literature

search was conducted using the main electronic database search engines to determine the

current evidence base for music therapy assessment and rehabilitation with DOC. It was

apparent that the range of publications was not extensive, and there was little in the way of

empirical work that might form the basis of a systematic literature review or meta-analysis.

Within the music therapy literature differences in paradigms persist in thinking about and

describing clinical work with DOC, where two contrasting approaches are found with

humanist/music centred or behavioural/pragmatic influences. There is, however, a range of

findings from the 'music neuroscience' literature with healthy normal subjects and stroke

patients to suggest that the qualities of music, in particular its ability to support

neuroplasticity, indicate transferable lessons for DOC assessment and rehabilitation (e.g.,

Särkomo et al., 2008; Schlaug et al., 2008; Soto et al., 2009). It is also apparent that there is

a rapidly expanding literature base covering neuroimaging studies with DOC comprising a

range of contrasting views of relevance to music therapy with this population. In drawing

these findings together, this paper combined a literature review of music therapy with DOC,

with setting the case for more dialogue between neuroscience and music therapy, a guiding

principal behind the second study (Paper III).


45

7.2 Paper II

The complementary role of music therapy in the detection of awareness in disorders of consciousness: An audit of concurrent SMART and MATADOC assessments

The first study was conducted in two specialist units for DOC assessment and rehabilitation

with a total bedded capacity for 27 patients, within one of the first specialist brain injury

hospitals to be established in the UK. The aim of the study was to address research question

two: 'Specifically what do concurrent music therapy and multimodal assessments reveal

about DOC patients in relation to their responsiveness to auditory and musical stimuli?'. In

doing so, it was hoped the study could also add to the evidence base in relation to the main

research question, i.e., whether music therapy might affect behavioural changes that

contribute to the diagnosis of awareness state.

The study made use of five years of archived patient records where patients had received

concurrent assessments with the multimodal 'Sensory Modality Assessment and

Rehabilitation Technique' (SMART) (Gill-Thwaites, 1997; Gill-Thwaites & Munday, 2004) and

the ‘Music Therapy Assessment Tool for Disorders of Consciousness’ (MATADOC) (Magee

et al., 2013), which focuses on patients’ behavioural responses to musical stimuli. Both tools

have diagnostic power to assess for awareness states VS and MCS, with MATADOC having

applicability with patients emerging from MCS, and SMART including the categories of

‘MCS/VS’ and 'MCS +' for cases where patients are borderline MCS/VS, or have emerged

from MCS to higher levels of functioning. A total of 42 records were retrieved (25 male, 17

female) where assessments were conducted within 4 weeks of each other (mean: 5.45 days

SD = 9).

Whilst the two tools produced a high level of agreement in diagnostic outcome (Spearman

Rho or rs of 0.8), divergent diagnoses and weaker correlations between behavioural

response items highlighted contrasting sensitivities of the tools. For example, MATADOC

displayed higher sensitivity within auditory and visual domains relative to SMART, but

SMART data indicated higher sensitivity in the motor domain. In addition, the important

contribution of musical response items in MATADOC, and the tactile response item in

SMART, indicated both tools provide unique behavioural data predictive of awareness. The

study supports the recommendation of Giacino (2002) that given the contrasting strengths of

assessment tools and heterogeneity of the DOC responses to stimuli, combining these tools


46

provides complementary data contributing to a fuller understanding of a patient’s level of

awareness.

This study, grounded in clinical practice and focussed on behavioural assessment, provided

a foundation for the more neurophysiological focus of the second study (Paper III). By

evidencing that music therapy is able to produce behavioural responses indicative of

awareness, a rationale for the investigation of the neurophysiological basis of the findings is

provided, in order to develop our understanding and evidence base for this practice.

7.3 Paper III

Neurophysiological and behavioural responses to music therapy in vegetative and minimally conscious states

The second study was designed to address the primary research question 'Can music

therapy treatment effect physiological and behavioural changes suggesting arousal and

awareness to contribute to diagnosis in the assessment of patients with DOC?'

In doing so the study also aimed to address the second sub-question: 'What information will

a combined behavioural and neurophysiological examination of VS, MCS and healthy

individuals presented with different music therapy treatments reveal in relation to a) the

differing effects of the range of techniques within and between individual and diagnostic

groups and b) DOC patients and their assessment through means of standardised

behavioural assessments alone?

The literature covering neurophysiological and behavioural assessment of DOC and normal

human neurophysiological responses to music was reviewed to contextualise this study. The

review indicated a number of useful measures such as heart rate variability (HRV) and

electroencephalogram (EEG) recordings might be used to assess for indications of arousal,

attention and cognitive processes associated with awareness, particularly in relation to

auditory stimuli such as music. Thus a rationale for a multiple baseline within-subjects study

to address the above questions was made, where EEG, heart rate (HR), heart rate variability

(HRV), respiration and behavioural responses contingent to music therapy and other auditory

stimuli were compared within individuals and between with healthy, VS and MCS cohorts.


47

MethodologyThe study was undertaken with patients and staff at the same unit as the first study, where

recruitment comprised 20 healthy subjects (13 female and 7 male staff) with 12 patients

diagnosed as VS (6 female, 6 male) and 9 as MCS (5 male, 4 female). Subjects were

presented with procedures typically used in music therapy: live preferred music (LM) and

improvised music entrained to respiration (EI). They were also presented with baseline

silence (BLS), recordings of disliked music (DM), and white noise (WN).

ResultsPost hoc ANOVA tests indicated a range of significant responses (p ≤ 0.05) across healthy

subjects corresponding to arousal and attention in response to LM including concurrent

increases in respiration rate with globally enhanced EEG amplitude responses across

frequency bandwidths and regions. Within patient findings, physiological responses were

heterogeneous, however, mean frontal midline theta (FMT) increased significantly for LM in

half (n: 6) of VS cases where ANOVA's were significant (p ≤ 0.05), and peaked significantly

for LM in 4 MCS cases (44%). Frontal alpha amplitude changed significantly in 3 VS and 4

MCS subjects (p ≤ 0.05) with the latter contributing to the significant finding for frontal alpha

across the MCS cohort [F(4, 1850.1) = 36.5, p < 0.001] with a peak for LM [post hoc contrast

F(1, 809) = 50.6, p < 0.001]. Furthermore, behavioural data showed a significantly increased

blink rate for LM (p = 0.029) within the VS cohort. Two VS cases highlight the occurrence of

concurrent changes (p ≤ 0.05) across measures indicative of discriminatory responses to

both music therapy procedures. A MCS case highlights how more sensitive selective

attention may distinguish MCS from VS.


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8. Discussion

The following sections will aim to discuss the findings of Papers II and III in relation to the

research questions, provided by each main heading below. Whilst there will be some overlap

with the text of the papers, the following will focus more on the individual research questions,

providing greater detail than found in the papers where required. To answer the primary

research question, sub questions 2, 3a and 3b will be addressed initially.

8.1 Sub Question 2

Specifically what do concurrent music therapy and global assessments reveal about DOC patients in relation to their responsiveness to auditory and musical stimuli? (Paper II)

Paper II compared archived clinical information on 42 patients’ behavioural responses to

musical stimuli in a music therapy assessment (MATADOC) and a wider range of sensory

stimuli in concurrent multimodal SMART records. It is first worth noting the high level of

diagnostic agreement between MATADOC and SMART (rs 0.80, p < 0.01, 2 tailed). This

indicates that behavioural assessment for awareness based on primarily musical stimuli is

able to produce a strong agreement with outcomes from SMART, a well-established,

multimodal assessment tool undertaken in ten sessions compared to the four sessions

required in the MATADOC. This is supported by a study which reports 100% diagnostic

agreement from 21 records collected under rigorous research conditions (Magee et al.,

2013).

A simplistic interpretation of the findings of study one would conclude that the visual, not the

auditory, domain provides the most significant contribution to assessing awareness with the

highest correlation between visual responsiveness with diagnosis for MATADOC (rs = 0.79)

and SMART (rs = 0.55) respectively. This interpretation would only be correct if visual

responses (such as eye movement towards an object) could be guaranteed as solely based

on non-sounding stimuli. In reality it is likely that auditory responses may sometimes be

conflated with visual responses, for example when asking a patient to track a moving object

using the verbal command ‘look at the pen'. The higher correlation with diagnosis in the

visual domain found for MATADOC also raises questions, i.e., does the musical focus and


49

use of more complex auditory stimuli have some form of synergistic effect on enhancing

visual responses? This interpretation resonates with the study by Soto et al. (2009), where

listening to 'pleasant music' activated spared parietal areas of the brain involved in emotional

and attentional processing, to ameliorate visual neglect in stroke patients. Two MATADOC

items in particular, 'behavioural responses to music' and 'attention to task', highlighted

discriminatory responses that correlated well with diagnosis (rs > 0.6). These findings provide

evidence from clinically derived data that music therapy can elicit unique behavioural

responses with diagnostic power in relation to the detection of awareness with DOC.

A stronger correlation with diagnosis was found in the auditory domain for MATADOC

(rs 0.57) compared to the auditory domain for SMART (rs 0.38). Consequently, this study

indicates that the added complexity provided by the mix of musical elements in MATADOC

(i.e., pitch, timbre, rhythm and harmony) compared to the auditory stimuli used in SMART

(i.e., wood blocks) are more effective in eliciting awareness responses. However, given the

range of findings detailed in Paper II, there is insufficient evidence to suggest any one

domain may be more relevant to diagnosis, or more sensitive in the detection of behaviours

indicating awareness. The data suggests that SMART and MATADOC elicit different levels of

response in comparable domains, and that the musical stimuli used in MATADOC have utility

in eliciting a range of responses indicative of awareness.

Finally, it is noteworthy that the correlation between diagnostic outcome and the item

measuring arousal for both tools was relatively weak (rs 0.46). This finding may have two

explanations. Either, the weak correlation may indicate an inconsistent relationship of arousal

with awareness, or, it may reflect that the range of behavioural arousal markers, such as

posture, breathing, and eye contact which clinicians rely upon in clinical observations, are

vulnerable to misinterpretation, or may be missed altogether. It has been noted that there are

inherent challenges in measuring this multi-dimensional domain (Robbins, 1997). The finding

presented here suggests that objective physiological measures such as heart rate (HR) and

respiration rate (RR) should be observed in addition to behavioural indicators for a more

robust assessment of arousal.


50

8.2 Sub question 3a

What information will a combined behavioural and neuro-physiological examination of VS, MCS and healthy individuals presented with different music therapy treatments reveal in relation to the differing effects of the treatments within and between individuals and diagnostic groups? (Paper III)

8.2.1 Healthy Neurophysiological Responses There is a lack of literature on healthy neurophysiological responses to receptive music

therapy methods with which to draw comparisons in relation to this question; indeed this

study goes some way to addressing this issue. Therefore, it is appropriate to draw

comparisons with music psychology and psychophysiology literature as detailed previously.

As detailed earlier, a debate exists as to how much ANS responses to music listening are

accounted for by unconscious entrainment to musical tempo, or 'tempo entrainment'

(Bernardi et al.,2006; Etzel et al., 2006; Gomez & Danuser, 2007; Khalfa et al., 2008), or

cortically mediated, emotional, or 'top down' processes, as reported by Salimpoor et al.

(2009).

In this study, comparing RR in relation to the beats per minute of the musical stimuli indicates

that the responses observed accord more to the Salimpoor et al. (2009) model of 'top down'

processing than to unconscious 'tempo entrainment'. As fig. 3 illustrates, faster tempi of DM

choices were not reflected in faster RR compared to LM, rather the converse (by a small

margin). Some caution is needed in interpreting this data, as it only reflects average, or 'tonic'

RR and BPM, and more detailed analysis might reveal phasic correlations between shifts in

music tempo and RR.

In contrast to the arousal response detailed above for RR, the significant increase in

respiration variability for WN detailed in Paper III (p. 6) points more clearly to a negative or

'upsetting' response related to WN according to Boiten (1994). Further discussion of valence

issues in relation to the EEG data may be found in Paper III (p. 10). In summary, the

significant increase in RR found for LM with the healthy cohort indicates an arousal affect

where a lack of tempo entrainment points to a top down 'pleasure' response. Given the

possibility of top down, cortically mediated mechanisms explaining RR increases, the

importance of this response occurring for patient subjects should not be underestimated. For

example, where patients diagnosed as in VS respond consistently with an increased RR


51

when presented with LM compared to other stimuli, further investigation is merited as to the

patients’ level of awareness and sensitivity to their auditory environment.

Figure 3: Healthy Respiration Rates and Beats per Minute Compared

In relation to the literature on HR and HRV and music listening detailed in Paper III (pp. 2-3),

this study provides little support for HRV time domain5 or frequency domain6 measures

providing consistent benchmarks for healthy 'aware' responses to the music therapy methods

used in the study. However, whilst the ANOVA tests revealed no significant change across

the healthy cohort, ANOVAs conducted on segmented data at the within-subject level did

reveal a range of often divergent significant change. For example, two male healthy subjects

aged 29 and 31 respectively showed significant change (i.e. ANOVA p ≤ 0.05) during the

experimental session for high frequency (HF) within the HRV data, but with divergent post

hoc peak behaviour for LM, with LM providing the highest and lowest mean level of the

subjects respectively. Thus, it appears that normal HR and HRV responses to music therapy

methods are idiosyncratic and divergent between individuals, yet often significant at the

within-subject level. However, caution is required in interpreting this finding; as will be

discussed in the limitations section of this thesis, the small sample and heterogeneity of

musical stimuli need to be considered.

5 as detailed in Paper III (p. 5) these refer to: SDNN: standard deviation of all 'NN' or peak intervals, RMSSD: square root of the mean of the sum of the squares of differences between adjacent NN intervals6 as detailed in Paper III (p. 5) these refer to LF: Low frequency, HF: High frequency, ULF: Ultra low frequency, LF/HF ratio: ratio of low-hi frequency power


RPM BPM RPM BPM RPM BPM

Liked Music Liked Music Disliked Music Disliked Music Ent. Improv. Ent. Improv.

KeyRPM: Respirations per minute

BPM: Beats per minute

52

There is a growing understanding of the role of neuroplasticity in neuro-rehabilitation, or how

the brain is capable of re-organisation and self-modification following neurological trauma

(Johansson & Grabowski, 1994; Mateer & Kerns, 2000; Stein, 2009). Music is a dynamic

stimulus eliciting neurological response through its intrinsic qualities of rhythm, pitch and

harmony, and through association in the emotional and memory processes elicited uniquely

in each individual. As detailed previously, listening to 'pleasant' and preferred music has

been shown to be effective in promoting neuroplasticity to meet functional goals for those

with acquired brain damage such as decreasing visual neglect (Särkamo & Soto, 2012; Soto

et al., 2009), and improving cognitive function (Särkamo et al., 2010). FMRI and specific

EEG paradigms such as mismatch-negativity (MMN) tend to be adopted as functional

measures of neuroplasticity (Münte, Altenmüller, & Jänck 2002). Whilst the second study did

not include such tests, table 2, figure 1 and 2 in Paper III (pp. 5-7) illustrate how LM

produced the most significant EEG amplitude increases, as measured by mean amplitude

peaks across bandwidths. Thus LM produced the most cortical activity, for left and right

hemispheres overall, with notable dominance in R frontal and temporal regions across

frequency bandwidths. According to the literature on the EEG behaviour of healthy

individuals detailed in Paper III (p. 3 & 10), these responses are typical for the processing of

musical stimuli, indicative of increased arousal, local and long distance cortical activity and

connectivity.

In summary, for the healthy cohort in study two, the findings of significant globally enhanced

post hoc EEG power spectra responses for LM (p ≤ 0.05) resonates with the literature on

music listening to support the use of LM for providing conditions appropriate for

neuroplasticity. The study also provides a range of normative data on EEG responses to

music therapy which are lacking in the literature. Finally, the EEG data coupled with the RR

increases observed for LM provides evidence from a normative perspective for the utility of

using this music therapy procedure to support arousal and 'top down' cortical activity with

DOC.

8.2.2 Patient Behavioural ResponsesOne of the most interesting findings in the VS data in the second study, was a significantly

increased blink rate observed, maximal for LM, where the ANOVA [F(2.3,13.9) = 3.6, p =

0.019] comprised a significant LM post hoc contrast with baseline silence [F(1,11) = 8.2, p =

0.029]. This was accompanied by non-significant trends for LM in increased eye and mouth

movement and 'eyes open no body movement' measures. The discussion section of Paper III


53

explores the literature on blink rate (p. 10), which is primarily based on healthy subjects, to

hypothesise that a basic arousal response was observed for VS subjects particularly in

relation to LM, but also (to a lesser extent) the other auditory stimuli. Overall, the behavioural

data indicates that LM offers the most effective stimuli for supporting arousal of the stimuli

tested and echoes the findings of Wilson, Brock, Powell, Thwaites and Elliott (1996), that VS

patients exhibit arousal profiles which vary considerably in nature and level of arousal in

relation to sensory stimuli.

The MCS data suggests a contrasting attention response where blink rate decreased and

awareness of the stimuli increased where visual attention was recruited, as illustrated in the

third case study in Paper III (pp. 19-21). Here blink rate decreased but spontaneous body

movement increased to LM. It should, however, be noted that this was the only subject which

gave consistent CRS R responses indicative of awareness, and who also gave these

responses after each stimulus. Therefore, the behavioural data in Paper III supports the use

of music therapy methods to increase arousal for VS patients, although significant findings

were not found for awareness responses within the experimental sessions at the level of

standardised behavioural assessment.

8.2.3 Patient Neurophysiological ResponsesAs detailed in Paper III (pp. 9-10), significant post hoc EEG amplitude peaks for LM were

found for frontal midline theta (FMT) in 6 VS and 4 MCS subjects, and frontal alpha in 3 VS

and 4 MCS subjects (p = 0.05 - 0.0001). These finding suggests that despite the

heterogeneity of DOC pathology, LM provides powerful stimuli in relation to eliciting frontal

theta and alpha responses within VS and MCS cohorts. Whilst detailed source localisation

work has not been undertaken on this data, a review of the literature on FMT points to

activation of hippocampal and anterior cingulate cortex regions involved in memory,

motivation, decision making, processing information, and attention in healthy individuals

(Mitchell, McNaughton, Flanagan, & Kirk, 2008). Given the complex, multi-layered nature of

music, these responses happening at beyond chance level are particularly noteworthy. If VS

patients were truly unaware of their auditory environment, one would not expect to find such

contrasting responses between LM and the other stimuli presented within the same volume

and source location parameters. This contrasting response is particularly noteworthy where

weaker responses were observed for DM [e.g., Paper III fig 5 (p. 7) and fig 6 & 7

(p. 8). Given DM is a a stimulus of similar complexity to LM in terms of the combination of

different timbres, melody, rhythm and harmony, one should not expect to see contrasting

responses in VS patients considered ‘unaware’ of their environment, or unable to

discriminate, or show enhanced responses across measures to different auditory stimuli.


54

Fig.'s 1 and 2 in Paper III (pp. 6-7) highlight that weaker neurophysiological responses to DM

are also a hallmark of the healthy data, particularly in the theta and alpha EEG frequency

bandwidths in frontal and temporal regions. Together, this information points to the possibility

that not only arousal, but also some form of selective attention, may be elicited by LM for

some VS and MCS patients, which may even suggest diagnostic error in cases where these

divergent responses are most pronounced or sustained.

It is noteworthy that less discrimination between music therapy conditions and white noise

characterised pooled VS data in a manner resonating with the concept of 'hypoarousal'

detailed previously, where subjects are unable to distinguish relevant from irrelevant

information (Heilman et al.,1978). Similarly, as detailed previously, discrimination evidenced

by heightened cortical activation in fMRI studies to auditory stimuli with emotional relevance

has been considered a defining feature of MCS (Laureys et al., 2004).Thus, harnessing EEG

technology alongside music therapy assessment in this manner may provide complementary

data for clinicians to draw upon when assessing for awareness and prognostic indicators.

Further research might explore the reliability of contrasting responses to LM, DM and WN in

predicting VS/MCS diagnosis. As noted previously, compared to EEG, more expensive and

invasive assessment technology such as fMRI is not applicable to all patients. Thus a novel,

and widely applicable, assessment method is suggested by these findings, which merits

further investigation.

In summary, the EEG results provide compelling, albeit pilot level, support for LM promoting

responses associated with both arousal and awareness at the neurophysiological level.

Indications that LM is also capable of eliciting selective attention, and the potential of this

response acting as a diagnostic or prognostic marker, merit further enquiry.

Paper III reports that whilst pooled physiological data (i.e., HR and RR derived data) did not

produce significant findings, significant change was observed in relation to these autonomic

nervous system (ANS) measures at the within-subject level. As with the healthy cohort, the

direction of change was often heterogeneous. Table 1 details the numbers of patients for

whom significant change was found at the individual level from ANOVAs conducted on

segmented data for HR, HRV comprising HF, low frequency (LF) low/high frequency ratio

(LF/HF), and root mean squared of successive differences of peak values (RMSSD),

respiration rate (RR) and standard deviation of normal to normal respiration peaks (SDNN),

or respiration variability. The table illustrates the heterogeneous post hoc peaks found for all

conditions (including BLS) across measures where ANOVA significance was found. Thus,


55

whilst a follow up study may find the significant ANS responses found for any auditory

stimuli, (particularly in relation to sympathetic nervous system increases) to be of prognostic

value as indicated by Wijnen et al. (2006), music therapy methods produced results in only a

handful of patients that resonated coherently with the literature on healthy responses to

music listening detailed in Paper III (p. 3). The most notable of these responses was found in

the time domain of HRV (RMSDD), where increases in RMSSD have been associated with

relaxation related positive valence (Cacioppo, Tassinary, and Berntson 2000). In this study 3

VS and 3 MCS subjects displayed predominantly peak levels of RMSDD for LM and 1 MCS

subject for EI. However, overall the heterogeneous findings for physiological measures

across cohorts casts doubt on their utility in providing reliable markers of responses

particular to music therapy methods, which might be useful in assessing for discriminatory

attention or processing suggestive of selective attention or awareness.


56

Table 1: Significant Change in Patient Physiological Measures

Patients with Significant ANOVA's (p ≤ 0.05)

Post Hoc Peak Mean(n of patients in brackets)

Heart Rate

VS 9 WN (3),LM (3), BLS (2), DM (1)

MCS 5 WN (3), LM (1), BLS (1)

Hi Frequency (HF)

VS 4 BLS (2), WN (1), WN,

LM, EI & DM tied (1)

MCS 3 EI (2), WN (1)

Low Frequency (LF)

VS 6 BLS (2) WN(2), LM (1), EI (1)

MCS 3 WN (2), WN & LM (1),

LF/HF Ratio Frequency

VS 3 WN (1), EI (1), BLS (1)

MCS 2 WN (1), DM (1)

RMSSD

VS 5 LM (2), DM &LM (1) DM (1), BLS (1)

MCS 4 LM (3), EI (1),

Respiration Rate (Respirations per minute)

VS 2 LM (2)

MCS 2 LM,EI, DM, WN tied (1), DM (1)

Respiration Variance (SDNN)

VS 3 LM (3)

MCS 2 DM (1)

In summary, the findings of study two (Paper III, pp. 10-11) provide one of the first

examinations of the neurophysiological effects of music therapy with healthy individuals,

indicating 'top down' mechanisms driving RR increases with concurrent widespread cortical

activation for LM, but less consistent effects for any of the auditory stimuli used within HR

and HRV measures. Within the patient cohorts, a significant increase in blink rate suggests

an arousal response for VS patients in relation to LM. A range of frontal EEG responses

across bandwidths and cohorts further supports an arousal effect for LM. Aside from

noticeable amplitude differences at baseline levels, greater discrimination between LM and

both WN and DM within frontal regions for the MCS cohort similar to healthy responses


57

suggests a potential aid to assessment of awareness is indicated by combining music

therapy and neurophysiological assessment. The study's findings provide pilot level support

for the use of music therapy in both promoting arousal and eliciting neuro-physiological

responses suggestive of awareness. Further exploration of the EEG data using MMN and

source localisation methods is indicated in order to underpin these findings with more

detailed information on the topography of responses and functional measures of neuroplastic

change.

8.3 Sub question 3b

What information will a combined behavioural and neuro-physiological examination of VS, MCS and healthy individuals presented with different music therapy treatments reveal in relation to DOC patients and their assessment through means of standardised behavioural assessments alone?

As detailed previously, the diagnosis of VS as defined by the Aspen Workgroup (1996) as “a

condition in which awareness of self and the environment is presumed to be absent and

there is an inability to interact with others, although the capacity for spontaneous or stimulus-

induced arousal (i.e., wakefulness) is preserved” (p. 7). Furthermore, the task force stated

that there should be "No evidence of sustained, reproducible, purposeful, or voluntary

behavioural responses to visual, auditory, tactile, or noxious stimuli" and "no evidence of

language comprehension or expression" (p. 8). More recently, alongside the proposal for the

term 'unresponsive wakefulness syndrome' to replace VS (Bruno et al., 2011), the conditions

of MCS + and MCS- have been proposed by Laureys et al. (2010) to denote high-level

behavioural responses (i.e., command following) and low-level behavioural responses (i.e.,

contingent responses such as appropriate smiling or crying to emotional stimuli) respectively.

In relation to the above DOC nosology the findings of Paper III make interesting and thought

provoking reading.

Within the VS cohort, significant increases in blink rate were observed for LM. This was

accompanied by half of VS patients (n: 6) displaying significant post hoc increases of FMT,

with 3 VS patients responding similarly with significant increases in frontal alpha power. Two

VS subjects also displayed significant increases in RR for LM in a similar fashion to the

healthy cohort. In some cases (e.g., the case studies in Paper III), these heightened

responses for LM occurred concurrently in individuals. As detailed earlier, change occurring


58

at peak levels in relation to the uniquely dynamic and multi layered stimuli of LM indicates

some form of awareness in terms of selective attention was elicited.

These covert responses are not given at the behavioural level detailed previously for 'MCS-'

(Bruno et al., 2011), and cannot be described as 'purposeful' in themselves. However, they

are significant at the within-subject level post hoc, sustained throughout the stimulus

presentation, and their prevalence would suggest they would be reproducible. Furthermore,

whilst it is unclear whether heightened responses observed for LM and EI relate to the

musical or lyrical content of the stimuli, or the combined effect of them, some form of

language or music syntactical processing cannot be ruled out.

In relating the findings of study two to this research question, it is useful to reflect further on

the literature detailed in the introductory sections of this thesis. The data points to an arousal

effect, particularly for LM, which would necessarily involve the ARAS. We now understand

the ARAS has activating structures extending as far as the forebrain, and cerebral

hemisphere (Robbins, 1997; Zeman, 2001), and that it is implicated in a range of behaviour

beyond wakefulness, such as mood, motivation, attention, learning, memory and movement

(Robbins, 1997). As dicussed in Paper III (pp. 10), blink rate in particular has been

associated with positive correlations with dopaminergic system activity, arousal (Karson,

Dykman, & Paige, 1990), and attention (Abe et al., 2011; Irwin, 2011). In this light, the

evidence for music therapy supporting arousal in these patients who were recently

diagnosed as VS, is significant in terms of its potential for supporting and encouraging intact

functioning at this extended level.

Aside from the fact that significant numbers of VS patients may be mis-diagnosed

(Hirschberg & Giacino, 2011), neuroimaging studies point to intact auditory (Laureys et al.,

2000), emotional, verbal, (Schiff et al., 2002), pain (Kassubek et al., 2003) and language

processing (Coleman et al., 2007), and 'cortical learning' (Kotchoubey et al., 2006) in VS. As

detailed earlier, several leading authorities stress that these responses may only represent

modular, or isolated, behaviours, evidencing a disconnect between primary cortex, thalamus

multi-modal or limbic regions and higher order integrative/associative cortices in correctly

diagnosed VS (Boly et al., 2004; Laureys et al., 2002). However, heightened responses

noted for VS patients in this study occurred at significant within-subject post hoc levels for

LM and EI in some cases, as detailed in the case studies in Paper III (pp. 8-10). As LM and

EI may be stimuli capable of stimulating language, memory and emotional processing in

response to their lyrical and/or musical content, it seems hard to conceive of these


59

responses as merely 'isolated' or modular responses. LM in particular may also relate to

historical events in one's personal life, such as weddings and other significant life events

involving significant relationships. Given the relationship between these responses and LM,

they might relate beyond Damasio's (2010) 'primordial feelings' to his conception of 'full

consciousness', defined in terms of the involvement of biographical knowledge (pp. 22-23),

or beyond Panksepp et al.’s conception of ‘primary process affects’ (2007, p.1), given the

responses are to stimuli characterised by specific memory and/or language associations.

The level of responses noted also accords with Celisia’s review (2013) of neuro-imaging

studies noted previously (i.e., 35% of VS research subjects had activation of primary sensory

cortices and higher-order associative areas, and 5% activation of cortical regions high-level

language processing). Furthermore Tulving (1993) stated that whereas consciousness

should denote the detection of basic sensory events, awareness involves the more advanced

interpretation and experience of these events. Using this conceptualisation, it is hard to deny

some of the VS subjects’ 'consciousness' in this sense, although the data does not provide

sufficient evidence to confirm or deny interpretative processing.

8.4 Primary Research Question

Can music therapy treatment effect physiological and behavioural changes suggesting arousal and awareness to contribute to diagnosis in assessment of patients with DOC? (Papers II and III)

Papers II and III provide evidence for the use of music therapy in providing an important

contribution to the diagnosis of awareness state with this population. In addition to the high

levels of diagnostic agreement mentioned previously, Paper II highlights how the MATADOC

is capable of recording unique responses elicited by musical stimuli, which might be missed

in global assessments with less focus on the auditory domain. A range of neuro-physiological

data providing evidence for the arousal effect of LM is provided by Paper III, contributing to

our understanding of mechanisms underpinning the behavioural responses elicited and

recorded by the MATADOC. In addition this study illustrates how the combination of music

therapy with neurophysiological assessment offers a novel aid to detecting awareness as

measured by the patients’ discriminatory cortical responses. Thus the thesis confirms that

music therapy can contribute to diagnosis of awareness through effecting change in

behavioural measures and cortical activity associated with arousal and awareness.

ANS reactivity was characterised by significant but divergent change in relation to both music

therapy and non-music therapy stimuli. Whilst this does not provide sufficient evidence to


60

suggest awareness, it merits follow up assessment according to Wijnen et al. (2006), as it

may indicate a greater likelihood of recovery.

8.5 LimitationsBoth music therapy and neuroscience have been recently evolving in the sophistication of

clinical practice and research with DOC. However, both disciplines may be considered as at

the start of a long journey of enquiry in this complex field, where patients have highly

heterogeneous pathologies, complex and multiple disabilities, and fluctuating arousal levels,

which may confound the best attempts to assess and rehabilitate them. Herein lies the

primary limitation of the research detailed in this thesis. Nonetheless, the study has been

undertaken in a naturalistic fashion, using archived clinical data, and collected measures of

responses to music therapy treatments provided by a trained music therapist within a clinical

setting. Therefore, significant responses noted in the thesis may be considered as

noteworthy in spite of the confounding factors, and in contrast with studies involving

laboratory based procedures or more invasive techniques such as fMRI, the findings are all

the more noteworthy for their authenticity.

Given the lack of understanding and empirical research in this area, the study is necessarily

of a pilot, exploratory nature. This is an important caveat in relation to the use of the term

‘significance’ in the thesis. The lack of known, appropriate, singular measures of arousal or

awareness precluded the use of power calculations to determine the numbers of subjects

required for significance testing in its fullest sense, so type I and II errors cannot be ruled out.

However, it should be noted that the studies provide data from the largest numbers of

subjects in research of its kind.

The music featured in study two (in particular LM and DM) comprised heterogeneous tempo,

harmonic, rhythmic and lyrical content. The lack of standardisation in this area may well have

provided a confounding effect on the data which could in part be responsible for the

divergent results, particularly in the physiological measures noted previously. However, it

would be antithetical to provide these musical items in standardised form in relation to

musical elements, as this would possibly obscure any elicitation of responses based on intact

memory function. Furthermore, standardised, recorded music arguably loses some of the

unique power of live performance in eliciting arousal or awareness responses. Certainly the

pre-recorded disliked music data in study two was notable for its lack of significant responses

across cohorts and measures. Finally, due to the limited resources and time scale of this


61

study, patients did not receive auditory brain stem testing to exclude patients with

undiagnosed hearing impairment, which may have provided a further confounding element to

the findings.


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9. Conclusions

This thesis addresses the lack of empirical evidence supporting music therapy in the

assessment and treatment of those with DOC. The shared belief of 'humanist/music centred'

and 'behavioural/pragmatic' clinicians that music therapy has powers to reach even the most

profoundly injured VS patients detailed in Paper I finds initial support in data from

assessment records in Paper II. In addition to the high levels of diagnostic agreement found

between music therapy and multimodal assessments, the use of musical stimuli in the

MATADOC was found to elicit unique responses which might be missed in global

assessments with less focus on the auditory domain.

Through a comparison of a range of responses to music therapy found in both healthy and

patient cohorts, Paper III offers further empirical support for music therapy assessment

with DOC patients. The paper provides a comprehensive record of DOC patients’ responses

to music therapy, in varying states of arousal, with heterogeneous pathologies, disabilities

and drug regimes. Whilst the studies in this thesis account for the largest samples found in

comparable research, the significance of findings may lack the robustness larger samples

offer, and so caution is needed in relation to interpreting their significance. Nonetheless,

despite many potential confounding issues, music therapy, in particular the live performance

of preferred music, produced significant increases in blink rate within the VS cohort,

concurrently with significant changes in neurophysiological measures at the within-subject

level. These findings contribute to our understanding of mechanisms underpinning the

behavioural responses elicited by the MATADOC. Furthermore, they emphasise the need to

appreciate the unique response profiles of each patient, be they diagnosed as VS or MCS,

and the distinctive contribution combined music therapy and neurophysiological assessment

may provide in revealing intact responsiveness to salient stimuli, even in patients

behaviourally assessed as ‘unaware’ of themselves and their environment.

Research exploring the behavioural and neurophysiological responses noted in Paper III in

follow up assessments is indicated, to determine their utility as prognostic indicators.

Furthermore, given our understanding of arousal in supporting awareness, and the positive

effects of music on neuroplasticity, a rationale is provided for harnessing the effects of music

therapy for rehabilitation with this population. Findings also indicate how the combination of

music therapy with neurophysiological assessment may offer a novel aid to detecting


63

awareness, as measured by the patients’ discriminatory cortical responses. This combination

offers potential advantages to more invasive, expensive assessments such as fMRI, which

are not applicable to all patients. Thus this thesis provides pilot level evidence that music

therapy can contribute to diagnosis of awareness in those with DOC, through effecting

behavioural and neurophysiological change associated with arousal and awareness.

Findings indicate potential for harnessing these responses both as prognostic indicators, and

to improve clinical outcomes through rehabilitation, which merits further investigation.


64

10. Summary

This thesis comprises research undertaken within a large UK neuro-rehabilitation unit aimed

at developing the evidence base for music therapy in the assessment of those with Disorders

of Consciousness (DOC), which is detailed in three peer reviewed papers. The papers

comprise a literature review, an audit of concurrent music therapy and global assessment

data, and a within-subjects neurophysiological and behavioural study of healthy and DOC

responses to music therapy and other auditory stimuli. This summary details the background

and theoretical framework for the study, and by doing so outlines Paper I: 'Music therapy with

disorders of consciousness and neuroscience: the need for dialogue', followed by summaries

of the two research papers.

BackgroundNeuro-rehabilitation is a dynamic process aimed at maximizing physical, psychological and

social functioning. Two frameworks underpin modern neuro-rehabilitation:

(i) Evidence Based Medicine (EBM) - the judicious used of clinically and scientifically

derived evidence to guide treatment decisions (Sackett et al., 2007)

(ii) Physical Rehabilitation Medicine (PRM) - an approach acknowledging the

interdependency of the individual with their environment, and value of

multidisciplinary input in meeting rehabilitative goals effectively (Stucki & Melvin,

2007).

DOC primarily comprise Vegetative States (VS) with retained sleep/wake cycles without

awareness, and Minimally Conscious States (MCS), where some form of awareness is

observed. The detection of consciousness is pivotal to the diagnosis of VS or MCS (Aspen

Neurobehavioral Conference Workgroup, 1996).

The music therapy literature contains a range of ‘rationale building’ material supporting the

use of music therapy with DOC, based on practical, neurological, psychological and social

observations. The practice of music therapy with those with DOC is characterised by two

contrasting models in the literature:


65

(i) the Humanist/Music Centered model, advocating the existence of a ‘mind’ or ‘soul’

separate from the body in our conception of consciousness (e.g. Aldridge, Gustorff &

Hannlich, 1990; Gustorff, 1995; Gustorff, 2002).

(ii) the Behavioural/Pragmatic model where consciousness is defined by brain function,

and consequently DOC by the lack thereof (e.g. Baker & Tamplin, 2006; Boyle, 1994;

Boyle & Greer, 1984; Magee, 2005; Magee et al. 2013; O’Kelly & Magee 2013 a & b).

Most research in this field contains methodological weaknesses and an inconsistent use of

diagnostic terminology (O'Kelly & Magee, 2013a). However, modern brain scanning studies

are revealing a wide range of ways in which music affects physiological states, cognition and

mood in healthy individuals. Whilst it is unclear how music may affect such states and

processes for those with DOC, the evidence from both healthy and stroke studies suggests a

potential role for music therapy in enhancing attention and supporting neuroplasticity to

produce functional gains in vision, speech and cognition (e.g. Särkomo et al., 2008; Schlaug,

Maechina & Norton, 2008; Soto, Funes, Guzman-Garcia, Warbrick, Rotshtein, & Humphreys,

2009).

The prominent model of consciousness within EBM and PRM views consciousness as

comprising:

(i) arousal function, or the ‘level’ of consciousness , which is required for

(ii) awareness, or the ‘contents’ of consciousness or the ability of the brain to process

sensory information (Giacino & Whyte, 2005).

Modern neuro-rehabilitation methods state that for consciousness to be present, individuals

must be awake, able to process internal and external stimuli, and able to demonstrate goal

directed behaviour (Giacino, 1997). However, there exists a debate on a range of issues

relating to assessment of DOC, chiefly:

(i) what level of awareness and functional capacity of the brain should be considered as

sufficient for consciousness

(ii) how reliable neuro-imaging data is in revealing 'covert' awareness not evident from

behavioural assessment

(iii) the functional capacity of those in VS in relation to auditory, language and pain

processing.


66

Research questionsThe primary research question for this thesis is:

1. Can music therapy treatment effect physiological and behavioural changes suggesting

arousal and awareness to contribute to diagnosis in assessment of patients with DOC?

(Papers II and III)

In order to answer this question, the following sub-questions are addressed :

2. Specifically what do concurrent music therapy and multimodal assessments reveal about

DOC patients in relation to their responsiveness to auditory and musical stimuli? (Paper II)

3. What information will a combined behavioural and neuro-physiological examination of VS,

MCS and healthy individuals presented with different music therapy treatments reveal in

relation to:

a) the differing effects of the treatments within and between individuals

and diagnostic groups i.e., healthy volunteers, VS and MCS (Paper III)

b) DOC patients and their assessment through means of standardised behavioural

assessments alone? (Paper III)

These research questions are addressed in the following summaries of Paper's II and III.

Paper II: The complementary role of music therapy in the detection of awareness in disorders of consciousness: An audit of concurrent SMART and MATADOC assessments

The aim of this study was to address research question two: 'Specifically what do concurrent

music therapy and global assessments reveal about DOC patients in relation to their

responsiveness to auditory and musical stimuli?' In doing so, it was hoped the study could

also add to the evidence base in relation to the main research question, i.e. whether music

therapy might affect behavioural changes which might contribute to the diagnosis of

awareness state.


67

The study used five years of archived patient records where patients had received

concurrent assessments with the multimodal 'Sensory Modality Assessment and

Rehabilitation Technique' (SMART) (Gill-Thwaites, 1997; Gill-Thwaites & Munday, 2004) and

the ‘Music Therapy Assessment Tool for Disorders of Consciousness’ or ’MATADOC’

(Magee et al., 2013), which focuses on patients’ behavioural responses to musical stimuli. A

total of 42 records were retrieved (25 male, 17 female), where assessments were conducted

within 4 weeks of each other (mean: 5.45 days, SD=9). Inclusion criteria comprised patients

aged 18–75 years, with complete SMART and MATADOC assessments undertaken within 4

weeks of each other during a 5 year period between January 2007 and January 2012.

Records were excluded where sections of the assessment hard copy were missing. In cases

where diagnostic outcome of either tool was unclear (n: 6), expert opinion was sought from a

music therapist or occupational therapist experienced in using and analysing the assessment

data for MATADOC and SMART. Data were analysed in SPSS (ver. 20) for statistical

analysis using descriptive statistics for central tendency, dispersion and correlation.

Whilst the two tools produced a high level of agreement in diagnostic outcome (rs 0.8),

divergent diagnosis and weaker correlations between behavioural response items highlighted

contrasting sensitivities of the tools. For example, MATADOC displayed higher sensitivity

within auditory and visual domains relative to SMART, but SMART data indicated higher

sensitivity in the motor domain. In addition, the important contribution of musical response

items in MATADOC, and the tactile response item in SMART, highlighted that both tools

provide unique behavioural data predictive of awareness. The study supports the

recommendation of Giacino et al. (2002) that given contrasting strengths of assessment tools

and heterogeneity of the DOC responses to stimuli, combining these tools provides

complementary data contributing to a fuller understanding of a patient’s level of awareness.

Paper III: Neurophysiological and behavioural responses to music therapy in vegetative and minimally conscious states

The second study was designed to address the primary research question 'Can music

therapy treatment effect physiological and behavioural changes suggesting arousal and

awareness to contribute to diagnosis in the assessment of patients with DOC?' In doing so

the study also aimed to address sub-questions: 'What information will a combined

behavioural and neurophysiological examination of VS, MCS and healthy individuals

presented with different music therapy treatments reveal in relation to a) the differing effects


68

of the range of techniques within and between individual and diagnostic groups and b) DOC

patients and their assessment through means of standardised behavioural assessments

alone?

The literature covering neurophysiological and behavioural assessment of DOC and normal

human neurophysiological responses to music was reviewed to contextualise this study. The

review indicated a number of useful measures such as heart rate variability (HRV),

electroencephalogram (EEG) recordings might be used to assess for indications of arousal,

attention and cognitive processes associated with awareness, particularly in relation to

auditory stimuli such as music. Thus a rationale for a multiple baseline within subjects study

to address the above questions was made, where EEG, heart rate (HR), heart rate variability

(HRV), respiration and behavioural responses contingent to music therapy and other auditory

stimuli were compared within individuals and between with healthy, VS and MCS cohorts.

The study was undertaken with patients at the same unit as the first study, where recruitment

comprised 20 healthy subjects (13 female and 7 male) with 12 patients diagnosed as VS (6

female, 6 male) and 9 as MCS (5 male, 4 female). Following five minutes of baseline silence

(BLS), subjects were presented with procedures typically used in music therapy: live

preferred music (LM) and improvised music entrained to respiration (EI). They were also

presented with recordings of disliked music (DM), and white noise (WN). Stimuli were

presented in randomised order to control for order effects.

Post hoc ANOVA tests indicated a range of significant responses (p ≤ 0.05) across healthy

subjects corresponding to arousal and attention in response to LM, including concurrent

increases in respiration rate with globally enhanced EEG amplitude responses across brain

regions and frequency bandwidths delta, theta, alpha and beta (p ≤ 0.05). Responses were

most significant in right frontal and temporal regions.

Whilst physiological responses were heterogeneous across patient cohorts, mean frontal

midline theta (FMT) increased significantly for LM in half (n: 6) of cases where ANOVA's

were significant (p ≤ 0.05), and peaked significantly for LM in 4 MCS cases (44%). Frontal

alpha amplitude changed significantly in 3 VS and 4 MCS subjects (p = 0.05 - 0.0001), with

the latter contributing to the significant finding for frontal alpha across the MCS cohort [F(4,

1850.1) =36.5, p < 0.001] with a peak for LM [post hoc contrast F(1, 809) = 50.6, p < 0.001].

Furthermore, behavioural data showed a significantly increased blink rate for LM (p = 0.029)

within the VS cohort. Two VS cases are presented in Paper III with concurrent changes (p ≤

0.05) across measures indicative of discriminatory responses to both music therapy


69

procedures. A third MCS case study is presented highlighting how more sensitive selective

attention may distinguish MCS from VS.

DiscussionPaper IIThe first study (Paper II) compared archived information on 42 patients’ behavioural

responses to musical stimuli in a music therapy assessment (MATADOC) and a wider range

of sensory stimuli in concurrent SMART records. It is first worth noting the high level of

diagnostic agreement between MATADOC and SMART (rs 0.80, p< 0.01, 2 tailed). This

indicates that behavioural assessment for awareness based on primarily musical stimuli is

able to produce a strong agreement with outcomes from SMART, a well-established,

multimodal assessment tool undertaken in ten sessions compared to MATADOC's four. This

is supported by the standardisation study by Magee et al., (2013) which reports 100%

diagnostic agreement with SMART from 21 records, under rigorous research conditions.

The range of statistical tests conducted upon MATADOC's 15 domain measures in relation to

diagnosis highlighted sensitive, discriminatory responses (i.e., with a correlation of rs ≥ 0.6

with diagnosis) in the 'behavioural responses to music', 'attention to task' domains. These

findings provide evidence from clinically derived data that music therapy can elicit unique

behavioural responses with diagnostic power in relation to the detection of awareness. In

addition, more sensitive responses were found in the MATADOC auditory and visual

domains compared to SMART 'consistent' response domains (auditory rs 0.79 compared to

SMART's rs of 0.38, and visual rs 0.79 compared to SMART rs of 0.55). These higher

correlations with diagnosis suggest the musical focus and use of more complex auditory

stimuli are more effective for discriminating awareness within the auditory domain, and may

have some form of synergistic effect to produce greater sensitivity within the visual domain.

Paper III: Healthy DataThere is a lack of normative or 'healthy' data available to guide clinicians and researchers

using receptive music therapy methods. Aside from addressing the thesis research

questions, study two (Paper III) provides a useful contribution to this field. The findings of

significant increases in respiration rate (RR) in relation to listening to LM are noteworthy. The

RR for all musical stimuli (LM, DM and EI), were compared to the tempo of the

accompanying music, to indicate no substantive unconscious 'entrainment' relationship

between RR and the tempo of music listened to. This finding indicates that these responses

are related to cortically mediated, emotional, or 'top down' processes, according to Salimpoor


70

et al. (2009), thus may provide a useful benchmark in comparing with patient responses,

where individuals are often unable to communicate verbally or non-verbally.

In relation to the literature on HR and HRV and music listening detailed in Paper III (p. 2-3),

this study provides little support for time or frequency domain measures providing consistent

benchmarks for healthy 'aware' responses to the music therapy methods used in the study.

However, whilst the ANOVA tests revealed no significant change across the healthy cohort,

ANOVAs conducted on segmented data at the within-subject level did reveal a range of often

divergent significant change. Thus, it appears that normal HR and HRV responses to music

therapy methods are idiosyncratic and divergent between individuals, yet often significant at

the within-subject level.

There is a growing understanding of neuroplasticity in neuro-rehabilitation, or how the brain

is capable of re-organisation and self-modification following neurological trauma (Johansson

& Grabowski, 1994; Mateer & Kerns, 2000; Stein, 2009). Listening to 'pleasant' and preferred

music has been shown to be effective in promoting neuroplasticity to meet functional goals

for those with acquired brain damage such as decreasing visual neglect (Särkamo & Soto,

2012; Soto et al., 2009), and improving cognitive function (Särkamo et al., 2010). The

findings of significant globally enhanced post hoc EEG amplitude responses for LM (p ≤

0.05) across EEG bandwidths resonate with this literature. Furthermore, the EEG data

coupled with the RR increases observed for LM provides evidence from a normative

perspective for the utility of using this music therapy procedure to support arousal with DOC.

Paper III: Patient DataThe diagnosis of VS as defined by the Aspen Neurobehavioral Conference Workgroup

group (1996) is “a condition in which awareness of self and the environment is presumed to

be absent and there is an inability to interact with others, although the capacity for

spontaneous or stimulus-induced arousal (i.e., wakefulness) is preserved”. Furthermore, the

task force stated that there should be 'no evidence of sustained, reproducible, purposeful, or

voluntary behavioural responses to visual, auditory, tactile, or noxious stimuli' and 'no

evidence of language comprehension or expression' (p. 8). In relation to the above DOC

nosology the findings of study two make interesting and thought provoking reading.

Across the VS cohort, significant increases in blink rate were observed for LM, accompanied

by half (n: 6) of VS patients displaying significant post hoc increases of EEG amplitude in the

theta frequency in the frontal midline region (FMT) and 3 for the alpha bandwidth in the

frontal region, with 2 subjects also displaying significant increases in RR for LM in a similar


71

fashion to the healthy cohort. In some cases these heightened responses for LM occurred

concurrently in individuals. These findings suggest that despite the heterogeneity of DOC

pathology, LM provides a powerful stimulus in relation to eliciting a range of unique

responses across VS and MCS cohorts, which is noteworthy in relation to studies with

healthy and other populations. For example, the literature on FMT points to activation of

hippocampal and anterior cingulate cortex regions involved in memory, motivation, decision

making, processing information, and attention in healthy individuals (Mitchell, McNaughton,

Flanagan, & Kirk, 2008). Blink rate is correlated positively with dopaminergic system activity,

arousal (Karson, Dykman & Paige 1990), attention (Abe et al., 2011; Irwin, 2011) and

creativity (Chermahini & Hommel, 2010).

Despite the lack of clear behavioural evidence of awareness, change in neurophysiological

measures occurring at peak levels in relation to the uniquely dynamic and multi layered

stimuli of LM suggests a form of selective attention was elicited in some cases. Whilst these

covert responses may not be considered as 'purposeful' in the behavioural sense, they were

significant post hoc, and sustained throughout the stimulus presentation. Furthermore, whilst

it is unclear whether heightened responses observed for LM and EI relate to the musical or

lyrical content of the stimuli, some form of language or music syntactical processing cannot

be ruled out.

Neuroimaging studies point to intact auditory (Laureys et al., 2000), emotional, verbal, (Schiff

et al., 2002), pain (Kassubek et al., 2003) and language processing (Coleman et al., 2007),

and 'cortical learning' (Kotchoubey et al., 2006) in VS. Several leading authorities stress that

these 'modular' responses may only represent isolated behaviours, evidencing a disconnect

between primary cortex, thalamus, multi-modal or limbic regions and higher order

integrative /associative cortices in correctly diagnosed VS (Boly et al., 2004; Laureys et al.,

2002). However, heightened responses noted for VS patients in the study occurred at

significant post hoc peak levels for LM and/or EI in some cases. As LM and EI are stimuli

which may stimulate language, memory and emotional processing in response to its lyrical

and/or musical content, it seems hard to conceive of these responses as merely 'isolated' or

modular responses. LM in particular may relate to historical events in one's personal life,

such as weddings and other significant life events. Given the unique relationship between

these responses and LM, they might relate beyond Damasio's (2010) 'primordial feelings' to

his conception of 'full consciousness', defined in terms of the involvement of biographical

knowledge (pp. 22-23). Furthermore Tulving (1993) stated that whereas consciousness

should denote the detection of basic sensory events, awareness involves the more advanced


72

interpretation and experience of these events. Using this conceptualisation, it is hard to deny

some of the VS subjects 'consciousness' if not awareness when observing these findings.

It is noteworthy that less discrimination between music therapy conditions and WN

characterised pooled VS data in a manner resonating with the concept of 'hypoarousal',

where subjects are unable to distinguish relevant from irrelevant information (Heilman,

Schwartz, & Watson, 1978). Discrimination evidenced by heightened cortical activation in

fMRI studies to auditory stimuli with emotional relevance has also been considered a defining

feature of MCS (Laureys, Owen, & Schiff, 2004). Harnessing EEG technology alongside

music therapy assessment in this manner may provide complementary data for clinicians to

draw upon when assessing for awareness and prognostic indicators. Thus, when coupled

with the behavioural data, compelling, albeit pilot level, support is given for music therapy

promoting neurophysiological responses associated with both arousal and awareness.

Limitations Given the lack of understanding and empirical research in this area, the study is necessarily

of a pilot, exploratory nature. This is an important caveat in relation to the use of the term

‘significance’ in the thesis. The lack of known, appropriate, and singular measures of arousal

or awareness precluded the use of power calculations to determine the numbers of subjects

required for significance testing in its fullest sense, so type I and II errors cannot be ruled out.

Nonetheless, the study uses the largest numbers of subjects in research of its kind to date. It

should also be noted that the music featured in study two (in particular LM and DM)

comprised heterogeneous tempo, harmonic, rhythmic and lyrical content. The lack of

standardisation in this area may well have provided a confounding effect on the data, thus

explaining the divergent results, particularly in the physiological measures. However, it would

be antithetical to provide these musical items in standardised form, as this would possibly

obscure any elicitation of responses based on intact memory function. Finally, due to the

limited resources and time scale of this study, patients did not receive auditory brain stem

testing to exclude patients with hearing impairment, which may have provided a further

confounding element to the findings.

Conclusions


73

This thesis addresses the lack of empirical evidence supporting music therapy in the

assessment and treatment of those with DOC. The shared belief of 'humanist/music centred'

and 'behavioural pragmatic' clinicians that music therapy has powers to reach even the most

profoundly injured VS patients detailed in Paper I finds initial support in data from

assessment records in Paper II. In addition to the high levels of diagnostic agreement found

between music therapy and global assessments, the use of musical stimuli in the MATADOC

was found to elicit unique responses which might be missed in global assessments with less

focus on the auditory domain.

Through a comparison of a range of responses to music therapy found in both healthy and

patient cohorts, Paper III gives further empirical support for music therapy in this field.

The paper provides a comprehensive record of DOC patients’ responses to music therapy, in

varying states of arousal, with heterogeneous pathologies and drug regimes. Despite these

confounding elements, music therapy, in particular the live performance of preferred music,

produced significant increases in blink rate across the VS cohort, concurrently with significant

changes in neurophysiological measures in several cases. These findings emphasise the

need to appreciate the unique response profiles of each patient, be they behaviourally

diagnosed as VS or MCS.

Given our understanding of arousal in supporting awareness, and the positive effects of

music on neuroplasticity, a rationale is provided by these findings for exploring the use of

music therapy in DOC rehabilitation. Differences observed between VS and MCS subjects

also highlight the enhanced ability of MCS patients to discriminate between meaningful and

meaningless stimuli. The combination of music therapy with neurophysiological assessment

may offer a novel aid to detecting awareness, as measured by the patients’ discriminatory

cortical responses. This combination offers potential advantages to more invasive, expensive

assessments such as fMRI, which are not applicable to all patients. Furthermore research

exploring responses observed here for their prognostic value is indicated.

In summary, this thesis provides pilot level evidence that music therapy can contribute to

assessment with DOC through effecting behavioural and neurophysiological change

associated with arousal and awareness, which may also be of prognostic value. The findings

indicate the potential for harnessing responses to music therapy to improve clinical outcomes

through rehabilitation, which merits further investigation.

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Appendix I


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Appendix 2


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Appendix 3a

Co-author statement in connection with submission of PhD thesis

With reference to Ministerial Order no. 18 of 14 January 2008 regarding the PhD Degree § 12, article 4, statements from each author about the PhD student’s part in the shared work must be included in case the thesis is based on already published or submitted papers.

Paper title: Music therapy with disorders of consciousness and neuroscience: the need for dialogue.

Publication outlet: Nordic Journal of Music Therapy (2013), 22(2), 93-106.

List of authors: O'Kelly, J., Magee, W.,

Description of authors’ roles:

Julian O’Kelly (JOK)

Principal Investigator, and author of the study, responsible for data collection, analysis and writing up of the paper.


As the principal authors PhD supervisor, responsible at all stages of the design, data collection and writing up of the study for ensuring the JOK was working to a level expected of a PhD candidate. This responsibility was undertaken through monthly supervision, email correspondence, and reviewing of the paper, including editorial input.

I hereby confirm the statement above is true and accurate.

Signed………………………………… Date:……………………………


Signed………………………………… Date:……………………………

Julian O’Kelly


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Appendix 3b



Paper title: O'Kelly, J. and Magee, W.L. (2012). The complementary role of music therapy in the detection of awareness in disorders of consciousness: an audit of concurrent SMART and MATADOC assessments..

Publication outlet: Neuropsychological Rehabilitation (2012), 23(2), 287-298 List of authors: O'Kelly, J., Magee, W.,



Principal Investigator, and author of the study, responsible for data collection, analysis and writing up of the paper.



I hereby confirm the statement above is true and accurate.

Signed………………………………… Date:……………………………


Signed………………………………… Date:……………………………

Julian O’Kelly


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Appendix 3c



Paper title: Neurophysiological and behavioural responses to music therapy in vegetative

and minimally conscious states

Publication outlet: Frontiers in Human Neuroscience.

List of authors: O'Kelly, J., Magee, W., James, L., Palaniappan, R., Taborin, J., Fachner, J.



Principal Investigator, research clinician and author of the study forming the basis of the paper, responsible for data collection, analysis and writing up of the paper.



Dr Leon James

As a research neurophysiologist employed at JOK’s workplace, responsible for teaching JOK the clinical skills required for the application of EEG recording, assisting with patient data collection, and technical support in the use and interpretation of EEG software.

Dr Ramaswamy Palaniappan

As a reader and senior lecturer in Signal Analysis, Dr Palaniappan provided on-going support during data collection and analysis by designing bespoke MATLAB software for the a analysis of physiological and EEG data, and support in its use and interpretation.

Jana Tamborin

Ms Tamborin was the independent observer for the behavioural component of the study. She assisted JOK by viewing video material from research sessions and recording behavioural


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data in a excel spread sheet she designed, for further analysis by JOK using statistical software (SPSS).

Professor Jörg Fachner

Professor Fachner contributed to the publication by reviewing the EEG data proposed for inclusion in the paper and discussing JOK's interpretation of this data in relation to his experience in this field

We hereby confirm the statement above is true and accurate.

Signed………………………………… Date:……………………………

Signed………………………………… Date:……………………………

Julian O’Kelly


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Thesis Papers I, II & IIINote on Publications and Copyright

Due to copyright restrictions in relation to the online version of this thesis, the following sections of this thesis do not contain full copies of Papers I II and III, rather publication details and the front page of each paper. However, a full copy of Paper III is available for free, as this is an open access paper. You may download the PDF of the paper from the drop down menu at:

http://www.frontiersin.org/Human_Neuroscience/10.3389/fnhum.2013.00884/abstract


http://www.frontiersin.org/Human_Neuroscience/10.3389/fnhum.2013.00884/abstract

101

Paper I

The following is the first page of an article: O'Kelly, J., & Magee, W.L. (2013). Music

therapy with disorders of consciousness and neuroscience: the need for dialogue. Nordic

Journal of Music Therapy. 22(2), 93-106 doi: 10.1080/08098131.2012.709269

The paper is available electronically from:

http://www.tandfonline.com/doi/abs/10.1080/08098131.2012.709269


http://www.tandfonline.com/doi/abs/10.1080/08098131.2012.709269

102


103

Paper II

The following is the first page of an article: O'Kelly, J., & Magee, W.L. (2013). The

complementary role of music therapy in the detection of awareness in disorders of

consciousness: an audit of concurrent SMART and MATADOC assessments.

Neuropsychological Rehabilitation, 23(2), 287-298.

doi:10.1080/09602011.2012.753395

The paper is available electronically from:

http://www.tandfonline.com/doi/full/10.1080/09602011.2012.753395#.UwtOLidTLcs


http://www.tandfonline.com/doi/full/10.1080/09602011.2012.753395#.UwtOLidTLcs

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Paper III

The following is the first page of an article: O'Kelly J., Magee, W.L. James, L., Palaniappan,

R., Taborin, J., & Fachner, J. (2013). Neurophysiological and behavioural responses to

music therapy in vegetative and minimally conscious states. Frontiers in Human

Neuroscience. 7:884. doi: 10.3389/fnhum.2013.00884

The paper is available as a free PDF electronic download from:

http://www.frontiersin.org/Journal/10.3389/fnhum.2013.00884/abstract


http://www.frontiersin.org/Journal/10.3389/fnhum.2013.00884/abstract

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Julian O'Kelly

The Development of Evidence Based Music Therapy with Disorders of Consciousness

Dissertation submitted for the degree of Doctor of Philosophy

Department of Communication and Psychology

Aalborg University, Denmark 2014

research environment - vbn.aau.dkvbn.aau.dk/.../195488717/okelly_2014_mt_doc_final_t… · web...

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