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
i
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
ii
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
iii
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
iv
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).
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
v
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 DOCpatientens 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 assessmentvurderinger ('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
(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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
vi
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
vii
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
2.8 Sensory Stimulation and Regulation......................................................................................27
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
viii
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
Reference List ................................................................................................................................ 74
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
ix
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............................................................................................................................................103
Paper III ..........................................................................................................................................105
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
1
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
for Music Perception and Cognition. Paper presented at the meeting of the Society for Music
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
2
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 Neurodisability, 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
3
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
4
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
White noise
WN
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
5
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.
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
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
6
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
7
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 ‘neurorehabilitation’, 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 neurorehabilitation – ‘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
such as ‘x’s heart rate increased by ‘y’ amount indicating an increase in arousal’. In this
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
8
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 Medicine
In 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)
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
9
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 PRMinterventions 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 Therapy
There 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 Consciousness
There 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
10
2.5.1 The Humanist Perspective
In 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 Perspective
With 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,
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 Consciousness
One 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
12
James described consciousness as predicated upon 'awareness of the self and the
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 Arousal
In 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
13
system’ (ARAS), residing in part of the upper brain stem, in our sleep-wake cycles and
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
14
irrelevant information (Heilman, Schwartz, & Watson, 1978; Testa Flaada, 2011). A useful
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
16
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
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
17
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
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 Coma
Coma 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
18
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
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
19
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
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
20
(Wilson, Brock, Powell, Thwaites & Elliott, 1996). More details on these contrasting views
are provided in Paper I (pp. 95-97).
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
21
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
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;
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
22
III.
Reaching for objects that demonstrates a clear relationship between object location
and direction of reach;
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,
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
23
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).
2.7 Assessment of DOC
The differential diagnoses of VS and MCS have significant implications on the nature of ongoing 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 medicolegal 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 Assessment
Music 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,
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
24
2009), respiration rate changes (Bernardi et al., 2006; Blood & Zatorre, 2001; Khalfa et al.,
2008; Krumhansl, 1997), and electrodermal responses (Koelsch, 2005; Krumhansl, 1997).
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
25
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
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
26
claim we may detect covert wilful or voluntary responses, without the need for observation of
behavioural responses such as speech or movement (2010).
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. TurnerStokes 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 DOC
The 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
27
DOC population it is recommended that a combination of different tools should be used in
assessment (Giacino et al., 2002).
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
28
(ii) humanitarian: early awakening from coma may ameliorate anxiety levels for both patient
and family
(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 Stimulation
Anecdotal 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
29
2.8.2 Sensory Regulation
Wood (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
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 nonspecific 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
30
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
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
31
2.8.3 Neuroplasticity
As 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
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 questions
The 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)
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 Strategy
To 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 Recruitment
A 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 nonmusical 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; GillThwaites 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 prerecorded 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,
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
38
1997; Gill-Thwaites & Munday, 2004). SMART incorporates the use of loud sound, bright
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 Materials
Data 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 Protocol
A 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
40
EEG data were obtained using a common average montage and 10:20 electrode
configuration. Due to the presence of craniotomies amongst patients, free electrode
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 Analysis
Raw 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
41
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
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. Ongoing 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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. 291296) and the summary of Paper II in this thesis.
6.1 Results from Healthy Data
Further 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
differences for θ in the frontal midline (FMT) region were particularly noteworthy, where a
3
4
Significance henceforth denoted by p ≤ 0.05
'increases' and 'decreases' henceforth in relation to post hoc ANOVA contrasts with BLS
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
43
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 Data
All 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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).
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
47
Methodology
The 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).
Results
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
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
48
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
use of more complex auditory stimuli have some form of synergistic effect on enhancing
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
49
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
Key
RPM: Respirations per minute
BPM: Beats per minute
RPM
BPM
RPM
BPM
Liked Music
Liked Music
Disliked Music
Disliked Music
RPM
Ent. Improv.
BPM
Ent. Improv.
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 intervals
6 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 Responses
One 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 Responses
As 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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,
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
56
Table 1: Significant Change in Patient Physiological Measures
Patients with Significant
Post Hoc Peak Mean
ANOVA's (p ≤ 0.05)
(n of patients in brackets)
VS
9
WN (3),LM (3), BLS (2), DM (1)
MCS
5
WN (3), LM (1), BLS (1)
Heart Rate
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)
VS
5
LM (2), DM &LM (1) DM (1), BLS (1)
MCS
4
LM (3), EI (1),
RMSSD
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 stimulusinduced 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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 Limitations
Both 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
62
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
awareness, as measured by the patients’ discriminatory cortical responses. This combination
offers potential advantages to more invasive, expensive assessments such as fMRI, which
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
63
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
Background
Neuro-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:
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
66
Research questions
The 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
67
therapy might affect behavioural changes which might contribute to the diagnosis of
awareness state.
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
68
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),
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)
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
69
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
procedures. A third MCS case study is presented highlighting how more sensitive selective
attention may distinguish MCS from VS.
Discussion
Paper II
The 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 Data
There 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
70
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
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 Data
The 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
71
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
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
72
knowledge (pp. 22-23). 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' 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
73
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 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.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
74
Reference List
Abe, T., Nonomura, T., Komada, Y., Asaoka, S., Sasai, T., Ueno, A., & Inoue, Y. (2011).
Detecting deteriorated vigilance using percentage of eyelid closure time during
behavioural maintenance of wakefulness tests. International Journal of
Psychophysiology, 82(3), 269-274. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.082655162002&partnerID=40&md5=91e76ea01d7803acf88256080aa2164e
Adams, J. H., Graham, D. I., & Jennett, B. (2000). The neuropathology of the vegetative
state after an acute brain insult. Brain, 123 (Pt. 7), 1327-1338.
Aldridge, D., Gustorff, D., & Hannlich, H. (1990). Where am I? Music therapy applied to coma
patients. Journal of the Royal Society of Medicine, 83, 345-346.
Aldridge, D. (1991). Spirituality, healing and medicine. British Journal of General Practice,
41(351), 425-427.
Altenmüller, E, E., Schürmann, K., Lim, V.K., & Parlitz, D. (2002). Hits to the left, flops to the
right: Different emotions during listening to music are reflected in cortical lateralisation
patterns. Neuropsychologia 40, 2242-2256.
American Congress of Rehabilitation Medicine. (1995). Recommendations for use of uniform
nomenclature pertinent to persons with severe alterations in consciousness. Archives
of Physical Medicine and Rehabilitation, 76, 205-209.
Andrews, K. (1993). Recovery of patients after four months or more in the persistent
vegetative state. British Medical Journal, 306(6892), 1597-1600.
Andrews, K. (1998). Prediction of recovery from post-traumatic vegetative state. Lancet,
351(9118), 1751. doi:S0140-6736(05)78740-7
Andrews K. (2005) Rehabilitation practice following profound brain damage.
Neuropsychological Rehabilitation,15:461–472.
Andrews,K., Duport,S., Haynes S., & Gale, E. (2005). Mental Capacity Act 2005: Research
involving people with complex neurological disabilities. London: Royal Hospital for
Neuro-disability.
Ansdell, G. (1996). Talking about music therapy: A dilemma and a qualitative experiment.
British Journal of Music Therapy, 10 (1), 4-16.
Ansell, B. J., & Keenan, J. E. (1989). The Western Neuro Sensory Stimulation Profile: A total
for assessing slow-to-recover head-injured patients. Archives of Physical Medicine
and Rehabilitation, 70(2), 104-108. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.00024502636&partnerID=40&md5=16e54688f463fb9916a134b28891984f
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
75
The Aspen Neurobehavioral Conference Consensus Statement on the Vegetative and
Minimally Conscious States. Aspen Neurobehavioral Conference Workshop (1996,
March) In: Proceedings of the Aspen Neurobehavioral Conference. Aspen, CO:
Biomedical Institute.
Baker, F.(2001). Rationale for the effects of familiar music on agitation and orientation levels
of people experiencing post-traumatic amnesia. Nordic Journal of Music Therapy,
10(1), 32-41.
Baker, F., & Roth, E. (2004). Neuroplasticity and functional recovery: training models and
compensatory strategies in music therapy. Nordic Journal of Music Therapy, 13(1),
20-32.
Baker, F., & Tamplin, J. (2006). Interventions for patients in altered states of consciousness.
In F. Baker & J. Tamplin (Eds), Music therapy methods in neurorehabilitation (pp. 3961). London: Jessica Kingsley.
Barnes, M. P. (1999). Rehabilitation after traumatic brain injury. British Medical Bulletin,
55(4), 927-943. Retrieved from http://www.scopus.com/inward/record.url?eid=2-s2.00033437140&partnerID=40&md5=c9d2aee253332fdaa1243ff04cf1b2c7.
Bernardi, L., Porta, C., & Sleight, P. (2006). Cardiovascular, cerebrovascular, and respiratory
changes induced by different types of music in musicians and non-musicians: The
importance of silence. Heart, 92, 445-452.
Bhattacharya, J., & Petsche, H. (2005). Phase synchrony analysis of EEG during music
perception reveals changes in functional connectivity due to musical expertise. Signal
Processing, 85(11), 2161-2177. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.025844469428&partnerID=40&md5=8ab615bdeaed8f927fb0e87efd098b2
Blood, A. J., & Zatorre, R. (2001). Intensely pleasurable responses to music correlate with
activity in brain regions implicated in reward and emotion. Proceedings of the
National Academy of Sciences of the United States of America, 98 (20), 1181811823.
Boiten, F. A. (1994). Emotions and respiratory patterns: Review and critical analysis.
International Journal of Psychophysiology, 17(2), 103-128. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.00028145094&partnerID=40&md5=6fb72101e3793e11541de57948d24ba0
Boly, M., Faymonville, M. E., Peigneux, P., Lambermont, B., Damas, P., Del, F. G.
....Laureys, S. (2004). Auditory processing in severely brain injured patients:
Differences between the minimally conscious state and the persistent vegetative
state. Archives of Neurology, 61(2), 233-238. doi:10.1001/archneur.61.2.233
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
76
Boly, M., Faymonville, M. E., Peigneux, P., Lambermont, B., Damas, F., Luxen, A., Lamy, M.,
... Laureys, S. (2005). Cerebral processing of auditory and noxious stimuli in severely
brain injured patients: Differences between VS and MCS. Neuropsychological
Rehabilitation, 15(3-4), 283-289.
Boyle, M., & Greer, M. D. (1984). Operant procedures and the comatose patient. Journal of
Applied Behaviour Analysis, 16, 3-12.
Boyle, M. (1994). On the vegetative state: Music and coma arousal interventions. In C. Lee
(Ed.), Lonely Waters: Proceedings of the international conference: Music therapy in
palliative care (pp. 163-172). Oxford: Sobell Publications.
Brandao, M. L., Anseloni, V. Z., Pandossio, J. E., de Araujo, J. E., & Castilho, V. M. (1999).
Neurochemical mechanisms of the defensive behaviour in the dorsal midbrain.
Neuroscience and Biobehavioural Reviews, 23(6), 863-875.
doi:S014976349900038X
Bruno, M. A., Vanhaudenhuyse, A., Thibaut, A., Moonen, G., & Laureys, S. (2011). From
unresponsive wakefulness to minimally conscious PLUS and functional locked-in
syndromes: Recent advances in our understanding of disorders of consciousness.
Journal of Neurology, 258(7), 1373-1384. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.079961026623&partnerID=40&md5=e205905be4e271a4de7dfd21ed132641
Cacioppo, J., Tassinary, L., & Berntson, G.G. (2000). Handbook of psychophysiology.
Cambridge: Cambridge University Press.
Calabrese, E. J. (2008a). Stress biology and heresies: The Yerkes-Dodson law in
psychology-a special case of the heresies dose response. Critical Reviews in
Toxicology, 38(5), 453-462. doi:793608206
Calabrese, E. J. (2008b). Converging concepts: Adaptive response, preconditioning, and the
Yerkes-Dodson Law are manifestations of heresies. Ageing Research Reviews, 7(1),
8-20. doi:S1568-1637(07)00035-9
Celesia, G.C. (2013.) Conscious awareness in patients in vegetative states: Myth or reality?
Current Neurology and Neuroscience Reports, 13(395). doi: 10.1007/s11910-13-0130395-7
Chermahini, S. A., & Hommel, B. (2010). The (b)link between creativity and dopamine:
Spontaneous eye blink rates predict and dissociate divergent and convergent
thinking. Cognition, 115(3), 458-465.
Childs, N. L., & Mercer, W. N. (1996). Brief report: Late improvement in consciousness after
post-traumatic vegetative state. New England Journal of Medicine, 334(1), 24-25.
Cohen, R. A. (1993). The neuropsychology of attention. London: Academic Press.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
77
Coleman, M. R., Rodd, J. M., Davis, M. H., Johnsrude, I. S., Menon, D. K., Pickard, J. D., &
Owen, A. (2007). Do vegetative patients retain aspects of language comprehension?
Evidence from fMRI. Brain, 130(Pt.10), 2494-2507.
Coleman, M. R., Bekinschtein, T., Monti, M. M., Owen, A. M., & Pickard, J. D. (2009). A
multimodal approach to the assessment of patients with disorders of consciousness.
Progress in Brain Research, 177, 231-248. doi: 10.1016/S0079-6123(09)17716-6
Callejas, A., Lupines, J., Funes, M. J., & Tudela, P. (2005). Modulations among the alerting,
orienting and executive control networks. Experimental Brain Research, 167(1), 2737. doi:10.1007/s00221-005-2365-z
Craig, P., Dieppe, P., Macintyre, S., Michie, S., Nazareth, I., & Petticrew, M. (2008).
Developing and evaluating complex interventions: the new Medical Research Council
guidance. British Medical Journal, 337, a1655.
Damasio, A. (2010). Self comes to mind - constructing the conscious brain. London:
Heinemann.
Daveson, B., Magee, W., Crewe, L., Beaumont, G., & Kenealy, P. (2007). The music therapy
assessment tool for low awareness states. International Journal of Therapy and
Rehabilitation, 14(12), 545-549.
Demertzi, A., Laureys, A., & Boly, M. (2009). Coma, persistent vegetative states, and
diminished consciousness. In W. Banks (Ed.), Encyclopedia of consciousness (1st
ed., pp. 147-156). Oxford: Elsevier.
Descartes, R. (1985). The Philosophical Writings of Descartes, trans, by John Cottingham,
Robert Stoothoff and Dugald Murdoch. Cambridge: Cambridge University Press, 2,
21-32.
Diamond, D. M., Campbell, A. M., Park, C. R., Halonen, J., & Zoladz, P. R. (2007). The
temporal dynamics model of emotional memory processing: A synthesis on the
neurobiological basis of stress-induced amnesia, flashbulb and traumatic memories,
and the Yerkes-Dodson law. Neural Plasticity, 2007. doi:10.1155/2007/60803
Doman, G., Dimancescu, M. D., Wilkinson, R., & Pelligra, R. (1993). The effect of intense
multisensory stimulation on coma arousal and recovery. Neuropsychological
Rehabilitation, 3, 203-212.
Easterbrook, J. (1959). The effect of emotion on cue utilization and the organization of
behaviour. Psychological Review, 66(3), 183-201.
Etzel, J. A., Johnsen, E. L., Dickerson, J., Tranel, D., & Adolphs, R. (2006). Cardiovascular
and respiratory responses during musical mood induction. International Journal of
Psychophysiology, 61(1), 57-69. Retrieved from
http://www.sciencedirect.com/science/article/pii/S0167876005002850
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
78
Evers, S., Dannert, J., Rodding, D., Rotter, G., & Ringelstein, E. B. (1999). The cerebral
haemodynamics of music perception: A transcranial Doppler sonography study. Brain
122 (Pt 1), 75-85.
Faran, S., Vatine, J. J., Lazary, A., Ohry, A., Birbaumer, N., & Kotchoubey, B. (2006). Late
recovery from permanent traumatic vegetative state heralded by event-related
potentials. Journal of Neurology, Neurosurgery and Psychiatry, 77(8), 998-1000.
doi:77/8/998
Fins, J. J., Schiff, N. D., & Foley, K. M. (2007). Late recovery from the minimally conscious
state: Ethical and policy implications. Neurology, 68(4), 304-307. doi:68/4/304
Galbraith, S., Jennert, B., & Raisman, G. (1978). Recovery from coma and reinnervationrate. Lancet, 1(8066), 710.
Georgiopoulos, M., Katsakiori, P., Kefalopoulou, Z., Ellul, J., Chroni, E., & Constantoyannis,
C. (2010). Vegetative state and minimally conscious state: A review of the therapeutic
interventions. Stereotactic and Functional Neurosurgery, 88(4), 199-207.
Ghiozzi, R (2005) Music therapy in coma states and post coma. In D. Aldridge, J. Fachner &
J. Erkkila (Eds.) Many faces of music therapy. Proceedings of the 6th European Music
Therapy Congress June 16-20 2004. (pp. 1044-1052) Jyvaskyla, Finland. Retrieved
from: http://www.sabinerittner.de/pdf/publikationen/FachRitt.pdf
Giacino, J. T. (1997). Disorders of consciousness: Differential diagnosis and neuropathologic
features. Seminars in Neurology, 17(2), 105-111. doi:10.1055/s-2008-1040919
Giacino, J. T., Ashwal, S., Childs, N., Cranford, R., Jennett, B., Katz, D. I.,... Zasler, N.D.
(2002). The minimally conscious state: definition and diagnostic criteria. Neurology,
58(3), 349-353.
Giacino, J., & Whyte, J. (2005). The vegetative and minimally conscious states: Current
knowledge and remaining questions. Journal of Head Trauma Rehabilitation, 20(1),
30-50. doi:00001199-200501000-00005
Giacino, J., & Kalmar, K. (2006). Introduction to the JFK Coma Recovery Scale-Revised
(CRS-R). The Center for Outcome Measurement in Brain Injury. Retrieved from
http://www.tbims.org/combi/crs
Gilbertson, S. K. (2005). Music therapy in neurorehabilitation after traumatic brain injury: a
literature review. In D.Aldridge (Ed.), Music therapy in neurorehabilitation: performing
health (pp. 83-139). London: Jessica Kingsley.
Gill-Thwaites, H. (1997). The Sensory Modality Assessment Rehabilitation Technique - a tool
for assessment and treatment of patients with severe brain injury in a vegetative
state. Brain Injury, 11, 723-734.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
79
Gill-Thwaites, H., & Munday, R. (1999) The sensory modality assessment and rehabilitation
technique (SMART): a comprehensive and integrated assessment and treatment
protocol of the vegetative state and minimally responsive patient. Neuropsychological
Rehabilitation. 9, 305–320
Gill-Thwaites, H., & Munday, R. (2004). The Sensory Modality Assessment and
Rehabilitation Technique (SMART): A valid and reliable assessment for vegetative
state and minimally conscious state patients. Brain Injury, 18, 1255-1269.
Goldenberg, M. J. (2006). On evidence and evidence-based medicine: Lessons from the
philosophy of science. Social Science & Medicine, 62(11), 2621-2632. doi:S02779536(05)00621-0
Gomez, P., & Danuser, B. (2007). Relationships between musical structure and
psychophysiological measures of emotion. Emotion., 7(2), 377-387. doi:2007-06782014
Gray, D. S. (2000). Slow-to-recover severe traumatic brain injury: A review of outcomes and
rehabilitation effectiveness. Brain Injury, 14(11), 1003-1014.
Gustorff, D. (1995). Herr G. In G. Ansdell (Ed.), Music for life: Aspects of creative music
therapy with adult clients (pp. 59-64). London: Jessica Kingsley.
Gustorff, D. (2002). Beyond words: Music therapy with comatose patients and those with
impaired consciousness in intensive care. In D. Aldridge & J. Fachner (Eds.), info cd
rom iv (pp. 353-377). Witten: University Witten Herdecke.
Gutenbrunner, C., Meyer, T., Melvin, J., & Stucki, G. (2011). Towards a conceptual
description of physical and rehabilitation medicine. Journal of Rehabilitation Medicine,
43(9), 760-764. Retrieved from http://www.scopus.com/inward/record.url?eid=2-s2.080054710553&partnerID=40&md5=57befd8356e26c30a28788d61f829664
Haugeland, J. (1985). Artificial intelligence: The very idea. Cambridge MA: MIT Press.
Heilman, K. M., Schwartz, H. D., & Watson, R. T. (1978). Hypoarousal in patients with the
neglect syndrome and emotional indifference. Neurology, 28(3), 229-232.
Herkenrath, A. (2005). Encounter with the conscious being of people in persistent vegetative
state. In D. Aldridge (Ed.), Music therapy and neurological rehabilitation: performing
health (pp. 139-160).London: Jessica Kingsley.
Hirschberg, R., & Giacino, J. T. (2011). The vegetative and minimally conscious states:
Diagnosis, prognosis and treatment. Neurologic Clinics, 29(4), 773-786. Retrieved
from http://www.scopus.com/inward/record.url?eid=2-s2.080055110802&partnerID=40&md5=ee8b790dec7de41fd2cd5440173908fa
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
80
Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A. C., & Jones, B.E.(1997).
Regional cerebral blood flow changes as a function of delta and spindle activity
during slow wave sleep in humans. Journal of Neuroscience, 17(12), 4800-4808.
Holstege, G., & Georgiadis, J. R. (2004). The emotional brain: Neural correlates of cat sexual
behavior and human male ejaculation. Progress in Brain Research, 143, 39-45.
doi:S0079-6123(03)43004-5
Homberg, V (2005). Evidence based medicine in neurological rehabilitation: A critical review.
Acta Neurochirurgica Supplementum, 93, 3-14.
Irwin, D.E. (2011).Where does attention go when you blink? Attention, Perception, and
Psychophysics, 73(5), 1374-1384. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.079959217569&partnerID=40&md5=59f7c934870bf3e25ad5b7bfd55312ee
Jennett, B., Adams, J. H., Murray, L. S., & Graham, D. I. (2001). Neuropathology in
vegetative and severely disabled patients after head injury. Neurology, 56(4), 486490.
Johansson, B. B., & Grabowski, M. (1994). Functional recovery after brain infarction:
Plasticity and neural transplantation. Brain Pathology, 4(1), 85-95.
Johansson, B. B. (1996). Functional outcome in rats transferred to an enriched environment
15 days after focal brain ischemia. Stroke, 27, 324-326.
Jones S.J., Vaz Pato M., Sprague L., Stokes M., & Haque N. (2000). Auditory evoked
potentials to spectro-temporal modulation of complex tones in normal subjects and
patients with severe brain injury. Brain, 123(5):1007-1016.
Karson, C. N., Dykman, R. A., & Paige, S. R. (1990). Blink rates in schizophrenia.
Schizophrenia Bulletin, 16(2), 345-354. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.00025350331&partnerID=40&md5=28e42c642c5c117e6741f42218f54886
Kassubek, J., Juengling, F. D., Els, T., Spreer, J., Herpers, M., & Krause, T. (2003).
Activation of a residual cortical network during painful stimulation in long-term
postanoxic vegetative state: A 15O-H2O PET study. Journal of the Neurological
Sciences, 212(1-2), 85-91. doi:S0022510X03001060
Khalfa, S., Roy, M., Rainville, P., Dalla, B. S., & Peretz, I. (2008). Role of tempo entrainment
in psychophysiological differentiation of happy and sad music? International Journal
of Psychophysiology, 68(1), 17-26. doi: S0167-8760(07)00250-4
Koelsch, S. (2005). Investigating emotion with music: Neuroscientific approaches. Annals of
the New York Academy of Sciences, 1060, 412-418.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
81
Kotchoubey, B., Lang, S., Mezger, G., Schmalohr, D., Schneck, M., Semmler, A.,...
Birbaumer, N. (2005). Information processing in severe disorders of consciousness:
Vegetative state and minimally conscious state. Clinical Neurophysiology, 116(10),
2441-2453. doi:S1388-2457(05)00183-5
Kotchoubey, B., Jetter, U., Lang, S., Semmler, A., Mezger, G., Schmalohr, D.,...
Birbaumer,N. (2006). Evidence of cortical learning in vegetative state. Journal of
Neurology, 253(10), 1374-1376. doi:10.1007/s00415-006-0221-0
Krumhansl, C. (1997). An exploratory study of musical emotions and psychophysiology.
Canadian Journal of Experimental Psychology, 51, 336-353.
Kuhn, T. (1996). The structure of scientific revolution. (3rd ed.). Chicago: University of
Chicago Press.
Lancioni, G. E., Bosco, A., Belardinelli, M. O., Singh, N. N., O'Reilly, M. F., & Sigafoos, J.
(2010). An overview of intervention options for promoting adaptive behavior of
persons with acquired brain injury and minimally conscious state. Research in
Developmental Disabilities., 31(6), 1121-1134. doi:S0891-4222(10)00153-8
Laureys, S., Lemaire, C., Maquet, P., Phillips, C., & Franck, G. (1999). Cerebral metabolism
during vegetative state and after recovery to consciousness. Journal of Neurology,
Neurosurgery, and Psychiatry, 67(1), 121.
Laureys, S., Faymonville, M. E., Degueldre, C., Fiore, G. D., Damas, P., & Lambermont, B.
(2000). Auditory processing in the vegetative state. Brain, 123 (8), 1589-1601.
Laureys, S., Antoine, S., Boly, M., Elincx, S., Faymonville, M. E., Berre, J.,...Maque,P.
(2002). Brain function in the vegetative state. Acta Neurologica Belgica, 102(4), 177185.
Laureys, S., Owen, A. M., & Schiff, N., D. (2004). Brain function in coma, vegetative state,
and related disorders. Lancet Neurology, 3(9), 537-546. doi:10.1016/S14744422(04)00852-X
Laureys, S., Perrin, F., Faymonville, M. E., Schnakers, C., Boly, M., Bartsch, V.,...Maquet, P.
(2004). Cerebral processing in the minimally conscious state. Neurology, 63(5), 916918. doi:63/5/916
Laureys, S., Perrin, F., Schnakers, C., Boly, M., & Majerus, S. (2005). Residual cognitive
function in comatose, vegetative and minimally conscious states. Current Opinion in
Neurology, 18(6), 726-733. doi:00019052-200512000-00017
Laureys, S. (2005). The neural correlate of (un)awareness: Lessons from the vegetative
state. Trends in Cognitive Science, 9(12), 556-559. doi:S1364-6613(05)00299-8
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
82
Laureys, S., Celesia, G. G., Cohadon, F., Lavrijsen, J., Leon-Carrion, J., Sannita, W.
G.,...Dolce, G. (2010). Unresponsive wakefulness syndrome: A new name for the
vegetative state or apallic syndrome. BMC Medicine, 8, 68. doi: 10.1186/1741-70158-68
Laureys, S., & Schiff, N. D. (2012). Coma and consciousness: Paradigms (re)framed by
neuroimaging. Neuroimage, 61(2), 478-491. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.084860729047&partnerID=40&md5=004030f1ab636cb6a0e84de74582a9b5
Leon-Carrion, J., Van, E. P., Dominguez-Morales, M. R., & Perez-Santamaria, F. J. (2002).
The locked-in syndrome: A syndrome looking for a therapy. Brain Injury, 16(7), 571582. doi:10.1080/02699050110119781
LeWinn, E. B., & Dimancescu, M. D. (1978). Environmental deprivation and enrichment in
coma. Lancet, 2(8081), 156-157.
Lombardi, F., Taricco, M., De Tanti, A., Telaro, E., & Liberati, A. (2002). Sensory stimulation
of brain-injured individuals in coma or vegetative state: results of a Cochrane
systematic review. Clinical Rehabilitation, 16(5), 464-472.
Luria, A. R. (1979). The Making of mind: A personal account of soviet psychology.
Cambridge MA: Harvard University Press.
Magee, W.L. (2002). Identity in clinical music therapy: Shifting self-constructs through the
therapeutic process. In R. Macdonald, D.J. Hargreaves, & D. Meill (Eds.), Musical
identities. Oxford: Oxford University Press.
Magee, W. L. (2005). Music therapy with patients in low awareness states: Approaches to
assessment and treatment in multidisciplinary care. Neuropsychological
Rehabilitation, 15(3-4), 522-536.
Magee, W. L. (2007). Music as a diagnostic tool in low awareness states: Considering limbic
responses. Brain Injury, 21, 593-599..
Magee, W. L., Siegert, R. J., Daveson, B. A., Lenton-Smith, G., & Taylor, S. M. (2013). Music
Therapy Assessment Tool for Awareness in Disorders of Consciousness
(MATADOC): Standardisation of the principal subscale to assess awareness in
patients with disorders of consciousness. Neuropsychological rehabilitation, (aheadof-print), 1-24. doi:10.1080/09602011.2013.844174
Majerus, S., Gill-Thwaites, H., Andrews.K., & Laureys, S. (2005). Behavioral evaluation of
consciousness in severe brain damage. Progress in Brain Research, 150, 397-414.
Majerus, S., Bruno, M. A., Schnakers, C., Giacino, J. T., & Laureys, S. (2009). The problem
of aphasia in the assessment of consciousness in brain-damaged patients. Progress
in Brain Research, 177, 49-61. doi: 10.1016/S0079-6123(09)17705-1
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
83
Mammarella, N., Fairfield, B., & Cornoldi, C. (2007). Does music enhance cognitive
performance in healthy older adults? The Vivaldi effect. Aging Clinical and
Experimental Research, 19, 394-399.
Mateer, C. A., & Kerns, K. A. (2000). Capitalizing on neuroplasticity. Brain and Cognition,
42(1), 106-109. doi:10.1006/brcg.1999.1175
Merker, B. (2007). Consciousness without a cerebral cortex: a challenge for neuroscience
and medicine. The Behavioural and Brain Sciences, 30(1), 63-81.
doi:S0140525X07000891
Meyer, M. J., Megyesi, J., Meythaler, J., Murie-Fernandez, M., Aubut, J., Foley, N.,.. Teasell
R. (2010). Acute management of acquired brain injury part III: An evidence-based
review of interventions used to promote arousal from coma. Brain Injury, 24(5), 722729.
Michaels, S. (2012, April 23) Robin Gibb stuns doctors by waking from coma. The Guardian.
Retrieved from http://www.theguardian.com/music/2012/apr/23/robin-gibb-wakingcoma
Mitchell, D. J., McNaughton, N., Flanagan, D., & Kirk, I. J. (2008). Frontal-midline theta from
the perspective of hippocampal "theta". Progress in Neurobiology, 86(3), 156-185.
Retrieved from http://www.scopus.com/inward/record.url?eid=2-s2.055049101149&partnerID=40&md5=d7c0f352f59c5aabbbcd013d987bd6f0
Mitchell, S., Bradley, V. A., Welch, J. L., & Britton, P. G. (1990). Coma arousal procedure: A
therapeutic intervention in the treatment of head injury. Brain Injury, 4(3), 273-279.
Monti, M., Vanhaudenhuyse, A., Coleman, M., Boly, M., Pickard, J., Tshibanda, L.,...Laureys,
S. (2010). Willful modulation of brain activity in disorders of consciousness. New
England Journal of Medicine, 362(7), 579-589.
Moruzzi, G., & Magoun, H. W. (1995). Brain stem reticular formation and activation of the
EEG. 1949.[classical article] Journal of Neuropsychiatry and Clinical Neurosciences,
7(2), 251-267.
Multi-Society Task Force on PVS. (1994). Medical aspects of the persistent vegetative state
(1). New England Journal of Medicine, 330(22), 1572-1579.
Münte, T., Altenmüller, E., & Jänck, L. (2002). The musician's brain as a model of
neuroplasticity. Nature Reviews Neuroscience, 3(6), 473-478. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.00036593192&partnerID=40&md5=d234b871221f78abe5a8d045cd93d137
Nachev, P., & Hacker, P. M. (2010). Covert cognition in the persistent vegetative state.
Progress in Neurobiology, 91(1), 68-76. doi:S0301-0082(10)00020-1
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
84
O'Callaghan, C. (1999). Recent findings about neural correlates of music pertinant to music
therapy across the lifespan. Music Therapy Perspectives, 17(1), 32-36.
O'Kelly, J., & Magee, W. L. (2013a). Music therapy with disorders of consciousness and
neuroscience: The need for dialogue. Nordic Journal of Music Therapy, 22(2), 93106. doi: 10.1080/08098131.2012.709269
O'Kelly, J., & Magee, W. L. (2013b). 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
O'Kelly, J., James, L., Palaniappan, P., Taborin, J., Fachner J., & Magee, W.L., (In press).
Neurophysiological and behavioural responses to music therapy in vegetative and
minimally conscious states. Frontiers in Human Neuroscience.
Ott, C. G. M., Stier, C., Herrmann, C. S., & Jäncke, L. (2013). Musical expertise affects
attention as reflected by auditory-evoked gamma-band activity in human EEG.
NeuroReport, 24(9), 445-450. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.084879159948&partnerID=40&md5=0f792bab062dff067dec99f1d4af6faf
Owen, A. M., Coleman, M. R., Boly, M., Davis, M. H., Laureys, S., & Pickard, J. D. (2007).
Using functional magnetic resonance imaging to detect covert awareness in the
vegetative state. Archives of Neurology, 64(8), 1098-1102. doi:64/8/1098
Owen, A. M., Schiff, N. D., & Laureys, A. (2009). A new era of coma and consciousness
science. Progress in Brain Research, 177(399-411).
Panksepp, J., Fuchs, T., Abella Garcia, V., & Lesiak, A. (2007). Does any aspect of mind
survive brain damage that typically leads to a persistent vegetative state? Ethical
considerations? Philosophy, Ethics and Humanities in Medicine, 2(32).
doi:10.1186/1747-5341-2-32
Peretz, I. (2002). Brain specialization for music. Neuroscientist., 8, 372-380
Pfaff, D., Ribeiro, A., Matthews, J., & Kow, L. M. (2008). Concepts and mechanisms of
generalized central nervous system arousal. Annals of the New York Academy of
Sciences, 1129, 11-25. doi:10.1196/annals.1417.019
Ponsford, J., Sloan, S., & Snow, P. (2013). Traumatic brain injury: Rehabilitation for everyday
adaptive living (2nd ed.). Hove, East Sussex, Psychology Press.
Posner, J., & Plum J. (1982). The diagnosis of stupor and coma (3rd ed.). Philadelphia: FA
Davis.
Posner, M. I., & Petersen, S. E. (1990). The attention system of the human brain. Annual
Review of Neuroscience, 13, 25-42. doi:10.1146/annurev.ne.13.030190.000325
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
85
Posner, M. I. (2008). Measuring alertness. Annals of the New York Academy of Sciences,
1129, 193-199. doi:10.1196/annals.1417.011
Rickard, N. S., Toukhsati, S. R., & Field, S. E. (2005). The effect of music on cognitive
performance: Insight from neurobiological and animal studies. Behavioral and
Cognitive Neuroscience Reviews, 4, 235-261.
Riganello, F., Candelieri, A., Quintieri, M., Conforti, D., & Dolce, G. (2010). Heart rate
variability: An index of brain processing in vegetative state? An artificial intelligence,
data mining study. Clinical Neurophysiology, 121, 2024-2034.
Robbins, T. W. (1997). Arousal systems and attentional processes. Biological Psychology,
45(1-3), 57-71. doi: 10.1016/S0301-0511(96)05222-2
Robson, C. (2011). Real world research. (3rd ed.) Oxford: Blackwell.
Rowe, G., Hirsh, J. B., & Anderson, A. K. (2007). Positive affect increases the breadth of
attentional selection. Proceedings of the National Academy of Sciences of the United
States of America, 104, 383-388.
Roy, M., Mailhot, J. P., Gosselin, N., Paquette, S., & Peretz, I. (2009). Modulation of the
startle reflex by pleasant and unpleasant music. Int.J Psychophysiol., 71, 37-4
Ruud, E. (2005). Philosophy and theory of science. In B.Wheeler (Ed.), Music therapy
research (2nd ed., pp. 33-44). New Braunfels, TX: Barcelona Publishers.
Sackett, D. L., Rosenberg, W. M. C., Gray, J. A. M., Haynes, R. B., & Richardson, W. S.
(1996). Evidence based medicine: What it is and what it isn't. It's about integrating
individual clinical expertise and the best external evidence. British Medical Journal,
312(7023), 71-72. Retrieved from http://www.scopus.com/inward/record.url?eid=2s2.0-0030027092&partnerID=40&md5=7bf2785765908b03d9432b3e96054191
Salimpoor, V. N., Benovoy, M., Longo, G., Cooperstock, J. R., & Zatorre, R. J. (2009). The
rewarding aspects of music listening are related to degree of emotional arousal. PLoS
One, 4(10). Retrieved from http://www.scopus.com/inward/record.url?eid=2-s2.070449441634&partnerID=40&md5=26959f2d9dae5f39b645fbabd4977309
Sancisi, E., Battistini, A., Di Stefano, C., Simoncini, L., Montagna, P., & Piperno, R. (2009).
Late recovery from post-traumatic vegetative state. Brain Injury, 23(2), 163-166.
doi:908448418
Sara, M., Sacco, S., Cipolla, F., Onorati, P., Scoppetta, C., Albertini, G., & Carolei, A. (2007).
An unexpected recovery from permanent vegetative state. Brain Injury, 21(1), 101103. doi:770495636
Särkamo, T., Tervaniemi, M., Laitinen, S., Forsblom, A., Soinila, S., Mikkonen,
M.,...Hietanen,M. (2008). Music listening enhances cognitive recovery and mood after
middle cerebral artery stroke. Brain, 131(3), 866-876.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
86
Särkamo, T., Pihko, E., Laitinen, S., Forsblom, A., Soinila, S., Mikkonen, M.,...Tervaniemi, M.
(2010). Music and speech listening enhance the recovery of early sensory processing
after stroke. Journal of Cognitive Neuroscience, 22(12), 2716-2727. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.078649486025&partnerID=40&md5=9b1c62882b9e1613b2de3cf55d0934ef
Särkamo, T., & Soto, D. (2012). Music listening after stroke: Beneficial effects and potential
neural mechanisms. Annals of the New York Academy of Sciences. 1252(1), 266281.
Schiff, N. D., Ribary, U., Moreno, D. R., Beattie, B., Kronberg, E., Blasberg, R.,...Plum, F.
(2002). Residual cerebral activity and behavioural fragments can remain in the
persistently vegetative brain. Brain, 125(Pt. 6), 1210-1234.
Schiff, N. D. (2005). Modelling the minimally conscious state: Measurements of brain function
and therapeutic possibilities. Progress in Brain Research, 150(473-493). doi:S00796123(05)50033-5
Schlaug, G., Maechina, S., & Norton, A. (2008). From singing to speaking: Why singing may
lead to recovery of expressive language function in patients with broca's aphasia.
Music Perception, 25(4), 315-323. Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.042449161930&partnerID=40&md5=5bdb6e88ae7572102906bffca3dc5690
Schuller, G., & Radtke-Schuller, S. (1990). Neural control of vocalization in bats: Mapping of
brainstem areas with electrical microstimulation eliciting species-specific echolocation
calls in the rufous horseshoe bat. Experimental Brain Research, 79(1), 192-206.
Seel, R. T., Sherer, M., Whyte, J., Katz, D. I., Giacino, J. T., Rosenbaum, A. M.,...Zasler,N.
(2010). Assessment scales for disorders of consciousness: Evidence-based
recommendations for clinical practice and research. Archives of Physical Medicine
and Rehabilitation. 91(12), 1795-1813. doi:S0003-9993(10)00603-9
Shiel, A., Horn, S. A., Wilson, B. A., Watson, M. J., Campbell, M. J., & McLellan, D. L.
(2000). The Wessex Head Injury Matrix (WHIM) main scale: A preliminary report on a
scale to assess and monitor patient recovery after severe head injury. Clinical
Rehabilitation, 14, 408-416.
Smith, E., & Delargy, M. (2005). Locked-in syndrome. British Medical Journal, 330(7488),
406-409. doi:330/7488/406
Soto, D., Funes, M. J., Guzman-Garcia, A., Warbrick, T., Rotshtein, P., & Humphreys, G. W.
(2009). Pleasant music overcomes the loss of awareness in patients with visual
neglect. Proceedings of the National Academy of Sciences of the United States of
America, 106(14), 6011-6016. doi:0811681106
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
87
Stein, D. G. (2009). Brain injury: Functional recovery after. In R.S. Larry (Ed.), Encyclopedia
of neuroscience (pp. 375-379). Oxford: Academic Press.
Stucki, G., & Melvin, J. (2007). The International Classification of Functioning, Disability and
Health: A unifying model for the conceptual description of physical and rehabilitation
medicine. Journal of Rehabilitation Medicine, 39, 286-292.
Tamplin, J. (2000). Improvisational music therapy approaches to coma arousal. Australian
Journal of Music Therapy, 11, 33-51.
Teasdale G., & Jennett B. (1974). Assessment of coma and impaired consciousness: A
practical scale. Lancet, 2, 81-84.
Testa Flaada, J. (2011). Hypoarousal. In J.S.Kreutzer, J.Deluca, & B. Caplan (Eds.),
Encyclopedia of clinical neuropsychology (p. 1285) New York: Springer.
Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study
of neuronal substrates of behaviour. Psychological Review, 73(1), 16-43.
Tulving, E. (1993). Varieties of consciousness and levels of awareness in memory. In A.
Baddely & L. Weiskrantz (Eds.), Attention, selection and control: a tribute to Donald
Broadbent (pp. 283-300). Oxford: Clarendon Press.
Turner-Stokes, L., Kitzinger, J., Gill-Thwaites, H., Playford, E. D., Wade, D., Allanson, J., &
Pickard,J. (2012). fMRI for vegetative and minimally conscious states. British Medical
Journal (Online), 345(7886). Retrieved from
http://www.scopus.com/inward/record.url?eid=2-s2.084870656819&partnerID=40&md5=b613de0f901a646e86a47d29617f15bd
Warm, J. S., Parasuraman, R., & Matthews, G. (2008). Vigilance requires hard mental work
and is stressful. Human Factors, 50(3), 433-441.
Watson, J. B. (1913). Psychology as the behaviourist views it. Psychological Review, 20(2),
158-177.
West, M. (2000). Music therapy in antiquity. In P.Horden (Ed.), Music as medicine (pp. 5168). Aldershot: Ashgate.
Wijnen, V. J., Heutink, M., van Boxtel, G. J., Eilander, H. J., & de Gelder, B. (2006).
Autonomic reactivity to sensory stimulation is related to consciousness level after
severe traumatic brain injury. Clinical Neurophysiology, 117(8), 1794-1807.
doi:S1388-2457(06)00135-0
Wilson, F. C., Harpur, J., Watson, T., & Morrow, J. I. (2002). Vegetative state and minimally
responsive patients - regional survey, long-term case outcomes and service
recommendations. NeuroRehabilitation, 17, 231-236.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
88
Wilson, S. L., Brock, D., Powell, G. E., Thwaites, H., & Elliott, K. (1996). Constructing arousal
profiles for vegetative state patients- a preliminary report. Brain Injury, 10(2), 105113.
Wilson, S. L., Powell, G. E., Brock, D., & Thwaites, H. (1996). Vegetative state and
responses to sensory stimulation: An analysis of 24 cases. Brain Injury, 10(11), 807818.
Wood, R. L. (1991). Critical analysis of the concept of sensory stimulation for patients in
vegetative states. Brain Injury, 5(4), 401-409.
World Medical Association. (2004). Declaration of Helsinki: Ethical principles for medical
research involving human subjects. Journal International de Bioethique, 15(1), 124129. Retrieved from http://www.scopus.com/inward/record.url?eid=2-s2.018744366077&partnerID=40&md5=779eb38616cb0a47c06edb07233c5d14
Yerkes, R. M., & Dodson, & J.D. (1908). The relation of strength of stimulus to rapidity of
habit-formation. Journal of Comparative Neurology and Psychology. (18), 459-482.
Retrieved from http://psychclassics.yorku.ca/Yerkes/Law/
Zeman, A. (2001). Consciousness. Brain, 124(7), 1263-1289.
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
89
Appendix I
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
90
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
91
Appendix 2
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
92
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
93
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
94
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
95
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
96
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.
Associate Professor Wendy Magee
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:……………………………
Associate Professor Wendy Magee
Signed…………………………………
Date:……………………………
Julian O’Kelly
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
97
Appendix 3b
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: 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.,
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.
Associate Professor Wendy Magee
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:……………………………
Associate Professor Wendy Magee
Signed…………………………………
Date:……………………………
Julian O’Kelly
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
98
Appendix 3c
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: 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.
Description of authors’ roles:
Julian O’Kelly (JOK)
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.
Associate Professor Wendy Magee
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.
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
99
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
100
Thesis Papers I, II & III
Note 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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
102
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
104
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
105
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
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
106
J O’Kelly, Music Therapy with Disorders of Consciousness, Aalborg University 2014
107
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