Journal of the Neurological Sciences 364 (2016) 110–115

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Journal of the Neurological Sciences

journal homepage: www.elsevier.com/locate/jns

Know thyself: Exploring interoceptive sensitivity in Parkinson's disease

Lucia Ricciardi a, Gina Ferrazzano b, Benedetta Demartini c, Francesca Morgante d, Roberto Erro a,
Christos Ganos a,e, Kailash P. Bhatia a, Alfredo Berardelli b,f, Mark Edwards a,⁎
a
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, London, UK
b
IRCCS Neuromed, Pozzilli (IS), Italy
c
Department of Psychiatry, San Paolo Hospital, University of Milan, Milan, Italy
d
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
e
Department of Neurology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
f
IRCCS Neuromed Institute, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Background: Although Parkinson's disease (PD) is defined by its motor symptoms, it is now well recognised that
Received 7 October 2015 cognitive, affective and emotion domains are also impaired. The pathophysiology of these disabling non-motor
Received in revised form 10 March 2016 symptoms (NMS) remains unclear; recently the involvement of limbic areas, including the insula, in the neuro-
Accepted 11 March 2016 degenerative process has been suggested to have a key role. These areas, and the insula in particular, are also been
Available online 12 March 2016
suggested as key regions for interoception; interoceptive sensitivity (IS) is a measure of the accuracy of percep-
tion of sensations from inside the body related to the function of internal organs.
Keywords:
Parkinson's disease
Objectives: To evaluate IS in PD patients by means of a well-established task: the heartbeat perception task. More-
Interoception over, we evaluated possible correlations between IS and psychological, affective and disease-related characteris-
Non-motor symptoms tics as well as fatigue perception in PD patients.
Emotion Methods: Twenty PD patients and 20 healthy subjects (HS) were included and underwent the heartbeat percep-
Fatigue tion task. An extensive evaluation of motor, non-motor, affective and emotion domains was carried out.
Results: PD patients showed lower IS than HS (0.58 ± 0.2 vs 0.72 ± 0.1; p = 0.04). PD reported higher scores in
scales assessing depression (Hamilton depression scale: 8.7 ± 5.8 vs 6.2 ± 7.5; p = 0.04); anhedonia (Snaith–
Hamilton Pleasure Scale: 26.8 ± 9.7 vs 15.4 ± 2.9; p = b 0.001) and apathy (Apathy Evaluation Scale: 35.8 ±
8.6 vs 27.8 ± 6.8; p = 0.008). No significant correlations were detected between IS and motor, non-motor, affec-
tive and emotion symptoms.
Conclusions: PD patients have reduced interoceptive sensitivity. Future studies are encouraged to evaluate the
importance of interoception in understanding the pathophysiology of affective/emotional symptoms in PD.
© 2016 Elsevier B.V. All rights reserved.

1. Introduction interoception: the representation and contextualisation of somatic and

Parkinson's disease (PD) is far from just a motor disorder. The im-
portance of non-motor symptoms has been increasingly recognised,
particularly in how they significantly add to the burden of PD for pa-
tients and impair quality of life. [1] Despite the clinical importance of
NMS, the pathophysiology of these symptoms remains unclear.
Limbic areas including insula, amygdala, anterior cingulate cortex
are key regions in emotional processing. All these regions, in particular
the insula, are involved in the process of interoception, the perception
of sensations from inside the body, including the perception of physical
sensations related to the function of internal organs. [2] It is proposed
that subjective “feeling states” are dependent on the process of
⁎ Corresponding author at: St. George's University of London, London, UK.
E-mail address: medwards@sglu.ac.ukuk (M. Edwards).
visceral responses elicited by emotional stimuli. [3].
In PD many components of the emotional processing are altered, [4]
however there is still a lack of clarity on the neurobiological basis of
these deficits. Nevertheless, the role of alpha-synuclein deposition and
subsequent degeneration of the insula has been highlighted, and sug-
gested as an anatomical region where degeneration could explain a
number of NMS, including depression, anxiety, apathy, anhedonia and
fatigue. [5].
When studying these aspects of emotion, researchers face two main
problems: first, studies are conducted in laboratory and clinical settings
and these contexts significantly differ from real life, therefore the gener-
alizability of findings obtained from this research is limited. [6] Second,
the diagnosis of these symptoms relies mainly on self-report question-
naires, the validity of which can be called into question when assessing
disorders characterized by an inability or an alteration in identifying and
judging one's own affective and emotional states. [7] The difficulty in

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 L. Ricciardi et al. / Journal of the Neurological Sciences 364 (2016) 110–115
evaluating affective and emotional disorders in PD patients has been
also demonstrated in several studies showing a lack of agreement be-
tween patients and their caregivers when scoring the severity of these
symptoms. [8–9].
For these reasons, it would be very useful to find an objective mea-
sure which would correlate to the severity of NMS such as fatigue per-
ception, affective and emotional symptoms, which could complement
and implement the assessment scales in the diagnosis and follow-up
of these aspects of the disease. If deficits in interoceptive processing
might reflect disease-related insula degeneration and this might under-
lie a proportion of NMS, then measurement of interoceptive sensitivity
(IS) could be a useful biomarker to study. In healthy individuals, higher
IS is associated with the experience of more intense emotional states
[10] and higher activation of brain areas thought to play a key role in
emotional processing (insular cortex, anterior cingulate cortex,
ventro-medial and dorsolateral prefrontal cortex and the somatosenso-
ry cortex). [2].
Moreover, the literature currently suggests an association between a
number of neuropsychiatric problems and reduced IS, including major
depression, somatoform disorder, functional neurological symptoms
and eating disorders. A disturbed interoceptive awareness of the state
of the body has been hypothesized to be linked to symptoms of chronic
fatigue and chronic pain [11–13]. One explanation for this might be that
a “noisy” interoceptive signal could result in an inaccurate perception of
internal state, which might in turn generate symptoms such as fatigue
and pain in the absence of a specific cause.
We hypothesized that due to the neurodegenerative processes in
limbic areas (involved in the interoceptive sensitivity) patients with
PD may present a disturbed IS which could make them prone to symp-
toms such as pain, fatigue, emotional/affective disorders. Therefore, we
aimed to evaluate using a validated and widely used measure of IS - the
heartbeat perception task – whether patients with PD would have dis-
turbed IS compared to healthy subjects, and whether disturbed IS
could be related to the presence and severity of NMS, especially affec-
tion/emotion symptoms, pain and fatigue perception.
2. Methods
2.1. Participants
We recruited 20 consecutive PD patients from the movement disor-
der outpatient clinics of the National Hospital for Neurology and Neuro-
surgery, London. Inclusion criteria were a diagnosis of PD according to
UK Brain Bank criteria, [14] with treatment and clinical condition stable
for at least 4 weeks prior to the study. Exclusion criteria were any major
concurrent neurological, cardiac or psychiatric disorders; clinically sig-
nificant cognitive deficits or score b 26 on the Montreal Cognitive As-
sessment (MOCA), [15] severe depression [diagnosed according to
both the DMS-IV TR criteria and a Hamilton depression Scale ≥14. [16]
Twenty healthy individuals, matched for age and gender were also re-
cruited and served as a control group. Individuals with a history of any
Table 1
Demographic and clinical characteristic of PD patients.
Gender (M/F) 13/7
Age at onset 53.4 ± 10.9
Disease duration 6.8 ± 3.3
UPDRS-I 2.1 ± 1.6
UPDRS-II 7.9 ± 4.3
UPDRS-III 15.9 ± 7.2
UPDRS-IV 2.4 ± 3.4
H&Y 1.5 ± 0.5
LEDD (total) 560.6 ± 345.5
NMSS 42.5 ± 20.0
Abbreviation: F: Female; H&Y: Hoehn and Yahr scale; LEDD: levo-
dopa equivalent daily dose; M: Male; NMSS: Non-motor symptoms
scale; UPDRS: Unified Parkinson's disease Rating scale.
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111
major concurrent neurological, cardiac or psychiatric disorders were ex-
cluded. Full demographical and clinical data are presented in Table 1.
All subjects agreed to participate to the study and signed a consent
form; the local institutional review board approved the study protocol.
2.2. Materials
2.2.1. Procedure
After arriving at the laboratory, all participants completed a ques-
tionnaire regarding socio-demographic and clinical information (for pa-
tients). Items included age, educational level, medical history,
medications taken.
For the patients, information on disease onset, progression and dura-
tion and on dopaminergic therapy expressed in terms of Levodopa
Equivalent Daily Dose (LEDD) [17] were collected. Patients underwent
a clinical evaluation including: assessment of motor severity and com-
plications, i.e. fluctuation and dyskinesia by means of the Unified
Parkinson's disease rating scale (UPDRS) section III and IV [18]; disabil-
ity and non-motor symptoms (NMS) [section II of the UPDRS and the
NMS scale (NMSS)]; [19] overall cognitive assessment by means of the
section I of the UPDRS, and the MOCA. The experimental procedures
and the self-report measures (see below) were conducted in a soft-
lighted, sound-attenuated room. All patient evaluations were per-
formed in their “best ON” state.
2.2.2. Heart beat detection task
Participants were seated, with their wrists gently resting on the
band of a heart rate monitor, which was located on a table in front of
them. The ‘Heartbeat Perception Task’ was performed according to the
protocol by Schandry. [20] Heart rate was recorded with a Polar wrist
worn heart rate monitor (model RS 800 CX). [20] Participants were
first asked to sit quietly and relax for 30 s, subsequently baseline heart
rate was recorded for 3 min before the task started in order to evaluate
differences in heart rate frequency. Participants were then asked to con-
centrate on their heartbeats and to count them silently. They were not
permitted to take their pulse or to attempt any other physical manipu-
lations, which could facilitate detection. There were three counting
phases lasting for 25 s, 35 s, and 45 s and separated by 30 s rest periods.
The order of the phases was randomized between participants of each
group. An acoustic signal provided the ‘start’ and ‘stop’ indications of
each counting phase. After each stop signal, participants were asked to
report the number of counted heartbeats. Participants were aware nei-
ther of the length of the counting phases, nor of their performance.
2.2.3. Psychiatric, affective and emotion assessment
The Toronto Alexithymia Scale (TAS-20; 21) was used as a measure
of alexithymia. The TAS-20 is the most commonly used self-report mea-
surement of alexithymia, [19] with demonstrated reliability and validi-
ty. [22] The scale consists of 20 items rated on a 5-point scale, anchored
at ‘1 = strongly disagree’ to ‘5 = strongly agree’, with a total score rang-
ing from 20 to 100. Three sub-scores can also be calculated but these
were not used in the current study due to the relatively small sample
sizes and related power issues. Higher scores indicate greater
alexithymia. A total score of above 61 is considered the cut off score
for alexithymia. [21].
The Hamilton Depression Rating Scale (HAMD) is the most used and
validated depression scale overall and has been used in PD. [23] The
HAMD is an interview-based rating scale and consists of 17 items: 16
question-based items and one observational item. The item scores
range from 0 to 4 (symptom is absent, mild, moderate, or severe) or
0–2 (absent, slight or trivial, clearly present). The total score can range
from 0 to 54. A cut-off score of 9/10 has been suggested for screening
depression in PD patients, and 14 as a cut-off for major depressive dis-
order in PD. [16].
The Hamilton Anxiety Rating Scale (Ham-A) is a 14-item clinician-
rated instrument designed to assess and quantify severity of anxiety
112 L. Ricciardi et al. / Journal of the Neurological Sciences 364 (2016) 110–115

[24]. Each item is rated on a five-point Likert-type scale ranging 0 to 4, Table 2

with a total score range from 0 to 56, where a score b 17 indicates Clinical evaluation of affective and emotional profiles of study populations.

mild severity, a score between 18 and 24 indicates moderate severity PD (n = 20) HC (n = 20) p-Value
and a score between 25 and 30 indicates a moderate to severe anxiety. Gender 13 M 8M 0.7
[24]. Age 61.4 ± 9.8 56.5 ± 10.8 0.13
The Apathy Evaluation Scale (AES) is a self-rated scale to identify MOCA 28.8 ± 1.4 28.3 ± 1.4 0.19
clinically significant apathy, it consists of 18 items scored on 4-point HB baseline 236.4 ± 46.2 220.6 ± 41.6 0.19
IS 0.58 ± 0.22 0.72 ± 0.14 0.04
Likert scale (not at all true, slightly true, somewhat true, very true).
TAS-20 total score 50.9 ± 11.4 44.7 ± 8.2 0.16
Total score ranges from 18 to 72 points (higher score indicates more se- TAS-20 DIF 13.4 ± 3.5 13.5 ± 12.7 0.05
vere apathy). The cut-off score ≥ 37 was generally used to divide apa- TAS-20 DDF 18.2 ± 4.9 14.7 ± 3.9 0.05
thetic from non-apathetic patients [25]. TAS-20 EOT 19.5 ± 4.2 20.7 ± 4.2 0.4
The Snaith–Hamilton Pleasure Scale (SHAPS) [26] is a 14 item scale Ham-Dep 8.7 ± 5.8 6.2 ± 7.5 0.04
Ham-Anx 12.8 ± 9.4 7.9 ± 9.5 0.05
designed to assess anhedonia in different psychiatric conditions. Re- SHAPS 26.8 ± 9.7 15.4 ± 2.9 b0.001
cently Ameli and coworkers have modified the initial version of the Empathy quotient 39.8 ± 9.2 46.2 ± 7.4 0.09
scale to improve its utility [27]. Items are scored from 1 to 4 (1 = lots Apathy (AES) 35.8 ± 8.6 27.8 ± 6.8 0.008
of pleasure, 4 = no pleasure) creating a score ranging from 14 to 56. Fatigue SS 37.4 ± 14.2 29.6 ± 15.1 0.12
The Empathy Quotient (EQ) is a psychological self-assessment ques- Values are means ± SD. Significantly different changes (Mann-Whitney U test) are bold
tionnaire measuring empathy levels. The EQ contains 60 items of which typed. Abbreviations: AES: Apathy Evaluation Scale; FSS: Fatigue Severity Scale; Ham-
40 are clinically relevant and 20 are for distraction only. For each item Dep: Hamilton depression scale; Ham-Anx: Hamilton anxiety scale; HB: heart beat; IS:
Interoception sensitivity; MOCA: Montreal Cognitive Assessment; SHAPS: The Snaith-
the possible answers are: strongly agree, slightly agree, slightly dis- Hamilton Pleasure Scale; TAS: Toronto Alexithymia Scale.
agree, or strongly disagree, with one point given if the empathic state-
ment is recognised mildly (slightly agree) or two points given it if is
endorsed strongly (strongly agree). The scored is from 0 (being the significantly higher IS compared to patients as measured by the heart-
least empathetic possible) to 80 (being the most empathetic possible) beat perception task (0.72 ± 0.1 vs 0.58 ± 0.2; p = 0.04) (Fig. 1).
[28]. PD patients had significantly higher scores compared to HC for
The Fatigue Severity Scale (FSS) is a self-administered fatigue rating Hamilton-depression total score (PD 8.7 ± 5.8; HC 6.2 ± 7.5; p =
scale [29], which reveals the functional impact of fatigue during the past 0.04); SHAPS total score (PD 26.8 ± 9.7; HC 15.4 ± 2.9; p ≤ 0.001)
week. The FSS, which consists of 9 questions, uses a 7 point Likert scale and AES (PD 35.8 ± 8.6; HC 27.8 ± 6.8; p = 0.008).
ranging from strongly disagrees (score: 1) to strongly agree (score: 7). A Spearman's correlation showed no relationship between IS and
total score of b 36 suggests that subjects may not be suffering from fa- Alexithymia (TAS-20 score), depression (Ham-Dep score), anxiety
tigue, instead a total score of 36 or more suggests fatigue. (Ham-Anx score), apathy (AES score), anhedonia (SHAPS score), empa-
thy (EQ score) or fatigue (FSS) (Fig. 2). No significant correlations were
2.3. Statistical analysis detected between IS and disease characteristics (disease duration, age
at disease onset, LEDD, UPDRS, and severity of NMS in general (as re-
The accuracy of heartbeat perception was calculated as the mean vealed by NMSS total and sub-scores)) (Supplementary online Table 1).
score of three heartbeat perception interval according to the following Moreover, since the patients enrolled reported significantly higher
transformation: scores compared to HC at assessment scales for depressive symptoms
(Han-dep) and apathy (AES), to evaluate the influence of depression
1=3∑½ð1−ðjrecordedheartbeats–countedheartbeatsj=recordedheartbeatsÞÞ: and apathy on IS we clustered the PD patients in: 1) PD with depression
(n = 14) and PD without depression (n = 6) taking the Ham-Dep
Using this formula, the interoceptive sensitivity score can vary be- score N 13 as cut-off [16]; and 2) PD-apathetic (n = 7) vs PD-no-
tween 0 and 1, with higher scores indicating smaller differences be- apathetic (n = 13) taking AES score N 37 as cut-off. Mann-Whitney U
tween recorded and perceived heartbeats (i.e. more accuracy, or test showed that there was no significant difference in IS between the
higher interoceptive sensitivity). All analyses were performed using
SPSS version 21. Mann-Whitney U test was used to evaluate differences
between groups. Gender differences between the two groups were
assessed using the Fisher-exact test.
Spearman's correlations were conducted to examine the possible re-
lationship between interoceptive sensitivity and Alexithymia (TAS-20
score), depression (Ham-Dep score), anxiety (Ham-Anx score), apathy
(AES score), anhedonia (SHAPS score), empathy (EQ score), fatigue
(FSS). In order to evaluate possible correlations between IS and disease
characteristics (disease duration, age at disease onset, LEDD, UPDRS,
and severity of NMS (as revealed by NMSS total and sub-scores),
Spearman's correlations were conducted on the PD patients group
only. Significance level was set at p b 0.05.

3. Results

Twenty PD patients (13 males, mean age 61.4 ± 9.8 years) and 20
healthy controls (HC) (8 male, mean age 56.5 ± 10.8) were included
in the study. Demographic and clinical data of the study populations
are shown in Tables 1 and 2.
Baseline heartbeats were not significantly different between PD pa-
tients and HC (3 min baseline measure: 236.4 ± 46.2 vs 220.6 ± 41.6, Fig. 1. Interoception sensitivity, assessed by means of the heartbeat perception task, is
p = 0.1). A Mann-Whitney U test revealed that healthy controls had a reduced in PD patients compared to healthy subjects.

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 L. Ricciardi et al. / Journal of the Neurological Sciences 364 (2016) 110–115 113

Fig. 2. Spearman correlation analysis showed that interoception sensitivity has no significant correlation with alexithymia (TAS-20 score, panel A), depression (HDRS score, panel B),
anxiety (HARS score, panel C), anhedonia (SHAPS score, panel D), apathy (AES score, panel E), and fatigue (FSS, panel F).

depressed and non-depressed groups of patients (p = 0.3) and between
the apathetic and non-apathetic ones (p = 0.9).
4. Discussion
This is the first work showing that interoceptive sensitivity, as mea-
sured by a heartbeat perception task, is reduced in PD. We have demon-
strated that PD patients have a lower IS compared to healthy
individuals. However, we found no correlation between IS and a range
of self-report measures of affective status, fatigue and non-motor symp-
toms in general.
Interoception is the body-to-brain axis of sensation concerning the
state of the internal body and the organs. It is a key process for “periph-
eral” theories of emotion which suggest that the central representation
and perception of changes in bodily physiology are the basis for emo-
tional feeling states [30]. The insula is thought to play a key role in
this process. Indeed, the connections and activation profile of the insula
suggest that it integrates visceral and somatic input and forms a repre-
sentation of the state of the body [3,29]. Alpha-synuclein has been
showed to be highly deposited throughout the insula by stage 5 in PD
patients [32].
While the deficit we found in IS in patients with PD would be consis-
tent with this degenerative process involving the insula, we did not find
any correlation between the degree of deficit in IS and the severity of
non-motor symptoms, specifically affective symptoms.
Recent research has suggested separate functional roles for the ante-
rior and posterior insula in more cognitive/affective and viscero-
sensory/somatosensory awareness, respectively [33] This could contrib-
ute to explaining our results, as there may be a dissociation between IS
as measured by the heartbeat perception task, and interoceptive pro-
cessing that is related more closely to affective/emotional function.
There are other caveats to our results. First, our sample of PD patients
did not have severe NMS, and this might have made difficult to show
a significant correlation between IS and severity of NMS because of
the lack of a group of patients with high score at NMSS. Second, reduced
IS in PD could be related to other aspects of the disease which we have
not measured or assessed in our protocol (such as emotional
expressivity and empathy). Finally, we did not collect any measure of
self-report interoceptive sensitivity (such as questionnaires or patients
‘confident level) which could have allow us to do further speculations
such as exploring the dissociation between different dimensions of
interoception [34]. Indeed, very little is known about IS deficits in clini-
cal populations and this is the first study in PD.
Recent studies using a heartbeat perception task have showed that
IS is positively correlated with intensity of emotional experience. [2,
35] PD patients exhibit significant deficits in non-verbal communica-
tion, having difficulties in both producing and recognising emotional fa-
cial expressions and affective prosody [4–6]. In a recent study a
correlation between deficits in facial emotional expression and recogni-
tion in PD patients has been demonstrated [36], hypothesizing for emo-
tion a mechanism similar to the one described for action execution and
observation based on mirror neurons [37]. This is in line with a study by
Wicker et al. [37–38] showing that the recognition of disgust may in-
volve simulation of interoceptive states. Recent studies have demon-
strated that PD patients also show a lack of self-awareness for their
motor symptoms, including levodopa-induced dyskinesia [39]. One
could speculate that the lack of ability to generate or recognise the emo-
tional content of facial expression or speech and the lack of awareness of
somatic symptoms could be related to the deficit of awareness of viscer-
al and somatic input that we found using the heart beat detection task in
this study.
We acknowledge our study limitations, first the small sample size;
second, as we have already pointed out, the fact that our PD patients
did not have severe NMS; third, PD patients were more depressed and
apathetic than healthy subjects, this does not allow to fully exclude a
possible influence of depression and apathy on IS, although there was
no correlation between IS and the score of the Hamilton-depression
scale. Finally, the fact that all patients' evaluations were performed in
their “best ON” state, thus not allowing us to evaluate how levodopa in-
fluences IS.
In conclusion, our data demonstrate in PD patients a lower intero-
ceptive sensitivity, a measure which might be related to insular degen-
eration. This deficit is related neither to the presence and severity of
non-motor symptoms nor to any other disease characteristic we

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114 L. Ricciardi et al. / Journal of the Neurological Sciences 364 (2016) 110–115
measured in this study. Nevertheless, given the evidence of a link be-
tween IS and emotional processing, the finding of reduced interoceptive
sensitivity in PD points the way to further studies in this area.
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.jns.2016.03.019.
Funding statement
This research received no specific grant from any funding agency in
the public, commercial or not-for-profit sectors.
Competing interest statement
Dr. Ricciardi, Dr. Ferrazzano, Dr. Demartini, Dr. Erro, Dr. Ganos and
Prof Berardelli report no disclosures.
Dr. Morgante is member of the advisory boards of UCB pharma,
Allergan and Lundbeck, has received honoraria from Allergan,
Medtronic, UCB pharma, Lundbeck, Chiesi pharma, and serves in the ed-
itorial board of Frontiers Neurology.
Prof Kailash P Bhatia: Funding for travel from GlaxoSmithKline,
Orion Corporation, Ipsen, and Merz Pharmaceuticals, LLC; serves on
the editorial boards of Movement Disorders and TherapeuticAdvances
in Neurological Disorders; receives royalties from the publication of Ox-
ford Specialist Handbook of Parkinson's Disease and Other Movement
Disorders (Oxford University Press, 2008); received speaker honoraria
from GlaxoSmithKline, Ipsen, Merz Pharmaceuticals, LLC, and Sun Phar-
maceutical Industries Ltd.; personal compensation for scientific adviso-
ry board for GSK and Boehringer Ingelheim; received research support
from Ipsen and from the Halley Stewart Trust through Dystonia Society
UK, and the Wellcome Trust MRC strategic neurodegenerative disease
initiative award (ref. number WT089698), a grant from the Dystonia Co-
alition and a grant from Parkinson's UK (ref. number G-10).
Prof Mark Edwards is funded by a fellowship awarded by the Nation-
al Institute for Health Research and is supported by researchers at the
National Institute for Health Research University College London Hospi-
tals Biomedical Research Centre. He receives grant support from
Parkinson's UK, the UK Dystonia Society, Bachmann Strauss Foundation.
He has received honoraria for speaking from The International Move-
ment Disorders Society and UCB Pharma.
Authors' role
1. Drafting/revising the manuscript for content, including medical writ-
ing for content
2. Study concept or design
3. Analysis or interpretation of data
4. Acquisition of data
5. Statistical analysis
6. Study supervision or coordination
LR: 1, 2, 3, 4, 5, 6
GF: 4
BD: 3, 4, 5
FM: 1, 6
RE:1
CG:1
KB:1
AB:1
MJE: 1, 2, 3, 6
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