Proof of Concept Study of Vagus Nerve Stimulation Using an External Device for the Treatment of Behaviour Problems in People With Neurodevelopmental Disorders, Specifically Prader Willi Syndrome
Phase: NA
Conditions: Transcutaneous Vagal Nerve Stimulation (tVNS), Prader-Willi Syndrome
Sponsor: Jessica Beresford-Webb

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Department of Psychiatry 
 
Proof of concept study of vagus nerve stimulation using an external device for the 
treatment of behaviour problems in people with neurodevelopmental disorders, 
specifically Prader Willi Syndrome. 
 
Short title 
Proof of concept study of vagus nerve stimulation. 
 
1 Background and Rationale 
Since our initial pilot study using implanted stimulators (Manning et al., 2015), externally worn 
vagus nerve stimulators are now available and for this reason, and given advice from scientific 
grant reviewers alongside the findings of the previous pilot study, a further small series of case 
studies are proposed. If the findings justify it, a larger study may then be indicated. 
Prader-Will syndrome (PWS) is a genetically determined neurodevelopmental disorder 
characterised from childhood by excessive eating, severe obesity, sex and growth hormone 
deficiencies, intellectual disabilities, and problem behaviours (e.g. excessive repetitive and 
ritualistic behaviours, mild irritability and verbal and physical outbursts, which can sometimes 
last for hours). In the earlier pilot study, it was found that vagus nerve stimulation (VNS) was 
safe and acceptable, but that any effects on the overeating behaviour were equivocal. However, 
in two of the three participants who had a previous history of problem behaviours, there were 
unexpected and marked improvements in these behaviours reported by the participants and 
their families (Manning et al., 2015). As the pilot study had been designed to investigate the 
eating behaviour, we did not have longitudinal data on the rates of these behaviours over time. 
Given this observation, a further trial is now proposed with the primary aim of determining 
whether VNS, now from an externally worn medical device using an established stimulus 
protocol, is associated with a significant difference in the number and severity of problem 
behaviours. 
These behaviours have a significant effect on the level of independence and quality of life of 
those with PWS and impact also on those who support them (Mazaheri et al., 2013). The UK 
PWS Association repeatedly receive requests for help following placement breakdown and, in 
some cases, the fact that the criminal justice system has become involved because of the 
behaviour. In over 800 queries received by the PWS Association in 2013, 25% of them were 
about severe problem behaviours (information from Jackie Waters, UK PWSA). In the absence 
of these outbursts support ratios could be reduced and the person with PWS could be more 
independent. This novel intervention, if effective, will enable people with PWS to live a more 
independent life without concerns that minor environmental triggers will result in episodes of 

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severe problem behaviour which then escalate to prolonged outbursts associated with verbal or 
physical aggression. We predict that such treatment would significantly decrease health and 
social care costs and improve quality of life for people with PWS and those who support them. 
Since the unexpected findings from the earlier pilot study in PWS, a review of the literature 
(see Manning et al., 2015) has found that there are reports of behavioural improvements where 
VNS has been used to treat epilepsy. Improvements in wellbeing have also been reported in 
people with autism spectrum conditions. These reports, however, are complicated by 
improvements, for example, in seizure control or mood. In addition to these observations the 
work of Porges and colleagues (the polyvagal theory; Porges & Furman, 2011) provides a 
useful explanatory model for why VNS might result in improvements in behaviour in people 
with neurodevelopmental syndromes where problem behaviours arise in the context of high 
arousal. It is for these reasons that we propose to extend the study beyond PWS. 
 
2    Objectives 
The primary objective is to determine whether vagus nerve stimulation (VNS) using an 
external device and established protocols, is associated with significantly fewer and less 
severe episodes of informant recorded outbursts, compared to no stimulation, thereby 
providing further evidence for its approval and use in the treatment of problem behaviours in 
people with PWS or with other neurodevelopmental disorders. 
 
Additionally, there are a number of secondary objectives: 
• To establish the percentage in each group who respond positively to vagus nerve 
stimulation with a clinically significant reduction of 50% or more and identify 
cognitive, autonomic and neural biomarkers associated with a positive response. 
• In addition to collecting evidence on efficacy, to investigate safety and acceptability of 
the treatment in order to inform further studies. 
• To investigate the characteristics of the behaviours that improve and the putative 
autonomic and neural mechanisms that are likely to mediate any reduction in such 
behaviours, in order to better understand the circumstances whereby the use of VNS 
might be generalized to treating problem behaviours more widely. 
• To assess potential effect of t-VNS on weight and energy expenditure. 
 
3   Endpoints 
The primary endpoint is the measurement of the number and severity of informant recorded 
outbursts, as operationally defined. Secondary endpoints include the completion of specific 
questionnaires (detailed below) and the investigation of biomarkers associated with positive 
behavioural outcomes. The study will identify the percentage of responders, defined as those 
with clinically significant reductions of maladaptive behaviour of 50% or greater. 
 

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4     Study Population 
4.1    Study participants. 
We intend to recruit a final sample of at least 6 individuals with PWS and 6 individuals with 
another neurodevelopmental disorder will be recruited to the study. At any one time, up to 8 
individuals with PWS may be taking part in the study owing to an expected relatively high 
dropout rate as well as the possibility for a lack of behaviours observed during the baseline 
period. Should all 8 continue to the stimulation phase, then all 8 would be included in the study.  
 
4.1.1 Inclusion criteria 
• Male or female aged over 18 years of age. 
• Genetically and clinically determined diagnosis of PWS or meeting clinical or the 
presence of another neurodevelopmental syndrome such as an autistic spectrum 
condition. 
• History of problem behaviours of, on average, at least one significant informant-
reported episode each week. 
• Capacity to consent.  
• Able to commit to the study duration and to attend assessments in Cambridge. 
 
 
4.1.2 Exclusion criteria 
• Meet exclusion criteria for MRI scanning and/or unable to tolerate MRI 
environment. 
• Serious co-morbid physical or psychiatric disorder which would disrupt ability to 
comply with study demands (e.g. a history of serious bipolar disorder; sleep apnoea 
not well-controlled with CPAP; insulin dependent diabetes). 
• Current or past history of neurological disorders or trauma, including epilepsy, and 
head injury. 
• Currently or recently (within 12 months) participating in a clinical trial of an 
investigational medicinal product (CTIMP) or another medical device. 
• Lacking the capacity to consent. 
 
5    Recruitment  
For all potential participants, no personal information about potential participants will be 
available to the research team until such point as the potential participant or his/her 
representative contacts the research team to make an expression of interest. This contact may 
be via the response slip in the information pack given to individuals identified either through 
their clinicians or through PWS supported living, providing the contact details of the interested 
participant (name, address, telephone) and nominating a ‘person who knows him/her best’ who 
can be contacted to arrange a date a for the initial visit, or through contacting the research team 
using the contact details available on an advertisement for the study. 

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5.1   Recruitment of participants with PWS 
Potential participants with PWS will be identified through one of 3 routes: 
1. Through self -identification in response to an advertisement, including on the website and in 
the newsletter of the Prader--Willi Syndrome Association UK (PWSA UK). Interested 
individuals will be able to contact the research team who will send out an information pack 
containing an information sheet for both the potential participant and his/her carer, a reply slip 
and a prepaid envelope. 
2. Through managers of PWS- specific supported living settings or other residential settings 
supporting one or more individuals with PWS. The research team will contact the managers of 
the settings to discuss the study and potential for residents to participate. With the agreement 
of managers, information packs will be sent to the setting and distributed to residents they know 
to be aged 18 and above and likely to have the capacity to consent. 
3. Via NHS trusts. This may be through identification via Cambridgeshire and Peterborough 
Foundation Trust clinicians, other NHS/learning disability practitioners/services as Participant 
Identification Centres (PICs). Information packs would be given by the identifying clinician, 
with reply slips for interested participants to contact the research team. 
 
5.1   Recruitment of participants with other neurodevelopmental disorders 
Potential participants with other neurodevelopmental disorders will be identified in the 
following ways: 
1. Through clinicians in the local specialist services for people with LD. In each case, clinicians 
will be asked to pass on information packs to those who may be appropriate for this study. The 
potential participant, or those who are supporting him/her, can then contact the research team. 
This contact will be followed-up by a visit.  
2. Through organisations that provide support to people with LD and challenging behaviour. 
There are both NHS and independent sector services that specialise in the support of people 
with LD and challenging behaviour. The senior manager/clinician in these services will be 
informed about the study and if appropriate be asked to pass on information packs to potential 
participants. The same procedure will then be followed as above. 
 
6 Informed consent 
When the research team receive reply slips, they will contact the participant or his/her carer, 
depending on whose contact details the participant has chosen to provide, to arrange an initial 
visit to the participants home. It is at this visit that the researcher will go through the easy read 
information photograph booklet, watch the film with the participant and ensure participant is 
suitable for the study. 

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If the potential participant thinks they may still want to take part following this initial home 
visit, an opportunity to visit the Clinical Research Facility at Addenbrooke’s Hospital in 
Cambridge will be arranged. This will enable the potential participant, as well as their 
accompanying parent or carer, to see what the travel demands are like and to get a better 
understanding of what will happen if he/she chooses to participate. There will also be an 
opportunity to try VNS to see what it feels like. 
Written informed consent will only be taken once this visit to Cambridge is complete, with the 
researcher, who will have completed training in informed consent and in the Mental Capacity 
Act. To ensure capacity to consent, the individual will be asked questions to assess his/her 
understanding and retention of the study details, their feelings about the study and ensure that 
their decision is consistent with these. This is in accordance with the assessment of capacity as 
described in Section 3 of the Mental Capacity Act 2005. Professor Holland and Dr Ring are 
both learning disability consultant psychiatrists with extensive experience working with people 
with PWS, Professor Holland is Chair in Learning Disabilities at the University of Cambridge 
and has expertise in gaining informed consent in this population. Katie Manning (research 
associate) is also experienced at assessing capacity and gaining consent in research with 
individuals with intellectual disabilities. 
 
6    Study design, procedures and assessment. 
 
6.1 Study design and assessments 
The study takes the form of a longitudinal single case cross-over design. The study cannot be 
blind as the stimulation is apparent to participants. After a baseline phase of between 4 to 6 
months of data collection and during which participants will be asked to wear the stimulator 
according to established protocols (four hours a day continuously or broken into 1 hour periods) 
but without it being activated, there will be an active treatment phase over a similar period of 
time. Towards the end of the active phase, there will be a period of reduction in the time the 
stimulator is worn and then no further stimulation. 
The stimulus protocol will be that used for treatment of epilepsy using established protocols. 
For these externally worn devices the stimulator is worn for at least 4 hours a day – this can be 
broken into segments of time but should avoid be used during sleep. The stimulus strength used 
is that which is just detectable by the participant. The stimulation is continuous over the period 
that the device is worn.  The stimulator consists of a pack similar to a mobile phone, a lead that 
the connects the pack with the electrode, and an electrode that is worn next to a specific place 
close to the ear so that it can stimulate through the skin a branch of the vagus nerve. The exact 
amount of time that participants are requested to wear the device will depend on early findings 
but it will always remain within established and accepted protocols for the treatment of 
epilepsy.  It is anticipated that at the end of the active treatment phase, if benefits are found, 
rather than immediately stopping wearing the device for 4 hours a day it will be reduced to 2 

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hours a day and after some time stopped altogether. This will enable us to determine whether 
or not a similar level of benefit can be obtained at a lower dose of stimulation. 
The primary outcome measures are the number and severity of informant-reported problem 
behaviours operationally defined and recorded using participant and observer diaries. This 
method of longitudinal data collection has been validated by Leah Bull for her completed PhD 
supervised by Prof Chris Oliver, a member of the research team. This data will be collated on 
a monthly basis by a research assistant. Where behaviour data is available through a care 
home’s own system for recording behaviour incidents and there are difficulties in obtaining 
completed behavioural diaries from that home, the participant will be asked to consent to the 
research team using the care home’s records to analyse the numbers of behaviours before and 
during t-VNS therapy. This will enable the participant to keep taking part when this may 
otherwise not be possible through minimising demands on those who support them. These 
records will be analysed by two researchers and interrater reliability assessed. Where this is the 
case, we may also ask permission to view records prior to recruitment in order to shorten the 
necessary baseline period.  
Secondary behavioural outcomes will include: a) the participants response to a specified 
challenge using a methodology developed by Prof Oliver, filmed and subsequently rated blind 
for emotional and behavioural changes by an independent rater thereby overcoming the 
problem of lack of blindness and also allowing some measure of changes in resilience to a 
standard challenge; b) at the beginning, middle and end of each phase interviews of informants 
will be undertaken using valid and reliable questionnaires including the Challenging Behaviour 
Interview (Oliver et al., 2003), Behaviour Problems Inventory (Rojahn et al., 2001) and the 
Aberrant Behaviour Checklist, (Aman et al., 1985); , the Personal Wellbeing Index (Cummins 
& Lau, 2005), and the. Also at the end of each phase a semi-structured interviews with 
participants and key informants will be undertaken to probe about any observed subtle changes 
in behaviours. These will be recorded and transcribed and rated against defined criteria blind 
to treatment status. 
In order to better understand what predicts a positive behavioural response, we will explore 
possible psychological and neural brain biomarkers by undertaking the following assessments 
at similar time points on three occasions in both the non-stimulation and stimulation phases: 
the Mood, Interests and Pleasure Questionnaire (Ross & Oliver, 2003); tests of attention and 
set shifting using go/no go tasks established for use by people with PWS (Woodcock et al 2009, 
2010); measures of cortical activation patterns and network activity using resting state and task-
based fMRI (developed as part of a PhD project). Blood samples will be taken to measure 
glucose, insulin, HbA1c,  and cytokine screening at regular intervals as well as a one-off sample 
for diagnosis of PWS subtype in those with PWS for whom this is not already documented. 
Salival cortisol measures will also be recorded across the course of four separate days during 
the course of study (at waking, 30 minutes post-waking, 45 minutes post-waking, 1 hour post-
waking and then four more times throughout the day at approximately +3h, +6h, +9h and +14h 
after waking).  Measures of vocal prosody will also be taken. This will be done using a very 
short procedure on four occasions (twice in the baseline phase and twice in the active phase). 
Two voice recordings of the participant talking will be collected on each of these occasions. 
Each recording will be at least 20 seconds long, with the participant asked to talk about a 

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positive experience (e.g. favourite birthday, best friend etc.) in one, a less positive time (e.g. a 
time when he/she was disappointed or sad) in the other. These will be analysed for changes in 
vocal prosody with t-VNS, which is suggested to be an indicator of autonomic nervous system 
flexibility under the influence of the vagus nerve, thus providing a further measure of 
autonomic functioning. 
Heart rate variability will be derived from ECG and respiration measured using an Intelesens 
(Belfast) 3-axis ‘Zensor’ wearable monitor. For each participant ECG recording will take place 
in 24-hour blocks, (which we (Bhatoa and Ring 2015) have previously observed to be 
acceptable to adults with intellectual disability and their carers), with such blocks being 
recorded monthly during the sham and active conditions. Data will be stored on an integral SD 
card, which can be encrypted for subsequent transferral of data to collaborators for off-line 
analysis. HRV will be determined from R-R intervals as root mean of squared successive 
differences and average HRV will be determined for each participant for brief (15 minutes) 
and prolonged (24 hours) periods. 
Sleep monitoring will also be regularly undertaken, due to the association of increased risk of 
sleep apnoea in both VNS and PWS, using as Somnoscreen TM plus RC system 
(SOMNOmedics, Germany). This uses a three electrode ECG, pulse oximeter and movement 
sensors to record heart rate, blood oxygen desaturations and sleeping position throughout the 
night. 
 
6.2 Procedures 
In both the baseline and active phases, we will visit participants at home approximately 
monthly. At the home visit, we will conduct the questionnaires with participants and/or their 
carers, as appropriate, and will conduct the semi-stuctured interview if it is the end of a phase. 
We will also ask participants to do the cognitive tasks at some of these visits.  
Throughout the study, parents or carers will fill out a daily diary entry on a form developed for 
this study, recording the participants behaviour during that day. These will be collated at the 
monthly home visit. 
The participant will be asked to wear the ambulatory physiological monitoring device 
(monitoring heart rate and respiration) for one week at a time, four times during the study – 
two in each phase. This can be worn while carrying out regular daily activities at home, and 
can be removed and replaced easily for washing. 
Participants will also be asked to provide saliva samples over the course of a single day on four 
occasions in the study, to measure cortisol levels. This will be done using a swab which is 
masticated for approximately two minutes before being return to a tube. These are stable at 
room temperature and can be returned via post. 
On four occasions – twice in each phase –we will ask the participant to come to visit us in 
Cambridge. Participants travel to and from Cambridge will be paid for, as will that of an 
accompanying parent/carer, as well as food and drink while in Cambridge. Participants will 
come to the Wellcome Trust Clinical Research Facility (CRF) at Addenbrooke’s hospital in 

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Cambridge, where they will stay overnight. At these visits, we will check the VNS settings, 
monitor their sleep using the Somnoscreen system, take the blood samples and carry out the 
fMRI scan. fMRI scans will be done at the Wolfson Brain Imaging Clinic, which is also located 
on the Addenbrooke’s site. Scans will include both resting-state and task-based fMRI, with the 
cognitive tests of attention and set-shifting completed in the scanner. While in Cambridge we 
will also carry out the videorecorded behavioural challenge test and the recordings for analysis 
of vocal prosody. At one of the visits to the CRF, participants will complete the step test. 
 
7    Data analysis 
 
7.1 Outcome measures 
 
The primary outcome measures are the number and severity of operationally defined 
outbursts as measured using participant and informant diaries.   
Secondary behavioural outcomes will include: 
1. During each treatment phase the participant's response to a specified challenge using a 
methodology developed by CO, filmed and subsequently rated blind for emotional 
and behavioural changes by an independent rater, thereby overcoming potential 
threats to blindness given that participants will be aware of active VNS 
2.  Percentage of responders with a clinically significant reduction of 50% or more in the 
rate of problem behaviours. 
3. Scores on specific valid and reliable rating scales repeated over time including the 
Challenging Behaviour Checklist, Behaviour Problems Inventory, Aberrant 
Behaviour Checklist, Repetitive Behaviour Questionnaire, and Life Exepeiences 
Checklist. 
4. The identification of cognitive, autonomic and neural biomarkers associated with 
positive behavioural outcomes. 
5. Findings from qualitative interviews of family or support staff. 
7.2 Planned analyses 
Longitudinal data obtained will be analyzed using established methods with cases as their own 
controls (see Perdices & Tate, 2009; de Vries & Morey, 2013). Data will be plotted out, 
visualized, and statistically analyzed using polynomial regression identify the ‘turning point’ 
in the treatment phase when behavior is observed to improve and establishing whether all those 
who improve do so at a similar time after treatment has started and in a similar way. Within 
the time constraints of the project, the point in time after which treatment was started past when 
improvement, if it hasn’t already occurred, is unlikely will be identified. Differences on 
behavioral measures in baseline and treatment conditions will be compared using Chi squared 
analyses giving confidence limits. 
 
FMRI data will be analysed using both 1st and 2nd level general linear model (GLM) analyses 
to compare within cases and across time points. Network analyses of functional connectivity 
may also be appropriate. 

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8    Data management 
8.1 Data handling. 
Participants will be allocated an ID code on entry into the study and all data that is kept will 
only be attributable to that person through the code. The key to the code will be kept separately 
in a locked filing cabinet. Information on databases will be coded and access to the system will 
be password protected.  
The analysis of fMRI data will take place via a secure network which allows a secure tunnel to 
be created into the WBIC server system from a remote computer by each researcher to access 
and analyse only their own project data. The remote computer used will be a university laptop. 
Personal telephone numbers of potential participants will be used, once provided by interested 
potential participants, to contact the participant or his/her carer to arrange the initial visit. This 
information along with personal addresses, postcodes, emails and faxes will be kept in a locked 
filing cabinet.  
All data transferred will be done in accordance to the NHS Code of Practice on Confidentiality 
and local Trust data protection policies and procedures using appropriate encryption. 
The participants GP will be notified of their involvement in the study, and of the results of 
blood tests carried out in the course of their participation, as well as if we were to find. 
Participants will endorse a clause on the consent form confirming their permission for us to 
contact their GP for these purposes. 
We will be sharing anonymised data with collaborators outside of the study team as part of 
open access as agreed by the funders and sponsor. 
Only anonymised data will be analysed on Departmental computing facilities. Anonymised 
electronic data, including data entered into the computer from study measures and 
questionnaires, would be stored with reference only to the participant identifier, not their name. 
8.2 Data storage 
All electronic data are stored and backed up daily and secured on a database hosted at the 
School of Clinical Medicine, University of Cambridge. 
The project will make use of Cambridge Clinical Trials Unit (CCTU) Data Management 
Service. This is a managed service for researchers where all aspects of data management, i.e. 
from design of data capture tool to data release for analysis will be catered. Data will be stored, 
managed and cleaned, as well as archived after project completion. The data backup services 
is in accordance to the security policy for Secure Data Hosting Service 2014 of the School of 
Clinical Medicine. Source data will be stored securely in the Principal Investigator’s (PI) 
laboratory (for a minimum of 10 years). 
All identifiable data will be securely sent for central secure storage and stored in compliance 
with the Data Protection Act on University computers and approved by the sponsor. Permission 

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for access will be granted only on a need -to -know basis to selected members of the study 
team. This is explained in the Information Sheets and included in the Informed Consent Forms. 
This will also be explained verbally when participants attend on the first visit with the 
opportunity to ask as many questions as they need. 
Paperwork containing personal information (including completed questionnaires and study 
measures) will be stored in a locked filing cabinet at the research office. These will be marked 
with the participant identifier, not their names. Consent forms, which will contain participant 
names, will be stored in a separate locked drawer. 
 
9    References 
Ager, A. K. (1990). The Life Experiences Checklist. Windsor: NFER-Nelson. 
Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985). The aberrant behavior checklist: a 
behavior rating scale for the assessment of treatment effects. American Journal of Mental 
Deficiency, 89, 485-491. 
Cummins, R.A. & Lau, A. (2005). Personal Wellbeing Index – Intellectual Disability. 3rd Edition. 
Victoria, Australia: School of Psychology, Deakin University 
de Vries, R.M., Morey, R.D. (2013). Bayesian hypothesis testing for single-subject designs. 
Psychological Methods, 18, 165-185. 
Honey, E., McConachie, H., Turner, M. & Rodgers, J., (2012) Validation of the repetitive behaviour 
questionnaire for use with children with autism spectrum disorders. Research in Autism 
Spectrum Disorders, 6, 355-364. 
Manning, K. E., McAllister, C. J., Ring, H. A., Finer, N., Kelly, C. L., Sylvester, K. P., ... Holland, A. 
J. (2015). Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous 
findings from an open trial of vagus nerve stimulation. Journal of Intellectual Disability 
Research. Online first: 27 May 2015. 
Mazaheri, M. M., Rae-Seebach, R. D., Preston, H. E., Schmidt, M., Kountz-Edwards, S., Field, N., 
Cassidy, S. & Packman, W. (2013). The impact of Prader–Willi syndrome on the family's 
quality of life and caregiving, and the unaffected siblings’ psychosocial adjustment. Journal of 
Intellectual Disability Research, 57, 861–873. 
Oliver, C., McClintock, K., Hall, S., Smith, M., Dagnan, D., & Stenfert-Kroese, B. (2003). Assessing 
the severity of challenging behaviour: psychometric properties of the Challenging Behaviour 
Interview. Journal of Applied Research in Intellectual Disability, 16, 53-61. 
Perdices, M., & Tate, R.L. (2009). Single-subject designs as a tool for evidence-based clinical practice: 
are they unrecognised and undervalued? Neuropsychological Rehabilitation, 19, 904-927. 
Porges, S. W., & Furman, S. A. (2011). The early development of the autonomic nervous system 
provides a neural platform for social behaviour: a polyvagal perspective. Infant and Child 
Development, 20, 106–118. 
Robinson, B. C. (1983). Validation of a caregiver strain index. Journal of Gerontology, 38,344-348. 

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Rojahn, J., Polster, L.M., Mulick, J.A., & Wisniewski, J.J. (1989). Reliability of the Behaviour 
Problems Inventory. Journal of the Multihandicapped Person, 2, 283-293. 
Ross, E. & Oliver, C. (2003). Preliminary analysis of the psychometric properties of the Mood, 
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disabilities. British Journal of Clinical Pyschology, 42, 81-93. 
Woodcock, K. A., Humphreys, G. W., Oliver, C., & Hansen, P. C. (2010). Neural correlates of task 
switching in paternal 15q11-q13 deletion Prader-Willi syndrome. Brain Research, 1363, 128-
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Woodcock, K. A., Oliver, C., & Humphreys, G, W. (2009). Task switching deficits and repetitive 
behaviour in genetic neurodevelopmental disorders: Data from children with Prader-Willi 
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Neuropsychology, 26, 172-194.