Clinical benefits and neural correlates of Constraint-Induced Movement Therapy

Lead Research Organisation: University of Surrey
Department Name: Psychology

Abstract

Brain Correlates of Motor Rehabilitation
This project is concerned with investigating the effects of constraint-induced movement therapy (CIMT), a new motor rehabilitation technique for patients who have lost motor function. It is an intervention that focuses on retraining the brain through practice using a combination of motor learning tasks and behavioural psychology elements.

About 75% of stroke survivors sustain motor problems that limit their abilities to perform every day activities and often reduces their independence. This is particularly so when the brain damage affects the arm and the hand.


Recent studies of CIMT shows that patients can make significant gains in their motor functions. This is even the case when the stroke or head injury had happened many years ago.

To make CIMT available as a standard rehabilitation method, more research is needed to show that how the treatment helps and how it can be applied in those patients who have more severe loss of arm function. In a five year research program we will determine how much patients gain from an adapted version of CIMT and to describe how the brain changes when a patient gets better with the treatment. The study program will use a combination behavioural test and brain imaging methods, including high-density EEG recordings, functional and structural MRI.

Technical Summary

Constraint-induced movement therapy (CIT, [1]), a new treatment concept derived from basic neuroscience research, can help to substantially reduce incapacitating motor deficits in patients with chronic hemiplegia and lessen their dependence. CIT involves two key aspects, constraining the ?good arm?, and daily training the ?affected arm? for six hours over a period of two weeks. Both measures are thought to support the two linked mechanisms, use-dependent reorganisation and overcoming learnt nonuse, which determine treatment success. The clinical results of CIT and the mechanisms proposed by CIT-theory led to the objectives of the present proposal. Aim 1 is to investigate the efficacy of less demanding CIT protocols, since the standard six hours protocol might be too strenuous for less-well recovered patients. To this end, a randomised trial, involving 112 lower-functioning hemiplegic patients will be conducted, using a range of behavioural measures to study treatment outcome. The 2nd aim is to use the CIT treatment as a model to study processes of treatment-related functional brain organisation, i.e. to characterise the neural correlates of the clinical benefits achieved by this intervention. For this purpose, neuroimaging experiments, including functional magnetic resonance imaging (fMRI) and event-related brain potentials (ERPs), will be conducted before and after CIT. With fMRI we will study, which brain regions are recruited by CIT and how this relates to functional improvements. With ERPs, the processes involved in movement preparation will be studied to assess the impact of different CIT protocols on the learnt-nonuse behaviour. In sum, the present proposal aims to bridge basic neuroscience research and potential applications, by using neuroimaging methods to study clinically relevant questions. We recognise the (often great) discrepancy between the desirable implementation of basic research outcome and the clinical ?reality?. Therefore, the research program has been tailored for practicability in the clinical setting.

Publications

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Frase L (2016) Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS). in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

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Hou W (2008) A behaviour study of the effects of visual feedback on fluctuating isometric force production with force tracking tasks in International Journal of Biomedical Engineering and Technology

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Hou W (2006) A behavior study of the effects of visual feedback on motor output. in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference

 
Description Recognition of CIMT as one of the most effective interventions for hemiplegia (including NICE guidelines)
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Constraint Induced movement therapy is now a well recognised treatment; is now also mentioned in the NICE guidelines as the most effective intervention from hemiplegia. The treatment is also becoming more and more main stream in the US. Our studies have contributed to the improved visibility and clinical implementation of CIMT.
 
Description Knowledge Transfer Partnership
Amount £46,000 (GBP)
Organisation Department for Business, Energy & Industrial Strategy 
Sector Public
Country United Kingdom
Start 08/2009 
End 12/2010
 
Description PHD studentship (joined MRC/ESRC)/ Medical Research Council (MRC) and ESRC
Amount £42,670 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 10/2009 
End 09/2013
 
Description PHD studentship (joined MRC/ESRC)/ Medical Research Council (MRC) and ESRC
Amount £40,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2009 
End 09/2013
 
Description PhD studentships (ESRC); 2x4 years starting 2005/Joint MRC/Economic and Social Sciences Research Council (ESRC)
Amount £40,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2006 
End 09/2009
 
Description PhD studentships (ESRC); 2x4 years starting 2005/Joint MRC/Economic and Social Sciences Research Council (ESRC)
Amount £42,760 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 10/2006 
End 09/2009
 
Description PhD studentships (ESRC); 2x4 years starting 2005/Joint MRC/Economic and Social Sciences Research Council (ESRC)
Amount £123,566 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 10/2006 
End 09/2009
 
Description Research Project
Amount £1,745,000 (GBP)
Organisation Eisai Ltd 
Sector Private
Country Japan
Start 04/2010 
End 03/2011
 
Description Research Project/Disability Challengers (Charity)
Amount £20,000 (GBP)
Organisation Disability Challengers 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2010 
End 02/2011
 
Description Small Grants Scheme
Amount £6,700 (GBP)
Organisation The British Academy 
Sector Academic/University
Country United Kingdom
Start 08/2006 
End 05/2008
 
Description International Insomnia Forum 
Organisation Northumbria University
Department School of Psychology and Sports Science Northumbria
Country United Kingdom 
Sector Academic/University 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description International Insomnia Forum 
Organisation Research Centre of the University Institute of Mental Health in Quebec (CRIUSMQ)
Department Clinical and Cognitive Neuroscience Research Axis
Country Canada 
Sector Academic/University 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description International Insomnia Forum 
Organisation University Medical Center Freiburg
Department Department of Psychiatry and Psychotherapy
Country Germany 
Sector Hospitals 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description International Insomnia Forum 
Organisation University of California, San Diego (UCSD)
Department Laboratory of Sleep & Behavioral Neuroscience UCSD
Country United States 
Sector Academic/University 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description International Insomnia Forum 
Organisation University of Pennsylvania
Department Department of Psychiatry
Country United States 
Sector Academic/University 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description International Insomnia Forum 
Organisation University of Surrey
Department Faculty of Health and Medical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution This forum has just been created and aims to bring colleagues with an interest in insomnia together to develop a joined research program. My role in this is to bring the clinical neuroscience/neurodegenerative disorders perspective to the table.
Collaborator Contribution Joined PhD supervision; opportunity for student placementsOpportunity for student exchangecollaboration on research papers and grant applications
Impact The network is presently formed. The first meeting is scheduled from 31st of January - 4th or February. The network draws together expertise from molecular biology, chronobiology, sleep medicine, sleep psychology and the clinical neurosciences. Some connections already exist between partners (e.g. Sterr/Ellis: joined PhD supervision; Sterr/Drummond: student exchange).
Start Year 2010
 
Description Mobile EEG and Neurofeedback 
Organisation Carl von Ossietzky University of Oldenburg
Department Department of Psychology
Country Germany 
Sector Academic/University 
PI Contribution I have been collaborating with Dr Kranczioch (University of Oldenburg) on motor learning for a few years. We are now in the processes of devising a study program on the use of a new mobile EEG system developed at Oldenburg, to (1) explore the use of neurofeedback training in stroke recovery and (2) to study cognitive processes in real world settings (e.g. navigating across campus) in older persons and patient groups. Because of the lack of funding in the UK, Oldenburg has made available a PhD studentship. Through an Erasmus agreement we have funding for the student to spent 1 year in my lab to perform some of the studies. The work associated with the studentship will for the bases for a grant application submitted jointly to RCUK and the German Research Foundation. Following and Erasmus-funded visit to Oldenburg in April 2013, we have now written a joint review paper, submitted a grant to the Royal Society (rejected unfortunately), and won funding for a mobile EEG project with the DSTL (10/13-09/17; £192k). The collaboration further helped us to win internal funding for a PhD studentship studying neural correlates of motor imagery of gait.
Collaborator Contribution Developed the mobile EEG system and the analysis tool Bilateral Erasmus exchange program
Impact 1) Kranczioch, C., S. Mathews, P.J.A. Dean and A. Sterr*, Task complexity differentially affects executed and imaginged sequential finger movements: Evidence from pre-movement CNV. Plos One, 2010. 5: p. e9284. doi:10.1371/journal.pone.0009284. 2) Kranczioch, C., S. Mathews, P.J. Dean and A. Sterr*, On the equivalence of executed and imagined movements: Evidence from lateralized motor and nonmotor potentials. Human Brain Mapping, 2009. 10: p. 3275-86 3) Kranczioch, C., S. Athanassiou, S. Shen, G. Gao and A. Sterr*, Short-term learning of a visually guided power-grip task is associated with dynamic changes in EEG oscillatory activity. Clinical Neurophysiology, 2008. 119(6): p. 1419-30.
Start Year 2007
 
Description National Co-operating Centre for Public Engagement 
Organisation University of the West of England
Department Bristol Business School
Country United Kingdom 
Sector Academic/University 
PI Contribution This is an RCUK funded working group aiming to determine how University should embed public engagement in the widest sense. My experience from the MRC project feeds directly into this activity
Collaborator Contribution It inspired my thinking about user-involvement in research and also the public communication of research results.
Impact A number of position papers resulting from the Action Research Project but I dont believe this is publicised yet.
Start Year 2009
 
Description Sleep in Neurological Disorders 
Organisation Brighton and Sussex University Hospitals NHS Trust
Department Stroke Rehabilitation Unit
Country United Kingdom 
Sector Hospitals 
PI Contribution We noted an issue with sleep and daytime sleepiness in the patients we saw for our CIT trial. I therefore linked-up with colleagues for Sleep Center (in particular Prof Derk-Jan Dijk). We submitted several grants to study the role of sleep in neurorehabilitation and/or stroke recovery (MRC and Stroke Association) but failed to get the funding despite excellent reviews.
Collaborator Contribution Allowed us to widen our research focus and ask new questions.This collaboration is essential to our work as it gives us access to patients in a rehabilitation setting, something we have struggled with in Guildford, partly because of the absence of a medical school. The link with Western Sussex Hospital is very recent and primarily supported through a part-time PhD studentship funded by the NHS.
Impact Outputs 1. A jointly supervised PhD project on sleep after stroke, funded through the ESRC 2. Conference presentations at the WorldSleepConference 2007 (Cairns), and the WorldStrokeConference 2010 (Seoul) 3. Publication (Time to wake-up: sleep problems and daytime sleepiness in long-term stroke survivors.; Sterr A, Herron K, Dijk DJ, Ellis J.; Brain Inj. 2008 Jul;22(7-8):575-9.) 4. Manuscript: Biomarkers of daytime sleepiness in patients with chronic low-functioning hemiparesis after stroke
 
Description Sleep in Neurological Disorders 
Organisation University of Surrey
Department Faculty of Health and Medical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We noted an issue with sleep and daytime sleepiness in the patients we saw for our CIT trial. I therefore linked-up with colleagues for Sleep Center (in particular Prof Derk-Jan Dijk). We submitted several grants to study the role of sleep in neurorehabilitation and/or stroke recovery (MRC and Stroke Association) but failed to get the funding despite excellent reviews.
Collaborator Contribution Allowed us to widen our research focus and ask new questions.This collaboration is essential to our work as it gives us access to patients in a rehabilitation setting, something we have struggled with in Guildford, partly because of the absence of a medical school. The link with Western Sussex Hospital is very recent and primarily supported through a part-time PhD studentship funded by the NHS.
Impact Outputs 1. A jointly supervised PhD project on sleep after stroke, funded through the ESRC 2. Conference presentations at the WorldSleepConference 2007 (Cairns), and the WorldStrokeConference 2010 (Seoul) 3. Publication (Time to wake-up: sleep problems and daytime sleepiness in long-term stroke survivors.; Sterr A, Herron K, Dijk DJ, Ellis J.; Brain Inj. 2008 Jul;22(7-8):575-9.) 4. Manuscript: Biomarkers of daytime sleepiness in patients with chronic low-functioning hemiparesis after stroke
 
Description Stroke Recovery 
Organisation University of Sao Paulo
Department Department of Neurology, Psychiatry and Medical Psychology
Country Brazil 
Sector Academic/University 
PI Contribution I have set up this collaboration as part of our mission to build up links with Brazil. As part of this mission I obtained £20000 for a staff and student exchange program with colleagues from USP and ABC Fedearal. This activity has led to a number of papers, 3 incoming student exchanges and the submission of a joint research grant to FAPESP under the CNPq scheme (funded). This activity has so far led to 5 published papers, 2 Science without Borders PhD studentships and a CAPES funded research project (PI Professor Conforto)
Collaborator Contribution -Colleagues at USP have hosted myself and members of my research group and provided input to the analysis of neuroimaging data and the write up of joint papers -Grant submissions to British Academy (rejected), MRC (rejected) and CAPES (funded)
Impact 1) Szameitat, A.J., S. Shen, A. Conforto and A. Sterr, Cortical activation during executed, imagined, observed, and passive wrist movements in healthy volunteers and stroke patients. Neuroimage, 2012. 62(1):266-80. 2) Szameitat, A.J., A. Mcnamara, S. Shen, A. Conforto Bastos and A. Sterr, Bimanual actions are associated with an altered state of functional connectivity. PlosOne, 2012. 7(6):e38506. 3) Sterr, A. and A.B. Conforto, Plasticity of adult sensorimotor system in severe brain infarcts: challenges and opportunities. Neural Plasticity, 2012. 2012: p. 970136. 4) Laurenti dos Santos-Fontes, R., K. Nocelo Ferreiro, C.E. da Rocha Correia, A. Sterr and A. Bastos Conforto, Home-based peripheral nerve stimulation enhances effects of motor training in patients in the chronic phase after stroke. Neural Rehabilitation and Repair, 27(6), 483-490. doi:10.1177/1545968313478488 5) Sterr, A., P.J.A. Dean, S. Shen, A. Conforto Bastos, G. Vieral, and J.R. Sato, Effects of arm immobilization during CI therapy on structural brain characteristics of the intact hemiphere in chronic hemiplegia. NeuroImage: Clinical, 2(1), 797-803. doi:10.1016/j.nicl.2013.05.005 6) Dean, P. J., Otaduy, M. C., Harris, L. M., McNamara, A., Seiss, E., & 1.Sterr, A. (2013). Monitoring long-term effects of mild traumatic brain injury with magnetic resonance spectroscopy: a pilot study.. Neuroreport, 24, 677-681. doi:10.1097/WNR.0b013e3283637aa4 6) A.Sterr, P.J.A. Dean, A.J. Szameitat, A. Bastos Conforto & S. Shen. Corticospinal Tract Integrity and Lesion Volume Play Different Roles in Chronic Hemiparesis and Its Improvement Through Motor Practice. Neurorehabilitation and Neural Repair, in press 7) S.M. Anjos, L.G. Cohen, E.A. Mello, K.N. Ferreiro, A. Sterr, A. B. Conforto. Translational neurorehabilitation research in the third world: what barriers to trial participation can teach us. Stroke, in revision
Start Year 2011
 
Description Stroke and Sleep 
Organisation Albert Ludwigs University of Freiburg
Country Germany 
Sector Hospitals 
PI Contribution I have established this collobration with Professor Riemann and Dr Nissen to further my studies on the role of sleep and daytime sleepiness in stroke recovery. I had submitted a grant to the Royal Society to fund the collaboration but it was rejected. I have also set up a staff and student Erasmus exchange with the group
Collaborator Contribution Professor Riemann hosted me for a 3 months sabbatical (June-September 2012) in which we set up a sleep study which is now running. The University of Freiburg is covering the study costs. By now this collaboration has resulted in two grant applications (one rejected, one pending), one paper in revision and two in submission
Impact there are no outputs so far but two coauthored systematic reviews and a review paper on plasticity and sleep are in preparation
Start Year 2012
 
Title CI therapy game 
Description Based on our observations in the treatment situation but also the information we obtained from exit interviews and interactions with significant others, we have devised a board game patients can 'play' with each other or significant others to practice their upper limb motor skills. The game is designed to implement the shaping & feedback principles of CIMT in a setting that is fun, encouraging but also stretching the player's ability. The development of the game is funded through a KTP; the industrial partner is Green Board Games. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2009
Licensed Yes
Impact None yet. We believe that the CI-therapy game can provide a good way for patients to practice their motor skill with their careers of significant other. We hope to obtain funding for a proof-of principle study. Interesting about this invention is not only the motor practice element and how it is actually implemented but the the way psychosocial aspects are addressed as well.
 
Description Focus Groups 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact We ran 2 focus groups with a mix of patients and carers who had participated in our trial and those who were interested in the work. We presented the basic outcome of our work and also the ideas we have to develop the therapy further into a game patients can play to practise their motor skills (funded through the KTP)

About 10 patients participated in each group
Year(s) Of Engagement Activity 2010
 
Description Presentations 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact We gave a series of talks/presentations/workshops to practicing rehabilitation specialists, aspiring students of rehabilitation professions as well as educators. Amongst these were St Georges Hospital, Institute of Neurology, Royal Surrey Hospital, Farnham Hospital, Universities of Nottingham, Southampton, Brunel, Sterling and Ulster, as well as international activities in Belgium, Jordan, Switzerland and Germany (note that this list is not exhaustive)

In all these activities, we noted increased interest in our work expressed by a request for further information, whether it was in terms of publications or project information. We also had a number of students wanting to join us for placements.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Project presentation on specialised websites (e.g. Younger Strokes) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact The activity triggered many enquiries about the work with many patients asking for access to CIMT treatment (including GB, India and Asia).
From those patients seeking contact by phone, it was very apparent that they lacked support and access to treatment in the chronic state. Moreover, the comments highlighted the neglect of the psychosocial dimension of hemiparesis, an issue we tried to capture better in our work through exit interviews.

Interest from health professionals working with patients who had contacted us (mainly physiotherapists)
Year(s) Of Engagement Activity 2006,2007