Cross education of movement function across the lifespan

Lead Research Organisation: Queen's University of Belfast
Department Name: Sch of Psychology

Abstract

The Context Older adults (> 65 years) already comprise a significant proportion (16% in 2008) of the UK population, yet their numbers will increase dramatically over the next twenty years. By 2033, those aged over 65 years will constitute 23% of the population. Between 30 and 40% of people over 65 years fall at least once annually. The proportion of falls resulting in a fracture increases markedly with age. In persons over 65 years, fractures are present in three-quarters of fall-related hospital admissions. In more than half of these cases a fracture of the arm is sustained. In most instances the arm is immobilised for an extended period, often in plaster. While this may allow the injury to heal, there are other less positive consequences. Immobilisation of a limb, even for a very short time, leads to a profound decrease in strength. The most significant risk associated with such a period of disuse is that the loss of physical capacity will leave an individual too frail to perform everyday activities, such as rising from a chair. The loss of independence that this represents has consequences not only for the person concerned, but also for their family, their caregivers and the community. This research is concerned with strategies that may be used to minimise the loss of function that would otherwise occur during recovery from upper limb injuries, particularly in older persons. The Aims and Objectives There is now a great deal of evidence that the older adult brain retains an extensive facility to undergo adaptive change or reorganisation. This capacity is referred to as plasticity. Adaptations within the brain play a significant role in relation to the gains that older adults derive from various forms of physical activity. In addition to contributing to the maintenance of strength, adaptations underpinned by brain plasticity form the basis of learning new strategies for performing tasks that compensate for loss of strength. The aims of the proposed research are to examine improvements in the functional capabilities of one limb that occur when only the other limb is trained, and to determine how brain plasticity may best be exploited in order to maximise the gains that can be achieved by such training. The Potential Applications and Benefits For many older people who suffer an injury such as a facture that requires casting, the scope of the treatment rarely extends beyond the injury itself. The potential consequences that arise when a limb is not used for an extended period of time are rarely considered. The proposed research project concerns the scientific basis of interventions that may be used harness brain plasticity during periods of limb immobilisation, with the aim of maintaining functional capacity in older persons. The knowledge gained through this research will have the potential for application to rehabilitation programs for those who undergo enforced periods of limb immobilisation, for example following fractures arising as a result of a fall. The benefits that may accrue from the application of this knowledge are likely to be expressed not only in terms of enhanced quality of life and functional life span for those who experience such injuries, but also as significantly more effective use of health care funds.

Technical Summary

A significant risk associated with the fractures that arise from falls by older adults, is that the loss of specific muscle strength or general capacity resulting from limb immobilisation will leave the person below the level of capability necessary to perform everyday tasks, and thus maintain independent living. The phenomenon of cross-education, whereby practice with one arm enhances subsequent performance with the other arm has led to the supposition that the effects of disuse may be counteracted by training movements of the non-affected limb performed during the period of immobilisation. Although the phenomenon has been studied for more than a century, there is little consensus in relation to the neural mechanisms that mediate its effects. Two major theoretical models can be delineated: the 'cross-activation' model and the 'bilateral access' model. In order to provide a direct comparison of the explanatory power of these models, it is necessary to examine in the context of single tasks the relative impact upon cross-education of variations in the complexity of training movements, and the level of neural drive required for their execution. This unique approach is taken in the current project. In addition to theoretical considerations, a comprehensive understanding of the principles governing cross-education is required to ensure the optimum design of training programs that have as their aim the maintenance of functional capacity in older persons during limb immobilisation. Additional key objectives of the research are therefore to: establish the degree to which the balance that exists between factors that govern levels of cross-education varies across the lifespan; investigate the neural mechanisms that mediate their age-dependent influence; and assess age-related changes in the functional generalisation of cross-education to other movement tasks.

Planned Impact

Who will benefit from this research? The proposed project comprises strategic pre-clinical science that focuses upon interventions to maintain functional capacity in older persons. The users of the research will be health-care professionals. The beneficiaries of the research will be individuals who have suffered injuries that require periods of limb immobilisation for their treatment. The most significant risk arising from such injuries, including fractures arising as a consequence of a fall, is that the loss of specific muscle strength or general capacity resulting from limb immobilisation will leave the person below the level of capability necessary to perform everyday tasks, and thus maintain independent living. The potential benefits of the research are therefore likely to extend beyond enhanced quality of life and functional life span for the individuals themselves, but also be expressed as a reduced level of burden on their families and care givers, and more effective use of health care funds. How will they benefit from this research? We will seek to determine the mechanisms that underpin improvements in the performance of an untrained limb induced by unilateral training of the opposite limb, and examine variations in the respective contributions of these mechanisms across the lifespan. In so doing, we aim to critically assess the potential for interventions based on the phenomenon of cross-education to be deployed in the treatment of individuals who undergo enforced periods of limb immobilisation. The knowledge thus derived will have the potential for direct application to the design of rehabilitation programs for older persons. What will be done to ensure that they benefit from this research? A number of strategies are already in place to increase the likelihood of impact, and encourage the uptake of the results arising from the research by users in the health services. The knowledge generated by the project will be disseminated to professional and community organisations, with the intent of enhancing the application of the findings in a manner that engages and informs the users and the beneficiaries. The team intend to pursue the policy that has been adopted successfully by the PI previously, of engaging directly with health-care professionals, particularly those working in Gerontology and Geriatrics, Rehabilitation Medicine, Physiotherapy, and Occupational Therapy, who deal with injuries in older person on a daily basis. The Principal Investigator is a member of the Department of Health (Northern Ireland) Mental Health, Ageing and Learning Disability Translational Research Group (TRG), and uniquely, he and his research group are also members of the Trauma and Rehabilitation Research TRG. These groups provide forums for the rapid exchange of knowledge between researchers and practitioners delivering front-line services. In addition to delivering regular talks at the Regional Acquired Brain Injury Unit in Belfast, the Applicant has since 2006 given two keynote presentations at meetings of the British Society of Rehabilitation Medicine, and recently addressed the Danish Society of Rehabilitation Medicine. By means of the networks thus established, the Applicant is confident of effective dissemination to clinicians and allied health professionals. The PI has established a close relationship with the Centre for Ageing Research and Development in Ireland (CARDI). In addition to providing a means of communicating to the wider community the outcomes of strategic research on ageing and older people that aims to improve quality of life, this partnership provides an ideal basis upon which to involve older people in all aspects of the research process. In this context, the research team has also been liasing with Go for Life an all-island (Ireland) programme for physical activity for older people, with a view to ensuring the direct communication of their research findings to the relevant sectors of the lay public.

Publications

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Carson RG (2016) What Do TMS-Evoked Motor Potentials Tell Us About Motor Learning? in Advances in experimental medicine and biology

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D. A. BOLTON (2014) Interhemispheric inhibition of corticospinal projections to wrist muscles. in Society for Neuroscience Abstracts

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Ibey RJ (2015) Interhemispheric inhibition of corticospinal projections to forearm muscles. in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

 
Description Cross Education is the process whereby training with one limb leads to subsequent improvement in performance by the opposite, untrained limb. We used multimodal neuroimaging to investigate the mediating neural mechanisms, by relating quantitative estimates of functional and structural cortical connectivity to individual levels of interlimb transfer. Following training, the increase in performance of the untrained limb was more than 80% of that observed for the trained limb, and significantly greater than that of a control group who undertook no training. We established that the structural integrity of tracts connecting specific regions in the left and right side of the brain predicted the individual-specific level of benefit that arose from training of the opposite limb.

Contrary to previous reports, we have determined that older adults (aged above 65 years) accrue benefits from training of the opposite limb that are equivalent to those exhibited by young adults (aged 18 to 30 years). Critically, an equivalent level of benefit was apparent for the older adults when their performance was assessed after a short break - following training. When assessed immediately after training, the level of transfer was lower than that exhibited by the young adults. This finding suggests that the possibility of short-term fatigue must be taken into account when assessing the efficacy of any training program that is geared towards the enhancement of upper limb function in older adults.

The received wisdom in relation to severely impaired chronic stroke survivors is that, for persons who exhibit some residual capacity, therapeutic interventions must be focussed exclusively upon the impaired limb. A central objective of the research program was to establish the manner in which this cross education may be best exploited in the service of rehabilitation. Our findings indicated that in a group of chronic stroke survivors, positive transfer of performance to the hemiplegic arm was exhibited following a cross-education training program. In most cases the level of interlimb transfer was within the range of values obtained for separate control groups of young and older adults without brain injury. These results indicate that focussed training of the non-impaired limb has the potential to aid in the restoration of motor function of the impaired limb in stroke survivors in the chronic phase of recovery.

Our preliminary results suggest that genotypic variations with respect to aspects of dopamine transmission and receptor function influence the degree of retained benefit that arises from movement training. It also appears that the extent to which improvements in performance transferred to the non-training limb are consolidated and retained is influenced by genotypic variation with respect to the expression of a particular neurotrophin - brain derived neurotrophic factor (BDNF). These novel findings have important implications, as they suggest different aspects of the learning process are mediated by distinct cellular mechanisms. As a consequence, improvements functional movement capacity are unlikely to be promoted by a single type of training regime, or augmented by a single type of adjuvant (e.g. pharmacological) therapy.
Exploitation Route In accordance with the original objective of the project, the findings of this project have the potential to inform the design of training programs (particularly for older adults) that have as their aim the maintenance of functional capacity during and following periods of upper limb immobilisation resulting from a fall-induced fracture.

The outcomes of this research furthermore indicate that therapeutic interventions that exploit the facility for cross education have role to play in the rehabilitation of upper limb function in stroke survivors. This approach - which can be readily and immediately incorporated in existing programs of rehabilitation, offers particular promise for the 90% of stroke survivors who present with a level of residual capacity below that which is necessary to engage in constraint induced movement therapy (CIMT).

The findings that concern to the impact of genotypic variations in dopamine function, and in the expression of brain derived neurotrophic factor (BDNF), reveal the possibility of using of specific pharmacological agents - that act on the related cellular pathways, to enhance motor learning in an individually tailored fashion. Specifically, our results suggest that the selection of a selected pharmacological agent (and the assigned dosage) can be based on the genotypic profile of each individual, and the specific aims of the therapeutic intervention i.e. direct improvements in the performance of the training limb versus derived benefits in the functional capacity of the untrained limb. The present findings therefore have the potential to contribute to the more general goal of developing and administering personalised medicine.
Sectors Healthcare

 
Description Wellcome Trust Biomedical Vacation Scholarship
Amount € 1,700 (EUR)
Funding ID 102244/Z/13/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2013 
End 08/2013
 
Description Wellcome Trust Biomedical Vacation Scholarship
Amount € 1,700 (EUR)
Funding ID 109295/Z/15/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2015 
End 08/2015
 
Title Interhemispheric inhibition of corticospinal projections to forearm muscles 
Description Objective: Interhemispheric inhibition (IHI) is typically examined via responses elicited in intrinsic hand muscles. As the cortical representations of proximal and distal muscles in the upper limb are distinguished in terms of their inter-hemispheric projections, we sought to determine whether the IHI parameters established for the hand apply more generally. Methods: We investigated IHI at 5 different conditioning stimulus (CS) intensities and a range of short-latency inter-stimulus intervals (ISIs) in healthy participants. Conditioning and test stimuli were delivered over the M1 representation of the right and left flexor carpi radialis respectively. Results: IHI increased as a function of CS intensity, and was present for ISIs between 7 and 15 ms. Inhibition was most pronounced for the 10 ms ISI at all CS intensities. Conclusions: The range of parameters for which IHI is elicited in projections to the forearm is similar to that reported for the hand. The specific utility lies in delineation of stimulus parameters that permit both potentiation and attenuation of IHI to be assessed. Significance: In light of evidence that there is a greater density of callosal projections between cortical areas that represent proximal muscles than between those corresponding to distal limb muscles, and in view of the assumption that variations in functional connectivity to which such differences give rise may have important implications for motor behavior, it is critical to determine whether processes mediating the expression of IHI depend on the effector that is studied. This issue is of further broad significance given the practical utility of movements generated by muscles proximal to the wrist in the context of upper limb rehabilitation. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2015 
Provided To Others? Yes  
Impact Google Scholar shows 2 citations as of 1st March 2016 
URL http://www.sciencedirect.com/science/article/pii/S1388245714008505
 
Description Analysis and interpretation of electromyographic and behavioural data 
Organisation Free University of Amsterdam
Country Netherlands 
Sector Academic/University 
PI Contribution Our research team collected the electromyographic and behavioural data
Collaborator Contribution The partner contributed expertise in relation to the analysis of the electromyographic and behavioural data, and contributed to the interpretation of the outcomes.
Impact Ruddy, K.L., Rudolf, A.K., Kalkman, B., King, M., Daffertshofer, A., Carroll, T.J., & Carson, R.G. Neural adaptations associated with interlimb transfer in a ballistic wrist flexion task. Manuscript submitted for publication.
Start Year 2014
 
Description Analysis and interpretation of functional and structural brain connectivity data 
Organisation ETH Zurich
Country Switzerland 
Sector Academic/University 
PI Contribution Our research team collected the behavioural and neuroimaging data.
Collaborator Contribution The partners assisted in the analysis and interpretation of functional and structural brain connectivity data. One member of our research team (K.L. Ruddy) has moved to this institution, and continues to contribute to the project.
Impact Carson, R.G., Ruddy, K.L., & McNickle, E. What do TMS evoked motor potentials tell us about motor learning? Manuscript submitted for publication. Ruddy, K.L., Leemans, A. & Carson, R.G. Transcallosal connectivity of the human cortical motor network. Manuscript submitted for publication. Ruddy, K.L., Leemans, A., Woolley, D.G., Wenderoth, N., & Carson, R.G. Structural and functional connectivity mediating cross education of motor function. Manuscript submitted for publication. Ruddy, K.L., Rudolf, A.K., Kalkman, B., King, M., Daffertshofer, A., Carroll, T.J., & Carson, R.G. Neural adaptations associated with interlimb transfer in a ballistic wrist flexion task. Manuscript submitted for publication.
Start Year 2013
 
Description Analysis and interpretation of functional and structural brain connectivity data 
Organisation University of Leuven
Country Belgium 
Sector Academic/University 
PI Contribution Our research team collected the behavioural and neuroimaging data.
Collaborator Contribution The partner assisted in the analysis and interpretation of the neuroimaging data.
Impact Ruddy, K.L., Leemans, A., Woolley, D.G., Wenderoth, N., & Carson, R.G. Structural and functional connectivity mediating cross education of motor function. Manuscript submitted for publication.
Start Year 2013
 
Description Analysis of Diffusion Weighted Imaging data 
Organisation University Medical Center Utrecht (UMC)
Country Netherlands 
Sector Academic/University 
PI Contribution Our research team generated the neuroimaging data, which was analysed in collaboration with the partner.
Collaborator Contribution The partner has specialised expertise in the application of the method of Constrained Spherical Deconvolution to Diffusion Weighted Imaging data. The partner provided instruction in the use of this technique and contributed to the interpretation of the analyses.
Impact Ruddy, K.L., Leemans, A. & Carson, R.G. Transcallosal connectivity of the human cortical motor network. Manuscript submitted for publication. Ruddy, K.L., Leemans, A., Woolley, D.G., Wenderoth, N., & Carson, R.G. Structural and functional connectivity mediating cross education of motor function. Manuscript submitted for publication.
Start Year 2012
 
Description Design of training protocols and analysis of behavioural data 
Organisation University of Queensland
Country Australia 
Sector Academic/University 
PI Contribution Our research team generated the behavioural data.
Collaborator Contribution The partner developed the software used to collect the behavioural data in a subset of the experiments conducted in this project. The partner also contributed to the design of analyses and interpretation of data.
Impact Ruddy, K.L., Rudolf, A.K., Kalkman, B., King, M., Daffertshofer, A., Carroll, T.J., & Carson, R.G. Neural adaptations associated with interlimb transfer in a ballistic wrist flexion task. Manuscript submitted for publication.
Start Year 2010
 
Description Hosting of Data Collection and Analysis 
Organisation Trinity College Dublin
Department Institute of Neuroscience
Country Ireland 
Sector Hospitals 
PI Contribution Our research team collected, analysed and interpreted the data.
Collaborator Contribution The partner provided the facilities (infrastructure and personnel) that enabled the collection of neuroimaging data, behavioural data, electrophysiological data, and genotyping data. The partner also provided the means of recruiting participants and hosted members of our research team for extended periods. Facilities for data analysis were also provided.
Impact Ruddy, K.L. & Carson R.G. (2013). Neural pathways mediating cross education of motor function. Front. Hum. Neurosci. 7:397. doi: 10.3389/fnhum.2013.00397. Published on-line 29th July 2013. Ibey, R. J., Bolton, D. A. E., Buick, A. R., Staines, W. R., & Carson, R. G. (2015). Interhemispheric inhibition of corticospinal projections to forearm muscles. Clinical Neurophysiology, 126(10), 1934-1940. Published on-line 15th December 2014. doi: 10.1016/j.clinph.2014.12.006. Carson, R.G., Ruddy, K.L., & McNickle, E. What do TMS evoked motor potentials tell us about motor learning? Manuscript submitted for publication. Ruddy, K.L., Leemans, A. & Carson, R.G. Transcallosal connectivity of the human cortical motor network. Manuscript submitted for publication. Ruddy, K.L., Leemans, A., Woolley, D.G., Wenderoth, N., & Carson, R.G. Structural and functional connectivity mediating cross education of motor function. Manuscript submitted for publication. Ruddy, K.L., Rudolf, A.K., Kalkman, B., King, M., Daffertshofer, A., Carroll, T.J., & Carson, R.G. Neural adaptations associated with interlimb transfer in a ballistic wrist flexion task. Manuscript submitted for publication.
Start Year 2011
 
Description Progress in Motor Control, Budapest 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Carson, R.G. Neural pathways mediating cross education of human motor function. Paper presented to Progress in Motor Control, Budapest, 22nd - 25th July 2015.
Year(s) Of Engagement Activity 2015
URL http://www.pmc2015.org
 
Description The effect of visual feedback on interlimb transfer of training during a ballistic movement 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Buick, A.R. "The effect of visual feedback on interlimb transfer of training during a ballistic movement". Sensory Motor Research Conference, Birmingham, UK, 15th May 2015
Year(s) Of Engagement Activity 2015
 
Description Transfer of Motor Learning: A Case Report 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Bolton, D.A. 'Transfer of Motor Learning: A Case Report'. Sensory Motor Research Conference, Birmingham, UK, 15th May 2015
Year(s) Of Engagement Activity 2015
 
Description What can genetic analyses tell us about human motor learning? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote presentation BrainDisC Ph.D. Conference. Bernstein Center Freiburg, Germany, 28-29th September 2017.
Year(s) Of Engagement Activity 2017
 
Description What can genetic analyses tell us about human motor learning? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote Presentation Canadian Society for Psychomotor Learning and Sport Psychology. St. John's Newfoundland, Canada, 12-14th October 2017.
Year(s) Of Engagement Activity 2017