Award details

Contribution of Spinal Commissural Circuits to Bimanual Co-ordination

Reference	BB/P019897/1
Principal Investigator / Supervisor	Professor David J. Maxwell
Co-Investigators / Co-Supervisors
Institution	University of Glasgow
Department	College of Medical, Veterinary, Life Sci
Funding type	Research
Value (£)	267,782
Status	Completed
Type	Research Grant
Start date	01/01/2018
End date	31/05/2021
Duration	41 months

Abstract

It is well accepted that the spinal commissural system is critical for the bilateral organisation of locomotion, but there is very little information of the organisation and role of this system during hand movements. The aim of this proposal is to firstly address if descending motor pathways contact spinal commissural systems, and secondly if spinal commissural systems play a role for bimanual movement control. Monkeys are the most appropriate model for this proposal due to similarity of their motor system to that in man, and because they use bimanual movements extensively during daily life. To answer the first question we will carry a series of anatomical studies, to see whether the corticospinal and reticulospinal tracts contact commissural circuits in the cervical spinal cord. Commissural neurones will be retrogradely labelled through injection of an viral vector on one side of the spinal cord, while descending terminals will be traced through anterograde tracer injections in the primary motor cortex and reticular formation. Following an appropriate survival time, animals will be euthanised and anatomical processing of the cervical spinal cord will allow us to address if commissural cells receive descending inputs, if these inputs show any preference towards commissural cells located on the ipsilateral or contralateral side of the spinal cord and if either descending pathway shows a stronger connectivity with commissural cells. To answer the second question we will carry out transient inactivation of spinal commissural circuits in the cervical spinal cord, and measure the deficits produced during a bimanual task. A 'pull and pick' task will be employed where a drawer has to be opened and an object picked from within. During such tasks the two hands show a high degree of temporal coupling. Deficits in this coupling following commissural inactivation will tell us how commissural circuits are engaged during normal manipulative movements.

Summary

Most of the voluntary movements we make on a daily basis require use of both hands together, whether to unscrew the lid off a bottle, to open a packet of crisps or to tie our shoe laces. The role of the cerebral cortex for planning and execution of bimanual movements has been studied for some time and is well established. However, for all the important contributions the cortex makes, none of it matters unless those commands are turned into actions by the spinal cord. Understanding how the brain controls the two hands together is important not just as a basic science question, but also because it has clinical implications as well. Deficits during bimanual movements are a symptom of many different brain pathologies, including Parkinson's Disease, stroke, motor neglect and spinal cord injury. In most cases this deficit is attributed to an imbalance of communication between the two sides of the brain while spinal contributions to such bilateral deficits, although very likely, are rarely considered. Thus viable spinal targets for rehabilitation may be overlooked. In addition, the formation of inappropriate new spinal connections following damage to the parts of the central nervous system that control movement is a potential cause of defective movement but we need to know more about the normal connections of the spinal cord before we can assess such changes. Although it has been known for some time that the spinal cord plays an essential role in the control of the legs for locomotive movements such as walking and running, its role for the control of the arms and hands is still relatively neglected. The spinal cord has its own dedicated neural circuit for synchronizing the movement of left and right legs during locomotion - the commissural system. The role of this system for co-ordinating the upper limbs is unknown, and this project aims to redress this knowledge gap. This will be done by studying how higher motor centres connect to the commissural system, and how transient inactivation of this system affects movements with either or both hands together. This information will allow us to address how the commissural system contributes to bimanual movements.

Impact Summary

Our proposal is a basic scientific study on the bilateral organization of spinal cord circuits during movement but we believe that there are areas, beyond the academic sphere described above, that our work could have an impact on in the longer term. Public Engagement: The importance of basic science can sometimes be hard to convey to the general public but their engagement is most productive through demonstrations - various bimanual 'party tricks' (such as trying to tap your head and rub your tummy at the same time or trying to draw a line with one hand and a circle with the other) are a very reliable way to show that use of our hands is not independent, and there are still un-answered questions on how such movements are controlled and constrained by neural pathways. Stakeholder engagements: Regardless of any personal views on use of primates in animal research, the only way forward in terms of justifying, assessing and refining this work is through extensive and open communications with the relevant stakeholders (funders, policy makers, regulators) both within the UK but also internationally. Since its formation just over a year ago, the UK Expert Group on Primate research, which represents the UK scientists working with non-human primates, has successfully strived to create and maintain robust lines of communications with several different stakeholders such as the BBSRC, MRC, Wellcome Trust, NC3Rs as well as with the regulators (Home Office), other policymakers (EU) and other organizations (such as UAR). Although primate research represents a tiny fraction of animals used yearly, funding this work represents a large ethical, monetary and legal load for the aforementioned stakeholders and through this forum, common issues and concerns can be openly discussed with all the relevant parties. Clinical Impact: Deficits during bimanual movements are a symptom of many different brain pathologies, such as Parkinson's, stroke, motor neglect and spinal cord injury, but also including normal ageing. In most cases this deficit is attributed to an imbalance between the interhemispheric interactions in the cortex, while spinal contributions to such bilateral deficits, although very likely, are rarely considered. Our proposal could redress this, and potentially highlight additional viable targets for rehabilitation and/or culprits for maladaptive plasticity in cases of motor system damage. Improvements in clinical practice now mean that an increasing number of patients are surviving stroke and spinal cord injury. Combined with an increasingly aged population, this has a huge potential socioeconomic cost

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/P019757/1 Contribution of Spinal Commissural Circuits to Bimanual Co-ordination

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