Bilateral organisation in the spinal cord.

Most of the movements we make require use of both hands, whether for an everyday task such as unscrewing the cap off a bottle, or for something much more elegant such as playing the violin. We know a substantial amount about how motor areas in the cerebral cortex contribute to bimanual movements but several other structures in the brain are also involved. One such structure is the spinal cord, as it has a strong bilateral anatomy, but its contribution in bimanual movements is far from clear.
In this project, I will study the bilateral organisation in the spinal cord firstly by recording in monkeys the responses in muscles from weak electrical stimulation of the two main descending pathways responsible for arm movements - namely the corticospinal tract, which carries information from the cerebral cortex to the spinal cord, and the reticulospinal tract, which carries information to from the brainstem to the spinal cord. By recording the responses in muscles from both arms it will be possible to assess how these structures can activate muscles bilaterally. The stimulation will be performed while the monkeys are at rest but also during raching and grasping movements with either or both hands together. This will tells us whether the bilateral context of a movement has an impact on these effects. In a similar fashion, sensory nerves in one hand will be stimulated at rest and during movement - the responses in the muscles of the other hand will be measured. This will tell us how sensory information can affect movements of the opposite arm and whether this depends if both or either hand is being used.
In the second part of the project, direct recordings of spinal activity will be made during arm movements. The activity of neurones during the same task as above will be recorded and subsequently the cells will be tested to see what bilateral sensory and descending inputs they receive. This will provide two types of information - firstly, it will tells us about the convergence of bilateral descending and sensory inputs - how many cells receive both, either or none, and secondly we can look at how the response of these cells during different movements relates to their inputs e.g. do cells that receive bilateral descending inputs fire differently from those that do not?
Previous studies in man have shown that perturbing one arm can cause a response on the other arm and these 'crossed effects' tend to be stronger during bilateral movements. Very little work has been done on crossed effects in hand muscles. In conjunction with the experiments in monkeys above, stimulation studies will also be carried out in human volunteers. These will assess how spinal circuits controlling the hand muscles can be modulated by sensory stimulation from the opposite hand. Subjects will perform a variety of movements that require use of the intrinsic hand muscles with either or both hands. By stimulating sensory nerves on one arm I will assess how crossed effects in hand muscles depend on the bilateral context of the movements. The expectation is that crossed effects will be stronger during bimanual movements compared to movements with one hand only.
The data collected in this project will provide information on how descending and sensory information can affect spinal circuits and muscles bilaterally and how bilateral movements can modulate these interactions. This has implications for patients with stroke or incomplete spinal cord injury.

Multiple structures contribute to the bilateral control of arm movements. The spinal cord has substantial bilateral connectivity, both in terms of descending corticospinal and reticulospinal projections, but also in terms of intrinsic commissural interneurones within the spinal cord itself. The impact of this connectivity, particularly during bilateral movements is not clear.
In macaque monkeys I will record the responses of muscles bilaterally to stimulation of corticospinal and reticulospinal systems during a bilateral "reach to grasp and pull" task. Movements will be with either or both hands together and for bilateral trials the two levers will be linked together. The responses in proximal and distal muscles from the stimulation of corticospinal and reticular formation will be used to assess how these two descending tracts can affect spinal excitability bilaterally and if this effect depends if one or both hands are used. Similar protocols will be applied to stimulation of sensory afferents (through implanted nerve cuffs) on one arm to assess effects in the other arm during movement, and how these vary with the bilateral movement context.
Recordings of spinal interneuronal (and pre-motoneuronal) activity in the same monkeys will be made to asses cell activity during this task, and how they respond to bilateral descending and sensory stimulation. This will show how bilateral descending and afferent inputs co-localise on the same spinal neural populations and how the inputs a cell receives can determine its response pattern.
Human experiments will also be performed to assess 1) crossed effects in distal hand muscles but also 2) if distal sensory information can affect more proximal muscles (forearm and elbow) in the opposite hand.

Although this project will not directly deal with patient populations, they are the primary, but indirect, non-academic beneficiaries. Bilateral training paradigms are becoming increasingly common rehabilitation tools for stroke and spinal cord injury patients - indeed a £1.5m grant was recently awarded from the Health Innovation Challenge Fund to Newcastle (Prof. Janet Eyre) for development of a computer game for rehabilitation - this involves stroke patients playing virtual games by moving wireless controllers with both arms. Despite the increasing importance of bilateral training paradigms there is still no clear understanding on how the hands interact across multiple levels and in particular at the spinal cord - this is information to be provided by this project by showing how spinal excitability changes during bilateral movements, and how spinal circuits respond to bilateral descending and afferent stimuli during such movements. This may provide a framework for designing novel bilateral training paradigms, but also on potentially combining afferent or central stimulation during training.
This information also has the potential to reshape current hypotheses regarding maladaptive neural responses to damage. For example following stroke, the interactions between the unlesioned and lesioned hemispheres is hypothesized to impede recovery (early on after stroke), but similar interactions could potentially also occur at the level of the spinal cord. Understanding the local and descending bilateral spinal interactions would show if rehabilitation strategies need to show a greater consideration in bilateral spinal interactions in their protocols.
The medical care providers (in the UK, the NHS) would also benefit from this work in the longer term as a result of improvements in patient rehabilitation. A decline in motor ability impacts on an individual's independence and psychological state of mind with a huge cost to the nation as a whole. For example, in the UK stroke alone has direct costs to the NHS in excess of £2.7 billion, to the wider economy £1.8 billion with care costs of £2.4 billion. Anything that improves clinical outcome and/or delays (even prevent) people losing their independence will have a huge impact on healthcare costs. The data generated from this project could have a relatively direct impact on bilateral training paradigms and hence the potential to impact on how medical care is provided.