Plasticity of Grey and White Matter in Response to Motor Skill Training in Healthy Individuals and Those With Spinal Cord Injury

Study Overview
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Brief Summary
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We aim to investigate the effect of motor skill training of the upper and lower limbs on the function and structure of the CNS as measured by neuroimaging parameters sensitive to changes in tissue volume and density and the properties of myelin.

Detailed Description
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Functional recovery following human spinal cord injury (SCI) remains frustratingly limited and the majority of patients are left with severe impairments. While rehabilitative training has been shown to improve clinical outcome following SCI and has a major effect on patients' quality of life, the neuronal mechanisms underpinning neurological and functional recovery are not well understood. Until recently, degenerative changes in components of the CNS remote to a SCI were thought to occur slowly (over years) and correlate with the degree of disability. Using longitudinal MRI protocols we have shown that these structural changes in fact occur early and progress both at the cord and brain level according to a specific spatial and temporal pattern (Freund et al 2013). It is thought that these trauma-induced structural changes progress retrogradely along central motor nerve fibres of the myelinated corticospinal tract (CST) and this is accompanied over time by shrinkage of corticospinal projecting neuronal bodies. Crucially, patients with less atrophy throughout the CST were those with better clinical recovery at twelve months. Despite this significant recovery advantage in some patients, all participants showed irreversible tissue loss, potentially hindering further recovery. Using the neuroimaging biomarkers established in the previous study cited above, we now aim to assess whether specific and intensive motor learning through tasks for the upper and lower limb might slow or reverse the atrophy seen in the sensorimotor system.

Conditions
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Investigating Spinal Atrophy in Patients With Spinal Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: Injury to the spinal cord which leads to any neurological deficits able to provide Informed consent Controls: - able to provide informed consent Exclusion Criteria: Pregnancy MRI incompatible Neurologic or physiatric disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SCI patients with upper limb impairment - Upper limb training<br> | |
| SCI patients with lower limb impairment - Lower limb training<br> | |
| Healthy controls - Upper limb training<br> | |
| Healthy controls - Lower limb training<br> | |
| Healthy controls - No intervention<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI parameters: tensor based morphometry, longitudinal relaxation rate, magnetisation transfer and diffusion index changes in the cervical and cranial corticospinal tract, basal ganglia, motor, premotor and parietal cortex. |  | MRI scans at weekly intervals (day 0, 7, 14, 28 and 84 after commencement of training) | 
| Raw performance data in the upper and lower limb training task, recorded at each training session. |  | Training sessions 4x1hour per week for 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall activity levels as recorded by a worn accelerometer and clinical scoring tests repeated immediately following the first and final training scan sessions (Day 0 and 28) and the 84 day follow-up scan. |  | Training sessions 4x1hour per week for 4 weeks; clinical assessments at day 0, 28, 84 | 
| 3D gait analysis will be performed on certain patients and control subjects at the first and final training scan sessions (Day 28) and the 84 day follow-up scan |  | 3D gait analysis at day 0, 28, 84 |