Imaging brain plasticity in multiple sclerosis
Dr Valentina Tomassini
Functional MRI of the Brain (FMRIB) Centre, University of Oxford, Department of Clinical Neurology, John Radcliffe Hospital, Oxford
Way Ahead 2008;12(4):8-9
Multiple sclerosis (MS) is characterised by a relapsing-remitting course in the earliest stages and typically reaches the progressive phase 10 to 15 years after onset1. Magnetic resonance imaging and neuropathological studies indicate that irreversible damage starts to accumulate in the earliest stages of a relapsing-remitting course - in spite of the clinical remissions suggestive of complete recovery2, 3. This clinical-radiological paradox may be explained by the compensatory mechanisms that account for the recovered function during remissions4.
Increasingly sophisticated brain imaging techniques indicate that brain plasticity - the brain's ability to reorganize neural pathways based on new experiences - is the compensatory mechanism largely responsible for the clinical remissions that are typical of early stages of relapsing remitting MS. The adult brain is capable of both functional and structural plasticity - processes that are operational in normal brain development such as learning and memory5.
Interestingly, functional and structural changes can also take place in the brain after injury or damage, and brain plasticity is seen to act as an adaptive mechanism to compensate for a loss of function6. Following tissue damage, the structure and function of undamaged parts of the brain can be remodeled and shaped by the sensorimotor experiences of the individual in the weeks to months following injury7, 8.
Non-conventional imaging techniques such as functional MRI (fMRI) and Diffusion Tensor Imaging (DTI) are useful tools in the study of brain plasticity as they are sensitive to both subtle brain damage and adaptive functional changes associated with movement or motor learning. Indeed, the learning paradigms of healthy controls are useful models in the study of adaptive functional compensation in neurological conditions such as MS. fMRI is used to assess dynamic brain changes associated with motor learning and the identification of networks responsible for the associated behavioral changes in healthy controls9. Based on the learning patterns of healthy controls, fMRI can be used to demonstrate how different regions of the brain can become active and take over the function of another region of the brain when it becomes damaged.
fMRI has been used in this way to demonstrate adaptive plasticity in MS. The process represents a 'rescue' mechanism after brain damage which allows clinical recovery to occur. Functional brain changes related to disease burden are therefore found in individuals with demonstrable pathology but no clinical deficit10-14. The set of areas activated in such individuals when performing a simple task are those areas that are usually engaged during complex motor tasks in healthy controls. This suggests that simple movements in people with MS demand different allocation of cognitive and motor resources to perform a motor task in the same way as healthy controls15, 16. While human studies have demonstrated the role of brain plasticity as an adaptive functional mechanism, experimental findings suggest that structural plasticity may also occur and contribute to the repair phase following demyelinating events in MS17. However, further research is needed to determine if, how, and to what extent, structural plasticity also contributes to the functional recovery that is seen during clinical remission.
Our understanding of brain plasticity in MS adds great value to our understanding of the importance of rehabilitation for people with MS. Non-conventional imaging techniques demonstrate that the training of motor skills is a potent modulator of brain function and structure in healthy subjects9, 18, 19. They also suggest that rehabilitation following brain damage - or relapse in the case of MS - can modulate brain plasticity. Functional changes can take place in the brain following damage as a result of rehabilitation-mediated improvements20. Recent evidence also suggests that there may be related structural changes occurring, whose magnitude is directly proportional to the extent of clinical improvement21. Alteration of neurotransmitters, recruitment of additional undamaged brain areas, and anatomical changes such as sprouting and synaptogenesis in the brain tissue surrounding the lesion or in the homologous region of the unaffected hemisphere are all part of the structural reorganizational processes that may take place22.
So while the value of rehabilitation as a non-pharmacological approach in MS is well recognized23-26, further studies on brain plasticity are needed to enhance our understanding of how these two modulators may interact more effectively. A study using functional MRI in people with MS is currently underway at Oxford University with the purpose of gaining greater insight into the mechanisms of brain plasticity in MS and its potential exhaustion in the later stages of the condition. It is hoped that such research could help in the development of strategies, pharmacological or otherwise, to adaptively modulate brain plasticity in MS and subsequently enhance functional recovery in people with MS.
Imaging techniques explained
Magnetic Resonance Imaging (MRI)
MRI is a scanning technique that creates images by using magnetic fields and radio waves to monitor the behaviour of hydrogen atoms in the body. The nucleus at the centre of a hydrogen atom spins like a top. The strong magnetic field in an MRI machine makes the atoms line up in the direction of the magnetic field. The machine then fires a pulse of radio waves that causes the atoms to spin in a different direction (causing 'resonance'). When the pulse is turned off, the atoms return to their natural alignment within the magnetic field and release energy. The machine picks up this signal and sends it to a computer, which converts it into an image.
Functional MRI (fMRI)
Functional MRI (fMRI) is a scanning technique that is used to investigate normal and abnormal brain function. fMRI study investigates regional blood flow changes and hence increased neuronal activity in different regions of the brain in response to different stimulus - motor, visual, sensory, cognitive or auditory. fMRI can be used to investigate cortical activation in healthy controls compared against cortical activation in people with MS when subject to the same stimulus.
Diffusion Tensor Imaging (DTI)
Diffusion Tensor Imaging is an MRI-based neuroimaging technique that is sensitive to the diffusion properties of water protons. It is used to assess tissue integrity. DTI indices are sensitive to structural damage in normal appearing brain tissue, detecting occult injury related to MS plaques, and providing information about different pathological aspects of MS. DTI measures allow for different white matter pathways to be identified, mapped, and quantified in motor learning and recovery studies.
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