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The role of sensorimotor cortical plasticity in pathophysiology of Parkinson’s disease and dystonia

Kojovic, M; (2014) The role of sensorimotor cortical plasticity in pathophysiology of Parkinson’s disease and dystonia. Doctoral thesis , UCL (University College London). Green open access

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Abstract

This PhD thesis is a study of cortical electrophysiology in two basal ganglia disorders: Parkinson’s disease (PD) and dystonia. Two diseases were chosen as being representative of hypokinetic and hyperkinetic movement disorders, respectively. In addition, current treatments seem to be imperfect to control many aspects of both diseases, hence the interest in exploring potential new therapeutic targets. PD and dystonia are basal ganglia diseases, but there is growing body of evidence of impaired cortical function and particularly of abnormal sensorimotor cortical plasticity in both disorders. We however still lack knowledge about functional significance of these cortical changes. Are they maladaptive or compensatory or of little functional significance? Techniques of Transcranial Magnetic (TMS) were used to determine 1) if clinical asymmetry of early PD is reflected in hemispheric asymmetry of sensorimotor cortical plasticity and intracortical inhibition, and 2) how these electrophysiological measures change with disease progression. We found that the hemisphere contralateral to the less affected side had preserved intracortical inhibition and a larger response to the plasticity protocol, whereas on the more affected hemisphere these were reduced. We further demonstrated that the decline in asymmetry of these measures correlated with the reduction in asymmetry of clinical symptoms, suggesting these were compensatory changes. In dystonia patients, we investigated using TMS 1) if change of afferent input induced by botulinum toxin injections may change response to plasticity protocol in primary dystonia, and if 2) secondary and primary dystonia patients share the same pattern of electrophysiological abnormalities. We demonstrated that sensorimotor cortical plasticity in primary dystonia is not permanent abnormality but may be transitory reduced with botulinum injections treatment. Secondary dystonia patients, as opposed to primary dystonia patients did not have enhanced sensorimotor plasticity or impaired cerebellar function. We provide evidence that different types of dystonia do not necessarily have the same neuroanatomical substrates, which might have therapeutic implications.

Type: Thesis (Doctoral)
Title: The role of sensorimotor cortical plasticity in pathophysiology of Parkinson’s disease and dystonia
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: sensorimotor cortical plasticity, paired associative stimulation, dystonia, Parkinson's disease
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/1432358
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