My research interests are to firstly to delineate clinical phenotypes of different forms of movement disorders particularly in dystonia and parkinsonian conditions. We are able to provide clinical material for the finding of new genes for these disorders and to carry out phenotype-genotype correlations. Furthermore we research and define pathophysiological mechanisms of well characterised (genetically or otherwise) movement disorder conditions using transcranial magnetic stimulation (TMS) techniques to study central nervous system (CNS) physiology. An example of this is our published research in DYT1 gene related dystonia where we have firstly showed that both manifesting and non-manifesting carriers of this gene defect have CNS abnormalities detected by electrophysiology ( Different patterns of electrophysiological deficits in manifesting and non-manifesting carriers of the DYT1 gene mutation. Brain. 2003) and more recently using a special way of delivering repetitive TMS (Theta burst stimulation of the human motor cortex. Neuron. 2005) showed that dystonia brains may be too plastic (Abnormalities in motor cortical plasticity differentiate manifesting and non-manifesting DYT1 carriers. Mov Disord. 2006).
We have had a number of research papers on phenotype- genotype correlations for different movement disorders. Apart from dystonia and parkinsonism mentioned earlier some recent work includes Huntington disease look-alike conditions which are negative for the HD (IT15 gene) and we have published some work in this area (Phenotypic homogeneity of the Huntington disease-like presentation in a SCA17 family. Neurology. 2006; Huntington's disease phenocopies are clinically and genetically heterogeneous. Mov Disord. 2008) and on myoclonic disorders (The natural history of Unverricht-Lundborg disease: a report of eight genetically proven cases. Mov Disord. 2008). Based on phenotype- genotype correlations we have been to give guidelines on what to test these HD-like disorders (The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test. Nat Clin Pract Neurol. 2007).
Our current interest is in defining endophenotypes for partially penetrant autosmal dominant genetic conditions of dystonia and parkinsonian families and we have done some work on this (Defective temporal processing of sensory stimuli in DYT1 mutation carriers: a new endophenotype of dystonia? Brain. 2007 ; Defective temporal discrimination of passive movements in Parkinson's disease. Neurosci Lett. 2007 ; Mental rotation of body parts and non-corporeal objects in patients with idiopathic cervical dystonia. Neuropsychologia. 2007) . Further work using these techniques to define carriers with endophenotype defects is being carried out in families with dystonia and parkinsonism.