Final Report Summary - BILATERAL MODULATION (Modulating interhemispheric interaction in physiology and disease) This project aimed to reveal how transcranial magnetic stimulation (rTMS) acts on the interhemispheric interaction in patient populations and healthy controls. A protocol for a significant and consistent alteration due to neurostimulation on the behavioural level as initially planned could not be established making corrective actions necessary. As a result, the research activities focused on the cerebral correlates of tremor in a patient population suffering from neuropathic tremor. This is a disease in which patients develop tremor of the upper limbs due to pathology of peripheral nerves. It belongs, like Parkinson's disease (PD) and dystonia, to a group of neurological diseases summarised as movement disorders. The research question here was to localise the brain areas which are involved in the generation of this specific tremor type using simultaneous muscle and brain recordings using magnetoencephalography (MEG). A group of patients was recorded during a motor task (lifting of the arm), which provoked the tremor. The performed analysis was based on an approach mapping so-called cerebro-muscular coherence in all parts of the brain. This demonstrates to what extend specific brain areas are involved in the generation of the tremor and thus, allows conclusion about the pathophysiological mechanism of the disease. The preliminary results suggest that we can differentiate two groups of patients: (i) a group with a primary driver of the tremor in the contralateral primary motor cortex; and (ii) another group with a primary driver in the ipsilateral cerebellum. Parts of the studied patients also seemed to demonstrate significant contributions of both of these brain areas and may constitute a third, intermediate group. Still ongoing analyses try to further disentangle the contributions from the brain areas at hand and may also answer the question, if the observed coupling is more of an afferent or efferent nature. In another strand of research, we still aim to optimise and refine both the neurostimulation protocol and the assessment of changes on the behavioural level to study motor performance in focal hand dystonia patients and PD patients. The aim of this effort is to scrutinise a study protocol even assessing subtle changes of behaviour, e.g. writing performance. To this end, we developed a protocol using transcranial direct current stimulation (tDCS) instead of rTMS aiming to down regulate the primary motor cortex and are in the process of developing an analysis software for the assessment and classification of writing performance in cooperation with the Gatsby Computational Neuroscience Unit. The result from our study on neuropathic tremor will lead to better insights into the pathophysiology of neuropathic tremor. The involvement of cerebral areas in the generation of this tremor was unknown so far. Especially, the contribution of the ipsilateral cerebellum in the generation of the tremor is of relevance as these results tally findings from other studies of this patient population within the department suggesting a prominent role of the cerebellum in this disease.
