 So good evening everyone, nice to be here and thank you very much to the scientific committee and to all the sponsors for this award. It's very valuable, believe me. They're very far, very difficult to get hold of. So anyway, my subject is on motor neurone disease. I'm a clinical researcher based at the Western Clinical School at Westmeat and I've been doing work into ALS research for a period of time now. So we began with trying to study the motor cortex because there is a hypothesis that the disease begins in the brain rather than in the periphery and we subscribe to that hypothesis. And we've studied the brain and found some changes in the brain which are quite predictive for a diagnosis of motor neurone disease. And this is a loss of excitability in the cortex. It's called a hyper excitability. So there's loss of inhibition basically and perhaps an increase in facilitation. And this has helped us as a research protocol to diagnose ALS more early. So now the question is why does this disease spread? And this is the interesting question we're trying to answer. I have tried one modality which is again studying the motor cortex alone and studying it over different body areas, some of which may be affected at the time the person presents and some of which appear unaffected to try and understand what happens. There have been problems with the motor cortex itself because muscles waste and the system gets affected very early, especially the brain. So that's where the thought came about how else can we study the brain. And we have explored a few avenues earlier. So some of them are going to be completely new and some of them have been tested earlier in small groups. And one of the modalities we will use is MRI to look at not just the brain structure but the connection between the various areas of the brain to understand what are the changes in the connectomes as we call it, the links between the different centers of the brain and will changes in these connections be the earliest indicator of a problem. So there is a large number of controls that we need to study and patients. And the second aspect or rather this will be the third modality that I'll use in order to understand progression of ALS and that will be a technique called TMS EEG where you stimulate the brain using a magnetic field but instead of recording over a muscle you record over the brain itself and then look at what happens with the potentials that are generated in other areas of the brain. So this might be another functional way of assessing the brain and we hope that with studying it using these three modalities of transcranial magnetic stimulation MRI and TMS EEG and studying a large number of controls to match the data we will be able to come up with the earliest changes that happen in sporadic ALS and therefore have ways of understanding why the problem progresses and can we do something about it. So thank you very much once again for the Brain Foundation gift.