 First, I'd like to thank the Brain Foundation, the sponsors, donors and the awards committee for this Neurone Fellowship. This fellowship will allow me to develop a clinical tour which began life as a research project a decade ago. Modern Neurone Disease is a universally fatal neurodegenerative disease with no known cure. More than 2,000 people in Australia are directly affected by Modern Neurone Disease with an average life expectancy of two to three years. Modern Neurone Disease presents initially with weakness and twitching in the muscles of one or more body regions that spread to other regions and usually leads to a failure of respiratory muscles. Classical amyotrophic lateral sclerosis or ALS accounts for some 80% of Modern Neurone Disease sufferers. A clinically definite diagnosis requires progression of symptoms in upper and lower motor neurons of several body regions. Upper motor neurons are the nerve cells in the motor cortex of the brain that extend down to the lower motor neurons in the spine and lower motor neurons are the nerve cells in the spinal cord that extend out to skeletal muscle. Diagnosis of ALS is delayed because there's no good biomarker for the disease and diagnosis requires the exclusion of all other mimics. The time from onset to confirmation of diagnosis has stubbornly remained around 12 months for the last 20 years and this diagnostic delay represents up to half of the total disease duration and prevents early intervention. It's been argued that Modern Neurone Disease begins in the upper motor neuron in the brain but it can be very difficult to demonstrate early upper motor neuron dysfunction clinically. Over the past decade we have undertaken research on a non-invasive technique for assessing the excitability of the brain using transcranial magnetic stimulation and have presented evidence that measurements of cortical excitability may provide a sensitive and specific biomarker for ALS. A robust marker of upper motor neuron dysfunction is also essential for clinical trials of new treatments that are in the pipeline. So the primary objective of this fellowship is to translate this research into a tool that clinicians can use to measure cortical excitability in motor neuron disease. In support of this goal I intend to further research which looks at patterns of progression by correlating cortical excitability to clinical deficits and to quantify the variability and minimum detectable changes in healthy controls in motor neuron disease cohorts. I'll also examine mechanisms of lower motor neuron dysfunction, degeneration, which may be compensatory or secondary to the primary insult but nonetheless contribute greatly to the patient's disability. So once again I'm extremely grateful to the Brain Foundation and particularly the Dawn Wallace estate for this fellowship. Thank you.