Cortical and Spinal Connectivity of Motor Units as a novel biomarker of Amyotrophic Lateral Sclerosis pathology

One in every 400 in Ireland is at risk of developing Motor Neurone Disease during their lifetime, with Ireland having the highest overall incidence of Amyotrophic lateral sclerosis (ALS) in Europe. ALS is a nervous system disease that causes a gradual loss of muscle control. It is characterised by the death of motor neurons, which are the nerve cells that control muscle movements (a motor neuron and its connected muscle fibres are collectively called a motor unit). ALS is confirmed by the detection of abnormal patterns in the electrical activity produced by motor units within a muscle. However, these recordings are not sensitive enough to detect early signs of ALS and up to 50-80% of motor units may be already lost before weakness is obvious. High density surface electromyography (HD-sEMG) is a new technology that can record motor unit activity noninvasively from the skin surface. This study will use HD-sEMG to develop methods that have the sensitivity to pick up small changes in motor function and to detect early signs of motor units losing their connection to the brain. We will use simultaneous recordings of HD-sEMG and brain waves (electroencephalography, EEG) to examine the functional connections between brain and muscle in ALS at specific frequencies. This will be the first study to incorporate direct estimates from motor units to examine brain-muscle connectivity in ALS. Combining information from EEG and direct recordings from motor units will increase the likelihood of identifying early signs of motor unit degeneration, enabling a faster diagnosis and earlier enrolment in clinical trials. Patterns of brain-muscle connectivity could also provide markers to identify different patient sub-groups and to objectively monitor disease progression. These types of biomarkers are urgently needed for clinical trials to improve the identification and testing of new drugs and therapies for ALS.

Award Date: 30 June 2022
Award Value: €717,321
Principal Investigator: Dr Lara McManus
Host Institution: Trinity College Dublin
Scheme: Emerging Investigator Awards 2022