Novel Neurophysical Biomarkers of Heterogeneous Network Degeneration in Motor Neuron Disease for Quantifying the Progression and Outcome in Clinical Trials

Motor Neurone Disease (MND)/Amyotrophic Lateral Sclerosis (ALS) is a terminal neurological condition in which the neurones (neural cells) that control movement degenerate. Despite encouraging results from studies in animals, translation of new treatments to humans has been disappointing. The aim of this study is to provide scientific basis for a new perspective on ALS. Rather than focussing on individual cells, this proposal suggests studying ALS as a disease with disruption of brain networks that control movement and cognition. We have already generated evidence that supports this. We now propose to develop new technologies that that can help to assess patients based on distinct patterns of network disruption exhibited in the brain. To achieve this, we will first collect non-invasively the brain waves (EEG) during rest to identify the networks that are disrupted. We will then study the networks that are engaged during cognitive tasks and during movement. Additionally, we activate movement-related networks in the brain by using a non-invasive device (magnetic stimulation). We will validate and improve these measures using the results of neurological examination, neuropsychological tests of cognition and behaviour, and MRI brain imaging. After these verifications, these cost-effective EEG measures can be used independently for assessment of disruptions in multiple brain networks. We will subsequently measure the network dysfunction in the same patients during the course of their illness and monitor the changes in the pattern of disruption as the disease progresses. This outcomes from this study will be useful in identifying different patient subgroups, and to measure disease progression over time, and to find better ways to measure the effects of new drugs in a clinical trial setting.

Award Date
28 June 2018
Award Value
Principal Investigator
Dr Bahman Nasseroleslami
Host Institution
Trinity College Dublin
MRCG-HRB Joint Funding Scheme