The purpose of this observational study is to improve understanding of the biology of why ALS, MS and FTD have different effects on different people and facilitate better measurement of the disease in future drug testing. To do this, brain and spinal cord neural network functionality will be measured over time, in addition to profiling of movement and non-movement symptoms, in large groups of patients, as well as in a population-based sample of the healthy population. Patterns of dysfunction which relate to patients' diagnosis and coinciding and future symptoms which align with categories of patients with similar prognoses will be investigated and their ability to predict incident patients' symptoms in future will be measured.

The aim of this project is to characterize spatiotemporal patterns of central nervous system dysfunction that correlate with clinical features of ALS, MS and FTD, to provide non-invasive electrophysiological measurements that can be used in a clinical setting to inform stratification of patients in clinical trials, and to provide data driven diagnostic and prognostic biomarkers and objective clinical trial outcome measures. Such dysfunction will be investigated by recording single- and paired-pulse transcranial magnetic stimulation (TMS)-associated electromyography (EMG) during rest and by recording electroencephalography (EEG) during rest and during cognitive-motor tasks.

Inclusion criteria:

• Age >18 years and able to give informed written or verbal (in the presence of two witnesses) consent.

• In the case of non-control subjects, a clinical diagnosis of:

  (i) Probable frontotemporal dementia (FTD) including behavioural variant FTD, semantic dementia or primary progressive aphasia) with supportive brain imaging or known FTD causing genetic mutation (ii) Multiple sclerosis (MS) according to the McDonald criteria (Polman et al., 2011) or (iii) Possible, probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial Criteria Revised (Brooks et al. 2000)

Exclusion criteria:

• Any diagnosed neurological/muscular disease other than ALS, MS or FTD
• Use of neuro- or myo-modulatory medications except riluzole
• Inability to participate due to disease-related motor symptoms (e.g. inability to sit for the required time or click the mouse to respond)
• Upper body metallic implants
• History of seizure disorders in the participant or immediate family members
• Anxiety-induced fainting
• Regular migraine
• Evidence of significant respiratory insufficiency
• Sleep time >2 hours below normal and/or alcohol consumption the night before data collection (in which case, recording session will be rescheduled).

Healthy controls and patients diagnosed with ALS, FTD or MS

Raw data from this study may be made available in anonymized form upon request from qualified investigators subject to the approval by the Data Protection Office (DPO) and Office of Corporate Partnership and Knowledge Exchanges (OCPKE) in Trinity College Dublin, the University of Dublin.

Due to ethical constraint and the time required for data quality checks, data will only be made available in fully anonymised format following publication of results.