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Measuring network disruption in neurodegenerative diseases: New approaches using signal analysis
  1. Roisin McMackin1,
  2. Muthuraman Muthuraman2,
  3. Sergiu Groppa2,
  4. Claudio Babiloni3,4,
  5. John-Paul Taylor5,
  6. Matthew C Kiernan6,7,
  7. Bahman Nasseroleslami1,
  8. Orla Hardiman1,8
  1. 1 Academic Unit of Neurology, Trinity College Dublin, the University of Dublin, Dublin, Ireland
  2. 2 Department of Neurology, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany
  3. 3 Dipartimento di Fisiologia e Farmacologia “Vittorio Erspamer”, Università degli Studi di Roma “La Sapienza”, Roma, Italy
  4. 4 Istituto di Ricovero e Cura San Raffaele Cassino, Cassino, Italy
  5. 5 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
  6. 6 Brain & Mind Centre, University of Sydney, Sydney, Sydney, Australia
  7. 7 Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Sydney, Australia
  8. 8 Beaumont Hospital, Dublin, Ireland
  1. Correspondence to Professor Orla Hardiman, Academic Unit of Neurology, Room 5.43, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, the University of Dublin, Dublin D02 R590, Ireland; hardimao{at}


Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer’s disease (AD), Lewy body dementia (LBD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. The gap between what imaging can discern and underlying pathophysiology can now be addressed by advanced techniques that explore the cortical neural synchronisation, excitability and functional connectivity that underpin cognitive, motor, sensory and other functions. Transcranial magnetic stimulation can show changes in focal excitability in cortical and transcortical motor circuits, while electroencephalography and magnetoencephalography can now record cortical neural synchronisation and connectivity with good temporal and spatial resolution.

Here we reflect on the most promising new approaches to measuring network disruption in AD, LBD, PD, FTD, MS, and ALS. We consider the most groundbreaking and clinically promising studies in this field. We outline the limitations of these techniques and how they can be tackled and discuss how these novel approaches can assist in clinical trials by predicting and monitoring progression of neurophysiological changes underpinning clinical symptomatology.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Contributors OH planned the review, convened the expert group, oversaw the project development and had final editorial oversight of the manuscript. OH and RM wrote the introduction, limitations and conclusions. BN, MM, SG and RM wrote the methodology section. All authors reviewed and reported on neurodegenerative disease literature. BN composed the figures. RM composed the tables. All authors edited and revised the manuscript prior to submission. OH and RM submitted the study.

  • Funding OH, BN and RM were supported by the Irish Health Research Board [grant numbers: EIA-2017-019, HRB-MRCG-2018-02, HRB-JPND-2017-1], Science Foundation Ireland [grant number: 16/ERCD/3854], the Irish Research Council [grant numbers: GOIPG/2017/1014,GOIPD/2015/213], the American ALS Association [grant number: ALS18-CM-396] and Research Motor Neurone. JPT was supported by the National Institute for Health Research (NIHR), Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. MM and SG were supported by Transregional Collaborative Research Center (CRC) SFB TR-128. MCK was supported by the National Health and Medical Research Council of Australia Program Grant [grant number: 1132524] and Practitioner Fellowship [grant number: 1156093]. Funding sources had no involvement in the writing of this review.

  • Competing interests OH receives personal fees from Taylor and Francis, Cytokinetics and Wave Pharmaceuticals, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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