Abstract
There is strong clinical, imaging and pathological evidence that neurodegeneration is associated with altered brain connectivity. While functional imaging (fMRI) can detect resting and activated states of metabolic activity, its use is limited by poor temporal resolution, cost and confounding vascular parameters. By contrast, electrophysiological (e.g. EEG/MEG) recordings provide direct measures of neural activity with excellent temporal resolution, and source localization methodologies can address problems of spatial resolution, permitting measurement of functional activity of brain networks with a spatial resolution similar to that of fMRI. This opens an exciting therapeutic approach focussed on pharmacological and physiological modulation of brain network activity.This review describes current neurophysiological approaches towards evaluating cortical network dysfunction in common neurodegenerative disorders. It explores how modern neurophysiologic tools can provide markers for diagnosis, prognosis, subcategorization and clinical trial outcome measures, and how modulation of brain networks can contribute to new therapeutic approaches.
Highlights
Modern clinical imaging, pathological (Yates, 2012) and genomic (Saura et al, 2015) data, support the evolving notion that neurodegenerative syndromes are best understood in terms of disrupted brain networking
Paired-pulse Transcranial magnetic stimulation (TMS) provides the use of a conditioning stimulus (CS) at different intervals in advance of the test stimulus (TS) from either the same coil or a separate coil placed above another cortical region, usually over the opposite hemisphere
Source localised EEG measures provide objective evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) have overlapping pathologies (Phukan et al, 2007), with cognitive networks disrupted in FTD, such as the frontoparietal attention networks (Zhou et al, 2010), dysfunctioning in ALS, while central and parietal activity known to be abnormal in ALS (Nasseroleslami et al, 2017), is found to distinguish FTD from Alzheimer's disease (AD) (Nishida et al, 2011)
Summary
Pathological (Yates, 2012) and genomic (Saura et al, 2015) data, support the evolving notion that neurodegenerative syndromes are best understood in terms of disrupted brain networking. Quantitative Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) provide compelling evidence of widespread network changes in neurodegenerations including Alzheimer's disease (AD) (Canter et al, 2016), Parkinson's disease (PD) (Gratwicke et al, 2015), amyotrophic lateral sclerosis (ALS) (Nasseroleslami et al, 2017) and frontotemporal dementia (FTD) (Bede et al, 2018). As fMRI measurements can be confounded by vascular pathology and are limited by the requirements of the technology (including the need for the patient to remain supine) (Glover, 2011), the use of fMRI is limited in the neurodegenerations. There remains an urgent and unmet need for user-friendly, non-invasive technologies that can rapidly and reliably detect network alteration with high temporal and spatial resolution. We explore the future potential of emerging electrophysiology-based technologies in providing enhanced temporal resolution, and in using source localization that improves spatial resolution to complement structural and functional imaging. ⁎ Corresponding author at: Academic Unit of Neurology, Trinity College Dublin, The University of Dublin, Room 5.43, Trinity Biomedical Sciences Institute, 152160 Pearse Street, Dublin D02 R590, Ireland
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