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Hum Brain Mapp. 2019 Jul 26. doi: 10.1002/hbm.24740. [Epub ahead of print]

Patterned functional network disruption in amyotrophic lateral sclerosis.

Author information

1
Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.
2
Department of Neurology, University Medical Centre Utrecht Brain Centre, Utrecht University, Utrecht, The Netherlands.
3
Computational Neuroimaging Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, University of Dublin, Dublin, Ireland.
4
Trinity Centre for Bioengineering, Trinity College Dublin, University of Dublin, Dublin, Ireland.
5
Movement disorders and Neurostimulation, Biomedical Statistics and Multimodal Signal Processing Unit, Department of Neurology, Johannes-Gutenberg-University Hospital, Mainz, Germany.
6
Trinity College Institute of Neuroscience, Trinity College Dublin, University of Dublin, Dublin, Ireland.
7
Department of Biomedical Engineering and Department of Neuroscience, University of Rochester, Rochester, New York.
8
Department of Neurology, Beaumont Hospital, Dublin, Ireland.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor function, with additional evidence of extensive nonmotor involvement. Despite increasing recognition of the disease as a multisystem network disorder characterised by impaired connectivity, the precise neuroelectric characteristics of impaired cortical communication remain to be fully elucidated. Here, we characterise changes in functional connectivity using beamformer source analysis on resting-state electroencephalography recordings from 74 ALS patients and 47 age-matched healthy controls. Spatiospectral characteristics of network changes in the ALS patient group were quantified by spectral power, amplitude envelope correlation (co-modulation) and imaginary coherence (synchrony). We show patterns of decreased spectral power in the occipital and temporal (δ- to β-band), lateral/orbitofrontal (δ- to θ-band) and sensorimotor (β-band) regions of the brain in patients with ALS. Furthermore, we show increased co-modulation of neural oscillations in the central and posterior (δ-, θ- and γl -band) and frontal (δ- and γl -band) regions, as well as decreased synchrony in the temporal and frontal (δ- to β-band) and sensorimotor (β-band) regions. Factorisation of these complex connectivity patterns reveals a distinct disruption of both motor and nonmotor networks. The observed changes in connectivity correlated with structural MRI changes, functional motor scores and cognitive scores. Characteristic patterned changes of cortical function in ALS signify widespread disease-associated network disruption, pointing to extensive dysfunction of both motor and cognitive networks. These statistically robust findings, that correlate with clinical scores, provide a strong rationale for further development as biomarkers of network disruption for future clinical trials.

KEYWORDS:

EEG; amyotrophic lateral sclerosis; functional connectivity; motor neurone disease; resting state; source localisation

PMID:
31348605
DOI:
10.1002/hbm.24740

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