Patterned functional network disruption in amyotrophic lateral sclerosis

Hum Brain Mapp. 2019 Nov 1;40(16):4827-4842. doi: 10.1002/hbm.24740. Epub 2019 Jul 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnostic imaging
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Amyotrophic Lateral Sclerosis / psychology
  • Beta Rhythm
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology
  • Cognition
  • Delta Rhythm
  • Electroencephalography
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Neuropsychological Tests
  • Psychomotor Performance
  • Theta Rhythm