Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis

PLoS One. 2015 Jun 19;10(6):e0128682. doi: 10.1371/journal.pone.0128682. eCollection 2015.

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is heterogeneous and overlaps with frontotemporal dementia. Spectral EEG can predict damage in structural and functional networks in frontotemporal dementia but has never been applied to ALS.

Methods: 18 incident ALS patients with normal cognition and 17 age matched controls underwent 128 channel EEG and neuropsychology assessment. The EEG data was analyzed using FieldTrip software in MATLAB to calculate simple connectivity measures and scalp network measures. sLORETA was used in nodal analysis for source localization and same methods were applied as above to calculate nodal network measures. Graph theory measures were used to assess network integrity.

Results: Cross spectral density in alpha band was higher in patients. In ALS patients, increased degree values of the network nodes was noted in the central and frontal regions in the theta band across seven of the different connectivity maps (p<0.0005). Among patients, clustering coefficient in alpha and gamma bands was increased in all regions of the scalp and connectivity were significantly increased (p=0.02). Nodal network showed increased assortativity in alpha band in the patients group. The Clustering Coefficient in Partial Directed Connectivity (PDC) showed significantly higher values for patients in alpha, beta, gamma, theta and delta frequencies (p=0.05).

Discussion: There is increased connectivity in the fronto-central regions of the scalp and areas corresponding to Salience and Default Mode network in ALS, suggesting a pathologic disruption of neuronal networking in early disease states. Spectral EEG has potential utility as a biomarker in ALS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / diagnosis*
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Biomarkers
  • Brain / pathology*
  • Brain / physiopathology*
  • Connectome* / methods
  • Electroencephalography*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neural Pathways
  • ROC Curve

Substances

  • Biomarkers

Grants and funding

This work was supported by the Health Research Board (HRB Ireland) grant HPF/2009/17 and the Research Motor Neuron (RMN) Foundation. The research leading to these results received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 259867 (EUROMOTOR) and by the Joint Programme for Neurodegeneration (JPND) SOPHIA project. The sponsors of the study had no role in study design, data acquisition, data analysis, data interpretation, or writing of the manuscript.