Abstract Details

Title Neuroelectric Biomarkers of Network Dysfunction in Amyotrophic Lateral Sclerosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-006

Objective To developed high-density EEG measures to quantify the functional neuroelectric activity in specific brain networks that are engaged during resting-state and cognitive tasks in Amyotrophic Lateral Sclerosis (ALS).

Background The quantification of phenotypes, progression and outcome in ALS trials remains a challenge, due to major shortcomings of the existing biomarkers: focus on focal structural degeneration rather than functional changes in motor/cognitive networks (emerging from the pathobiology), invasiveness and cost.

Design/Methods High-density surface electroencephalography (EEG) was recorded from ALS patients and controls in resting-state (n=74) and in an auditory mismatch negativity (MMN) paradigm (n=58), and compared to healthy age-matched controls (n=47, n=39).

Results

Crossectional “resting-state” EEG showed characteristic patterns of increased connectivity. When we source-localised the activity to the underlying brain source, we observed a frequency-specific pattern of change in spectral power, synchrony and co-modulation. We found increased average co-modulation of neural oscillations with other brain regions in the central and posterior regions of the brain (δ-, θ- and γ_l-band) and frontal regions (δ- and γ_l-band). Furthermore, the average synchrony to other brain regions was decreased in the temporal and frontal lobes (δ-, θ- and α-band) and in the motor cortex (β-band), with decreased region-to-region connectivity in frontal (δ-band) and motor (β-band) network.

The MMN “cognitive task”, further revealed the network dysfunction: increased activity in the left posterior parietal, central and dorsolateral prefrontal cortices and a decrease in the inferior frontal and left superior temporal gyri.

The correlations of the EEG changes with structural degeneration (MRI) and functional scores, revealed the nature of these network impairments. The afforded discriminatory powers (AUC=0.79), exceeded the levels in (f)MRI studies.

Conclusions

Our findings demonstrate that the quantitative EEG measure of neural activity and connectivity elucidate the network pathology in ALS and can serve as prognostic biomarkers and outcome measures for clinical trials.

Authors/Disclosures
PRESENTER	No disclosure on file
Stefan Dukic (Trinity College Dublin)	No disclosure on file
	No disclosure on file
Amina Coffey (Trinity College Dublin)	No disclosure on file
	No disclosure on file
Ibrahim Laleka	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Parameswaran M. Iyer, Jr., MD, MBBS (St. James's Hospital)	No disclosure on file
	No disclosure on file
Niall Pender, PhD	No disclosure on file
Peter Bede, MD, PhD (Academic Unit of Neurology)	Dr. Bede has nothing to disclose.
Orla Hardiman, MD, DSc, FRCPI, MRIA, FAAN (Trinity Biomedical Sciences Institute)	Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.

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