EEG beta-power and beta-synchrony in the Sensorimotor Network as a Potential Biomarker for Disease Severity and Progression of Motor Symptoms in ALS

Objective: To investigate resting-state EEG β-band power and β-band functional synchrony in the cortical sensorimotor network as a robust measure of severity and progression of motor symptoms in ALS patients. Background: In ALS, the slope of decline of the ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) is accepted as a primary outcome measure in clinical trials, but is limited by variance (Rooney, J Neurol. Neurosurg. Psychiatry 2017). There is a need for direct quantitative markers of the neurodegenerative process. Quantitative high-density EEG directly measures the synchronous activity of underlying populations of neurons. Altered EEG patterns in ALS correlate with behavioural impairment and MRI measures of motor-system degeneration (Nasseroleslami, Cereb. Cortex 2017; Dukic, Hum. Brain. Mapp. 2019). Design/Methods: Using 6 minutes of 128-channel resting-state EEG, source-reconstructed β-power and β-synchrony (β-band imaginary coherence) in the sensorimotor network (pre- and post-central gyrus bilaterally) were calculated in 18 ALS patients using the automated anatomical labelling atlas (AAL) (Tzourio-Mazoyer, N., NeuroImage, 2002). Clinical examination included: ALSFRS-R (Fine/Gross-Motor functions sub-scores, Bulbar and Respiratory sub-scores), manual muscle testing (deltoid, triceps, biceps, wrist flexors and extensors, fingers flexors and extensors, FDI, APB) and standardised measures of upper motor neuron impairment. Both ALSFRS-R and sub-score Progression Rates were calculated between disease onset and recording time. Lower/Upper Motor Neuron-scores were found for the upper limbs (LMN/UMN-scores). Partial Pearson’s correlation coefficient (controlled for age) was used to test the clinical relevance of the EEG measures. Results: Mean β-power in the sensorimotor network correlated with Fine Motor Functions sub-score (r=−0.522, p=0.026), Fine Motor Functions-Progression Rate (r=0.602, p=0.008), LMN-score (r=−0,572, p=0,013). Mean β-synchrony correlated with the LMN-score (r=−0,503, p=0,033). Conclusions: Source-reconstructed β-band power and β-synchrony likely reflect cortical hyperexcitability observed in ALS with structural degeneration of motoneurons and cortical inhibitory interneurons, and they have potential to be developed as data-driven quantitative markers of severity and progression in ALS. Disclosure: Dr. Fasano has nothing to disclose. Dr. Dukic has nothing to disclose. Dr. Coffey has nothing to disclose. Dr. Buxo has nothing to disclose. Dr. Mc Mackin has nothing to disclose. Dr. Chipika has nothing to disclose. Dr. Heverin has nothing to disclose. Dr. Bede has nothing to disclose. Dr. Muthuraman has nothing to disclose. Dr. Lowery has nothing to disclose. Dr. Carson has nothing to disclose. Dr. Nasseroleslami has nothing to disclose. Dr. Hardiman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Wave Life Sciences, Cytokinetics, and Treeway. Dr. Hardiman has received personal compensation in an editorial capacity for Taylor and Francis.