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

Abstract

BackgroundAmyotrophic 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.Methods18 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.ResultsCross 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).DiscussionThere 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.

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis

“…This is in contrast with the study by Iyer and colleagues14, who used a set of connectivity metrics in combination with network analysis. In contrast to their work, we used different methods of functional connectivity (PLI) and network reconstruction (MST), as well as a conservative statistical approach.…”

“…Other resting-state fMRI studies111213 have reported alterations in specific resting-state networks. Recently, Iyer and colleagues14 have investigated the use of resting-state electroencephalographic (EEG) as a potential biomarker for ALS, suggesting that a pathologic disruption of the network can be observed in early stages of the disease. However, it still remains relevant to address methodological issues that may affect both connectivity estimation and network reconstruction15.…”

Patterned functional network disruption in amyotrophic lateral sclerosis

“…Characteristic patterned changes of cortical function in ALS signify widespread disease-associated network disruption, pointing to extensive dysfunction of both motor and cognitive networks. Clinical and neuroimaging evidence confirms extensive involvement of motor (Douaud et al, 2011;Nasseroleslami et al, 2019;Proudfoot, van Ede, et al, 2018) and cognitive (Iyer et al, 2015;McMackin, Dukic, et al, 2019) pathways and networks. (Hardiman, Van Den Berg, & Kiernan, 2011).…”

“…Previous EEG studies have shown altered patterns, such as increased frontal-to-parietal connectivity in ALS (Blain-Moraes, Mashour, Lee, Huggins, & Lee, 2013;Iyer et al, 2015;Nasseroleslami et al, 2019). To date, however, there have been limited attempts to localise abnormal EEG patterns to specific brain regions.…”

Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

“…Dysphagia has also been reported in humans following the administration of either benzodiazepines 38– 40 or alcohol 41 . Administration of benzodiazepines reduces voluntary saccadic eye movement function 42 and increases EEG beta-wave activity 42 , clinical manifestations that also occur in neuromuscular and neurological diseases 18, 43, 44 . Increased GABAergic inhibitory activity can also cause bladder 45, 46 and gastrointestinal dysfunction 47, 48 , both of which can manifest in neuromuscular and neurological diseases 19– 21 .…”