Distinct longitudinal changes in EEG measures reflecting functional network disruption in ALS cognitive phenotypes

Abstract Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures the dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of the network-level dysfunction patterns remains unclear, particularly in the networks related to cognitive-behavioural functions. We examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 27), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53). Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, fine motor symptoms, and survival. We observed significant decline in \(\theta\)-band spectral power over time in the temporal region along with increased \({\gamma }_{l}\)-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes varied between ALS subgroups, correlating with motor, cognitive, and behavioural decline. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalized treatments in ALS.