Beta oscillation changes in ALS: A Dual-Site International Replication Study

Abstract

Reproducible biomarkers that monitor motor and cognitive dysfunction in amyotrophic lateral sclerosis (ALS) are needed. Previous work reported reduced beta-band event-related desynchronization (ERD) and attenuated post-movement event-related synchronization (ERS) in frontal and parietal channels during the sustained attention to response task (SART). We aimed to validate these findings in Dutch and Irish cohorts. A randomized SART with 128-channel electroencephalography (EEG) was performed in Dutch (ALS n=63; matched controls n=64) and Irish (ALS n=36; controls n=36) cohorts. Non-phase-locked activity was quantified using complex Morlet wavelets to compute baseline-normalized post-stimulus ERD and ERS. Group differences and EEG associations with task performance were examined for Go and NoGo trials. In both control cohorts, the SART elicited theta ERS and alpha- and beta-band ERD, followed by rebound beta ERS across the frontoparietal axis, with greater theta ERS, stronger alpha ERD, and weaker beta ERS on NoGo than Go trials. In contrast to previous null findings, people with ALS showed reduced Go and total accuracy in both centres (p<0.002) and slower Go responses in the Irish cohort (p=0.02). The ALS cohorts differed in NoGo accuracy, Go response time, and anticipation errors (all p=0.03). Replicating prior work, the Irish ALS cohort showed reduced beta ERD and ERS versus controls, with no such differences in the Dutch cohort. Greater beta ERS was associated with faster Go responses in both centres (p<0.011). ERD and ERS changes replicated in the Irish but not the Dutch cohort. Cohort differences in these metrics reflected, at least in part, varying functional impairment. Reproducible control findings and consistent associations with motor performance indicate reliable capture of cortical motor network dysfunction, supporting these measures as EEG markers of motor decline in ALS.