High power transient 15-29Hz beta event features as early biomarkers of Alzheimer's Disease conversion: a MEG study

A typical pattern observed in M/EEG recordings of Mild Cognitive Impairment (MCI) patients progressing to Alzheimer's disease is a continuous slowing of brain oscillatory activity. Definitions of oscillatory slowing are imprecise, as they average across time and frequency bands, masking the finer structure in the signal and potential reliable biomarkers of the disease. Recent studies show that high averaged band power can result from transient increases in power, termed 'events' or 'bursts'. To better understand MEG oscillatory slowing in AD progression, we analyzed features of high-power oscillatory events and their relationship to cognitive decline. MEG resting-state oscillations were registered in age-matched patients with MCI who later convert (CONV, N=41) or do not convert (NOCONV, N=44) to AD, in a period of 2.5 years. To distinguish future CONV from NOCONV, we characterised the rate, duration, frequency span and power of transient high-power events in the alpha and beta band in anterior cingulate (ACC) and precuneus (PC). Results revealed event-like patterns in resting-state power in both the alpha and beta-bands, however only beta-band features were predictive of conversion to AD, particularly in PC. Specifically, compared to NOCONV, CONV had a lower number of beta events, along with lower power events and a trend toward shorter duration events in PC (p < 0.05). Beta event durations were also significantly shorter in ACC (p < 0.01). Further, this reduced expression of beta events in CONV predicted lower values of mean relative beta power, increased probability of AD conversion, and poorer cognitive performance. Our work paves the way for reinterpreting M/EEG slowing and examining beta event features as a new biomarker along the AD continuum, and a potential link to theories of inhibitory cognitive control in neurodegeneration. These results may bring us closer to understanding the neural mechanisms of the disease that help guide new therapies.