The electrophysiological basis of resting-state fMRI hyperconnectivity in early Alzheimer’s disease

One of the most intriguing findings in Alzheimer’s disease connectivity studies is resting-state fMRI hyperconnectivity in the preclinical and prodromal phase. We examined how this phenomenon relates to electrophysiological connectivity. Resting-state fMRI, 128-electrodes EEG, and amyloid PET data were collected from 41 cognitively unimpaired amyloid negative, 17 cognitively unimpaired amyloid positive, and 14 prodromal Alzheimer’s disease participants. Based on the Shen50 atlas, global fMRI network measures – characteristic path length and global clustering coefficient – were calculated using the absolute values of the partial correlations as weights. EEG-based global graph measures were calculated for delta, theta, alpha and beta bands using the average undirected weighted Phase Lag Index in sensor space as weights. We assessed between-group differences in resting-state fMRI and in EEG connectivity and examined the associations between fMRI-derived and EEG-derived global graph measures across the delta, theta, alpha and beta bands. In line with prior findings, prodromal Alzheimer’s disease patients showed decreased fMRI-derived characteristic path length. This correlated positively with EEG-derived characteristic path length within the delta band across the total group and within the cognitively unimpaired amyloid positive and prodromal Alzheimer’s disease subgroup. Conversely, in the alpha band, global clustering coefficient was decreased and the characteristic path length increased. No correlation was observed between either of these two graph measures in the alpha EEG band versus the corresponding resting-state fMRI connectivity measures. In conclusion, the electrophysiological correlate of the hyperconnectivity measured with resting-state fMRI is situated in the low-frequency delta band while the alpha frequency band shows opposite effects unrelated to resting-state fMRI.