resting-state fMRI studies using ICA or seed-based methods.57-61 Similar changes have been reported in subjects with mild cognitive impairment, a condition which is believed to often represent pre-clinical AD.62-64 Early DMN functional disruption in AD involves the medial temporal lobe and posterior cingulate cortex/precuneus,57,58,62,63 subsequently worsening and extending to the lateral parietal and medial frontal regions with increasing disease severity.59 Structural connectivity disruption follows a similar pattern: the posterior WM tracts, connecting the hippocampus/medial temporal lobe with the posterior cingulate cortex and the limbic regions, are affected first,65-67 whereas frontal WM tracts (genu of corpus callosum, anterior cingulum) are minimally affected, except for the uncinate and arcuate fasciculi, which connect temporal to frontal cortex.66-68 Electrophysiological studies are consistent with fMRI studies in reporting a reduction of cortico-cortical connectivity in AD. EEG and MEG analyses have shown reduced connectivity between long distance fronto-parietal and fronto-temporal regions in the alpha and beta frequency bands.69-71 These frequency bands show good topographic correspondence with the DMN and the greatest correlation between EEG power and DMN fMRI fluctuations.72,73
