Functional connectivity (FC) alterations represent a key feature in Alzheimer's Disease (AD) and provide a useful tool to characterize and predict the course of the disease. Those alterations have been also described in Mild Cognitive Impairment (MCI), a prodromal stage of AD. There is a growing interest in detecting AD pathology in the brain in the very early stages of the disorder. Subjective Cognitive Decline (SCD) could represent a preclinical asymptomatic stage of AD but very little is known about this population. In the present work we assessed whether FC disruptions are already present in this stage, and if they share any spatial distribution properties with MCI alterations (a condition known to be highly related to AD). To this end, we measured electromagnetic spontaneous activity with MEG in 39 healthy control elders, 41 elders with SCD and 51 MCI patients. The results showed FC alterations in both SCD and MCI compared to the healthy control group. Interestingly, both groups exhibited a very similar spatial pattern of altered links: a hyper-synchronized anterior network and a posterior network characterized by a decrease in FC. This decrease was more pronounced in the MCI group. These results highlight that elders with SCD present FC alterations. More importantly, those disruptions affected AD typically related areas and showed great overlap with the alterations exhibited by MCI patients. These results support the consideration of SCD as a preclinical stage of AD and may indicate that FC alterations appear very early in the course of the disease.

The coordinated activity of the resting-state brain can be evaluated with magnetoencephalography (MEG) for distinct brain rhythms by performing source reconstruction to estimate the activities of target brain regions and employing one of the many existent functional connectivity (FC) algorithms. Although this procedure has been applied in a great amount of studies both with healthy and pathological populations, the reliability of such FC estimates is unknown, and this impairs the use of resting-state MEG FC at the individual level. In this study, the test-retest reliability of MEG resting FC was evaluated by exploring both within- and between-subject variability in FC in 16 healthy subjects who underwent three resting-state MEG scans. FC was computed after beamforming source reconstruction with four popular FC metrics: phase-locking value (PLV), phase lag index (PLI), direct envelope correlation (d-ecor), and envelope correlation with leakage correction (lc-ecor). Then, test-restest reliability and within- and between-subject agreement were evaluated with the intraclass correlation coefficient (ICC) and Kendall's W, respectively. Reliability was found to depend on the FC metric, the frequency band, and the specific link. As a general trend, greater test-retest reliability was found for PLV in theta to gamma, and for lc-ecor and d-ecor in beta. Further inspection of the ICC distribution revealed that volume conduction effects could be contributing to high ICC in PLV and d-ecor. In addition, stronger links were found to be more reliable. Overall, this encourages the further use of resting-state MEG FC for individual-level studies, especially with PLV or envelope correlation metrics.