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. Here the test-retest reliability of MEG resting FC was evaluated by exploring both within- and between-subject variability in FC in 16 healthy subjects that 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 volume conduction effects could be contributing to high ICC in PLV and d-ecor. Additionally, 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.

Significance: How do we adaptively switch from perceiving the external world to retrieving goal-relevant internal memories? To tackle this question, we used—in a cued-recall paradigm—direct intracranial recordings from the human hippocampus complemented by high-density scalp electroencephalography (EEG). We found that a hippocampal signal ∼500 ms after a perceptual cue marks the conversion from external (perceptual) to internal (mnemonic) representations. This sets in motion a recall cascade involving posterior parietal and medial prefrontal cortex, revealed via source-localized and time-resolved EEG alpha power. Together, these results unveil the hippocampal–cortical dynamics supporting rapid and flexible memory recall.

To form an episodic memory, we must first process a vast amount of sensory information about the to-be-encoded event and then bind these sensory representations together to form a coherent memory trace. While these two cognitive capabilities are thought to have two distinct neural origins, with neocortical alpha/beta oscillations supporting information representation and hippocampal theta-gamma phase-amplitude coupling supporting mnemonic binding, evidence for a dissociation between these two neural markers is conspicuously absent. To address this, seventeen human participants completed an associative memory task that first involved processing information about three sequentially-presented stimuli, and then binding these stimuli together into a coherent memory trace, all the while undergoing MEG recordings. We found that decreases in neocortical alpha/beta power during sequence perception, but not mnemonic binding, correlated with enhanced memory performance. Hippocampal theta/gamma phase-amplitude coupling, however, showed the opposite pattern; increases during mnemonic binding (but not sequence perception) correlated with enhanced memory performance. These results demonstrate that memory-related decreases in neocortical alpha/beta power and memory-related increases in hippocampal theta/gamma phase-amplitude coupling arise at distinct stages of the memory formation process. We speculate that this temporal dissociation reflects a functional dissociation in which neocortical alpha/beta oscillations could support the processing of incoming information relevant to the memory, while hippocampal theta-gamma phase-amplitude coupling could support the binding of this information into a coherent memory trace.

Memories for past experiences can range from vague recognition to full-blown recall of associated details. Electroencephalography has shown that recall signals unfold a few hundred milliseconds after simple recognition, but has only provided limited insights into the underlying brain networks. Functional magnetic resonance imaging (fMRI) has revealed a “core recollection network” (CRN) centered on posterior parietal and medial temporal lobe regions, but the temporal dynamics of these regions during retrieval remain largely unknown. Here we used Magnetoencephalography in a memory paradigm assessing correct rejection (CR) of lures, item recognition (IR) and associative recall (AR) in human participants of both sexes. We found that power decreases in the alpha frequency band (10–12 Hz) systematically track different mnemonic outcomes in both time and space: Over left posterior sensors, alpha power decreased in a stepwise fashion from 500 ms onward, first from CR to IR and then from IR to AR. When projecting alpha power into source space, the CRN known from fMRI studies emerged, including posterior parietal cortex (PPC) and hippocampus. While PPC showed a monotonic change across conditions, hippocampal effects were specific to recall. These region-specific effects were corroborated by a separate fMRI dataset. Importantly, alpha power time courses revealed a temporal dissociation between item and associative memory in hippocampus and PPC, with earlier AR effects in hippocampus. Our data thus link engagement of the CRN to the temporal dynamics of episodic memory and highlight the role of alpha rhythms in revealing when and where different types of memories are retrieved.SIGNIFICANCE STATEMENTOur ability to remember ranges from the vague feeling of familiarity to vivid recollection of associated details. Scientific understanding of episodic memory thus far relied upon separate lines of research focusing on either temporal (via electroencephalography) or spatial (via functional magnetic resonance imaging) dimensions. However, both techniques have limitations that have hindered understanding of when and where memories are retrieved. Capitalizing on the enhanced temporal and spatial resolution of magnetoencephalography, we show that changes in alpha power reveal both when and where different types of memory are retrieved. Having access to the temporal and spatial characteristics of successful retrieval provided new insights into the cross-regional dynamics in the hippocampus and parietal cortex.