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The ε4 allele of the apolipoprotein E ( APOE 4+) genotype is a major genetic risk factor for Alzheimer's disease (AD), but the mechanisms underlying its influence remain incompletely understood. The study aimed to investigate the possible effect of the APOE genotype on spontaneous electroencephalogram (EEG) alpha characteristics, resting-state functional MRI (fMRI) connectivity (rsFC) in large brain networks and the interrelation of alpha rhythm and rsFC characteristics in non-demented adults during aging. We examined the EEG alpha subband's relative power, individual alpha peak frequency (IAPF), and fMRI rsFC in non-demented volunteers (age range 26-79 years) stratified by the APOE genotype. The presence of the APOE4+ genotype was associated with lower IAPF and lower relative power of the 11-13 Hz alpha subbands. The age related decrease in EEG IAPF was more pronounced in the APOE4+ carriers than in the APOE4+ non-carriers ( APOE4 -). The APOE4+ carriers had a stronger fMRI positive rsFC of the interhemispheric regions of the frontoparietal, lateral visual and salience networks than the APOE4- individuals. In contrast, the negative rsFC in the network between the left hippocampus and the right posterior parietal cortex was reduced in the APOE4+ carriers compared to the non-carriers. Alpha rhythm slowing was associated with the dysfunction of hippocampal networks. Our results show that in adults without dementia APOE4+ genotype is associated with alpha rhythm slowing and that this slowing is age-dependent. Our data suggest predominant alterations of inhibitory processes in large-scale brain network of non-demented APOE4+ carriers. Moreover, dysfunction of large-scale hippocampal network can influence APOE -related alpha rhythm vulnerability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ponomareva, Andreeva, Protasova, Konovalov, Krotenkova, Kolesnikova, Malina, Kanavets, Mitrofanov, Fokin, Illarioshkin and Rogaev.)

Aging is associated with decreased functional connectivity in the main brain networks, which can underlie changes in cognitive and emotional processing. Neurofeedback is a promising non-pharmacological approach for the enhancement of brain connectivity. Previously, we showed that a single session of infra-low frequency neurofeedback results in increased connectivity between sensory processing networks in healthy young adults. In the current pilot study, we aimed to evaluate the possibility of enhancing brain connectivity during aging with the use of infra-low frequency neurofeedback. Nine females aged 52 ± 7 years with subclinical signs of emotional dysregulation, including anxiety, mild depression, and somatoform symptoms, underwent 15 sessions of training. A resting-state functional MRI scan was acquired before and after the training. A hypothesis-free intrinsic connectivity analysis showed increased connectivity in regions in the bilateral temporal fusiform cortex, right supplementary motor area, left amygdala, left temporal pole, and cerebellum. Next, a seed-to-voxel analysis for the revealed regions was performed using the post- vs. pre-neurofeedback contrast. Finally, to explore the whole network of neurofeedback-related connectivity changes, the regions revealed by the intrinsic connectivity and seed-to-voxel analyses were entered into a network-based statistical analysis. An extended network was revealed, including the temporal and occipital fusiform cortex, multiple areas from the visual cortex, the right posterior superior temporal sulcus, the amygdala, the temporal poles, the superior parietal lobule, and the supplementary motor cortex. Clinically, decreases in alexithymia, depression, and anxiety levels were observed. Thus, infra-low frequency neurofeedback appears to be a promising method for enhancing brain connectivity during aging, and subsequent sham-controlled studies utilizing larger samples are feasible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dobrushina, Dobrynina, Arina, Kremneva, Novikova, Gubanova, Pechenkova, Suslina, Aristova, Trubitsyna and Krotenkova.)