Dissociation Between Neural Functional Connectivity and Brain Volume Loss with Age: Insights from Resting-State Magnetoencephalography

To investigate the relationship between age-related brain volume loss and neural functional connectivity (FC), whole brain volume and mean FC were calculated in 75 healthy participants aged 20 to 86 years (39 women, 36 men; mean age: 59.31 years). Resting-state MEG with eyes closed and MRI were conducted. Correlations between age and whole brain volume, mean neural connectivity expressed as amplitude envelope correlation (AEC) in the alpha frequency band across 66 functional parcellations, and the standard deviation (SD) of AEC were analyzed. In seven brain regions showing significant age-related volume loss, mean AEC and SD of AEC with other regions were assessed. Whole brain volume decreased with age (r = -0.322, p = .00480), particularly in participants older than 75 years (p < .05, ANOVA). AEC values also declined with age (r = -0.359, p = .00153), with significant differences observed between generational subgroups under 45 and over 75 years (p < .05). The SD of AEC decreased across the brain with age (r = -0.326, p = .0043). However, seven brain regions with significant age-related volume loss did not consistently show significant differences in AEC or its SD between generational subgroups, in contrast to consistent volume differences observed. Overall, brain volume and neural FC declined with age, accompanied by reduced variability in FC across the brain. Nevertheless, regions exhibiting significant volume loss were not always associated with functional decline in FC or its variability, suggesting the brain may compensate for global decline through localized functional adaptations.