Increased frontal functional connectivity correlates with structural disconnection in the anterior corpus callosum in healthy older adults

Abstract

Abstract Cognitive aging is a heterogeneous process characterized by a varied decline in brain performance. While the neurophysiological basis of this decline remains poorly understood, age-related alterations in structural connectivity (SC) and functional connectivity (FC) have been implicated. Understanding the relationship between these changes is crucial for identifying early markers of cognitive impairment. In our previous work, we observed that in healthy older adults, diminished performance in a tactile recognition task was associated with reduced fractional anisotropy (FA) in the anterior corpus callosum (aCC). The aim of this study was to investigate the impact of this age-related SC degeneration on the FC between the connected regions. In the current analysis, we examined resting-state functional MRI data from 29 healthy older adults, who were categorized into two subgroups - high and low performers - based on their performance in a tactile recognition task and a younger control group (N = 20). We conducted a region of interest (ROI) to ROI analysis to evaluate FC between frontal regions connected via the aCC. Subsequently, we compared the FC between the groups and assessed its correlation with FA values in the aCC across all older participants based on a TBSS analysis from our previous work. We found that poorer performance in a tactile recognition task was associated with increased FC between frontal regions. The second main finding was a negative correlation between FA in the aCC and FC between frontal regions. Our findings suggest that structural degradation of the underlying pathways may initially lead to increased FC within the connected regions, possibly as a compensatory mechanism to preserve cognitive function. However, as no direct brain–behavior correlation was assessed, this interpretation remains tentative. The aCC appears to be particularly vulnerable to age-related structural decline, which may underlie functional changes in frontal regions observed with aging.