Brainstem Dysfunction in Healthy Aging

The brainstem controls sub-cortical and cortical activity and influences the processing of incoming information. The goal of this study was to characterize age related alterations of brainstem-brain interactions during different brain states detected by dynamic analysis of task-free fMRI. 79 young (20-40 years) and 51 older adults (55-80 years) were studied. Internal brainstem structures were segmented using a new multi-contrast segmentation approach. Brain and brainstem gray matter segmentations were warped onto a population template. The ICV-corrected Jacobian determinants were converted into z-score maps and the means from 420 cortical/subcortical/brainstem rois extracted. The fMRI was preprocessed in SPM12/Conn18 and the BOLD signal from 420 cortical/subcortical/brainstem rois extracted. A dynamic task-free analysis approach based on hierarchical cluster analysis was used to identify 15 brain states that were characterized using graph analysis (strength, diversity, modularity). Kruskal-Wallis tests and Spearman correlations were used for statistical analysis. One brain state (cluster 21) occurred more often in older adults (p=0.008). It was characterized by a lower mean modular strength and brainstem-cortical strength in older adults compared to younger adults. Global age related gray matter differences were positively correlated with brain state 21's modular strength. Furthermore, brain state 21 duration was negatively correlated with working memory (r = -0.28, p=0.002). The findings suggest an age related weakening of the within and between network synchronization at the brainstem level during brain state 21 in older adults that negatively affects cortical and subcortical synchronization and working memory performance.