Influence of age and cognitive performance on resting-state functional connectivity of dopaminergic and noradrenergic centers.

Aging is associated with structural and functional changes in the brain, with a decline in cognitive functions observed as its inevitable concomitant. The body of literature suggests dopamine and noradrenaline as prominent candidate neuromodulators to mediate these effects; however, knowledge regarding the underlying mechanisms is scarce. To fill this gap, we compared resting-state functional connectivity (FC) patterns of ventral tegmental area (VTA), substantia nigra pars compacta (SNc) and locus coeruleus (LC) in healthy young (20-35 years; N = 37) and older adults (55-80 years; N = 27). Additionally, we sought FC patterns of these structures associated with performance in tasks probing executive, attentional and reward functioning, and we compared the functional coupling of the bilateral SNc. The results showed that individual SNc had stronger coupling with ipsilateral cortical and subcortical areas along with the contralateral cerebellum in the whole sample, and that the strength of connections of this structure with angular gyrus and lateral orbitofrontal cortex predicted visuomotor search abilities. In turn, older age was associated with greater local synchronization within VTA, its lower FC with caudate, mediodorsal thalamus, and SNc, as well as higher FC of both midbrain dopaminergic seeds with red nuclei. LC functional coupling showed no differences between the groups and was not associated with any of the behavioral functions. To the best of our knowledge, this work is the first to report the age-related effects on VTA local synchronization and its connectivity with key recipients of dopaminergic innervation, such as striatum and mediodorsal thalamus.