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

The process of ageing is associated with structural and functional changes in the brain, with a decline in cognitive functions observed as its inevitable symptom, even in the absence of neurodegenerative changes. A body of literature suggests dopamine and noradrenaline as prominent candidate molecules to mediate these effects, however, the knowledge regarding the underlying mechanisms is scarce. To fill this gap, we compared local and distant resting-state functional connectivity patterns of ventral tegmental area, substantia nigra pars compacta and locus coeruleus in healthy young (20-35 years; N = 37) and older adults (55-80 years; N = 27). Additionally, we sought long-range functional connectivity patterns of these structures associated with performance in tasks probing executive, attentional and reward functioning, as well as compared the functional coupling of the left and right substantia nigra. The results showed that each substantia nigra had stronger coupling with ipsilateral cortical and subcortical areas along with contralateral cerebellum, and that strength of functional connections of this structure with angular gyrus and lateral orbitofrontal cortex predicted the visuomotor search abilities. In turn, ageing was associated with increased local synchronisation in the ventral tegmental area, and differences in functional connectivity of the dopaminergic midbrain with numerous cortical and subcortical structures. Locus coeruleus functional coupling showed no differences between the groups and was not associated with any of the behavioural functions. To the best of our knowledge, this work is the first one to report the age-related effects on midbrain local synchronisation and its connectivity with key recipients of dopaminergic innervation, such as striatum, anterior cingulate and insula.