Attention-dependent coupling with forebrain and brainstem neuromodulatory nuclei changes across the lifespan.

Changes in attentional control across the lifespan may originate from cortical control networks or subcortical neuromodulatory systems, which are the first sites of age-related neuropathology. In young adults, we demonstrated functional coupling of the basal forebrain with the hippocampus, and locus coeruleus with the posterior cingulate cortex varies with task relevance. This coupling changed in middle age and most strikingly in older adults. In old age, task-dependent coupling between the locus coeruleus and basal forebrain was the predominant connection remaining within the observed network. Older adults exhibit reduced subcortical-cortical connectivity, consistent with a relative neuromodulatory deafferentation, replaced by subcortical-subcortical deep nuclear connectivity. This alteration in noradrenergic and cholinergic signaling has important implications for attention and memory formation and neurocognitive aging.