Abstract
The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. A multidimensional account of the hippocampus functional integration with neocortex, however, remains to be established and evaluated in terms of functional specialization and cognitive decline in aging. Here, we identify two long-axis modes of cortical functional connectivity (FC) during rest: a principal gradient of gradual anterior-posterior variation reflecting a task-positive/task-negative cortical motif, and a second-order gradient, representing unimodal-transmodal macroscale cortical organization. The second-order gradient predicted episodic memory and reflected underlying distribution of postsynaptic dopamine D1 receptors, suggesting shared principles of functional and neuromolecular organization. Older age was associated with less distinct transitions in FC along gradients, and a youth-like gradient profile, i.e. maintained distinctiveness, was linked to superior memory – highlighting age-related gradient dedifferentiation as a potential marker of cognitive decline. Our results support the notion that hippocampal function stands to inform general principles of brain organization, and emphasize a critical role of a second-order long-axis connectivity mode in mnemonic function across the lifespan.
Competing Interest Statement
The authors have declared no competing interest.