Two long-axis dimensions of hippocampal cortical integration support memory function across the adult lifespan

Abstract

AbstractMultiple overlapping spatial modes define the organization of hippocampal function along its longitudinal and transverse axes, but remain unexplored in relation to behavior and to cognitive decline in aging. Here, we identify two long-axis modes of hippocampal-cortical functional connectivity (FC), each representing a distinct neurocognitive cortical hierarchy: a principal anterior-posterior gradient reflecting a task-positive/task-negative cortical motif, and a second-order gradient separating the middle hippocampus from anterior and posterior ends, reflecting unimodal-transmodal cortical organization. The second-order gradient predicted episodic memory and mirrored hippocampal dopamine D1 receptor distribution, capturing shared functional and neuromolecular organization. Older age was associated with less gradual FC change along gradients, and a youth-like gradient profile was linked to preserved memory – highlighting age-related gradient dedifferentiation as a marker of cognitive decline. Our results indicate that hippocampal function stands to inform general principles of brain organization, and emphasize a critical role of long-axis organization in memory across the lifespan.