The fornix serves as backbone of the limbic system and main output tract of the hippocampus into the cortex. This tract guides axonal fibers from structures in the medial temporal space memory system to communicate with cortical association areas (28) by intermediates such as the anterior thalamic radiation. Consistent with our demonstrated population association between the fornix and the vmPFC, probabilistic diffusion tractography in humans and monkeys showed that fornix-carried fiber bundles play a prominent role in connections of the hippocampus with the vmPFC (29). Moreover, hippocampal lesions in six neurological patients led to significant FA reductions in the fornix but no other white matter tracts, functional connectivity alterations in the DMN, and episodic memory impairments (30). Similarly, in patients with posttraumatic amnesia, functional connectivity between the medial temporal lobe and the posteromedial DMN correlated with associative memory performance and information processing speed (31). Building on these studies, our work leverages large-scale population data to highlight the relevance of the hippocampal−neocortical pathways in the functioning of the DMN and suggests that subregions, such as vmPFC and TPJ, which are most selective structural predictors of fornix anatomy, may be particularly important in this process.
