The role of the pre-commissural fornix in episodic autobiographical memory and simulation

Neuropsychological and functional magnetic resonance imaging (MRI) evidence suggests that the ability to vividly remember our personal past, and imagine future scenarios, involves two closely connected regions: the hippocampus and ventromedial prefrontal cortex (vmPFC). Despite evidence of a direct anatomical connection from hippocampus to vmPFC, it is unknown whether hippocampal-vmPFC structural connectivity supports both past and future-oriented episodic thinking. To address this, we applied diffusion-weighted magnetic resonance imaging (dMRI) and a novel deterministic tractography protocol to reconstruct distinct subdivisions of the fornix previously detected in axonal tracer studies, namely pre-commissural (connecting the hippocampus to vmPFC) and post-commissural (linking the hippocampus and medial diencephalon) fornix, in a group of healthy young adult humans who undertook an adapted past-future autobiographical interview. As predicted, we found that inter-individual differences in pre-commissural - but not post-commissural - fornix microstructure (fractional anisotropy) was significantly correlated with the episodic richness of both past and future autobiographical narratives. Notably, these results remained significant when controlling for both non-episodic narrative content and grey matter volumes of the hippocampus and vmPFC. This study provides novel evidence that reconstructing events from one’s personal past, and constructing possible future events, involves a distinct, structurally-instantiated hippocampal-vmPFC pathway.Significance StatementA novel anatomically-guided protocol that allows the pre-commissural and post-commissural fornix fibers to be separately reconstructed in vivo (Christiansen et al., 2016) was applied to reconstruct the pre-commissural subdivision of the white matter fornix tract (anatomically linking the hippocampal formation to the vmPFC) and investigate its contribution to episodic memory and future simulation. We demonstrated that the amount of episodic details contained in past and future narratives, collected via an adapted autobiographical interview, was positively correlated with pre-, but not post-, commissural fornix microstructure. These findings highlight how inter-individual variation in the pre-commissural subdivision of the fornix underpins the construction of self-reflective, contextual events – for both the past and future.