Abstract
Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum, and to diencephalon, striatum, and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions, but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices, the first (PC1) capturing axonal packing/myelin, the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating network communication within an extended hippocampal system.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Data Availability Statement: Anonymised output data that support the findings of this study are available from the corresponding author upon reasonable request.
Ethics Approval Statement: This research was approved by the Cardiff University School of Psychology Research Ethics Committee.
Funding statement: This work was supported by a Wellcome Strategic Award (104943/Z/14/Z) to K.G., a Wellcome Institutional Strategic Support Fund award to A.D.L, a departmental PhD studentship from the School of Psychology, Cardiff University to M-L.R, a Biotechnology and Biological Sciences Research Council Award to A.D.L and K.G (BB/V008242/1), & a Vannevar Bush Faculty Fellowship (Office of Naval Research Grant N00014-15-1-0033) to C.R (any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the U.S. Department of Defence), and MC is supported by the Radboud Excellence Initiative Fellowship.