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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, lateral septum 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 Free-Water Elimination 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 and 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 inter-regional communication within an extended hippocampal system.

Experiments on rodents have demonstrated that transecting the white matter fibre pathway linking the hippocampus with an array of cortical and subcortical structures - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion magnetic resonance imaging (dMRI) studies in humans have linked inter-individual differences in fornix microstructure to episodic memory abilities, its role in human spatial learning is currently unknown. We used high-angular resolution diffusion MRI combined with constrained spherical deconvolution-based tractography, to ask whether inter-individual differences in fornix microstructure in healthy young adults would be associated with spatial learning in a virtual reality navigation task. To efficiently capture individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a statistically significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a comparison tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for both hippocampal volume and participant gender. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human spatial learning in a virtual reality environment, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.

Studies in rats and non-human primates suggest that medial temporal lobe (MTL) structures play a role in perceptual processing, with the hippocampus necessary for spatial discrimination, and the perirhinal cortex for object discrimination. Until recently, there was little convergent evidence for analogous functional specialisation in humans, or for a role of the MTL in processes beyond long-term memory. A recent series of novel human neuropsychological studies, however, in which paradigms from the animal literature were adapted and extended, have revealed findings remarkably similar to those seen in rats and monkeys. These experiments have demonstrated differential effects of distinct stimulus categories on performance in tasks for which there was no explicit requirement to remember information across trials. There is also accruing complementary evidence from functional neuroimaging that MTL structures show differential patterns of activation for scenes and objects, even on simple visual discrimination tasks. This article reviews some of these key studies and discusses the implications of these new findings for existing accounts of memory. A non-modular view of memory is proposed in which memory and perception depend upon the same anatomically distributed representations (emergent memory account). The limitations and criticisms of this theory are discussed and a number of outstanding questions proposed, including key predictions that can be tested by future studies. (Contains 10 figures.)

There has been considerable debate as to whether structures in the medial temporal lobe (MTL) support both memory and perception, in particular whether the perirhinal cortex may be involved in the perceptual discrimination of complex objects with a large number of overlapping features. Similar experiments testing the discrimination of blended images have obtained contradictory findings, and it remains possible that reported deficits in object perception are due to subtle learning in controls, but not patients. To address this issue, a series of trial-unique object ''oddity'' tasks, in which subjects selected the odd stimulus from a visual array, were administered to amnesic patients with either selective bilateral damage to the hippocampus or more extensive damage to MTL regions, including the perirhinal cortex. Whereas patients with damage limited to the hippocampus performed similarly to controls on all conditions, patients with perirhinal damage were significantly impaired when the task required discrimination between objects with a large number of features in common. By contrast, when the same stimuli could be discriminated using simple visual features, patients with perirhinal damage performed normally. These results are consistent with a theoretical view which holds that rostral inferotemporal cortical regions, including perirhinal cortex, represent the complex conjunctions of stimulus features necessary for both perception and memory of objects. (Contains 3 figures and 1 table.)