Topographic separation of fornical fibers associated with the anterior and posterior hippocampus in the human brain: An MRI-diffusion study.

BACKGROUND AND OBJECTIVE: Evidence from rat and nonhuman primate studies indicates that axons comprising the fornix have a characteristic topographical organization: projections from the temporal/anterior hippocampus mainly occupy the lateral fornix, whereas the more medial fornix contains fibers from the septal/posterior hippocampus. The aim of this study was to investigate whether the same topographical organization exists in the human brain. METHODS: Using high angular resolution diffusion MRI-based tractography at 3T, subdivisions of the fornix were reconstructed in 40 healthy adults by selecting fiber pathways from either the anterior or the posterior hippocampus. RESULTS: The tract reconstructions revealed that anterior hippocampal fibers predominantly comprise the lateral body of the fornix, whereas posterior fibers make up the medial body of the fornix. Quantitative analyses support this medial:lateral distinction in humans, which matches the topographical organization of the fornix in other primates. CONCLUSION: This novel tractography protocol enables the separation of fornix fibers from anterior and posterior hippocampal regions in the human brain and, hence, provides a means by which to compare functions associated with different sets of connections along the longitudinal axis of the hippocampus.

Complementary subicular pathways to the anterior thalamic nuclei and mammillary bodies in the rat and macaque monkey brain.

The origins of the hippocampal (subicular) projections to the anterior thalamic nuclei and mammillary bodies were compared in rats and macaque monkeys using retrograde tracers. These projections form core components of the Papez circuit, which is vital for normal memory. The study revealed a complex pattern of subicular efferents, consistent with the presence of different, parallel information streams, whose segregation appears more marked in the rat brain. In both species, the cells projecting to the mammillary bodies and anterior thalamic nuclei showed laminar separation but also differed along other hippocampal axes. In the rat, these diencephalic inputs showed complementary topographies in the proximal-distal (columnar) plane, consistent with differential involvement in object-based (proximal subiculum) and context-based (distal subiculum) information. The medial mammillary inputs, which arose along the anterior-posterior extent of the rat subiculum, favoured the central subiculum (septal hippocampus) and the more proximal subiculum (temporal hippocampus). In contrast, anterior thalamic inputs were largely confined to the dorsal (i.e. septal and intermediate) subiculum, where projections to the anteromedial nucleus favoured the proximal subiculum while those to the anteroventral nucleus predominantly arose in the distal subiculum. In the macaque, the corresponding diencephalic inputs were again distinguished by anterior-posterior topographies, as subicular inputs to the medial mammillary bodies predominantly arose from the posterior hippocampus while subicular inputs to the anteromedial thalamic nucleus predominantly arose from the anterior hippocampus. Unlike the rat, there was no clear evidence of proximal-distal separation as all of these medial diencephalic projections preferentially arose from the more distal subiculum.

The status of the precommissural and postcommissural fornix in normal ageing and mild cognitive impairment: An MRI tractography study.

The fornix connects the hippocampal formation with structures beyond the temporal lobe. Previous tractography studies have typically reconstructed the fornix as one unified bundle. However, the fornix contains two rostral divisions: the precommissural fornix and the postcommissural fornix. Each division has distinct anatomical connections and, hence, potentially distinct functions. Diffusion weighted MRI and spherical deconvolution based tractography were employed to reconstruct these separate fornix divisions and to examine their microstructural properties in both healthy ageing and Mild Cognitive Impairment (MCI). Reliable reconstructions of precommissural and postcommissural fibres were achieved in both groups, with their fibres retaining largely separate locations within the anterior body of the fornix. Ageing and MCI had comparable effects on the two segments. Ageing was associated with changes in mean, axial and radial diffusivity but not with alterations of fibre population-specific diffusion properties, estimated with the hindrance modulated orientational anisotropy (HMOA). Individual HMOA variation in postcommissural, but not precommissural, fibres correlated positively (and unrelated to age) with visual recall performance. This provides novel evidence for a role of postcommissural fibres, which connect structures of the extended hippocampal network, in episodic memory function. Separating the fornix into its two principal divisions brings new opportunities for distinguishing different hippocampal networks.

The subiculum: the heart of the extended hippocampal system.

While descriptions of the subiculum often emphasize its role as a recipient of hippocampal inputs, the area also has particular importance as a source of hippocampal projections. The extrinsic projections from the subiculum not only parallel those from hippocampal fields CA1-4 but also terminate in sites that do not receive direct inputs from the rest of the hippocampus. Both electrophysiological and lesion studies reveal how, despite its very dense CA1 inputs, the subiculum has functional properties seemingly independent from the rest of the hippocampus. In understanding the subiculum, it is necessary to appreciate that its connections are topographically organized along all three planes (longitudinal, transverse, and depth). These topographies may enable the subiculum to separate multiple information types and, hence, support multiple functions. The particular significance of the subiculum for learning and memory is underlined by its importance as a source of hippocampal projections to nuclei in the medial diencephalon, which are themselves vital for human memory and rodent spatial learning. Of particular note are its reciprocal connections with the anterior thalamic nuclei, which are not shared by the rest of the hippocampus (CA1-4). These thalamosubiculum connections may be of especial significance for resolving memory problems that suffer high interference and require the flexible use of stimulus representations.

Cingulum white matter in young women at risk of depression: the effect of family history and anhedonia.

BACKGROUND: Altered white matter microstructure in tracts integral to mood regulation networks could underlie vulnerability to major depressive disorder (MDD). Guided by functional magnetic resonance studies, we explored whether a positive family history of MDD (FH+) and anhedonia (reduced capacity for pleasure) were associated with altered white matter microstructure in the cingulum bundles and uncinate fasciculi. METHODS: Diffusion tensor magnetic resonance imaging data were acquired on 34 healthy female student volunteers (mean age 22 years). Exclusion criteria included other current or previous psychiatric disorder, current depression, and current psychotropic medication. Family history was determined using established criteria. Fiber tractography was performed for each individual for a priori tracts of interest and a comparison tract. Mean fractional anisotropy (FA), an index of microstructure, was calculated for each tract. RESULTS: Tracts were reconstructed in 18 FH+ individuals and 15 FH- individuals, who did not differ by age or subclinical depressive symptoms. FH+ subjects had 3% to 5% lower FA in the right and left cingulum bundles than FH- individuals (p = .012, p = .059, respectively). Post hoc analysis demonstrated 8% lower FA in the left subgenual cingulate (p = .007). Hedonic tone correlated positively with FA in the right and left cingulum bundles (r = .342, p = .052; r = .477, p = .005, respectively), and the left subgenual cingulum (r = .500, p = .003). CONCLUSIONS: Both family history of MDD and subclinical anhedonia are associated with reduced FA in the bilateral cingulum bundles, particularly in the left subgenual cingulum. Altered cingulum white matter architecture is implicated in the etiology of MDD.