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

Abstract

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 cingulum bundle: Anatomy, function, and dysfunction

“…Metzler-Baddeley and co-workers ( Metzler-Baddeley et al, 2011 ; Metzler-Baddeley et al, 2012b , c ; Christiansen et al, 2016 ) addressed the problem of potential CSF partial volume biases in DTI metrics in MCI patients by applying the bi-tensor Free Water Elimination (FWE) model that fits an isotropic and an anisotropic compartment to the dMRI data and allows for the correction of free water contamination in DTI metrics ( Pasternak et al, 2009 ). The authors compared corrected mean FA, MD, RD and AD metrics for the parahippocampal cingulum, the fornix, and uncinate fasciculus between 25 MCI patients and 20 matched controls ( Metzler-Baddeley et al, 2012b ), with the cortico-spinal tract as a comparison pathway.…”

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

“…A previous study employing a similar methodology (Christiansen, Aggleton, et al., 2016) demonstrated that the fornix can also be divided between its precommissural and postcommissural fiber subdivisions (Poletti & Creswell, 1977). The precommissural fornix contains hippocampal connections with the basal forebrain, ventral striatum, and prefrontal cortex, whereas the postcommissural fornix connections reach the medial diencephalon and hypothalamus (Poletti & Creswell, 1977).…”

“…The precommissural fornix contains hippocampal connections with the basal forebrain, ventral striatum, and prefrontal cortex, whereas the postcommissural fornix connections reach the medial diencephalon and hypothalamus (Poletti & Creswell, 1977). Using diffusion imaging, the precommissural and postcommissural fibers were found to occupy different locations within the body of the fornix: the postcommissural fornix fibers were located dorsally, whereas the precommissural fibers were located ventrally (Christiansen, Aggleton, et al., 2016). Together with the present results, these findings suggest that there is a topography along the two planes of the fornix, that is, within both the dorsal–ventral and medial–lateral axes of the tract, with both topographies reflecting different sets of hippocampal connections.…”

“…In addition, various white matter microstructural properties of these two subpopulations of fornical fibers were characterized by diffusion tensor‐based indices of fractional anisotropy (FA), radial diffusivity (RD) (Basser, Mattiello, & LeBihan, 1994; Pierpaoli & Basser, 1996), tissue volume fraction ( f ) (Pasternak, Sochen, Gur, Intrator, & Assaf, 2009), and by the hindrance‐modulated orientational anisotropy (HMOA) (Dell'Acqua, Simmons, Williams, & Catani, 2013). The HMOA provides a novel fiber population‐specific index of the diffusion properties along the reconstructed pathways, which may be more sensitive to inter‐individual differences in white matter microstructure than tensor‐based metrics (Christiansen, Aggleton, et al., 2016; Dell'Acqua et al., 2013). The purpose of comparing these various indices between the two populations of fornical fibers (anterior and posterior hippocampus) was to appreciate if these potentially distinct pathways might be distinguishable in ways additional to their physical location.…”

Dissociable Networks of the Lateral/Medial Mammillary Body in the Human Brain

“…In humans, diffusion-weighted imaging studies revealed several tracts that connect with the MB, such as the fornix and mammillotegmental tract (Granziera et al, 2011;Kwon et al, 2011;Mori and Aggarwal, 2014;Christiansen et al, 2016;Cacciola et al, 2017;Wei et al, 2017;Kamali et al, 2018;Choi et al, 2019;Maller et al, 2019). Clinical studies also revealed that memory-impaired patients with Korsakoff syndrome exhibit atrophy of the MB (Squire et al, 1990;Harding et al, 2000;Tsivilis et al, 2008;Fama et al, 2012;Kril and Harper, 2012;Aggleton, 2014;Kopelman, 2015;Isenberg-Grzeda et al, 2016;Arts et al, 2017;Johnson and Fox, 2018).…”