Fornix Microstructure Research Articles

Dissociable roles of the inferior longitudinal fasciculus and fornix in face and place perception.

We tested a novel hypothesis, generated from representational accounts of medial temporal lobe (MTL) function, that the major white matter tracts converging on perirhinal cortex (PrC) and hippocampus (HC) would be differentially involved in face and scene perception, respectively. Diffusion tensor imaging was applied in healthy participants alongside an odd-one-out paradigm sensitive to PrC and HC lesions in animals and humans. Microstructure of inferior longitudinal fasciculus (ILF, connecting occipital and ventro-anterior temporal lobe, including PrC) and fornix (the main HC input/output pathway) correlated with accuracy on odd-one-out judgements involving faces and scenes, respectively. Similarly, blood oxygen level-dependent (BOLD) response in PrC and HC, elicited during oddity judgements, was correlated with face and scene oddity performance, respectively. We also observed associations between ILF and fornix microstructure and category-selective BOLD response in PrC and HC, respectively. These striking three-way associations highlight functionally dissociable, structurally instantiated MTL neurocognitive networks for complex face and scene perception.

Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment.

The fornix and hippocampus are critical to recollection in the healthy human brain. Fornix degeneration is a feature of aging and Alzheimer's disease. In the presence of fornix damage in mild cognitive impairment (MCI), a recognized prodrome of Alzheimer's disease, recall shows greater dependence on other tracts, notably the parahippocampal cingulum (PHC). The current aims were to determine whether this shift is adaptive and to probe its relationship to cholinergic signaling, which is also compromised in Alzheimer's disease. Twenty-five human participants with MCI and 20 matched healthy volunteers underwent diffusion MRI, behavioral assessment, and volumetric measurement of the basal forebrain. In a regression model for recall, there was a significant group × fornix interaction, indicating that the association between recall and fornix structure was weaker in patients. The opposite trend was present for the left PHC. To further investigate this pattern, two regression models were generated to account for recall performance: one based on fornix microstructure and the other on both fornix and left PHC. The realignment to PHC was positively correlated with free recall but not non-memory measures, implying a reconfiguration that is beneficial to residual memory. There was a positive relationship between realignment to PHC and basal forebrain gray matter volume despite this region demonstrating atrophy at a group level, i.e., the cognitive realignment to left PHC was most apparent when cholinergic areas were relatively spared. Therefore, cholinergic systems appear to enable adaptation to injury even as they degenerate, which has implications for functional restoration.

Interindividual variation in fornix microstructure and macrostructure is related to visual discrimination accuracy for scenes but not faces.

Transection of the nonhuman primate fornix has been shown to impair learning of configurations of spatial features and object-in-scene memory. Although damage to the human fornix also results in memory impairment, it is not known whether there is a preferential involvement of this white-matter tract in spatial learning, as implied by animal studies. Diffusion-weighted MR images were obtained from healthy participants who had completed versions of a task in which they made rapid same/different discriminations to two categories of highly visually similar stimuli: (1) virtual reality scene pairs; and (2) face pairs. Diffusion-MRI measures of white-matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] and macrostructure (tissue volume fraction, f) were then extracted from the fornix of each participant, which had been reconstructed using a deterministic tractography protocol. Fornix MD and f measures correlated with scene, but not face, discrimination accuracy in both discrimination tasks. A complementary voxelwise analysis using tract-based spatial statistics suggested the crus of the fornix as a focus for this relationship. These findings extend previous reports of spatial learning impairments after fornix transection in nonhuman primates, critically highlighting the fornix as a source of interindividual variation in scene discrimination in humans.

Constrained spherical deconvolution-based tractography to depict and characterize a case of “hyperplastic fornix dorsalis”

The authors report the relevance of Constrained Spherical Deconvolution (CSD)-based tractography in demonstrating and quantitatively assessing a complex midline structure malformation in a 9-year-old girl with moderate intellectual disability and thickening of corpus callosum (CC) body discovered through conventional MRI (cMRI). Color-encoded fractional anisotropy (FA) maps clearly demonstrated what the cMRI showed as a thicknening of CC: a green, longitudinal bundle running dorsally to the body of CC. A more complex midline maldevelopmental disorder was suspected. CSD-based tractography was performed to virtually dissect the anomalous supracallosal longitudinal bundle (SLB), CC, fornix, anterior commissure (AC) and cingula. In addition, DTI-derived metrics were calculated for each virtually dissected fiber tract.The tractography study evidenced projections of the anomalous SLB in left forceps minor and to parietal regions, and projections of the fornix in right forceps minor. CC virtual dissection showed no gross abnormality, and cingula appeared slightly less extended than normal. The considerable thinning of AC hampered its virtual dissection. DTI-derived metrics suggested alterations in fornix microstructure, attributable to higher fiber density.In investigating white matter, cMRI may not be sufficient in addressing and assessing possible anomalies, while advanced CSD-based tractography and DTI-derived metrics may prove helpful in depicting and characterizing white matter anomalies in developmental disorders.

Early Brain Loss in Circuits Affected by Alzheimer's Disease is Predicted by Fornix Microstructure but may be Independent of Gray Matter.

In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter (WM) microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fornix significant ROI, fSROI), which overlaps circuits known to be selectively vulnerable to Alzheimer’s dementia pathology. Other WM and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain-tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.

CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment

Diffusion MRI is used widely to probe microstructural alterations in neurological and psychiatric disease. However, ageing and neurodegeneration are also associated with atrophy, which leads to artefacts through partial volume effects due to cerebrospinal-fluid contamination (CSFC). The aim of this study was to explore the influence of CSFC on apparent microstructural changes in mild cognitive impairment (MCI) at several spatial levels: individually reconstructed tracts; at the level of a whole white matter skeleton (tract-based spatial statistics); and histograms derived from all white matter. 25 individuals with MCI and 20 matched controls underwent diffusion MRI. We corrected for CSFC using a post-acquisition voxel-by-voxel approach of free-water elimination. Tracts varied in their susceptibility to CSFC. The apparent pattern of tract involvement in disease shifted when correction was applied. Both spurious group differences, driven by CSFC, and masking of true differences were observed. Tract-based spatial statistics were found to be robust across much of the skeleton but with some localised CSFC effects. Diffusivity measures were affected disproportionately in MCI, and group differences in fornix microstructure were exaggerated. Group differences in white matter histogram measures were also partly driven by CSFC. For diffusivity measures, up to two thirds of observed group differences were due to CSFC. Our results demonstrate that CSFC has an impact on quantitative differences between MCI and controls. Furthermore, it affects the apparent spatial pattern of white matter involvement. Free-water elimination provides a step towards disentangling intrinsic and volumetric alterations in individuals prone to atrophy.

Individual Differences in Fornix Microstructure and Body Mass Index

The prevalence of obesity and associated health conditions is increasing in the developed world. Obesity is related to atrophy and dysfunction of the hippocampus and hippocampal lesions may lead to increased appetite and weight gain. The hippocampus is connected via the fornix tract to the hypothalamus, orbitofrontal cortex, and the nucleus accumbens, all key structures for homeostatic and reward related control of food intake. The present study employed diffusion MRI tractography to investigate the relationship between microstructural properties of the fornix and variation in Body Mass Index (BMI), within normal and overweight ranges, in a group of community-dwelling older adults (53–93 years old). Larger BMI was associated with larger axial and mean diffusivity in the fornix (r = 0.64 and r = 0.55 respectively), relationships that were most pronounced in overweight individuals. Moreover, controlling for age, education, cognitive performance, blood pressure and global brain volume increased these correlations. Similar associations were not found in the parahippocampal cingulum, a comparison temporal association pathway. Thus, microstructural changes in fornix white matter were observed in older adults with increasing BMI levels from within normal to overweight ranges, so are not exclusively related to obesity. We propose that hippocampal-hypothalamic-prefrontal interactions, mediated by the fornix, contribute to the healthy functioning of networks involved in food intake control. The fornix, in turn, may display alterations in microstructure that reflect weight gain.

Frontotemporal Connections in Episodic Memory and Aging: A Diffusion MRI Tractography Study

Human episodic memory is supported by networks of white matter tracts that connect frontal, temporal, and parietal regions. Degradation of white matter microstructure is increasingly recognized as a general mechanism of cognitive deterioration with aging. However, atrophy of gray matter regions also occurs and, to date, the potential role of specific white matter connections has been largely ignored. Changes to frontotemporal tracts may be important for the decline of episodic memory; while frontotemporal cooperation is known to be critical, the precise pathways of interaction are unknown. Diffusion-weighted MRI tractography was used to reconstruct three candidate fasciculi known to link components of memory networks: the fornix, the parahippocampal cingulum, and the uncinate fasciculus. Age-related changes in the microstructure of these tracts were investigated in 40 healthy older adults between the ages of 53 and 93 years. The relationships between aging, microstructure, and episodic memory were assessed for each individual tract. Age-related reductions of mean fractional anisotropy and/or increased mean diffusivity were found in all three tracts. However, age-related decline in recall was specifically associated with degradation of fornix microstructure, consistent with the view that this tract is important for episodic memory. In contrast, a decline in uncinate fasciculus microstructure was linked to impaired error monitoring in a visual object-location association task, echoing the effects of uncinate transection in monkeys. These results suggest that degradation of microstructure in the fornix and the uncinate fasciculus make critical but differential contributions to the mechanisms underlying age-related cognitive decline and subserve distinct components of memory.

Fornix Microstructure Correlates with Recollection But Not Familiarity Memory

The fornix is the main tract between the medial temporal lobe (MTL) and medial diencephalon, both of which are critical for episodic memory. The precise involvement of the fornix in memory, however, has been difficult to ascertain since damage to this tract in human amnesics is invariably accompanied by atrophy to surrounding structures. We used diffusion-weighted imaging to investigate whether individual differences in fornix white matter microstructure in neurologically healthy participants were related to differences in memory as assessed by two recognition tasks. Higher microstructural integrity in the fornix tail was found to be associated with significantly better recollection memory. In contrast, there was no significant correlation between fornix microstructure and familiarity memory or performance on two non-mnemonic tasks. Our findings support the idea that there are distinct MTL-diencephalon pathways that subserve differing memory processes.