Fornix White Matter is Correlated with Resting-State Functional Connectivity of the Thalamus and Hippocampus in Healthy Aging but Not in Mild Cognitive Impairment - A Preliminary Study

Abstract

In this study, we wished to examine the relationship between the structural connectivity of the fornix, a white matter (WM) tract in the limbic system, which is affected in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease, and the resting-state functional connectivity (FC) of two key related subcortical structures, the thalamus, and hippocampus. Twenty-two older healthy controls (HC) and 18 older adults with aMCI underwent multi-modal MRI scanning. The fornix was reconstructed using constrained-spherical deconvolution-based tractography. The FC between the thalamus and hippocampus was calculated using a region-of-interest approach from which the mean time series were exacted and correlated. Diffusion tensor imaging measures of the WM microstructure of the fornix were correlated against the Fisher Z correlation values from the FC analysis. There was no difference between the groups in the fornix WM measures, nor in the resting-state FC of the thalamus and hippocampus. We did however find that the relationship between functional and structural connectivity differed significantly between the groups. In the HCs, there was a significant positive association between linear diffusion (CL) in the fornix and the FC of the thalamus and hippocampus, however, there was no relationship between these measures in the aMCI group. These preliminary findings suggest that in aMCI, the relationship between the functional and structural connectivity of regions of the limbic system may be significantly altered compared to healthy ageing. The combined use of diffusion weighted imaging and functional MRI may advance our understanding of neural network changes in aMCI, and elucidate subtle changes in the relationship between structural and functional brain networks.

Keywords: diffusion MRI; fornix; functional connectivity; hippocampus; mild cognitive impairment (MCI); thalamus; tractography.

Figure 1

Placement of the regions of interests (ROIs) for the dissection of the fornix in ExploreDTI. (A) The five ROIs used to segment the fornix (B) coronal view of the seed ROI (C) ROI used to split the tracts and isolate the left fornix. The blue ROI is a SEED/OR gate, the green ROI is an AND gate, whilst the red ROIs are NOT gates. These ROIs were drawn for one subject and once deemed to be accurate and robust they were applied to all other subjects using an “atlas-based” tract segmentation method. The atlas in this case was the FA image of this subject.

Figure 2

(A) Position of the resting-state regions of interest (ROIs) in relation to (B) the fornix in one HC subject. ROIs for the resting-state analysis were placed in the hippocampus (indicated in red) and the thalamic region probabilistically connected to the temporal lobe (indicated in blue), as defined by the Oxford thalamic connectivity atlas (Behrens et al., 2003a,b).

Figure 3

Example fornix tracts in a (A) healthy control and (B) amnestic aMCI subject. The top panel in each case shows the tracts color-encoded with the first eigenvector (FE); the bottom panel shows the same tracts color-encoded with FA values. For each subject, the left and right fornix is shown in isolation on the left, and on the right the fornix can be seen overlaid on the subject’s T1-weighted structural image, with the FE shown in semi-transparent color (note the corpus callosum in red for example). The DWI data were co-registered to the structural images during the processing to correct for EPI-induced geometric distortions, however as illustrated by these figures this also facilitates the inspection of the white tracts in reference to the high-resolution anatomical image of the brain.

Figure 4

Scatterplots indicating the correlations between functional and structural connectivity measures. In the HCs but not the MCIs there was a significant positive relationship between CL in the fornix and the resting-state connectivity of the thalamus and hippocampus.