Distinct Components of the Cingulum Bundle Revealed by Diffusion MRI

INTRODUCTION: The cingulum bundle is a prominent white matter tract extending longitudinally above the callosum. Its descriptions have a long history, and it has been appreciated for over a century that it contains many short association fibres, as well as longer fibres that potentially link the frontal and temporal lobes. The fibres include connections with sites such as the anterior and dorsal thalamic nuclei and dorsolateral prefrontal cortex, while others are assumed to connect to structures in the temporal lobe, including the parahippocampal and subicular cortices, and amygdala. Thus, the cingulum bundle is a complex tract comprised of many different connections with trajectories of different lengths. However, this complex composition is rarely reflected in published diffusion tractography images, which most often show a continuous band of white matter that seemingly links (uninterrupted) the caudal medial temporal lobe with retrosplenial, cingulate, prefrontal, and subgenual areas. We suggest that this discrepancy arises from the common practice of placing regions of interest (ROIs) dorsal to the body of the corpus callosum and identifying all white matter linking them. Our concern is that that the cingulum bundle may comprise several distinct subregions that only appear united due to the numerous short association fibres within the tract and the resulting overlap in their trajectories. This work examined the unity of the cingulum bundle using tractography by comparing results from ROIs at different points along the tract and reveals a set of overlapping, but largely separate, connections within what is often visualised as a unified bundle. METHODS: Diffusion weighted data (cardiac-gated, b = 1200 s mm, 60 directions, 6 b=0s; 2.4 mm isotropic resolution) were collected from 20 healthy individuals (dextral males, age range 25-40 years). After motion/ distortion correction, fibre orientational density functions (fODFs) were derived in each voxel using constrained spherical harmonic decovolution. Streamline tracking – following peaks in the fODFwas performed from all voxels in the brain. First the ‘standard’ approach of placing two ‘AND’ ROIs above the body of the corpus callosum, one caudal and rostral to its midpoint (Figure A(i) below) was used. The reconstructed tract covered much of the entire extent of the cingulum bundle. Three other reconstructions were then visualised: 1) the ‘subgenual cingulum’ (SGC)– 2 ‘AND’ ROIs were placed in the subgenual cingulum and above the rostral part of the body of the corpus callosum; 2) the ‘retrosplenial cingulum’ (RSC) – 2 ‘AND’ ROIs were placed at the most inferior level of the splenium and above the more caudal part of the body of the corpus callosum; 3) the ‘parahippocampal cingulum’ (PHC)2 ‘AND’ ROIs were placed at the most inferior level of the splenium and within the temporal lobe. These three subregions were selected as tract tracing studies suggest that each subregion might contain a preponderance of fibres that arise from different sources.For each subject, the tracking result was binarized – so that if a voxel is intersected by a streamline, it is assigned a value of one, (zero otherwise). Each subject’s FA map was then nonlinearly normalized to the FMRIB58 MNI FA template using FNIRT (www.fmrib.ox.ac.uk/fsl) and the transformations applied to the tracking results. The 20 tract maps for a given segment were then summed to give an overlap-map – which was thresholded at 70% (i.e., > 14 of the 20 subjects have a streamline passing through a voxel). The analysis was repeated by 2 independent observers to derive inter-observer reliability. Finally, the mean FA and radial diffusivity (RD) in each of the three tracts were compared with one another using paired t-tests.