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. 2019 Aug 20;9(1):12117.
doi: 10.1038/s41598-019-48164-7.

The cortico-rubral and cerebello-rubral pathways are topographically organized within the human red nucleus

Alberto Cacciola  1 , Demetrio Milardi  2   3 , Gianpaolo Antonio Basile  2 , Salvatore Bertino  2 , Alessandro Calamuneri  3 , Gaetana Chillemi  3 , Giuseppe Paladina  3 , Federica Impellizzeri  3 , Fabio Trimarchi  2 , Giuseppe Anastasi  2 , Alessia Bramanti  3 , Giuseppina Rizzo  2
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The cortico-rubral and cerebello-rubral pathways are topographically organized within the human red nucleus

Alberto Cacciola et al. Sci Rep. .

Abstract

The Red Nucleus (RN) is a large nucleus located in the ventral midbrain: it is subdivided into a small caudal magnocellular part (mRN) and a large rostral parvocellular part (pRN). These distinct structural regions are part of functionally different networks and show distinctive connectivity features: the mRN is connected to the interposed nucleus, whilst the pRN is mainly connected to dentate nucleus, cortex and inferior olivary complex. Despite functional neuroimaging studies suggest RN involvement in complex motor and higher order functions, the pRN and mRN cannot be distinguished using conventional MRI. Herein, we employ high-quality structural and diffusion MRI data of 100 individuals from the Human Connectome Project repository and constrained spherical deconvolution tractography to perform connectivity-based segmentation of the human RN. In particular, we tracked connections of RN with the inferior olivary complex, the interposed nucleus, the dentate nucleus and the cerebral cortex. We found that the RN can be subdivided according to its connectivity into two clusters: a large ventrolateral one, mainly connected with the cerebral cortex and the inferior olivary complex, and a smaller dorsomedial one, mainly connected with the interposed nucleus. This structural topography strongly reflects the connectivity patterns of pRN and mRN respectively. Structural connectivity-based segmentation could represent a useful tool for the identification of distinct subregions of the human red nucleus on 3T MRI thus allowing a better evaluation of this subcortical structure in healthy and pathological conditions.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Comparison of maximum connectivity maps applying different thresholds. (A) Axial slices on the MNI152 template showing the topographical distribution of parvocellular (orange) and magnocellular (light blue) clusters when three different thresholds (25%, 50%, 75%) are applied. (B) Axial slices showing the topography of connectivity clusters of the cerebral cortex (red), inferior olivary complex (green), interposed nucleus (blue) and dentate nucleus (yellow) when the above-mentioned thresholds are applied. Note that the arrangements of the connectivity clusters are always maintained, even if higher thresholds lead to a cluster shrinkage.
Figure 2
Figure 2
Connectivity clusters. Three-dimensional view of the identified connectivity clusters superimposed on the MNI152 space. MPM are thresholded at 75%. (A) Dentate nucleus (yellow) localized in the rostral and ventral portion of the red nucleus. (B) Interposed nucleus (green) clustered in the most caudal and medial part of the red nucleus. (C) Inferior olivary complex (green) occupied the most inferior region of the red nucleus. (D) Cerebral cortex (red) localized in the most lateral part of the red nucleus volume. (E) 3D visualization of parvocellular and magnocellular subregions on the MNI space, the parvocellular part is located in the ventrolateral aspect of the red nucleus while the magnocellular region is situated in its caudal and medial part.
Figure 3
Figure 3
Red nucleus connectivity based parcellation. Multiple axial slices showing the identified connectivity clusters on the MNI152 template. MPM are thresholded at 75%. On the upper row the parvocellular (orange) and the magnocellular (light blue) clusters are shown; note that the magnocellular regions appears well delineated in the upper slices located dorsally while the parvocellular regions appears clearly from the second slides and quite disappears in the most cranial one. On the inferior row connectivity clusters for dentate nucleus (yellow), interposed nucleus (blue), inferior olivary complex (green) and cerebral cortex (red) are depicted. Transparency has been modulated to show the way different clusters overlap within red nucleus volume.
Figure 4
Figure 4
Inferior olivary complex manual segmentation. The figure shows a TDI (track density imaging) map of a sample subject. The superior row consists of axial slices where the inferior olivary complex ROI is superimposed on the left (green); a hypointense regions corresponding to the olivary complex can be observed on the right side just posterior to cortico-spinal tract. The same color-coding is maintained in the inferior row which consists of coronal slices showing the left ROI in green; notice that inferior olive is well contrasted from the surrounding white matter bundles.
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