Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

Abstract

The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders.

Keywords: CSD; basal ganglia; cerebellum; connectivity; tractography.

FIGURE 1

Brain areas segmentation. A semi-oblique axial view of 3D T2 weighted images shows the right substantia nigra (circles), the right subthalamic nucleus (STN; asterisks), and the right internal globus pallidus GPI. Thalamus (Th) can be also seen. In the top right corner, the same slice is shown; now a different colormap (jet) was used to display it. Here; advantages of using T2w image are clear, as evident from the substantia nigra (arrowheads), the STN (arrows) and the red nucleus (R).

FIGURE 2

Connectivity results are visualized by means of a graph. Red nodes correspond to specific brain areas (labeled near to them). Edges (in blue) correspond to the pathways analyzed. Edge thickness is proportional to connectivity strength as measured from individual subjects; average weights are reported on top of each corresponding edge as well.

FIGURE 3

Dento-thalamic pathways. Representation of the dento-thalamo connections. Dentate nucleus (orange VOI) and thalamus (red VOI) are connected by a direct pathway. Connections between thalamus and striatum complete the circuit. (A) Coronal view of the pathway connecting the right dentate nucleus (orange VOI) to the left thalamus (red VOI). The fibers exited the cerebellum via the right superior cerebellar peduncle, crossed the midline at the level of the midbrain (decussation of brachium conjunctivum) and reached the contralateral thalamus through the left cerebral peduncle. (B) Coronal view of the pathway connecting the right dentate nucleus (orange VOI) to the ipsilateral thalamus (red VOI). The fibers exited the cerebellum via the right superior cerebellar peduncle, ran through the midbrain and reached the thalamus through the right cerebral peduncle.

FIGURE 4

Subthalamic-cerebellar cortex connections. The ipsilateral cerebello-subthalamic connection linking cerebellar cortex with ipsilateral STN (yellow VOI) is showed on frontal view. Please note that this pathway also run externally to dentate nucleus (orange VOI).

FIGURE 5

Dentate-nigral connections. (A) Coronal view shows the connections between the right dentate nucleus (orange VOI) and the ipsilateral substantia nigra (black VOI). (B) An oblique para-coronal view allows evaluating the white matter bundle connecting the right dentate nucleus (orange VOI) to the ipsilateral subtantia nigra (black VOI). The bulk of this white matter bundle passes through the superior cerebellar peduncle (red arrow) with a small component running through the middle cerebellar peduncle (red arrowhead). Note the hypointense iron-loaded RN (white arrowhead) and STN (yellow arrowhead) close to the substantia nigra.

FIGURE 6

Course of ipsilateral dentate-nigral connections. Fourtheen axial T2 weighted scans show the course of the connections between dentate nucleus and substantia nigra. On the right fibers are red colored, on the left side blue colored. The first two images depict tracts leaving the dentate nucleus. From the dentate nucleus the fibers enter the brainstem through the middle and superior cerebellar peduncles and reach the substantia nigra running laterally to the RN.

FIGURE 7

Dentate-pallidal connections. (A) Contralateral dento-pallidal connection. Representation on coronal view of the pathway connecting right dentate nucleus (orange VOI) with contralateral globus pallidus (GP; green VOI). The pathway crosses the midline above the RN (cyan VOI) at the level of the midbrain. (B) Ipsilateral dento-pallidal connection. Coronal view shows the direct dento-pallidal pathway linking dentate nucleus (orange VOI) to the GP (green VOI). An enlarged view focused on the cranial part of the bundle reveals, with better magnification, the close relationship between the bundle, the RN (cyan VOI) and the substantia nigra (black VOI), which are surrounded by the fibers. Note that the fibers converge mainly on the antero-medial part of the Gpi.

FIGURE 8

Course of ipsilateral dentate-pallidal connections. Representation of the course of the connections between dentate nucleus and GP. On the right fibers are red colored, on the left blue colored. The first two images depict tracts leaving the dentate nuclues. From the dentate nucleus the fibers enter the brainstem through the superior cerebellar peduncle, then they encircle the RN, avoid the substantia nigra and pass through the cerebral peduncle to reach the internal GP.