Investigating the Anatomy and Microstructure of the Dentato-rubro-thalamic and Subthalamo-ponto-cerebellar Tracts in Parkinson's Disease

Abstract

Cerebellar-thalamic connections play a central role in deep brain stimulation-based treatment of tremor syndromes. Here, we used diffusion Magnetic Resonance Imaging (MRI) tractography to delineate the main cerebellar peduncles as well as two main white matter tracts that connect the cerebellum with the thalamus, the dentato-rubro-thalamic tract (DRTT) and the subthalamo-ponto-cerebellar tract (SPCT). We first developed a reconstruction protocol in young healthy adults with high-resolution diffusion imaging data and then demonstrate feasibility of transferring this protocol to clinical studies using standard diffusion MRI data from a cohort of patients with Parkinson's disease (PD) and their matched healthy controls. The tracts obtained closely corresponded to the previously described anatomical pathways and features of the DRTT and the SPCT. Second, we investigated the microstructure of these tracts with fractional anisotropy (FA), radial diffusivity (RD), and hindrance modulated orientational anisotropy (HMOA) in patients with PD and healthy controls. By reducing dimensionality of both the microstructural metrics and the investigated cerebellar and cerebellar-thalamic tracts using principal component analyses, we found global differences between patients with PD and controls, suggestive of higher fractional anisotropy, lower radial diffusivity, and higher hindrance modulated orientational anisotropy in patients. However, separate analyses for each of the tracts did not yield any significant differences. Our findings contribute to the characterization of the distinct anatomical connections between the cerebellum and the diencephalon. Microstructural differences between patients and controls in the cerebellar pathways suggest involvement of these structures in PD, complementing previous functional and diffusion imaging studies.

Keywords: Parkinson's disease; basal ganglia; cerebellum; cortico-cerebellar pathways; dentato-rubro-thalamic tract; diffusion tractography; microstructure; subthalamo-ponto-cerebellar tract.

Figure 1

The dentato-rubro-thalamic tract (DRTT) tract along with the regions of interest (ROIs) in axial, sagittal, and coronal views of T1 anatomical scan in an example data set. (A) Visualizes the DRTT tract from the dentate nucleus, (B) shows the DRTT decussating in the midbrain, and (C) shows the DRTT passing through the thalamus in the axial view. (D) Shows the entire DRTT with its cortical connections on a sagittal view and (E) shows the entire DRTT with its cortical connections on a coronal view.

Figure 2

Region of Interest(s) (ROIs) and reconstruction of the subthalamo-ponto-cerebellar tract (SPCT) in an example dataset in coronal view in T1 anatomical (A) and diffusion color-coded image (B). The first ROI (1) is drawn around the subthalamic nucleus and the second ROI (2) is drawn around the contralateral pons region.

Figure 3

The alternative Region of Interest(s) (ROIs) used for reconstruction of the DRTT and the SPCT. The ROI around the thalamus covering the internal capsule is shown in (A), the ROI covering the contralateral cerebellar peduncle is shown in (B,C). An example of the SPCT obtained using this alternative method is shown in (D).

Figure 4

Different sections of the Montreal Neurological Institute (MNI) brain showing the probability (in percent) of the dentato-rubro-thalamic tract (DRTT) and the subthalamo-ponto-cerebellar tract (SPCT) in the Parkinson's disease (PD) group. The display range is set to 10–50%, hence areas of the brain showing yellow and light blue colors have at least 50% of participants' tracts passing through those voxels.