Fiber tractography of the axonal pathways linking the basal ganglia and cerebellum in Parkinson disease: implications for targeting in deep brain stimulation

Abstract

Object: Stimulation of white matter pathways near targeted structures may contribute to therapeutic effects of deep brain stimulation (DBS) for patients with Parkinson disease (PD). Two tracts linking the basal ganglia and cerebellum have been described in primates: the subthalamopontocerebellar tract (SPCT) and the dentatothalamic tract (DTT). The authors used fiber tractography to evaluate white matter tracts that connect the cerebellum to the region of the basal ganglia in patients with PD who were candidates for DBS.

Methods: Fourteen patients with advanced PD underwent 3-T MRI, including 30-directional diffusion-weighted imaging sequences. Diffusion tensor tractography was performed using 2 regions of interest: ipsilateral subthalamic and red nuclei, and contralateral cerebellar hemisphere. Nine patients underwent subthalamic DBS, and the course of each tract was observed relative to the location of the most effective stimulation contact and the volume of tissue activated.

Results: In all patients 2 distinct tracts were identified that corresponded closely to the described anatomical features of the SPCT and DTT, respectively. The mean overall distance from the active contact to the DTT was 2.18 ± 0.35 mm, and the mean proportional distance relative to the volume of tissue activated was 1.35 ± 0.48. There was a nonsignificant trend toward better postoperative tremor control in patients with electrodes closer to the DTT.

Conclusions: The SPCT and the DTT may be related to the expression of symptoms in PD, and this may have implications for DBS targeting. The use of tractography to identify the DTT might assist with DBS targeting in the future.

FIG. 1

To identify the tracts, 2 ROIs were defined on MRI FLAIR sequences, one overlying the right STN and the red nucleus (left) and the other overlying the contralateral cerebellar hemisphere (right).

FIG. 2

For the subset of individuals who underwent DBS of the STN, we created patient-specific computer models of DBS. Each model integrated into a common platform the patient imaging data, 3D subcortical nuclei, DBS electrode, and the VTA. The relevant nuclei were contoured and include the globus pallidus and putamen (blue), the thalami (yellow), the red nuclei (red), the STN (green), and the dentate nuclei (pink).

FIG. 3

A: The active contact of each electrode was determined from postoperative programming sessions, and was defined as the cathodal electrode for either monopolar or bipolar stimulation. The active contact is shown on a postoperative CT scan (left) and on image fusion on MRI (right). B: The VTA was calculated from each patient's specific stimulation parameter settings by using a custom Python-based program from Python libraries. The VTA is shown in dark pink alone (left) and in conjunction with the contoured nuclei (right).

FIG. 4

Two distinct tracts were identified, corresponding to the previously described course of the SPCT and the DTT.

FIG. 5

Bar graphs showing outcomes according to electrode position. Upper: There was a nonsignificant trend toward better outcome when the active contact was closer to the DTT. Lower: There was a greater trend toward correlation with outcome when the distance proportional to VTA rather than actual distance was considered.