Theoretical Evaluation of a Parietal Trajectory for Subthalamic Deep Brain Stimulation

The subthalamic region consists of a complex intersection of many different axonal pathways. Emerging hypotheses in deep brain stimulation (DBS) for Parkinson's disease (PD) suggest that direct stimulation of specific axonal pathways may be linked to the control of specific motor symptoms (e.g., cerebellothalamic (CT) - tremor; motor hyperdirect (mHD) - bradykinesia; pallidothalamic (PT) - rigidity). However, the typical frontal DBS lead trajectory limits opportunities to co-activate all of these pathways.

We used advanced biophysical DBS models to evaluate the theoretical utility of a parietal lead trajectory into the subthalamic region that could facilitate activation of the PT, mHD, and CT pathways. We compared a typical frontal DBS lead trajectory with a traditional 8-contact directional DBS lead to the parietal alternative with a 16-contact directional DBS lead. The analyses were performed within the context of the CIT168 human atlas brain populated with the Petersen axonal pathway models.

PT, mHD, and CT fibers are distributed in an anterior-to-posterior fashion within the subthalamic white matter. Given this anatomical feature, traditional frontal trajectories limit opportunities for multi-pathway DBS because the electrode contacts are primarily aligned dorsal-ventrally. Alternatively, the span of DBS contacts along a parietal trajectory can provide better opportunities to activate all of the pathways of interest, while also avoiding unwanted activation of the internal capsule.

Parietal DBS trajectories warrant consideration in PD therapy as the research concepts of pathway-targeted stimulation begin migrating into clinical practice.