Coupled Activation of the Hyperdirect and Cerebellothalamic Pathways with Zona Incerta Deep Brain Stimulation

Area of Science:

• Neuroscience
• Computational modeling
• Neurosurgery

Background:

• Deep brain stimulation (DBS) targets the subthalamic nucleus (STN) for Parkinson's disease (PD) and the ventral intermediate nucleus (VIM) for essential tremor (ET).
• The zona incerta (ZI) is a potential DBS target for both PD and ET.
• Therapeutic mechanisms are linked to activating specific neural pathways: VIM DBS via the cerebellothalamic (CBT) pathway and STN DBS via the hyperdirect (HD) pathway.

Purpose of the Study:

• To computationally model and assess the zona incerta's (ZI) capacity to co-activate the hyperdirect (HD) and cerebellothalamic (CBT) pathways using deep brain stimulation (DBS).

Main Methods:

• An existing computational model of the human HD pathway was enhanced to include axon collaterals to the ZI and red nucleus (RN).
• The model incorporated anatomical representations of the CBT pathway and internal capsule (IC) fibers.
• Biophysical simulations quantified DBS activation of HD, CBT, and IC pathways with STN or ZI electrode placement.

Main Results:

• Both STN DBS and ZI DBS effectively activated the HD pathway.
• STN DBS led to internal capsule (IC) activation at higher amplitudes, unlike ZI DBS.
• ZI DBS demonstrated the ability to activate both the HD and CBT pathways while avoiding IC activation.

Conclusions:

• The zona incerta (ZI) is a promising DBS target for simultaneously activating the hyperdirect (HD) and cerebellothalamic (CBT) pathways.
• ZI DBS offers neuroanatomical and biophysical advantages for combined pathway activation compared to STN DBS.