Introduction: Direct stimulation of the hyperdirect pathway has been linked to therapeutic benefit in subthalamic deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD). Cortical evoked potentials generated by subthalamic DBS represent an electrophysiological signal that can be associated with hyperdirect pathway activation and represent possible biomarkers for use in closed-loop DBS control systems. The objective of this study was to quantify the axonal conduction biophysics of corticofugal axons directly stimulated by subthalamic DBS and reconcile those findings with cortical evoked potential results that suggest a very fast component (R1) occurring ~1 ms after the stimulus pulse, as well as a slower component (R2) that reaches its peak in ~6 ms.
Methods: We used a detailed computational model of human subthalamic DBS to quantify axonal activation and conduction. Signal propagation to cortex was quantified for medium (5.7 µm), large (10.0 µm), and exceptionally large (15.0 µm) diameter corticofugal axons.
Results: Subthalamic stimulation of hyperdirect axons with 5.7 µm corticofugal axon diameters propagated action potentials to cortex with timings that matched very well with the R2 evoked potential, representing a convergence between histological, biophysical, and electrophysiological results. However, only the 15.0 µm axon models, which would be extremely rare, generated signals that could approach the R1 timing.
Conclusions: Origin of the R1 signal remains unclear, but R2 can be attributed to antidromic activation of the hyperdirect pathway.
Patient Care: Identification of electrophysiological biomarkers for DBS control systems.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the hyperdirect pathway, 2) Understand the role of axon diameter in signal conduction speed 3) Identify cortical evoked potentials associated with hyperdirect pathway stimulation.