Biophysical Reconstruction of the Signal Conduction Underlying Short-Latency Cortical Evoked Potentials Generated by Subthalamic Deep Brain Stimulation

Clin Neurophysiol. 2020 Feb;131(2):542-547. doi: 10.1016/j.clinph.2019.09.020. Epub 2019 Nov 5.

Abstract

Objective: Direct activation of the hyperdirect (HD) pathway has been linked to therapeutic benefit from subthalamic deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD). We sought to quantify the axonal conduction biophysics of corticofugal axons directly stimulated by subthalamic DBS and reconcile those findings with short-latency cortical evoked potential (EP) results.

Methods: We used a detailed computational model of human subthalamic DBS to quantify axonal activation and conduction. Signal propagation to cortex was evaluated for medium (5.7 µm), large (10.0 µm), and exceptionally large (15.0 µm) diameter corticofugal axons associated with either internal capsule (IC) fibers of passage or the HD pathway. We then compared the modeling results to human cortical EP measurements that have described an exceptionally fast component (EP0) occurring ~1 ms after the stimulus pulse, a fast component (EP1) at ~3 ms, and a slower component (EP2) at ~5 ms.

Results: Subthalamic stimulation of the HD pathway with large and medium diameter axons propagated action potentials to cortex with timings that coincide with the EP1 and EP2 signals, respectively. Only direct activation of exceptionally large diameter fibers in the IC generated signals that could approach the EP0 timing. However, the action potential biophysics do not generally support the existence of a cortical EP less than 1.5 ms after DBS onset.

Conclusions: The EP1 and EP2 signals can be biophysically linked to antidromic activation of the HD pathway.

Significance: Theoretical reconstruction of cortical EPs from subthalamic DBS demonstrate a convergence of anatomical, biophysical, and electrophysiological results.

Keywords: Corticofugal axon; Hyperdirect pathway; Pyramidal neuron; Subthalamic nucleus.