Resonant Antidromic Cortical Circuit Activation as a Consequence of High-Frequency Subthalamic Deep-Brain Stimulation

• Type of Material: Article
• Authors: S. Li, Emory University; G. W. Arbuthnott, University of Edinburgh; M. J. Jutras, Emory University; J. A. Goldberg, University of Texas San Antonio; Dieter Jaeger, Emory University
• Language: English
• Date: 2007-10-10
• Publisher: American Physiological Society
• Publication Version: Final Published Version
• Copyright Statement: © 2007 by the American Physiological Society.
• Final Published Version (URL): https://doi.org/10.1152/jn.00808.2007
• Title of Journal or Parent Work: Journal of Neurophysiology
• Grant/Funding Information: The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; This study was supported by a FastTrack Award from the Michael J. Fox Foundation to D. Jaeger and National Institute of Neurological Disorders and Stroke Grant R01-NS-039852.
• Keywords: implanted depth electrode; deep brain stimulation (DBS); antidromic cortical activation; cortical microcircuits; intracellular cortical recordings; cortical network; high-frequency biphasic stimulation; oscillatory activity; anesthesia; basal ganglia network; cortical efferent pathways; antidromic spikes; subthalamic nucleus (STN-DBS); Parkinson's disease (PD); synchronous activity
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery

Abstract

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)–lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.