Subthalamic nucleus conditioning reduces premotor-motor interaction in Parkinson's disease

Martje G Pauly; Magdalena Barlage; Feline Hamami; Julia Steinhardt; Julianne Baarbé; Stephanie Tran; Henrike Hanssen; Rebecca Herzog; Vera Tadic; Norbert Brüggemann; Robert Chen; Alexander Münchau; Tobias Bäumer; Anne Weissbach

doi:10.1016/j.parkreldis.2022.01.014

Subthalamic nucleus conditioning reduces premotor-motor interaction in Parkinson's disease

Parkinsonism Relat Disord. 2022 Mar:96:6-12. doi: 10.1016/j.parkreldis.2022.01.014. Epub 2022 Jan 22.

Authors

Affiliations

¹ Institute of Systems Motor Science, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Department of Neurology, University Hospital Schleswig Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany.
² Institute of Systems Motor Science, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
³ Department of Neurology, University Hospital Schleswig Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany.
⁴ Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁵ Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Department of Neurology, University Hospital Schleswig Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany.
⁶ Institute of Systems Motor Science, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Department of Neurology, University Hospital Schleswig Holstein, Ratzeburger Allee 160, 23538, Lübeck, Germany.
⁷ Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
⁸ Institute of Systems Motor Science, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. Electronic address: anne.weissbach@neuro.uni-luebeck.de.

PMID: 35093853
DOI: 10.1016/j.parkreldis.2022.01.014

Abstract

Background: Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear.

Objective: To investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies.

Methods: In 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings.

Results: There was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here.

Conclusions: Premotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway.

Keywords: Deep brain stimulation; Parkinson's disease; Premotor-motor; Transcranial magnetic stimulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Deep Brain Stimulation*
Humans
Motor Cortex*
Parkinson Disease* / therapy
Subthalamic Nucleus* / physiology
Transcranial Magnetic Stimulation