Non-invasive Assessment of Changes in Corticomotoneuronal Transmission in Humans

Summary

The aim of the present study was to assess changes in transmission at the corticomotoneuronal synapses in humans after repetitive transcranial magnetic stimulation. For this purpose, an electrophysiological method is introduced that allows assessment of pathway specific corticospinal transmission, i.e. differentiation of fast, direct corticospinal pathways from polysynaptic connections.

Abstract

The corticospinal pathway is the major pathway connecting the brain with the muscles and is therefore highly relevant for movement control and motor learning. There exists a number of noninvasive electrophysiological methods investigating the excitability and plasticity of this pathway. However, most methods are based on quantification of compound potentials and neglect that the corticospinal pathway consists of many different connections that are more or less direct. Here, we present a method that allows testing excitability of different fractions of the corticospinal transmission. This so called H-reflex conditioning technique allows one to assess excitability of the fastest (monosynaptic) and also polysynaptic corticospinal pathways. Furthermore, by using two different stimulation sites, the motor cortex and the cervicomedullary junction, it allows not only differentiation between cortical and spinal effects but also assessment of transmission at the corticomotoneural synapse. In this manuscript, we describe how this method can be used to assess corticomotoneural transmission after low-frequency repetitive transcranial magnetic stimulation, a method that was previously shown to reduce excitability of cortical cells. Here we demonstrate that not only cortical cells are affected by this repetitive stimulation but also transmission at the corticomotoneuronal synapse at the spinal level. This finding is important for the understanding of basic mechanisms and sites of neuroplasticity. Besides investigation of basic mechanisms, the H-reflex conditioning technique may be applied to test changes in corticospinal transmission following behavioral (e.g., training) or therapeutic interventions, pathology or aging and therefore allows a better understanding of neural processes that underlie movement control and motor learning.

Introduction

In primates, the corticospinal tract constitutes the major descending pathway controlling voluntary actions¹. The corticospinal pathway connects motor cortical areas to spinal α-motoneurons via direct monosynaptic corticomotoneuronal connections and via indirect oligo- and polysynaptic connections^2,3. Although the motor cortex can easily be excited non-invasively by Transcranial Magnetic Stimulation (TMS), the evoked electromyographic response to this stimulation is often difficult to interpret. The reason for this is that the compound Motor Evoked Potential (MEP) can be influenced....

Protocol

This protocol was approved by the local ethics committee and the experiments are in accordance with the Declaration of Helsinki (1964).

1. Subject Preparation

NOTE: Subject instructions - Before starting with the experiment, instruct each subject about the purpose of the study and potential risk factors. For transcranial magnetic stimulation (TMS), medical risks include any history of epileptic seizure, mental implants in eyes and/or head, any diseases of the cardiovascular system, and pregnancy. Exclude all subjects affirming to one of these risk factors. Furthermore, in the exper....

Results

Occurrence of the early facilitation after M1- and CMS-conditioning

H-reflex conditioning with TMS over M1 resulted in an early facilitation that occurred around ISI -3 & -4 ms. The early facilitation after CMS-conditioning occurred around 3 ms earlier (ISI -6 & -7 ms, respectively). Exemplary ISI-curves of one subject are displayed in Figure 1. In the present study, the early facil.......

Discussion

The H-reflex conditioning procedure described here has been specifically addressed to assess acute changes in transmission over the corticomotoneuronal synapse following repetitive activation of the corticospinal pathway²⁸. In this respect, H-reflex conditioning has highlighted that rTMS does not only affect excitability of cortical structures but also has an effect on the corticomotoneural transmission at the corticomotoneural synapse. However, this method may indeed have broader application as c.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Self-adhesive EMG electrodes	Blue sensor N, Ambu, Ballerup, Denmark		Used to record EMG signals
Electrical stimulator	Digitimer DS7A, Hertfordshire, UK		Used to elicit the soleus H-reflex
Stimulating electrode	Blue sensor N, Ambu, Ballerup, Denmark		Used to elicit the soleus H-reflex
Magnetic stimulator #1	Magstim Rapid2 TMS stimulator, Magstim Company Ltd., Whitland, UK		Used to elicit contralateral motor evoked potentials in the soleus muscle
Coil #1: 90 mm figure-of-eight coil	Magstim Company Ltd., Whitland, UK		Used to elicit contralateral motor evoked potentials in the soleus muscle
			Stimulator #1 and coil #1 were used in the original publication (Taube et al. 2014; Cerebral Cortex)
Magnetic stimulator #2	MagPro X100 with MagOption, MagVenture A/S, Farum, Denmark		Used to elicit contralateral motor evoked potentials in the soleus muscle
Co#2: 95 mm focal “butterfly-shaped” coil (D-B80)	MagVenture A/S, Farum, Denmark
Stimulator no2 and coil no2 were used in the video session
Magnetic stimulator #3	Magstim Company Ltd., Whitland, UK		Used to stimulate at the cervicomedullary junction
Coil #3: double-cone magnetic coil	Magstim Company Ltd., Whitland, UK		Used to stimulate at the cervicomedullary junction
Image-guided TMS navigational system #1	Brainsight 2, Rouge Research, Montreal, Canada		Used in the original publication (Taube et al. 2014; Cerebral Cortex) to monitor coil position throughout the experiment
Image-guided TMS navigational system #2	TMS Navigator SW-Version 2.0, LOCALITE GmbH, Sankt Augustin, Germany	Used for the video session
Literature:
Taube et al. 2014	Taube, W., Leukel, C., Nielsen, J. B. & Lundbye-Jensen, J. Repetitive Activation of the Corticospinal Pathway by Means of rTMS may Reduce the Efficiency of Corticomotoneuronal Synapses. Cerebral cortex, doi:10.1093/cercor/bht359 (2014).