Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Summary

We demonstrate protocols for the modulation (tDCS, HD-tDCS) and mapping (robotic TMS) of the motor cortex in children.

Abstract

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries unique challenges in children. Similarly, transcranial direct current stimulation (tDCS) can improve motor learning in adults but has only recently been applied to children. The use of tDCS and emerging techniques like high–definition tDCS (HD-tDCS) require special methodological considerations in the developing brain. Robotic TMS motor mapping may confer unique advantages for mapping, particularly in the developing brain. Here, we aim to provide a practical, standardized approach for two integrated methods capable of simultaneously exploring motor cortex modulation and motor maps in children. First, we describe a protocol for robotic TMS motor mapping. Individualized, MRI-navigated 12x12 grids centered on the motor cortex guide a robot to administer single-pulse TMS. Mean motor evoked potential (MEP) amplitudes per grid point are used to generate 3D motor maps of individual hand muscles with outcomes including map area, volume, and center of gravity. Tools to measure safety and tolerability of both methods are also included. Second, we describe the application of both tDCS and HD-tDCS to modulate the motor cortex and motor learning. An experimental training paradigm and sample results are described. These methods will advance the application of non-invasive brain stimulation in children.

Introduction

Non-invasive brain stimulation can both measure and modulate human brain function^1,2. The most common target has been the motor cortex, due in part to an immediate and measurable biological output (motor evoked potentials) but also the high prevalence of neurological diseases resulting in motor system dysfunction and disability. This large global burden of disease includes a high proportion of conditions affecting children such as cerebral palsy, the leading cause of lifelong disability affecting some 17 million persons worldwide³. Despite this clinical relevance and the diverse and inc....

Protocol

All the methods described in this protocol have been approved by Conjoint Health Research Ethics Board, University of Calgary (REB16-2474). The protocol is described in Figure 1.

1. Non-invasive brain stimulation contraindications

1. Screen all participants for contraindications for TMS¹⁵ and tDCS¹ prior to recruitment.

2. Transcranial magnetic stimulation motor mapping

1. Preparing MRI for navigated TMS
   1. Obtain each participant’s structural MRI (T1). If an MRI is unobtainable, use a template MRI from Mo....

Results

Using the methods presented here, we completed a randomized, sham-controlled interventional trial⁸. Right-handed children (n = 24, ages 12-18) with no contraindications for both types of non-invasive brain stimulation were recruited. Participants were specifically excluded in this study if on neuropsychotropic medication or if they were not naïve to tDCS. There were no dropouts.

Robotic TMS motor maps wer.......

Discussion

TMS has also been explored in clinical pediatric populations, including perinatal stroke²² and cerebral palsy, where TMS motor maps were successfully created in children with cerebral palsy to explore mechanisms of interventional plasticity. Using an established protocol⁸, TMS motor maps were successfully collected in typically developing children, and are currently being collected in an ongoing multicenter clinical trial for children with perinatal stroke and hemiplegic ce.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
1x1 SMARTscan Stimulator	Soterix Medical Inc.	https://soterixmedical.com/research/1x1/tdcs/device
4x1 HD-tDCS Adaptor	Soterix Medical Inc.	https://soterixmedical.com/research/hd-tdcs/4x1
Brainsight Neuronavigation	Roge Resolution	https://www.rogue-resolutions.com/catalogue/neuro-navigation/brainsight-tms-navigation/
Carbon Rubber Electrode	Soterix Medical Inc.	https://soterixmedical.com/research/1x1/accessories/carbon-ruber-electrode
EASYpad Electrode	Soterix Medical Inc.	https://soterixmedical.com/research/1x1/accessories/1x1-easypad
EASYstraps	Soterix Medical Inc.	https://soterixmedical.com/research/1x1/accessories/1x1-easystrap
EMG Amplifier	Bortec Biomedical	http://www.bortec.ca/pages/amt_16.htm
HD1 Electrode Holder	Soterix Medical Inc.	https://soterixmedical.com/research/hd-tdcs/accessories/hd1-holder	Standard Base HD-Electrode Holder for High Definition tES (HD-tES)
HD-Electrode	Soterix Medical Inc.	https://soterixmedical.com/research/hd-tdcs/accessories/hd-electrode	Sintered ring HD-Electrode.
HD-Gel	Soterix Medical Inc.	https://soterixmedical.com/research/hd-tdcs/accessories/hd-gel	HD-GEL for High Definition tES (HD-tES)
Micro 1401 Data Acquisition System	Cambridge Electronics http://ced.co.uk/products/mic3in
Purdue Pegboard	Lafayette Instrument Company
Saline solution	Baxter	http://www.baxter.ca/en/products-expertise/iv-solutions-premixed-drugs/products/iv-solutions.page
Soterix Medical HD-Cap	Soterix Medical Inc.	https://soterixmedical.com/research/hd-tdcs/accessories/hd-cap
TMS Robot	Axilium Robotics	http://www.axilumrobotics.com/en/
TMS Stimulator and Coil	Magstim Inc	https://www.magstim.com/neuromodulation/