Name: non-invasive modulation and robotic mapping of motor cortex in the developing brain
Uploaded: 2019-07-01T12:30:00
Description: Watch this Scientific Journal Video about Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain at JoVE.com

This study was supported by the Canadian Institutes of Health Research.

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
<ol>
	<li>Screen all participants for contraindications for TMS15 and tDCS1 prior to recruitment.</li>
</ol>
2. Transcranial magnetic stimulation motor mapping
<ol>
	<li>Preparing...

<ol>
	<li>Woods, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+technical+guide+to+tDCS,+and+related+non-invasive+brain+stimulation+tools.">A technical guide to tDCS, and related non-invasive brain stimulation tools.</a> Clinical Neurophysiology. 127 (2), 1031-1048 (2016).</li><li>Nitsche, M. 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B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+adaptive+plasticity+in+recovery+of+function+after+damage+to+motor+cortex.">Role of adaptive plasticity in recovery of function after damage to motor cortex.</a> Muscle &amp; Nerve. 24 (8), 1000-1019 (2001).</li><li>Grab, J. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robotic+TMS+mapping+of+motor+cortex+in+the+developing+brain.">Robotic TMS mapping of motor cortex in the developing brain.</a> Journal of Neuroscience Methods. , (2018).</li><li>Bikson, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+of+Transcranial+Direct+Current+Stimulation:+Evidence+Based+Update+2016.">Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.</a> Brain Stimulation. 9 (5), 641-661 (2016).</li><li>Kessler, S. K., Minhas, P., Woods, A. J., Rosen, A., Gorman, C., Bikson, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dosage+considerations+for+transcranial+direct+current+stimulation+in+children:+a+computational+modeling+study.">Dosage considerations for transcranial direct current stimulation in children: a computational modeling study.</a> PloS One. 8 (9), e76112 (2013).</li><li>Ciechanski, P., Carlson, H. L., Yu, S. S., Kirton, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modeling+Transcranial+Direct-Current+Stimulation-Induced+Electric+Fields+in+Children+and+Adults.">Modeling Transcranial Direct-Current Stimulation-Induced Electric Fields in Children and Adults.</a> Frontiers in Human Neuroscience. 12, 268 (2018).</li><li>Ciechanski, P., Kirton, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+Direct-Current+Stimulation+(tDCS):+Principles+and+Emerging+Applications+in+Children.">Transcranial Direct-Current Stimulation (tDCS): Principles and Emerging Applications in Children.</a> Pediatric Brain Stimulation: Mapping and Modulating the Developing Brain. , 475 (2016).</li><li>Kirton, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+direct+current+stimulation+for+children+with+perinatal+stroke+and+hemiparesis.">Transcranial direct current stimulation for children with perinatal stroke and hemiparesis.</a> Neurology. 88 (3), 259-267 (2017).</li><li>Cole, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+High-Definition+and+Conventional+Transcranial+Direct-Current+Stimulation+on+Motor+Learning+in+Children.">Effects of High-Definition and Conventional Transcranial Direct-Current Stimulation on Motor Learning in Children.</a> Front Neurosci. , (2018).</li><li>Rossi, S., Hallett, M., Rossini, P. 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J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+pilot+study+investigating+the+effects+of+fast+left+prefrontal+rTMS+on+chronic+neuropathic+pain.">A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain.</a> Pain Medicine (Malden, Mass.). 10 (5), 840-849 (2009).</li><li>Villamar, M. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Focal+modulation+of+the+primary+motor+cortex+in+fibromyalgia+using+4&#215;1-ring+high-definition+transcranial+direct+current+stimulation+(HD-tDCS):+immediate+and+delayed+analgesic+effects+of+cathodal+and+anodal+stimulation.">Focal modulation of the primary motor cortex in fibromyalgia using 4&#215;1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation.</a> The Journal of Pain. 14 (4), 371-383 (2013).</li><li>Ciechanski, P., Kirton, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+Direct-Current+Stimulation+Can+Enhance+Motor+Learning+in+Children.">Transcranial Direct-Current Stimulation Can Enhance Motor Learning in Children.</a> Cerebral Cortex. 27 (5), 2758-2767 (2017).</li><li>Kirton, A., Andersen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+stimulation+and+constraint+for+hemiparesis+after+perinatal+stroke:+The+PLASTIC+CHAMPS+trial.">Brain stimulation and constraint for hemiparesis after perinatal stroke: The PLASTIC CHAMPS trial.</a> European Journal of Paediatric Neurology. 19 (S1), S10 (2015).</li><li>Ginhoux, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+custom+robot+for+Transcranial+Magnetic+Stimulation:+First+assessment+on+healthy+subjects.">A custom robot for Transcranial Magnetic Stimulation: First assessment on healthy subjects.</a> 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). , 5352-5355 (2013).</li><li>Grau, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conscious+brain-to-brain+communication+in+humans+using+non-invasive+technologies.">Conscious brain-to-brain communication in humans using non-invasive technologies.</a> PloS One. 9 (8), e105225 (2014).</li><li>Julkunen, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methods+for+estimating+cortical+motor+representation+size+and+location+in+navigated+transcranial+magnetic+stimulation.">Methods for estimating cortical motor representation size and location in navigated transcranial magnetic stimulation.</a> Journal of Neuroscience Methods. 232, 125-133 (2014).</li><li>van de Ruit, M., Perenboom, M. 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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...

Non-invasive brain stimulation can both measure and modulate human brain function1,2. 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 increasing capacities of neurostimulation technologies, applications in the developing brain are only beginning to be defined4. Improved characterization of existing and emerging non-invasive brain stimulation methods in children are required to advance applications in the developing brain.
Transcranial magnetic stimulation (TMS) is a well-established neurophysiological tool being increasingly used for its non-invasive, painless, well-tolerated and safety profile in adults. TMS experience in children is relatively limited but steadily increasing. TMS delivers magnetic fields to induce regional activation of cortical neuronal populations in the brain with net outputs reflected in target muscle motor evoked potentials (MEP). Systematic application of single pulse TMS can define maps of the motor cortex in vivo. Seminal animal studies5 and emerging human TMS studies6 have shown how motor maps may help inform mechanisms of cortical neuroplasticity. Navigated motor mapping is a TMS technique that is used to map out the human motor cortex to interrogate functional cortical regions. Changes in motor map have been associated with plastic changes of the human motor system7. Recent advancements in robotic TMS technology have brought new opportunities to improve motor mapping efficiency and accuracy. Our group has recently demonstrated that robotic TMS motor mapping is feasible, efficient, and well tolerated in children8.
Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that can shift cortical excitability and modulate human behaviors. There has been a multitude of studies examining the effect of tDCS in adults (&#62;10,000 subjects) but less than 2% of studies have focused on the developing brain9. Translation of adult evidence to pediatrics applications is complex, and modified protocols are needed due to complex differences in children. For example, we and others have shown that children experience larger and stronger electric fields compared to adults10,11. Standardization of tDCS methods in children is important to ensure safe and consistent application, improve replication, and advance the field. Experience of motor learning modulation tDCS in children is limited but increasing12. Translational applications of tDCS to specific cerebral palsy populations are advancing towards late phase clinical trials13. Efforts toward more focal stimulation applied through high-definition tDCS (HD-tDCS) has only just been studied for the first time in children14. We demonstrated that HD-tDCS produces similar improvements in motor learning as conventional tDCS in healthy children14. Describing HD-tDCS methods will allow for replication and further applications of such protocols in children.

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

non-invasive modulation and robotic mapping of motor cortex in the developing brain

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&#8211;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.

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 na&#239;ve to tDCS. There were no dropouts.
Robotic TMS motor map...

Watch this Scientific Journal Video about Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain at JoVE.com

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

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

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries ...

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