This work was supported by grants from the Deutsche Forschungsgemeinschaft (AF: 379-8/1; 379-10/1, 379-11/1 and by DFG-Exc-257, UL: 423/1-1), the Bundesministerium f&#252;r Bildung und Forschung (AF: FKZ0315673A and 01GY1144; AF and MM: 01EO0801), the German Academic Exchange Service (AF: DAAD-54391829), Go8 Australia - Germany Joint Research Cooperation Scheme (DC: 2011001430), the Else-Kr&#246;ner Fresenius Stiftung (AF: 2009-141; RL: 2011-119) and the Australian Research Council (DC: ARC FT100100976; MM: ARC FT120100608). We thank Kate Riggall for editorial assistance.

1. Contraindications and Special Considerations
<ol>
	<li>Thoroughly screen participants for MRI contraindications (e.g.&#160;pacemakers, claustrophobia, etc.)&#160; and exclude if necessary. Acquire standard questionnaires at clinical or research institutions that operate MRI scanners. Always obey standard safety procedures when entering the scanner room.</li>
	<li>Thoroughly screen participants for contraindications for tDCS. These may overlap with contraindications for MRI. See Villamar et al.<...

<ol>
	<li>Stagg, C. J., Nitsche, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physiological+basis+of+transcranial+direct+current+stimulation.">Physiological basis of transcranial direct current stimulation.</a> Neuroscientist. 17, 37-53 (2011).</li><li>Nitsche, M., Paulus, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sustained+excitability+elevations+induced+by+transcranial+DC+motor+cortex+stimulation+in+humans.">Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.</a> Neurology. 57, 1899-1901 (2001).</li><li>Fl&#246;el, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=tDCS-enhanced+motor+and+cognitive+function+in+neurological+diseases.">tDCS-enhanced motor and cognitive function in neurological diseases.</a> NeuroImage. 85, 934-947 (2014).</li><li>Brunoni, A. 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Neurophysiol. 117, 845-850 (2006).</li><li>Jacobson, L., Koslowsky, M., Lavidor, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=tDCS+polarity+effects+in+motor+and+cognitive+domains:+a+meta-analytical+review.">tDCS polarity effects in motor and cognitive domains: a meta-analytical review.</a> Exp. Brain Res. 216, 1-10 (2012).</li><li>Kuo, M. F., Nitsche, M. A. <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+transcranial+electrical+stimulation+on+cognition.">Effects of transcranial electrical stimulation on cognition.</a> Clin. 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U.S.A. 106, 1590-1595 (2009).</li><li>Meinzer, 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=Transcranial+direct+current+stimulation+over+multiple+days+improves+learning+and+maintenance+of+a+novel+vocabulary.">Transcranial direct current stimulation over multiple days improves learning and maintenance of a novel vocabulary.</a> Cortex. 50, 137-147 (2014).</li><li>Cohen Kadosh, R., Soskic, S., Iuculano, T., Kanai, R., Walsh, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulating+neuronal+activity+produces+specific+and+long-lasting+changes+in+numerical+competence.">Modulating neuronal activity produces specific and long-lasting changes in numerical competence.</a> Curr. Biol. 20, 2016-2020 (2010).</li><li>Crosson, B., 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=Functional+imaging+and+related+techniques:+an+introduction+for+rehabilitation+researchers.">Functional imaging and related techniques: an introduction for rehabilitation researchers.</a> J. Rehabil. Res. Dev. 47, (2010).</li><li>Schestatsky, P., Morales-Quezada, L., Fregni, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simultaneous+EEG+monitoring+during+transcranial+direct+current+stimulation.">Simultaneous EEG monitoring during transcranial direct current stimulation.</a> J. Vis. Exp. (10), (2013).</li><li>Zheng, X., Alsop, D. C., Schlaug, G. <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+transcranial+direct+current+stimulation+(tDCS)+on+human+regional+cerebral+blood+flow.">Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow.</a> NeuroImage. 58, 26-33 (2011).</li><li>Meinzer, M., Lindenberg, R., Antonenko, D., Flaisch, T., Fl&#246;el, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anodal+transcranial+direct+current+stimulation+temporarily+reverses+age-associated+cognitive+decline+and+functional+brain+activity+changes.">Anodal transcranial direct current stimulation temporarily reverses age-associated cognitive decline and functional brain activity changes.</a> J. Neurosci. 33, 12470-12478 (2013).</li><li>Meinzer, 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=Electrical+brain+stimulation+improves+cognitive+performance+by+modulating+functional+connectivity+and+task-specific+activation.">Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation.</a> J. Neurosci. 32, 1859-1866 (2012).</li><li>Lindenberg, R., Nachtigall, L., Meinzer, M., Sieg, M. M., Floel, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+dual+and+unihemispheric+motor+cortex+stimulation+in+older+adults.">Differential effects of dual and unihemispheric motor cortex stimulation in older adults.</a> J. Neurosci. 33, 9176-9183 (2013).</li><li>Holland, 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=Speech+facilitation+by+left+inferior+frontal+cortex+stimulation.">Speech facilitation by left inferior frontal cortex stimulation.</a> Curr. Biol. 21, 1403-1407 (2011).</li><li>Antal, A., Polania, R., Schmidt-Samoa, C., Dechent, P., Paulus, W. <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+over+the+primary+motor+cortex+during+fMRI.">Transcranial direct current stimulation over the primary motor cortex during fMRI.</a> NeuroImage. 55, 590-596 (2011).</li><li>Stagg, C. 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=Widespread+modulation+of+cerebral+perfusion+induced+during+and+after+transcranial+direct+current+stimulation+applied+to+the+left+dorsolateral+prefrontal+cortex.">Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex.</a> J. Neurosci. 33, 11425-11431 (2013).</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=Technique+and+considerations+in+the+use+of+4x1+ring+high-definition+transcranial+direct+current+stimulation+(HD-tDCS).">Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS).</a> J. Vis. Exp. (77), (2013).</li><li>DaSilva, A. F., Volz, M. S., Bikson, M., Fregni, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrode+positioning+and+montage+in+transcranial+direct+current+stimulation.">Electrode positioning and montage in transcranial direct current stimulation.</a> J. Vis. Exp. (51), (2011).</li><li>Turi, Z., Paulus, W., Antal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+neuroimaging+and+transcranial+electrical+stimulation.">Functional neuroimaging and transcranial electrical stimulation.</a> Clin. EEG Neurosci. 43, 200-208 (2012).</li><li>Saiote, C., Turi, Z., Paulus, W., Antal, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combining+functional+magnetic+resonance+imaging+with+transcranial+electrical+stimulation.">Combining functional magnetic resonance imaging with transcranial electrical stimulation.</a> Front. Hum. 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The combined application of tDCS with simultaneous fMRI has shown potential for elucidating the neural underpinnings of the immediate effects of the stimulation across the entire brain with high spatial resolution13-19. In the future, such studies may be complemented by combined EEG-tDCS studies, to exploit the superior temporal resolution of the latter technique. In addition, intrascanner stimulation allows verification of correct positioning of the electrodes on the scalp (e.g.&#160;using T-weighted...

Transcranial direct current stimulation (tDCS) is a noninvasive method of brain stimulation in which cortical functioning is modulated by means of a weak electrical current (typically 1-2 mA) projected between two scalp-affixed electrodes. Physiologically, tDCS induces a polarity-dependent shift in neuronal resting membrane potential (RMP) within the targeted cortical region through the manipulation of sodium and calcium channels, thereby promoting changes in cortical excitability1. Specifically, anodal stimulation (atDCS) has been shown to increase cortical activity via depolarization of neuronal RMP while cathodal stimulation (ctDCS) reduces cortical excitability2. Compared to other types of brain stimulation (e.g.&#160;transcranial magnetic stimulation) safety has been well established and thus far no serious side effects have been reported even in vulnerable populations3,4. Also, at least for lower stimulation intensities (up to 1 mA), an effective placebo (&#8220;sham&#8221;) stimulation condition exists5, allowing effective blinding of participants and investigators to the stimulation conditions, rendering tDCS an attractive tool in experimental and clinical research settings.
Numerous studies so far have shown that these changes in cortical excitability may result in behavioral modulations. In the motor system, consistent polarity dependent effects have been reported1,6 for both atDCS and ctDCS. In cognitive studies, the majority of studies that employed atDCS to enhance cognitive functions reported beneficial effects on performance7, while ctDCS frequently did not result in impaired cognitive processing. The latter may be explained by the greater redundancy of neural processing resources underlying cognition6. The majority of tDCS studies have employed cross-over designs to study the immediate effects of the stimulation, which outlast the termination of the current only for short periods of time1. However, it has been suggested that repeated stimulation impacts on protein synthesis, i.e.&#160;the neural mechanism underlying skill acquisition8. Indeed, motor or cognitive training success may be enhanced when combined with repeated tDCS sessions and long-term stability of these improvements have been reported to last up to several months in healthy adults8-10. Such findings have also sparked an interest in the use of tDCS in clinical contexts and preliminary data suggests that it may also be useful as a primary or adjunct treatment approach in various clinical populations3. However, while a relatively large number of studies addressed neurophysiological effects of tDCS in the motor system, little is known about the underlying neural mechanisms of tDCS effects on cognitive brain functions in health and disease. A better understanding of the mode of action of tDCS is a necessary prerequisite for more targeted applications of tDCS in research and clinical settings.
This issue can be addressed by combining tDCS with functional brain imaging techniques like electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). The majority of studies investigating the neural mechanisms underlying cognition and motor functions have chosen to employ fMRI11. In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions11. Moreover, when combined with concurrent application of tDCS, fMRI allows examination of the neural mechanisms underlying behavioral tDCS effects with higher spatial resolution across the entire brain compared to EEG (for recent descriptions of combined tDCS-EEG see Schestatsky et al.12). The present manuscript describes the combined use of tDCS during simultaneous fMRI. This novel technique has successfully been used to study the neural mechanisms underlying tDCS-induced modulations of motor and cognitive functions13-19. In the future, this combined protocol will yield new insights into the mechanisms of tDCS action in health and disease. Understanding the impact of tDCS on large-scale neural networks as assessed with this technique may lay the groundwork for more targeted application of tDCS in research and clinical settings.
The manuscript will focus on differences between behavioral tDCS experiments and the combined use of tDCS during simultaneous fMRI, with a specific emphasis on hardware requirements, implementation of the technique, and safety considerations. As an example, a single session of tDCS administered to the left inferior frontal gyrus (IFG) during task-absent resting-state (RS) fMRI and during a language task14,15 will be described, though many other applications are possible16,19. Details of the experimental design, participant characteristics and fMRI data analysis procedures have been described in detail in the original publications14,15 and are beyond the scope of the present manuscript. Moreover, in these studies, an additional fMRI scan that involved sham tDCS was acquired and compared to the results of the atDCS session (see &#34;Representative results&#34; for details). This session was identical to the one described in the present manuscript, except that the stimulation was discontinued prior to the start of the scanning session (see Figure 1 for details). The present procedure has been successfully implemented at a 3-Tesla Siemens Trio MRI scanner at the Berlin Centre for Advanced Imaging (Charit&#233; University Medicine, Berlin, Germany), and should in principle be applicable to other scanners as well13.

<table border="0" cellpadding="0" cellspacing="0" width="662">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">DC-Stimulator Plus</td>
			<td style="width:147px;">NeuroConn, Illmenau, Germany</td>
			<td align="right" style="width:133px;">21</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="126">
			<td height="126" style="height:126px;width:216px;">Hardware extension DC-Stimulator MR (2 MRI compatible rubber electrodes, electrode and box cable and inner filter box; outer filter box and stimulator cable)</td>
			<td style="width:147px;">NeuroConn, Illmenau, Germany</td>
			<td style="width:133px;"></td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">2 sponge pads for rubber electrodes (7x5 and 10x10 ccm)</td>
			<td style="width:147px;">NeuroConn, Illmenau, Germany</td>
			<td style="width:133px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Rubber head band</td>
			<td style="width:147px;"></td>
			<td style="width:133px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">NaCL solution</td>
			<td style="width:147px;"></td>
			<td style="width:133px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Measurement tape</td>
			<td style="width:147px;"></td>
			<td style="width:133px;"></td>
			<td>To determine electrode position using the EEG 10-20 system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pen</td>
			<td style="width:147px;"></td>
			<td style="width:133px;"></td>
			<td>Used during electrode positioning</td>
		</tr>
	</tbody>
</table>

transcranial direct current stimulation and simultaneous  functional magnetic resonance imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG).
In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site&#160;and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity.
Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Functional MRI is the most widely used functional imaging technique to address the underlying neural mechanisms of motor or cognitive functions. More recently, fMRI has also been used to evaluate tDCS effects on cortical activity and connectivity. However, most of these studies administered tDCS outside of the scanner and evaluated offline effects of the stimulation (i.e.&#160;administered tDCS prior to scanning22,23). Only a few studies so far have administered tDCS during simul...

Watch this Scientific Journal Video about Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging at JoVE.com

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS effects.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp ...

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