DaSilva AF received funding support from CTSA high-tech funding grant, University of Michigan to complete this review. Volz MS is funded by a grant scholarship from Stiftung Charit&eacute;.

<ol>
	<li>Fregni, F., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technology+insight:+noninvasive+brain+stimulation+in+neurology-perspectives+on+the+therapeutic+potential+of+rTMS+and+tDCS.">Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS.</a> Nat Clin Pract Neurol. 3 (7), 383-383 (2007).</li><li>Wagner, T., Valero-Cabre, A., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+human+brain+stimulation.">Noninvasive human brain stimulation.</a> Annu Rev Biomed Eng. 9, 527-527 (2007).</li><li>Fregni, F., Freedman, S., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+the+treatment+of+chronic+pain+with+non-invasive+brain+stimulation+techniques.">Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques.</a> Lancet Neurol. 6 (2), 188-188 (2007).</li><li>Lefaucheur, J. P., Antal, A., Ahdab, R., Ciampi de Andra, D., Fregni, F., Khedr, E. M., 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=The+use+of+repetitive+transcranial+magnetic+stimulation+(rTMS)+and+transcranial+direct+current+stimulation+(tDCS)+to+relieve+pain.">The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain.</a> Brain Stimul. 1 (4), 337-337 (2008).</li><li>Antal, A., 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+magnetic+and+direct+current+stimulation+in+the+therapy+of+pain.">Transcranial magnetic and direct current stimulation in the therapy of pain.</a> Schmerz Apr. 24 (2), 161-161 (2010).</li><li>Nitsche, M. A., 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=Excitability+changes+induced+in+the+human+motor+cortex+by+weak+transcranial+direct+current+stimulation.">Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.</a> J Physiol. 527 (Pt 3), 633-633 (2000).</li><li>Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., 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=Transcranial+direct+current+stimulation:+state+of+the+art.">Transcranial direct current stimulation: state of the art.</a> Brain Stimul. 11, 642-642 (2008).</li><li>Merrill, D. R., Bikson, M., Jefferys, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrical+stimulation+of+excitable+tissue:+design+of+efficacious+and+safe+protocols.">Electrical stimulation of excitable tissue: design of efficacious and safe protocols.</a> J Neurosci Methods. 141 (2), 171-171 (2005).</li><li>Boggio, P. S., Khoury, L. P., Martins, D. C., Martins, O. E., de Macedo, E. C., 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=Temporal+cortex+direct+current+stimulation+enhances+performance+on+a+visual+recognition+memory+task+in+Alzheimer+disease.">Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease.</a> J Neurol Neurosurg Psychiatry. 80 (4), 444-444 (2009).</li><li>Fregni, F., Boggio, P. S., Nitsche, M., Bermpohl, F., Antal, A., Feredoes, E., Marcolin, M. A., Rigonatti, S. P., Silva, M. T., Paulus, W., Pascual-Leone, 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+of+prefrontal+cortex+enhances+working+memory.">Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory.</a> Exp Brain Res. 166 (1), 23-23 (2005).</li><li>Dundas, J. E., Thickbroom, G. W., Mastaglia, F. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perception+of+comfort+during+transcranial+DC+stimulation:+effect+of+NaCl+solution+concentration+applied+to+sponge+electrodes.">Perception of comfort during transcranial DC stimulation: effect of NaCl solution concentration applied to sponge electrodes.</a> Clin Neurophysiol. 118 (5), 1166-1166 (2007).</li><li>Minhas, P., Datta, A., 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=Cutaneous+perception+during+tDCS:+Role+of+electrode+shape+and+sponge+salinity.">Cutaneous perception during tDCS: Role of electrode shape and sponge salinity.</a> Clin Neurophysiol. 11, (2010).</li><li>Antal, A., Terney, D., Poreisz, C., 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=Towards+unravelling+task-related+modulations+of+neuroplastic+changes+induced+in+the+human+motor+cortex.">Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex.</a> Eur J Neurosci. 26 (9), 2687-2687 (2007).</li><li>Datta, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gyri-precise+head+model+of+transcranial+direct+current+stimulation:+improved+spatial+focality+using+a+ring+electrode+versus+conventional+rectangular+pad.">Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad.</a> Brain Stimul. 2 (4), 201-201 (2009).</li><li>Minhas, P., Bansal, V., Patel, J., Ho, J. S., Diaz, J., Datta, A., 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=Electrodes+for+high-definition+transcutaneous+DC+stimulation+for+applications+in+drug+delivery+and+electrotherapy,+including+tDCS.">Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS.</a> J Neurosci Methods. 190 (2), (2010).</li><li>Brunoni, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Systematic+Review+on+Reporting+and+Assessment+of+Adverse+Effects+associated+with+Transcranial+Direct+Current+Stimulation.">A Systematic Review on Reporting and Assessment of Adverse Effects associated with Transcranial Direct Current Stimulation.</a> Int J Neuropsychopharmacol. , (2011).</li><li>Wagner, T. <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:+a+computer-based+human+model+study.">Transcranial direct current stimulation: a computer-based human model study.</a> Neuroimage. 35 (3), 1113-1113 (2007).</li><li>Nitsche, M. A., Doemkes, S., Karaköse, T., Antal, A., Liebetanz, D., Lang, N., Tergau, F., 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=Shaping+the+effects+of+transcranial+direct+current+stimulation+of+the+human+motor+cortex.">Shaping the effects of transcranial direct current stimulation of the human motor cortex.</a> J Neurophysiol. 97 (4), 3109-3109 (2007).</li><li>Wagner, T., Fregni, F., Fecteau, S., Grodzinsky, A., Zahn, M., Pascual-Leone, 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:+a+computer-based+human+model+study.">Transcranial direct current stimulation: a computer-based human model study.</a> Neuroimage. 35 (3), 1113-1113 (2007).</li><li>Boggio, P. S., Rigonatti, S. P., Ribeiro, R. B., Myczkowski, M. L., Nitsche, M. A., Pascual-Leone, A., 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=A+randomized,+double-blind+clinical+trial+on+the+efficacy+of+cortical+direct+current+stimulation+for+the+treatment+of+major+depression.">A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression.</a> Int J Neuropsychopharmacol. 11 (2), 249-249 (2008).</li><li>Williams, J. A., Pascual-Leone, A., 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=Interhemispheric+modulation+induced+by+cortical+stimulation+and+motor+training.">Interhemispheric modulation induced by cortical stimulation and motor training.</a> Phys Ther. 90 (3), 398-398 (2010).</li><li>Lang, N., Nitsche, M. A., Rothwel, J. C., Williams, J. A., Lemon, R. N. <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+over+the+human+motor+cortex+on+corticospinal+and+transcallosal+excitability.">Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability.</a> Exp Brain Res. 156 (4), 439-439 (2004).</li><li>Bikson, M., Datta, A., Rahman, A., Scaturro, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrode+montages+for+tDCS+and+weak+transcranial+electrical+stimulation:+role+of+"return"+electrode's+position+and+size.">Electrode montages for tDCS and weak transcranial electrical stimulation: role of "return" electrode's position and size.</a> Clin Neurophysiol. 121 (12), (1976).</li><li>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=Transcranial+direct+current+stimulation+in+patients+with+skull+defects+and+skull+plates:+high-resolution+computational+FEM+study+of+factors+altering+cortical+current+flow.">Transcranial direct current stimulation in patients with skull defects and skull plates: high-resolution computational FEM study of factors altering cortical current flow.</a> Neuroimage. 52 (4), 1268-1268 (2010).</li><li>Datta, A., Baker, J. M., Bikson, M., Fridriksson, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Individualized+model+predicts+brain+current+flow+during+transcranial+direct-current+stimulation+treatment+in+responsive+stroke+patient.">Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.</a> Brain Stimulation. , (2011).</li><li>Palm, U., Keeser, D., Schiller, C., Fintescu, Z., Nitsche, M., Reisinger, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Padberg+Skin+lesions+after+treatment+with+transcranial+direct+current+stimulation+(tDCS).">Padberg Skin lesions after treatment with transcranial direct current stimulation (tDCS).</a> Brain Stimul. 1 (4), 386-386 (2008).</li><li>Datta, A., Elwassif, M., 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=Bio-heat+transfer+model+of+transcranial+DC+stimulation:+comparison+of+conventional+pad+versus+ring+electrode.">Bio-heat transfer model of transcranial DC stimulation: comparison of conventional pad versus ring electrode.</a> Conf Proc IEEE Eng Med Biol Soc. , 670-670 (2009).</li><li>Miranda, P. C., Faria, P., Hallett, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=What+does+the+ratio+of+injected+current+to+electrode+area+tell+us+about+current+density+in+the+brain+during+tDCS?.">What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS?.</a> Clin Neurophysiol. 120 (6), 1183-1183 (2009).</li><li>Gandiga, P. C., Hummel, F. C., Cohen, L. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+DC+stimulation+(tDCS):+a+tool+for+double-blind+sham-controlled+clinical+studies+in+brain+stimulation.">Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation.</a> Clin Neurophysiol. 117 (4), 845-845 (2006).</li><li>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=Comparatively+weak+after-effects+of+transcranial+alternating+current+stimulation+(tACS)+on+cortical+excitability+in+humans.">Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans.</a> Brain Stimul. 1 (2), 97-97 (2008).</li><li>Terney, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increasing+human+brain+excitability+by+transcranial+high-frequency+random+noise+stimulation.">Increasing human brain excitability by transcranial high-frequency random noise stimulation.</a> J Neurosci Methods. 28 (52), 14147-14147 (2008).</li><li>Fregni, F., Boggio, P. S., Mansur, C. G., Wagner, T., Ferreira, M. J., Lima, M. C., Rigonatti, S. P., Marcolin, M. A., Freedman, S. D., Nitsche, M. A., Pascual-Leone, 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+of+the+unaffected+hemisphere+in+stroke+patients.">Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.</a> Neuroreport. 16 (14), 1551-1551 (2005).</li><li>Antal, A., Terney, D., K hnl, S., 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=Anodal+transcranial+direct+current+stimulation+of+the+motor+cortex+ameliorates+chronic+pain+and+reduces+short+intracortical+inhibition.">Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition.</a> J Pain Symptom Manage. 39 (5), (2010).</li><li>Fregni, F., Gimenes, R., Valle, A. C., Ferreira, M. J., Rocha, R. R., Natalle, L., Bravo, R., Rigonatti, S. P., Freedman, S. D., Nitsche, M. A., Pascual-Leone, A., Boggio, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomized,+sham-controlled,+proof+of+principle+study+of+transcranial+direct+current+stimulation+for+the+treatment+of+pain+in+fibromyalgia.">A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.</a> Arthritis Rheum. 54 (12), (2006).</li><li>Boggio, P. S., Zaghi, S., Lopes, 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=Modulatory+effects+of+anodal+transcranial+direct+current+stimulation+on+perception+and+pain+thresholds+in+healthy+volunteers.">Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers.</a> Eur J Neurol. 15 (10), 1124-1124 (2008).</li><li>Fregni, F., Liguori, P., Fecteau, S., Nitsche, M. A., Pascual-Leone, A., Boggio, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+stimulation+of+the+prefrontal+cortex+with+transcranial+direct+current+stimulation+reduces+cue-provoked+smoking+craving:+a+randomized,+sham-controlled+study.">Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study.</a> J Clin Psychiatry. 69 (1), 32-32 (2006).</li></ol>

The City University of New York holds patents on brain stimulation, on which Marom Bikson is an inventor. Marom Bikson is a co-founder of Soterix Medical Inc.

Critical Steps:
Aspects to be checked prior to starting procedure:
<ul>
<li>First of all, patients should be screened for whether there are any contraindications for tDCS - these contraindications may be application specific. This includes questions such as presence of severe or frequent headache, chronic skin disorder, or adverse reactions to a previous tDCS treatment. If he or she has any metal in the head or had a serious brain injury, the anatomical changes may modify current flow23,24. History of seizure, pregnancy and history of a stroke are usually not strict contraindications - and indeed, might be inclusion criteria in some clinical trials.</li> 
<li>Check for any lesions on the scalp- additionally subjects should be specifically interviewed and inspected for the existence of skin diseases. If there are any lesions, tDCS procedure should be avoided or, if appropriate, ensured that stimulation will not be conducted directly over or across the lesion. Stimulation of a different site can be considered. It is reported that repeated daily tDCS causes clinically significant skin irritation under the electrodes in some patients7. There is evidence of tDCS induced lesions according to skin integrity. For instance, it has been shown extensive redness and brown crusty intracutaneous changes with irregular round shapes due to tDC stimulation at an intensity of 2 mA for a period of 2 weeks including five sessions each week25. If tDCS is strongly indicated or has to be conducted, it is possible to take into consideration to stimulate with a lower intensity such as 0.5- 1.0 mA, but it is not guaranteed that this will prevent skin irritations or lesions. Thus, the condition of the skin under the electrodes should be inspected before and after tDCS7.</li>
<li>Check connectors of cables for electrolysis. Use another pair if evident. It is recommended to check the cables after approximately two months of use.</li>
</ul>
During both- active or sham- tDCS always ask whether subject still feels comfortable and is able to continue procedure.
Possible modifications:
<ul>
<li>There are many varieties of electrode positioning7 (Table 2).</li>
<li>There are many varieties of electrode sizes26 (Figure 7). For a given applied current, electrode size influences the current density18 and influences the focality of brain modulation (Figure 8). Clinical studies have suggest the smaller the size of the electrode the larger the current density26, however modelling studies suggest that the relationship between electrode size and area of brain modulation may be more complex27. Furthermore, the effects of small electrodes can differ qualitatively due to differential shunting of current in the scalp, and greater edge effect relative to the overall electrode area7. There were drastically superior levels of shunting for small electrode sizes reported than for the larger electrode schemes19.</li> 
<li>High-Definition tDCS (HD-tDCS) is a technology that improves spatial focality but requires special hardware and procedural controls15.</li> 
<li>The electrode montage (electrode position and size) along with the applied current determine the generated electrical field strength in the brain which, in turn, determines the efficacy of tDCS. The use of just electrode current density, defined by the ratio between the current strength and the electrode size, has been proposed to normalize clinical outcomes &#x2013; but modelling studies suggest this may only apply over a limited range and that overall electrode montage design determines outcome. Generally, increasing current intensity (or current density) for any given montage result in stronger effects. It is important to note that the current density at the skin surface is much higher than that in the brain19 (Figure 9).</li>
<li>The position of the "return" ("reference") electrode may influence the overall current flow pattern through the brain, and thus even influence brain modulation under the active electrodes22. Thus the potion of both electrodes should be considered.</li>
<li>The duration of the stimulation depends on the aim of the experimental approach. An increase of duration of the stimulation is associated with the occurrence and a longer duration of after-effects3,4. However at least one study reported a reversal of effects directions when stimulation duration was increased, suggesting that more intensity does not necessarily translate into a more robust clinical outcome. Though tDCS within published parameters is considered safe and well tolerated, the potential for undesired side-effects increases with increasing intensity (time, duration, or repetition rate/number).</li>
<li>Orientation of the electric field: defined by the electrodes positions and polarity. Cathodal stimulation typically decreases cortical excitability, whereas anodal stimulation typically increases the cortical excitability2,3.</li> 
<li>Placebo: For sham-tDCS the same protocol above is used. However, the current will be applied for 30 seconds. This is one of the advantages of tDCS compared to other non-invasive brain stimulation methods. Since the arising sensations resulted from active-tDCS tend to occur only at early stages of application, this sham method makes it difficult for the patient to distinguish the placebo from active tDCS application. This initial and brief stimulation is a reliable method of placebo28.</li>
<li>Note that the technique can also be applied when using other transcranial electric therapies such as tACS29 or tRNS30.</li> 
</ul>
Rationale for using tDCS in chronic pain:
The fact that multiple therapeutic pharmacological modalities provide only modest relief for chronic pain patients raises the possibility that the cause for the persistence of this debilitating disorder may lie within plastic changes in pain related neural networks. Interestingly, modulation of cortical activity can be achieved non-invasively by tDCS, as described earlier, which has been reported to produce lasting therapeutic effects in chronic pain due to changes in cortical plasticity.
Clinical effect of tDCS in chronic pain:
It has been shown that tDCS applied to the motor cortex changes the local cortical excitability (Figure 6)6. More precisely, anodal stimulation results in an increase of neuronal excitability, whereas cathodal stimulation has opposite results6. Indeed, anodal tDCS application over M1 leads to a greater improvement in visual analogue scale (VAS) pain ratings than sham tDCS. This therapeutic effect on pain following M1 stimulation, although transient, was reproduced in several groups of patients with neuropathic pain syndromes like trigeminal neuralgia, poststroke pain syndrome31, back pain and fibromyalgia32. Interestingly, clinical trials in neuropathic pain, due to spinal cord injury, stimulation of the motor cortex by tDCS showed pain improvement and cumulative analgesic effect that lasted two weeks after the stimulation. There is also evidence of its analgesic effect in fibromyalgia patients33 that is still significant after three weeks of follow-up for anodal tDCS of the M1 compared with sham stimulation, and as well as stimulation of the DLPFC33. Although the effects of anodal tDCS over DLFPC for pain improvement have not been explored extensively, it was shown it can be used to modulate pain thresholds in healthy subjects34. Nevertheless, stimulation of this brain area is a reliable technique for enhancing working memory 10, increasing performance on memory tasks in Alzheimer disease9 and reducing cue-provoked smoking craving significantly35 for instance; therefore it is also conceivable that this might be a useful strategy to modulate affective-emotional cognitive networks associated with pain processing in patients with chronic pain.

electrode positioning and montage in transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a non-invasive and safe alternative to change cortical excitability2. The effects of one session of tDCS can last for several minutes, and its effects depend on polarity of stimulation, such as that cathodal stimulation induces a decrease in cortical excitability, and anodal stimulation induces an increase in cortical excitability that may last beyond the duration of stimulation6. These effects have been explored in cognitive neuroscience and also clinically in a variety of neuropsychiatric disorders &#x2013; especially when applied over several consecutive sessions4. One area that has been attracting attention of neuroscientists and clinicians is the use of tDCS for modulation of pain-related neural networks3,5. Modulation of two main cortical areas in pain research has been explored: primary motor cortex and dorsolateral prefrontal cortex7. Due to the critical role of electrode montage, in this article, we show different alternatives for electrode placement for tDCS clinical trials on pain; discussing advantages and disadvantages of each method of stimulation.

Watch this Scientific Journal Video about Electrode Positioning and Montage in Transcranial Direct Current Stimulation at JoVE.com

Electrode Positioning and Montage in Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is an established technique to modulate cortical excitability1,2. It has been used as an investigative tool in neuroscience due to its effects on cortical plasticity, easy operation, and safe profile. One area that tDCS has been showing encouraging results is pain alleviation 3-5.

Transcranial direct current stimulation (tDCS) is a technique that has been intensively investigated in the past decade as this method offers a ...

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Neuroscience

262.0K Views.  University of Michigan. Stimolazione transcranica in corrente continua (tDCS) è una tecnica per modulare l'eccitabilità corticale 1,2. E 'stato utilizzato come strumento di indagine nel campo delle neuroscienze grazie ai suoi effetti sulla plasticità corticale, facilità d'uso, e profilo di sicurezza. Un settore che tDCS ha mostrato risultati incoraggianti è alleviare il dolore 3-5.

Video: Electrode Positioning and Montage in Transcranial Direct Current Stimulation

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels.

Studies have shown that cathodal transcranial direct-current stimulation can produce suppressive effects on drug-resistant seizures. In this study, an in vitro experimental setup was devised in which the direct-current stimulation and multielectrode array recording of seizure-like activity were evaluated in mice brain slice preparation. The direct-current stimulation parameters were evaluated.

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while maintaining clinical standards. The current consensus regarding the efficacy of tDCS is that multiple treatment sessions are needed to observe targeted behavioral reductions in symptom burden. However, the requirement for patients to travel to clinic daily for stimulation sessions presents a major obstacle for potential participants, due to work or family obligations or limited ability to travel. This study presents a protocol that directly overcomes these obstacles by eliminating the need to travel to clinic for daily sessions.
This is an updated protocol for remotely supervised self-administration of tDCS for daily treatment sessions paired with a program of computer-based cognitive training for use in clinical trials. Participants only need to attend clinic twice, for a baseline and study-end visit. At baseline, participants are trained and provided with a study stimulation device, and a small laptop computer. Participants then complete the remainder of their stimulation sessions at home while they are monitored via videoconferencing software.
Participants complete computerized cognitive remediation during stimulation sessions, which may serve a therapeutic role or as a &#34;placeholder&#34; for other computer-based activity. Computers are enabled for real-time monitoring and remote control by study staff.
Outcome measures that assess feasibility and tolerance are administered remotely with the aid of visual analogue scales that are presented onscreen. Following completion of all RS-tDCS sessions, participants return to clinic for a study end visit in which all study equipment is returned.
Results support the safety, feasibility, and scalability of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS-tDCS sessions have been completed. This protocol serves as a model for use in future clinical trials involving tDCS.

This manuscript provides an updated remote supervision protocol that enables participation in transcranial direct current stimulation (tDCS) clinical trials while receiving treatment sessions from home. The protocol has been successfully piloted in both patients with multiple sclerosis and Parkinson&#39;s disease.

The remotely supervised tDCS (RS-tDCS) protocol enables participation from home through guided and monitored self-administration of tDCS treatment while ...

Transcranial Electrical Brain Stimulation in Alert Rodents

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

Transcranial Direct Current Stimulation (tDCS) in Mice

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for several neuropsychiatric diseases. The biological effects of tDCS are not fully understood, which is in part explained due to the difficulty in obtaining human brain tissue. This protocol describes a tDCS mouse model that uses a chronically implanted electrode allowing the study of the long-lasting biological effects of tDCS. In this experimental model, tDCS changes the cortical gene expression and offers a prominent contribution to the understanding of the rationale for its therapeutic use.

Transcranial Direct Current Stimulation tDCS in Mice

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for ...

Stimulation Location Determination using a 3D Digitizer with High-Definition Transcranial Direct Current Stimulation

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, causal evidence of brain area activation leading to a behavior is often left missing. Transcranial direct current stimulation (tDCS), which can temporarily alter brain cortical excitability and activity, is a noninvasive neurophysiological tool used to study causal relationships in the human brain. High-definition transcranial direct current stimulation (HD-tDCS) is a noninvasive brain stimulation (NIBS) technique that produces a more focal current compared to conventional tDCS. Traditionally, the stimulation location has been roughly determined through the 10-20 EEG system, because determining precise stimulation points can be difficult. This protocol uses a 3D digitizer with HD-tDCS to increase accuracy in determination of stimulation points. The method is demonstrated using a 3D digitizer for more accurate localization of stimulation points in the right temporo-parietal junction (rTPJ).

Presented here is a protocol to achieve higher accuracy in determination of stimulation location combining a 3D digitizer with high-definition transcranial direct current stimulation.

The abundance of neuroimaging data and rapid development of machine learning has made it possible to investigate brain activation patterns. However, ...

In Vivo Intracellular Recording of Type-Identified Rat Spinal Motoneurons During Trans-Spinal Direct Current Stimulation

Intracellular recording of spinal motoneurons in vivo provides a &#8220;gold standard&#8221; for determining the cells&#8217; electrophysiological characteristics in the intact spinal network and holds significant advantages relative to classical in vitro or extracellular recording techniques. An advantage of in vivo intracellular recordings is that this method can be performed on adult animals with a fully mature nervous system, and therefore many observed physiological mechanisms can be translated to practical applications. In this methodological paper, we describe this procedure combined with externally applied constant current stimulation, which mimics polarization processes occurring within spinal neuronal networks. Trans-spinal direct current stimulation (tsDCS) is an innovative method increasingly used as a neuromodulatory intervention in rehabilitation after various neurological injuries as well as in sports. The influence of tsDCS on the nervous system remains poorly understood and the physiological mechanisms behind its actions are largely unknown. The application of the tsDCS simultaneously with intracellular recordings enables us to directly observe changes of motoneuron membrane properties and characteristics of rhythmic firing in response to the polarization of the spinal neuronal network, which is crucial for the understanding of tsDCS actions. Moreover, when the presented protocol includes the identification of the motoneuron with respect to an innervated muscle and its function (flexor versus extensor) as well as the physiological type (fast versus slow) it provides an opportunity to selectively investigate the influence of tsDCS on identified components of spinal circuitry, which seem to be differently affected by polarization. The presented procedure focuses on surgical preparation for intracellular recordings and stimulation with an emphasis on the steps which are necessary to achieve preparation stability and reproducibility of results. The details of the methodology of the anodal or cathodal tsDCS application are discussed while paying attention to practical and safety issues.

This protocol describes in vivo intracellular recording of rat lumbar motoneurons with simultaneous trans-spinal direct current stimulation. The method enables us to measure membrane properties and to record rhythmic firing of motoneurons before, during and after anodal or cathodal polarization of the spinal cord.