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Practical Guide to Transcranial Direct Current Stimulation pp 347–377Cite as

Methodological Considerations for Transcranial Direct Current Stimulation in Clinical Trials

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Abstract

While recent years have witnessed a steady rise in the number of studies exploring transcranial direct current stimulation (tDCS) as a potential therapy for disorders of the central nervous system, there are to date no FDA approved clinical indications for this form of noninvasive neuromodulation. Successful development of tDCS as an approved therapy in the US and elsewhere will require the implementation of well designed, appropriately powered clinical trials, which, in turn, requires careful consideration of a variety of methodological factors. The choice of study design (e.g. between-subjects, within-subjects) is one the most fundamental decisions in designing a clinical trial. This choice is often influenced by the specific symptoms and natural histories of the disorders being investigated. Disease-related symptoms and disability may influence the design and execution of tDCS trials in other ways, for instance interfering with the ability of patients to participate in studies that involve frequent stimulation sessions in a research setting, or complicating the ability of patients to provide informed consent. Common medical co-morbidities may also influence the efficacy of tDCS as a therapy, either negatively by interfering with the effectiveness of brain stimulation, or positively by providing new treatment targets. The parameters being used to deliver tDCS including stimulation intensity, frequency, and duration, as well as electrode size, number, and location, also play a critical but only partially understood role in tDCS studies. Finally, the use of robust control conditions is an important concern in all clinical trials, including those involving tDCS. This chapter will review these issues as they pertain to the design of tDCS clinical trials, and will conclude with recommendations for the standardization of methods for tDCS clinical trial reporting.

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References

  • Angelakis, E., Liouta, E., Andreadis, N., Korfias, S., Ktonas, P., Stranjalis, G., & Sakas, D. E. (2014). Transcranial direct current stimulation effects in disorders of consciousness. Archives of Physical Medicine and Rehabiliattion, 95(2), 283–289.

    Article  PubMed  Google Scholar 

  • Antal, A., Kincses, T. Z., Nitsche, M. A., Bartfai, O., & Paulus, W. (2004). Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: Direct electrophysiological evidence. Investigative Opthalmology & Visual Science, 45, 702–707.

    Article  Google Scholar 

  • Antal, A., Polania, R., Schmidt-Samoa, C., Dechent, P., & Paulus, W. (2011). Transcranial direct current stimulation over the primary motor cortex during fMRI. NeuroImage, 55(2), 590–596.

    Article  PubMed  Google Scholar 

  • Antal, A., Terney, D., Poreisz, C., & Paulus, W. (2007). Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex. European Journal of Neuroscience, 26(9), 2687–2691.

    Article  PubMed  Google Scholar 

  • Bang, D., & Bong, S. (2015). Effect of combination of transcranial direct current stimulation and feedback training on visuospatial neglect in patients with subacute stroke: A pilot randomized controlled trial. Journal of Physical Therapy Science, 27(9), 2759–2761.

    Article  PubMed  PubMed Central  Google Scholar 

  • Batsikadze, G., Moliadze, V., Paulus, W., Kuo, M.-F., & Nitsche, M. A. (2013). Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. Journal of Physiology, 591, 1987–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bikson, M., Datta, A., Rahman, A., & Scaturro, J. (2010). Electrode montages for tDCS and weak transcranial electrical stimulation: Role of “ return” electrode’s position and size. Clinical Neurophysiology, 121, 1976–1978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boggio, P. S., Ferrucci, R., Rigonatti, S. P., Covre, P., Nitsche, M., Pascual-Leone, A., & Fregni, F. (2006). Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. Journal of the Neurological Sciences, 249(1), 31–38.

    Article  PubMed  Google Scholar 

  • Borckardt, J. J., Bikson, M., Frohman, H., Reeves, S. T., Datta, A., Bansal, V., … George, M. S. (2012). A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception. Journal of Pain, 13, 112–120.

    Article  PubMed  Google Scholar 

  • Borckardt, J. J., Reeves, S. T., Robinson, S. M., May, J. T., Epperson, T. I., Gunselman, R. J., … George, M. S. (2013). Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA). The Clinical Journal of Pain, 29(11), 925–928.

    Article  PubMed  Google Scholar 

  • Bortoletto, M., Pellicciari, M. C., Rodella, C., & Miniussi, C. (2015). The interaction with task-induced activity is more important than polarization: A tDCS study. Brain Stimulation, 8(2), 269–276.

    Article  PubMed  Google Scholar 

  • Brunoni, A. R., Ferrucci, R., Bortolomasi, M., Scelzo, E., Boggio, P. S., Fregni, F., … Priori, A. (2012). Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the major depressive episode: Findings from a naturalistic study. European Psychiatry, 28(6), 356–361.

    Article  CAS  PubMed  Google Scholar 

  • Brunoni, A. R., Ferrucci, R., Bortolomasi, M., Vergari, M., Tadini, L., Boggio, P. S., … Priori, A. (2011). Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35, 96–101.

    Article  CAS  PubMed  Google Scholar 

  • Brunoni, A. R., & Fregni, F. (2011). Clinical trial design in non-invasive brain stimulation psychiatric research. International Journal of Methods in Psychiatric Research, 20(2), E19–E30.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brunoni, A. R., Valiengo, L., Baccaro, A., Zanão, T. A., Oliveira, J. F., Goulart, A., … Fregni, F. (2013). The sertraline vs electrical current therapy for treating depression clinical study: Results from a factorial, randomized, controlled trial. JAMA Psychiatry, 70(4), 383–391.

    Article  CAS  PubMed  Google Scholar 

  • Celnik, P., Paik, N., Vandermeeren, Y., Dimyan, M., & Cohen, L. G. (2009). Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke. Stroke, 40(5), 1764–1771.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cha, Y., Urbano, D., & Pariseau, N. (2016). Randomized single blind sham controlled trial of adjunctive home-based tDCS after rTMS for Mal De Debarquement syndrome: Safety, efficacy, and participant satisfaction assessment. Brain Stimulation, 9(4), 537–544.

    Article  PubMed  Google Scholar 

  • Chang, M. C., Kim, D. Y., & Park, D. H. (2015). Enhancement of cortical excitability and lower limb motor function in patients with stroke by transcranial direct current stimulation. Brain Stimulation, 8(3), 561–566.

    Article  PubMed  Google Scholar 

  • Charvet, L. E., Kasschau, M., Datta, A., Knotkova, H., Stevens, M. C., Alonzo, A., … Bikson, M. (2015). Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: Guidelines for technology and protocols. Frontiers in Systems Neuroscience, 9.

    Google Scholar 

  • Chow, S.-C., & Chang, M. (2008). Adaptive design methods in clinical trials – A review. Orphanet Journal of Rare Diseases, 3, 11.

    Google Scholar 

  • Clark, V. P., Coffman, B. A., Mayer, A. R., Weisend, M. P., Lane, T. D., Calhoun, V. D., … Wassermann, E. M. (2010). TDCS guided using fMRI significantly accelerates learning to identify concealed objects. NeuroImage, 59(1), 117–128.

    Article  PubMed  Google Scholar 

  • ClinicalTrials.gov. (2016). Retrieved July 14, 2016, from http://clinicaltrials.gov/

  • Cramer, S. C. (2008). Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery. Annals of Neurology, 63(3), 272–287.

    Article  PubMed  Google Scholar 

  • Cruciani, R. A., Esteban, S., Sibirceva, U., & Knotkova, H. (2009). Non-invasive brain stimulation therapy for the management of complex regional pain syndrome (CRPS). Journal of Pain Management, Special issue on “Brain stimulation for treatment of pain”, 2(3), 277–285.

    Google Scholar 

  • D’Urso, G., Mantovani, A., Micillo, M., Priori, A., & Muscettola, G. (2013). Transcranial direct current stimulation and cognitive-behavioral therapy: Evidence of a synergistic effect in treatment-resistant depression. Brain Stimulation, 6(3), 465–467.

    Article  PubMed  Google Scholar 

  • Dasilva, A. F., Volz, M. S., Bikson, M., & Fregni, F. (2011). Electrode positioning and montage in transcranial direct current stimulation. Journal of Visualized Experiments, 54.

    Google Scholar 

  • Datta, A., Bansal, V., Diaz, J., Patel, J., Reato, D., & Bikson, M. (2009). Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimulation, 2(4), 201–207.e1.

    Article  Google Scholar 

  • Di Lazzaro, V., Dileone, M., Capone, F., Pellegrino, G., Ranieri, F., Musumeci, G., … Fregni, F. (2014). Immediate and late modulation of interhemipheric imbalance with bilateral transcranial direct current stimulation in acute stroke. Brain Stimulation, 7(6), 841–848.

    Article  PubMed  Google Scholar 

  • Duncan, P., Studenski, S., Richards, L., Gollub, S., Lai, S. M., Reker, D., … Johnson, D. (2003). Randomized clinical trial of therapeutic exercise in subacute stroke. Stroke, 34(9), 2173–2180.

    Article  PubMed  Google Scholar 

  • Edwards, D., Cortes, M., Datta, A., Minhas, P., Wassermann, E. M., & Bikson, M. (2013). Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS. NeuroImage, 74, 266–275.

    Article  PubMed  Google Scholar 

  • Electronic Code of Federal Regulations. (2016). Retrieved July 15, 2016, from http://www.ecfr.gov/

  • Elsner, B., Kugler, J., Pohl, M., & Mehrholz, J. (2013). Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke. Cochrane Database of Systematic Reviews, 11.

    Google Scholar 

  • Faber, M., Vanneste, S., Fregni, F., & Ridder, D. D. (2012). Top down prefrontal affective modulation of tinnitus with multiple sessions of tDCS of dorsolateral prefrontal cortex. Brain Stimulation, 5(4), 492–498.

    Article  PubMed  Google Scholar 

  • Fagerlund, A. J., Hansen, O. A., & Aslaksen, P. M. (2015). Transcranial direct current stimulation as a treatment for patients with fibromyalgia. Pain, 156(1), 62–71.

    Article  PubMed  Google Scholar 

  • Ferrucci, R., Vergari, M., Cogiamanian, F., Bocci, T., Ciocca, M., Tomasini, E., … Priori, A. (2014). Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis. NeuroRehabilitation, 34, 121–127.

    Google Scholar 

  • Flöel, A. (2014). TDCS-enhanced motor and cognitive function in neurological diseases. NeuroImage, 85(3), 934–947.

    Article  PubMed  Google Scholar 

  • Fregni, F., Boggio, P. S., Nitsche, M. A., Rigonatti, S. P., & Pascual-Leone, A. (2006). Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression. Depression and Anxiety, 23(8), 482–484.

    Article  PubMed  Google Scholar 

  • Friedman, L. M., Furberg, C. D., & DeMets, D. L. (2014). Fundamentals of clinical trials (3rd ed.). Cham, Switzerland: Springer.

    Google Scholar 

  • Fusco, A., Assenza, F., Iosa, M., Izzo, S., Altavilla, R., Paolucci, S., & Vernieri, F. (2014). The ineffective role of cathodal tDCS in enhancing the functional motor outcomes in early phase of stroke rehabilitation: An experimental trial. BioMed Research International, 2014, 1–9.

    Article  Google Scholar 

  • Galeotti, F., Vanacore, N., Gainotti, S., Izzicupo, F., Menniti-Ippolito, F., Petrini, C., … Raschetti, R. (2012). How legislation on decisional capacity can negatively affect the feasibility of clinical trials in patients with dementia. Drugs Aging Drugs & Aging, 29(8), 607–614.

    Google Scholar 

  • Gartlehner, G., Hansen, R. A., & Nissman, D. (2006). Criteria for distinguishing effectiveness from efficacy trials in systematic reviews. Agency for Healthcare Research and Quality, 12, 1–17.

    Google Scholar 

  • Giampieri, M. (2012). Communication and informed consent in elderly people. Minerva Anestesiologica, 78(2), 236–242.

    Google Scholar 

  • Gill, J., Shah-Basak, P. P., & Hamilton, R. (2014). It’s the thought that counts: Examining the task-dependent effects of transcranial direct current stimulation on executive function. Brain Stimulation, 8, 253–259.

    Google Scholar 

  • Glaser, J., Reeves, S. T., Stoll, W. D., Epperson, T. I., Hilbert, M., Madan, A., … Borckardt, J. J. (2016). Motor/prefrontal transcranial direct current stimulation (tDCS) following lumbar surgery reduces postoperative analgesia use. Spine, 41(10), 835–839.

    Article  PubMed  Google Scholar 

  • Hankey, G. J., Spiesser, J., Hakimi, Z., Bego, G., Carita, P., & Gabriel, S. (2007). Rate, degree, and predictors of recovery from disability following ischemic stroke. Neurology, 68(19), 1583–1587.

    Article  CAS  PubMed  Google Scholar 

  • Hesse, S., Werner, C., Schonhardt, E. M., Bardeleben, A., Jenrich, W., & Kirker, S. B. (2007). Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: A pilot study. Restorative Neurology & Neuroscience, 25(1), 9–15.

    Article  PubMed  Google Scholar 

  • Ho, K., Taylor, J. L., Chew, T., Gálvez, V., Alonzo, A., Bai, S., … Loo, C. K. (2016). The effect of transcranial direct current stimulation (tDCS) electrode size and current intensity on motor cortical excitability: Evidence from single and repeated sessions. Brain Stimulation, 9(1), 1–7.

    Article  CAS  PubMed  Google Scholar 

  • Horn, S. D., Dejong, G., Smout, R. J., Gassaway, J., James, R., & Conroy, B. (2005). Stroke rehabilitation patients, practice, and outcomes: Is earlier and more aggressive therapy better? Archives of Physical Medicine and Rehabilitation, 86(12), 101–114.

    Article  Google Scholar 

  • Iacono, T., & Carling-Jenkins, R. (2012). The human rights context for ethical requirements for involving people with intellectual disability in medical research. Journal of Intellectual Disability Research, 56(11), 1122–1132.

    Article  CAS  PubMed  Google Scholar 

  • Iuculano, T., & Kadosh, R. C. (2013). The mental cost of cognitive enhancement. Journal of Neuroscience, 33(10), 4482–4486.

    Article  CAS  PubMed  Google Scholar 

  • Jones, K. T., Stephens, J. A., Alam, M., Bikson, M., & Berryhill, M. E. (2015). Longitudinal neurostimulation in older adults improves working memory. PLoS One, 10(4), e0121904.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jørgensen, H. S., Nakayama, H., Raaschou, H. O., & Olsen, T. S. (1999). Stroke: Neurologic and functional recovery. The Copenhagen stroke study. Physical Medicine and Rehabilitation Clinics of North America, 10(4), 887–906.

    Article  Google Scholar 

  • Jørgensen, H. S., Nakayama, H., Raaschou, H. O., Vive-Larsen, J., Støier, M., & Olsen, T. S. (1995). Outcome and time course of recovery in stroke. Part II: Time course of recovery. The Copenhagen stroke study. Archives of Physical Medicine and Rehabilitation, 76(5), 406–412.

    Article  PubMed  Google Scholar 

  • Kang, N., Summers, J. J., & Cauraugh, J. H. (2015). Transcranial direct current stimulation facilitates motor learning post-stroke: A systematic review and meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry, 87(4), 345–355.

    Article  Google Scholar 

  • Kasschau, M., Reisner, J., Sherman, K., Bikson, M., Datta, A., & Charvet, L. E. (2016). Transcranial direct current stimulation is feasible for remotely supervised home delivery in multiple sclerosis. Neuromodulation: Technology at the Neural Interface, 19, 824–831.

    Article  Google Scholar 

  • Kessler, S. K., Minhas, P., Woods, A. J., Rosen, A., Gorman, C., & Bikson, M. (2013). Dosage considerations for transcranial direct current stimulation in children: A computational modeling study. PLoS One, 8(9), e76112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kessler, S. K., Turkeltaub, P. E., Benson, J. G., & Hamilton, R. H. (2012). Differences in the experience of active and sham transcranial direct current stimulation. Brain Stimulation, 5(2), 155–162.

    Article  PubMed  Google Scholar 

  • Khedr, E. M., Shawky, O. A., El-Hammady, D. H., Rothwell, J. C., Darwish, E. S., Mostafa, O. M., & Tohamy, A. M. (2013, September 22). Effect of anodal versus cathodal transcranial direct current stimulation on stroke rehabilitation: A pilot randomized controlled trial. Neurorehabilitation and Neural Repair, 27(7), 592–601.

    Article  PubMed  Google Scholar 

  • Kim, D., Lim, J., Kang, E. K., You, D. S., Oh, M., Oh, B., & Paik, N. (2010). Effect of transcranial direct current stimulation on motor recovery in patients with subacute stroke. American Journal of Physical Medicine & Rehabilitation, 89(11), 879–886.

    Article  Google Scholar 

  • Knotkova, H., Homel, P., & Cruciani, R. A. (2009). Cathodal tDCS over the somatosensory cortex relieved chronic neuropathic pain in a patient with complex regional pain syndrome (CRPS/RSD). Journal of Pain Management, Special issue on “Brain stimulation for treatment of pain”, 2(3), 365–368.

    Google Scholar 

  • Knotkova, H., Malamud, S. C., & Cruciani, R. A. (2014). Transcranial direct current stimulation (TDCS) improved cognitive outcomes in a cancer survivor with chemotherapy-induced cognitive difficulties. Brain Stimulation, 7(5), 767–768.

    Article  PubMed  Google Scholar 

  • Knotkova, H., Riggs, A., Patel, V., Troung, D., Arce, D., Datta, A., & Bikson, M. (2016). Adjustment of headgear for easy use by chronically ill patients performing non-invasive neurostimulation at home. Poster. New York, NY: Metropolitan Jewish Health System Research Day.

    Google Scholar 

  • Knotkova, H., Rosedale, M., Strauss, S. M., Horne, J., Soto, E., Cruciani, R. A., … Malamud, D. (2012). Using transcranial direct current stimulation to treat depression in HIV-infected persons: The outcomes of a feasibility study. Frontiers in Psychiatry, 3.

    Google Scholar 

  • Kuo, H., Bikson, M., Datta, A., Minhas, P., Paulus, W., Kuo, M., & Nitsche, M. A. (2013). Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: A neurophysiological study. Brain Stimulation, 6(4), 644–648.

    Article  PubMed  Google Scholar 

  • Kutner, J. S., Blatchford, P. J., Taylor, D. H., Ritchie, C. S., Bull, J. H., Fairclough, D. L., … Abernethy, A. P. (2015). Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness. JAMA Internal Medicine, 175(5), 691–700.

    Article  PubMed  Google Scholar 

  • Kwon, Y. H., & Jang, S. H. (2011). The enhanced cortical activation induced by transcranial direct current stimulation during hand movements. Neuroscience Letters, 492(2), 105–108.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S., Walker, J. R., Jakul, L., & Sexton, K. (2004). Does elimination of placebo responders in a placebo run-in increase the treatment effect in randomized clinical trials? A meta-analytic evaluation. Depression and Anxiety, 19(1), 10–19.

    Article  PubMed  Google Scholar 

  • Lefebvre, S., Dricot, L., Laloux, P., Gradkowski, W., Desfontaines, P., Evrard, F., … Vandermeeren, Y. (2014). Neural substrates underlying stimulation-enhanced motor skill learning after stroke. Brain, 138(1), 149–163.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lefebvre, S., Laloux, P., Peeters, A., Desfontaines, P., Jamart, J., & Vandermeeren, Y. (2013). Dual-tDCS enhances online motor skill learning and long-term retention in chronic stroke patients. Frontiers in Human Neuroscience, 6.

    Google Scholar 

  • López-Alonso, V., Cheeran, B., Río-Rodríguez, D., & Fernández-Del-Olmo, M. (2014). Inter-individual variability in response to non-invasive brain stimulation paradigms. Brain Stimulation, 7(3), 372–380.

    Article  PubMed  Google Scholar 

  • Martin, D. M., Liu, R., Alonzo, A., Green, M., & Loo, C. K. (2014). Use of transcranial direct current stimulation (tDCS) to enhance cognitive training: Effect of timing of stimulation. Experimental Brain Research, 232(10), 3345–3351.

    Article  PubMed  Google Scholar 

  • Martin, D. M., Liu, R., Alonzo, A., Green, M., Player, M. J., Sachdev, P., & Loo, C. K. (2013). Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. The International Journal of Neuropsychopharmacology, 16(9), 1927–1936.

    Article  PubMed  Google Scholar 

  • Mattioli, F., Bellomi, F., Stampatori, C., Capra, R., & Miniussi, C. (2015, May 26). Neuroenhancement through cognitive training and anodal tDCS in multiple sclerosis. Multiple Sclerosis Journal, 22(2), 222–230.

    Article  PubMed  Google Scholar 

  • Meinzer, M., Darkow, R., Lindenberg, R., & Floel, A. (2016). Electrical stimulation of the motor cortex enhances treatment outcome in post-stroke aphasia. Brain, 139(4), 1152–1163.

    Article  PubMed  Google Scholar 

  • Meinzer, M., Lindenberg, R., Phan, M. T., Ulm, L., Volk, C., & Floel, A. (2015). Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms. Alzheimer’s & Dementia, 11(9), 1032–1040.

    Article  Google Scholar 

  • Mendonca, M. E., Simis, M., Grecco, L. C., Battistella, L. R., Baptista, A. F., & Fregni, F. (2016). Transcranial direct current stimulation combined with aerobic exercise to optimize analgesic responses in fibromyalgia: A randomized placebo-controlled clinical trial. Frontiers in Human Neuroscience, 10.

    Google Scholar 

  • Minhas, P., Bikson, M., Woods, A. J., Rosen, A. R., & Kessler, S. K. (2012). Transcranial direct current stimulation in pediatric brain: A computational modeling study. 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

    Google Scholar 

  • Mori, F., Codecà, C., Kusayanagi, H., Monteleone, F., Buttari, F., Fiore, S., … Centonze, D. (2010). Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. The Journal of Pain, 11(5), 436–442.

    Article  PubMed  Google Scholar 

  • New England Institutional Review Board. (2016). Retrieved August 15, 2016, from http://www.neirb.com/

  • Ng, M. F., Tong, R. K., & Li, L. S. (2008). A pilot study of randomized clinical controlled trial of gait training in subacute stroke patients with partial body-weight support electromechanical gait trainer and functional electrical stimulation: Six-month follow-up. Stroke, 39(1), 154–160.

    Article  PubMed  Google Scholar 

  • Nikolin, S., Loo, C. K., Bai, S., Dokos, S., & Martin, D. M. (2015). Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning. NeuroImage, 117, 11–19.

    Article  PubMed  Google Scholar 

  • Nikulina, V., Guarino, H., Acosta, M. C., Marsch, L. A., Syckes, C., Moore, S. K., … Rosenblum, A. (2016). Patient vs provider reports of aberrant medication-taking behavior among opioid-treated patients with chronic pain who report misusing opioid medication. Pain, 157(8), 1791–1798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., … Pascual-Leone, A. (2008). Transcranial direct current stimulation: State of the art 2008. Brain Stimulation, 1(3), 206–223.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., Fricke, K., Henschke, U., Schlitterlau, A., Liebetanz, D., Lang, N., … Paulus, W. (2003a). Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. Journal of Physiology, 553(1), 293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche, M. A., Kuo, M. F., Karrasch, R., Wachter, B., Liebetanz, D., & Paulus, W. (2009). Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biological Psychiatry, 66(5), 503–508.

    Article  CAS  PubMed  Google Scholar 

  • Nitsche, M. A., Liebetanz, D., Schlitterlau, A., Henschke, U., Fricke, K., Frommann, K., … Tergau, F. (2004). GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. European Journal of Neuroscience, 19(10), 2720–2726.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., Nitsche, M. S., Klein, C. C., Tergau, F., Rothwell, J. C., & Paulus, W. (2003). Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clinical Neurophysiology, 114(4), 600–604.

    Article  PubMed  Google Scholar 

  • Nitsche, M. A., & Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology, 527(3), 633–639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche, M. A., & Paulus, W. (2001). Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology, 57(10), 1899–1901.

    Article  CAS  PubMed  Google Scholar 

  • Oliveira, L. B., Lopes, T. S., Soares, C., Maluf, R., Goes, B. T., Sá, K. N., & Baptista, A. F. (2015, April 20). Transcranial direct current stimulation and exercises for treatment of chronic temporomandibular disorders: A blind randomised-controlled trial. Journal of Oral Rehabilitation, 42(10), 723–732.

    Article  CAS  PubMed  Google Scholar 

  • Palm, U., Schiller, C., Fintescu, Z., Obermeier, M., Keeser, D., Reisinger, E., … Padberg, F. (2012). Transcranial direct current stimulation in treatment resistant depression: A randomized double-blind, placebo-controlled study. Brain Stimulation, 5(3), 242–251.

    Article  CAS  PubMed  Google Scholar 

  • Palmer, B. W., Savla, G. N., Roesch, S. C., & Jeste, D. V. (2013, June 09). Changes in capacity to consent over time in patients involved in psychiatric research. The British Journal of Psychiatry, 202(6), 454–458.

    Article  Google Scholar 

  • Parazzini, M., Fiocchi, S., Liorni, I., & Ravazzani, P. (2015). Effect of the interindividual variability on computational modeling of transcranial direct current stimulation. Computational Intelligence and Neuroscience, 2015, 1–9.

    Article  Google Scholar 

  • Park, J., Hong, S. B., Kim, D., Suh, M., & Im, C. (2011). A novel array-type transcranial direct current stimulation (tDCS) system for accurate focusing on targeted brain areas. IEEE Transactions on Magnetics, 47(5), 882–885.

    Article  Google Scholar 

  • Park, S., Seo, J., Kim, Y., & Ko, M. (2014). Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults. Neuroreport, 25(2), 122–126.

    Article  PubMed  Google Scholar 

  • Reis, J., Fischer, J. T., Prichard, G., Weiller, C., Cohen, L. G., & Fritsch, B. (2015). Time- but not sleep-dependent consolidation of tDCS-enhanced visuomotor skills. Cerebral Cortex, 25(1), 109–117.

    Article  PubMed  PubMed Central  Google Scholar 

  • Reis, J., Schambra, H. M., Cohen, L. G., Buch, E. R., Fritsch, B., Zarahn, E., … Krakauer, J. W. (2009). Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proceedings of the National Academy of Sciences of the United States, 106(5), 1590–1595.

    Article  CAS  Google Scholar 

  • Richmond, L. L., Wolk, D., Chein, J., & Olson, I. R. (2014). Transcranial direct current stimulation enhances verbal working memory training performance over time and near transfer outcomes. Journal of Cognitive Neuroscience, 26(11), 2443–2454.

    Article  PubMed  Google Scholar 

  • Rosedale, M., Malaspina, D., Malamud, D., Strauss, S. M., Horne, J. D., Abouzied, S., … Knotkova, H. (2012). Developing patient-centered treatment protocols in brain stimulation: A rationale for combining quantitative and qualitative approaches in persons with HIV. Journal of the American Psychiatric Nurses Association, 18(3), 166–174.

    Article  PubMed  Google Scholar 

  • Rosenkranz, G. K. (2016). Remarks on designs enriching for placebo non-responders. Clinical Trials, 13(3), 338–343.

    Article  PubMed  Google Scholar 

  • Rushmore, R. J., Desimone, C., & Valero-Cabré, A. (2013). Multiple sessions of transcranial direct current stimulation to the intact hemisphere improves visual function after unilateral ablation of visual cortex. European Journal of Neuroscience, 12, 3799–3807.

    Article  CAS  PubMed  Google Scholar 

  • Sandrini, M., Brambilla, M., Manenti, R., Rosini, S., Cohen, L. G., & Cotelli, M. (2014). Noninvasive stimulation of prefrontal cortex strengthens existing episodic memories and reduces forgetting in the elderly. Frontiers in Aging Neuroscience, 6.

    Google Scholar 

  • Sattler, V., Acket, B., Raposo, N., Albucher, J., Thalamas, C., Loubinoux, I., … Simonetta-Moreau, M. (2015). Anodal tDCS combined with radial nerve stimulation promotes hand motor recovery in the acute phase after ischemic stroke. Neurorehabilitation and Neural Repair, 29(8), 743–754.

    Article  PubMed  Google Scholar 

  • Segrave, R. A., Arnold, S., Hoy, K., & Fitzgerald, P. B. (2014). Concurrent cognitive control training augments the antidepressant efficacy of tDCS: A pilot study. Brain Stimulation, 7(2), 325–331.

    Article  CAS  PubMed  Google Scholar 

  • Stagg, C. J., Lin, R. L., Mezue, M., Segerdahl, A., Kong, Y., Xie, J., & Tracey, I. (2013). Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex. Journal of Neuroscience, 33(28), 11425–11431.

    Article  CAS  PubMed  Google Scholar 

  • Stagg, C. J., & Nitsche, M. A. (2011). Physiological basis of transcranial direct current stimulation. The Neuroscientist, 17(1), 37–53.

    Article  PubMed  Google Scholar 

  • The CONSORT Statement. (2016). Retrieved July 7, 2016, from http://www.consort-statement.org/

  • Triccas, L. T., Burridge, J., Hughes, A., Pickering, R., Desikan, M., Rothwell, J., & Verheyden, G. (2016). Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis. Clinical Neurophysiology, 127(1), 946–955.

    Article  CAS  PubMed  Google Scholar 

  • Valle, A., Roizenblatt, S., Botte, S., Zaghi, S., Riberto, M., Tufik, S., … Fregni, F. (2009). Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: Results of a randomized, sham-controlled longitudinal clinical trial. Journal of Pain Management, 2(3), 353–362.

    Google Scholar 

  • Villamar, M. F., Wivatvongvana, P., Patumanond, J., Bikson, M., Truong, D. Q., Datta, A., & Fregni, F. (2013). Focal modulation of the primary motor cortex in fibromyalgia using 4×1-ring high-definition transcranial direct current stimulation (HD-tDCS): Immediate and delayed analgesic effects of cathodal and anodal stimulation. The Journal of Pain, 14(4), 371–383.

    Article  PubMed  Google Scholar 

  • Werner, C., Frankenberg, S. V., Treig, T., Konrad, M., & Hesse, S. (2002). Treadmill training with partial body weight support and an electromechanical gait trainer for restoration of gait in subacute stroke patients: A randomized crossover study. Stroke, 33(12), 2895–2901.

    Article  CAS  PubMed  Google Scholar 

  • Wirth, M., Rahman, R. A., Kuenecke, J., Koenig, T., Horn, H., Sommer, W., & Dierks, T. (2011). Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production. Neuropsychologia, 49(14), 3989–3998.

    Article  PubMed  Google Scholar 

  • Woods, A., Antal, A., Bikson, M., Boggio, P., Brunoni, A., Celnik, P., … Nitsche, M. (2016). A technical guide to tDCS, and related non-invasive brain stimulation tools. Clinical Neurophysiology, 127(2), 1031–1048.

    Article  CAS  PubMed  Google Scholar 

  • Woods, A. J., Bryant, V., Sacchetti, D., Gervits, F., & Hamilton, R. (2015). Effects of electrode drift in transcranial direct current stimulation. Brain Stimulation, 8(2), 320–321.

    Article  Google Scholar 

  • Woods, A. J., Hamilton, R. H., Kranjec, A., Minhaus, P., Bikson, M., Yu, J., & Chatterjee, A. (2014). Space, time, and causality in the human brain. NeuroImage, 92, 285–297.

    Article  PubMed  Google Scholar 

  • You, D. S., Kim, D., Chun, M. H., Jung, S. E., & Park, S. J. (2011). Cathodal transcranial direct current stimulation of the right Wernicke’s area improves comprehension in subacute stroke patients. Brain and Language, 119(1), 1–5.

    Article  PubMed  Google Scholar 

  • Zimerman, M., Heise, K. F., Hoppe, J., Cohen, L. G., Gerloff, C., & Hummel, F. C. (2012). Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand. Stroke, 43(8), 2185–2191.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA

    Roy H. Hamilton

  2. Department of Physical Medicine and Rehabilitation, University of Pennsylvania, Philadelphia, PA, USA

    Roy H. Hamilton

  3. Goddard Laboratories, Room 518, University of Pennsylvania, Philadelphia, PA, USA

    Roy H. Hamilton

  4. Departments of Neurology and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Sudha K. Kessler

  5. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Sudha K. Kessler

  6. Spaulding Neuromodulation Center, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA

    Laura Castillo-Saavedra & Felipe Fregni

  7. Black Dog Institute, The University of New South Wales, Sydney, NSW, Australia

    Donel Martin

  8. School of Psychiatry, Black Dog Institute, The University of New South Wales, Sydney, NSW, Australia

    Colleen Loo

  9. MJHS Institute for Innovation in Palliative Care, New York, NY, USA

    Helena Knotkova

  10. Department of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

    Helena Knotkova

  11. Center for Cognitive Aging and Memory (CAM), McKnight Brain Institute, Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA

    Adam J. Woods

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  1. Roy H. Hamilton
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  5. Donel Martin
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  6. Colleen Loo
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  7. Helena Knotkova
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  8. Adam J. Woods
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Correspondence to Roy H. Hamilton .

Editor information

Editors and Affiliations

  1. MJHS Institute for Innovation in Palliative Care, New York, NY, USA

    Helena Knotkova

  2. Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany

    Michael A. Nitsche

  3. Department of Biomedical Engineering, The City College of New York, New York, NY, USA

    Marom Bikson

  4. Center for Cognitive Aging and Memory (CAM), McKnight Brain Institute, Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA

    Adam J. Woods

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Hamilton, R.H. et al. (2019). Methodological Considerations for Transcranial Direct Current Stimulation in Clinical Trials. In: Knotkova, H., Nitsche, M., Bikson, M., Woods, A. (eds) Practical Guide to Transcranial Direct Current Stimulation. Springer, Cham. https://doi.org/10.1007/978-3-319-95948-1_12

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