Transcranial direct-current stimulation

There is some evidence tDCS might be of moderate benefit as treatment for mild and moderate depression,{{Cite journal |last1=Cheng |first1=Ying-Chih |last2=Kuo |first2=Po-Hsiu |last3=Su |first3=Min-I |last4=Huang |first4=Wei-Lieh |date=2022-04-01 |title=The efficacy of non-invasive, non-convulsive electrical neuromodulation on depression, anxiety and sleep disturbance: a systematic review and meta-analysis |journal=Psychological Medicine |language=en |volume=52 |issue=5 |pages=801–812 |doi=10.1017/S0033291721005560 |issn=0033-2917|doi-access=free |pmid=35105413 }}{{Cite journal |last1=Zheng |first1=Esther Zhiwei |last2=Wong |first2=Nichol M. L. |last3=Yang |first3=Angela S. Y. |last4=Lee |first4=Tatia M. C. |date=2024-07-18 |title=Evaluating the effects of tDCS on depressive and anxiety symptoms from a transdiagnostic perspective: a systematic review and meta-analysis of randomized controlled trials |journal=Translational Psychiatry |language=en |volume=14 |issue=1 |page=295 |doi=10.1038/s41398-024-03003-w |pmid=39025832 |issn=2158-3188|pmc=11258305 }} major depressive disorder{{cite journal | vauthors = Moffa AH, Martin D, Alonzo A, Bennabi D, Blumberger DM, Benseñor IM, Daskalakis Z, Fregni F, Haffen E, Lisanby SH, Padberg F, Palm U, Razza LB, Sampaio-Jr B, Loo C, Brunoni AR | display-authors = 6 | title = Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 99 | pages = 109836 | date = April 2020 | pmid = 31837388 | doi = 10.1016/j.pnpbp.2019.109836 | s2cid = 209373871 | hdl = 1959.4/unsworks_81424 | url = https://unsworks.unsw.edu.au/bitstreams/967e9af1-ae7e-4a90-98f0-7f943f35d83b/download | hdl-access = free }} and treatment-resistant depression.{{Cite journal |last1=Li |first1=John |last2=Kung |first2=Simon |last3=Croarkin |first3=Paul |last4=Lapid |first4=Maria |date=2024-04-01 |title=Transcranial Direct Current Stimulation (tDCS) for Treatment Resistant Depression (TRD): A Systematic Review |url=https://linkinghub.elsevier.com/retrieve/pii/S1064748124001921 |journal=The American Journal of Geriatric Psychiatry |language=en |volume=32 |issue=4 |pages=S99 |doi=10.1016/j.jagp.2024.01.181|url-access=subscription }}

Recent research on tDCS has shown promising results in treating other mental health conditions such as anxiety and PTSD.{{cite journal | vauthors = Ahmadizadeh MJ, Rezaei M, Fitzgerald PB | title = Transcranial direct current stimulation (tDCS) for post-traumatic stress disorder (PTSD): A randomized, double-blinded, controlled trial | journal = Brain Research Bulletin | volume = 153 | pages = 273–278 | date = November 2019 | pmid = 31560945 | doi = 10.1016/j.brainresbull.2019.09.011 | s2cid = 202733889 }} More research is required on the topic. There is also evidence that tDCS is useful in treating neuropathic pain after spinal cord injury.{{cite journal | vauthors = Soler MD, Kumru H, Pelayo R, Vidal J, Tormos JM, Fregni F, Navarro X, Pascual-Leone A | display-authors = 6 | title = Effectiveness of transcranial direct current stimulation and visual illusion on neuropathic pain in spinal cord injury | journal = Brain | volume = 133 | issue = 9 | pages = 2565–2577 | date = September 2010 | pmid = 20685806 | pmc = 2929331 | doi = 10.1093/brain/awq184 }} There is evidence of very low to moderate quality that tDCS can improve activities of daily living assessment in the short-term after stroke.{{cite journal | vauthors = Elsner B, Kwakkel G, Kugler J, Mehrholz J | title = Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials | journal = Journal of Neuroengineering and Rehabilitation | volume = 14 | issue = 1 | pages = 95 | date = September 2017 | pmid = 28903772 | pmc = 5598049 | doi = 10.1186/s12984-017-0301-7 | doi-access = free }}

Transcranial direct-current stimulaiton is also used to augment speech therapy in patients with acquired language disorders like aphasia, or to help maintain language abilities in the case of primary progressive aphasia, a neurodegenerative condition.{{cite journal | url=https://pubs.asha.org/doi/abs/10.1044/2016_AJSLP-15-0133 | doi=10.1044/2016_AJSLP-15-0133 | title=Use of TDCS in Aphasia Rehabilitation: A Systematic Review of the Behavioral Interventions Implemented with Noninvasive Brain Stimulation for Language Recovery | year=2016 | last1=Galletta | first1=Elizabeth E. | last2=Conner | first2=Peggy | last3=Vogel-Eyny | first3=Amy | last4=Marangolo | first4=Paola | journal=American Journal of Speech-Language Pathology | volume=25 | issue=4S | pages=S854–S867 | pmid=27997958 | url-access=subscription }}

According to the British National Institute for Health and Care Excellence (NICE), the evidence on tDCS for depression raises no major safety concerns.{{Cite web|title=1 Recommendations {{!}} Transcranial direct current stimulation (tDCS) for depression {{!}} Guidance |url= https://www.nice.org.uk/guidance/ipg530/chapter/1-Recommendations |access-date=2020-05-12 | work = The National Institute for Health and Care Excellence (NICE) |date= 26 August 2015 | location = UK }}  

As of 2017, at stimulation up to 60 min and up to 4 mA over two weeks, adverse effects include skin irritation, a phosphene at the start of stimulation, nausea, headache, dizziness, and itching under the electrode. Typical treatment sessions lasting for about 20–30 min repeated daily for several weeks in the treatment of depression.{{Cite web|title=3 The procedure {{!}} Transcranial direct current stimulation (tDCS) for depression {{!}} Guidance {{!}} NICE|url=https://www.nice.org.uk/guidance/ipg530/chapter/3-The-procedure | work = The National Institute for Health and Care Excellence (NICE) |date=26 August 2015 | location = UK |access-date=2020-05-12}} Adverse effects of long term treatment were not known as of 2017. Nausea most commonly occurs when the electrodes are placed above the mastoid for stimulation of the vestibular system. A phosphene is a brief flash of light that can occur if an electrode is placed near the eye.{{cite journal | vauthors = Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W | display-authors = 6 | title = Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines | journal = Clinical Neurophysiology | volume = 128 | issue = 9 | pages = 1774–1809 | date = September 2017 | pmid = 28709880 | pmc = 5985830 | doi = 10.1016/j.clinph.2017.06.001 }}

People susceptible to seizures, such as people with epilepsy should not receive tDCS. Studies have been completed to determine the current density at which overt brain damage occurs in rats. It was found that in cathodal stimulation, a current density of 142.9 A/m² delivering a charge density of 52400 C/m² or higher caused a brain lesion in the rat. This is over two orders of magnitude higher than protocols that were in use as of 2009.

tDCS stimulates and activates brain cells by delivering electrical signals. The lasting modulation of cortical excitability produced by tDCS makes it an effective solution to facilitate rehabilitation and treat a range of neuropsychiatric disorders.{{cite journal | vauthors = Edwards D, Cortes M, Datta A, Minhas P, Wassermann EM, Bikson M | title = Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: a basis for high-definition tDCS | journal = NeuroImage | volume = 74 | issue = | pages = 266–75 | date = July 2013 | pmid = 23370061 | pmc = 4359173 | doi = 10.1016/j.neuroimage.2013.01.042 }} The way that the stimulation changes brain function is either by causing the neuron’s resting membrane potential to depolarize or hyperpolarize. When positive stimulation (anodal tDCS) is delivered, the current causes a depolarization of the resting membrane potential, which increases neuronal excitability and allows for more spontaneous cell firing. When negative stimulation (cathodal tDCS) is delivered, the current causes a hyperpolarization of the resting membrane potential. This decreases neuron excitability due to the decreased spontaneous cell firing.

In case of treating depression, tDCS currents specifically target the left side of the dorsolateral prefrontal cortex (DLPFC) located in the frontal lobe. Left DLPFC has been shown to be associated with lower activity in the depressed population.{{Cite web | vauthors = Fitzgerald PB |title=Transcranial direct current stimulation in the treatment of depression |url= https://www.medicographia.com/2011/10/transcranial-direct-current-stimulation-in-the-treatment-of-depression/ | archive-url = https://web.archive.org/web/20200711031207/https://www.medicographia.com/2011/10/transcranial-direct-current-stimulation-in-the-treatment-of-depression/ | archive-date = 11 July 2020 |date=2011-10-24| work = Medicographia | publisher = Servier Laboratories |access-date=2020-05-12}}

tDCS is able to achieve cortical changes even after the stimulation is ended. The duration of this change depends on the length of stimulation as well as the intensity of stimulation. The effects of stimulation increase as the duration of stimulation increases or the strength of the current increases. tDCS has been proposed to promote both long term potentiation and long term depression, and further research is needed for validation.

Transcranial direct current stimulation works by sending constant, low direct current through the electrodes. When these electrodes are placed in the region of interest, the current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used. This change of neuronal excitability leads to alteration of brain function, which can be used in various therapies as well as to provide more information about the functioning of the human brain.

Transcranial direct current stimulation is a relatively simple technique requiring only a few parts. These include two electrodes and a battery-powered device that delivers constant current. Control software can also be used in experiments that require multiple sessions with differing stimulation types so that neither the person receiving the stimulation nor the experimenter knows which type is being administered. Each device has an anodal, positively charged electrode and a cathodal, negative electrode. Current is "conventionally" described as flowing from the positive anode, through the intervening conducting tissue, to the cathode, creating a circuit. Note that in traditional electric circuits constructed from metal wires, charge drift is created by the motion of negatively charged electrons, which actually flow from cathode to anode. However, in biological systems, such as the head, current is usually created by the flow of ions, which may be positively or negatively charged{{snd}}positive ions will flow towards the cathode; negative ions will flow toward the anode. The device may control the current as well as the duration of stimulation.

To set up the tDCS device, the electrodes and the skin need to be prepared. This ensures a low resistance connection between the skin and the electrode. The careful placement of the electrodes is crucial to successful tDCS technique. The electrode pads come in various sizes with benefits to each size. A smaller sized electrode achieves a more focused stimulation of a site while a larger electrode ensures that the entirety of the region of interest is being stimulated. If the electrode is placed incorrectly, a different site or more sites than intended may be stimulated resulting in faulty results. One of the electrodes is placed over the region of interest and the other electrode, the reference electrode, is placed in another location in order to complete the circuit. This reference electrode is usually placed on the neck or shoulder of the opposite side of the body than the region of interest. Since the region of interest may be small, it is often useful to locate this region before placing the electrode by using a brain imaging technique such as fMRI or PET. Once the electrodes are placed correctly, the stimulation can be started. Many devices have a built-in capability that allows the current to be "ramped up" or increased gradually until the necessary current is reached. This decreases the amount of stimulation effects felt by the person receiving the tDCS. After the stimulation has been started, the current will continue for the amount of time set on the device and then will automatically be shut off. Recently a new approach has been introduced where instead of using two large pads, multiple (more than two) smaller sized gel electrodes are used to target specific cortical structures. This new approach is called High Definition tDCS (HD-tDCS). In a pilot study, HD-tDCS was found to have greater and longer lasting motor cortex excitability changes than sponge tDCS.

There are three different types of stimulation: anodal, cathodal, and sham. The anodal stimulation is positive (V+) stimulation that increases the neuronal excitability of the area being stimulated. Cathodal (V−) stimulation decreases the neuronal excitability of the area being stimulated. Cathodal stimulation can treat psychiatric disorders that are caused by the hyper-activity of an area of the brain. Sham stimulation is used as a control in experiments. Sham stimulation emits a brief current but then remains off for the remainder of the stimulation time. With sham stimulation, the person receiving the tDCS does not know that they are not receiving prolonged stimulation. By comparing the results in subjects exposed to sham stimulation with the results of subjects exposed to anodal or cathodal stimulation, researchers can see how much of an effect is caused by the current stimulation, rather than by the placebo effect.

Recently, tDCS devices are being researched and created intended for at-home use{{snd}}ranging from treating medical conditions such as depression to enhancing general cognitive well-being.{{cite journal | vauthors = Riggs A, Patel V, Paneri B, Portenoy RK, Bikson M, Knotkova H | title = At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms | journal = Frontiers in Behavioral Neuroscience | volume = 12 | pages = 93 | date = 2018-05-22 | pmid = 29872381 | pmc = 5972211 | doi = 10.3389/fnbeh.2018.00093 | doi-access = free }}{{Cite web|title=Europe's first home brain-zap device for depression launched in UK|url=https://www.newscientist.com/article/2221743-europes-first-home-brain-zap-device-for-depression-launched-in-uk/| vauthors = Thomson H |website=New Scientist|language=en-US|access-date=2020-05-12}} Clinical trials are needed to establish the efficacy, feasibility and acceptability of home-based tDCS treatment.{{cite journal | vauthors = Woodham R, Rimmer RM, Mutz J, Fu CH | title = Is tDCS a potential first line treatment for major depression? | journal = International Review of Psychiatry | volume = 33 | issue = 3 | pages = 250–265 | date = May 2021 | pmid = 33706656 | doi = 10.1080/09540261.2021.1879030 | s2cid = 232209376 | url = https://repository.uel.ac.uk/download/ed192b17a26c6dc14f46488abd2402249bd5f7b71c27528419001271b49f3e99/474262/Is%20tDCS%20a%20potential%20first%20line%20treatment%20in%20major%20depression.pdf }}

The basic design of tDCS, using direct current (DC) to stimulate the area of interest, has existed for over 100 years. There were a number of rudimentary experiments completed before the 19th century using this technique that tested animal and human electricity. Luigi Galvani and Alessandro Volta were two such researchers that utilized the technology of tDCS in their explorations of the source of animal cell electricity [citation needed]. It was due to these initial studies that tDCS was first brought into the clinical scene. In 1801, Giovanni Aldini (Galvani's nephew) started a study in which he successfully used the technique of direct current stimulation to improve the mood of melancholy patients.{{cite journal | vauthors= Parent A |date=November 2004 |title=Aldini's Essay on Galvanism |url=http://www.biusante.parisdescartes.fr/chn/docpdf/parent_aldini.pdf |journal=The Canadian Journal of Neurological Sciences |volume=31 |issue=4 |pages=576–584|doi=10.1017/S0317167100003851 |pmid=15595271 |s2cid=11048877 }} (Lanzarini pdf 5 of 9)

• {{cite book | vauthors = Essai AJ | title = Théorique et expérimental sur le galvanisme, avec une série d'expériences faites devant des commissaires de l'Institut national de France, et en divers amphithéâtres anatomiques de Londres. | trans-title = Theoretical and experimental on galvanism, with a series of experiments made before commissioners of the National Institute of France, and in various anatomical amphitheatres in London. | language = fr | location = Paris | publisher = Fournier Fils | date = 1804 }}

There was a brief rise of interest in transcranial direct current stimulation in the 1960s when studies by researcher D. J. Albert proved that the stimulation could affect brain function by changing the cortical excitability.{{cite journal | vauthors = Albert DJ | title = The effect of spreading depression on the consolidation of learning. | journal = Neuropsychologia | date = February 1966 | volume = 4 | issue = 1 | pages = 49–64 | doi = 10.1016/0028-3932(66)90020-0 | hdl = 2027.42/33480 | hdl-access = free }} He also discovered that positive and negative stimulation had different effects on the cortical excitability.{{cite journal | vauthors = Albert DJ | title =The effects of polarizing currents on the consolidation of learning. | journal = Neuropsychologia | date = February 1966 | volume = 4 | issue = 1 | pages = 65–77 | doi = 10.1016/0028-3932(66)90021-2 | hdl =2027.42/33481 | hdl-access = free }}

Research continued, further fueled by knowledge gained from other techniques like TMS and fMRI.

File:Fnhum-07-00435-g001.jpg

In transcranial magnetic stimulation (TMS), an electric coil is held above the region of interest on the scalp that uses rapidly changing magnetic fields to induce small electrical currents in the brain. There are two types of TMS: repetitive TMS and single pulse TMS. Both are used in research therapy but effects lasting longer than the stimulation period are only observed in repetitive TMS. Similar to tDCS, an increase or decrease in neuronal activity can be achieved using this technique, but the method of how this is induced is very different. Transcranial direct current stimulation has the two different directions of current that cause the different effects. Increased neuronal activity is induced in repetitive TMS by using a higher frequency and decreased neuronal activity is induced by using a lower frequency.

Variants related to tDCS include tACS, tPCS and transcranial random noise stimulation (tRNS), a group of technologies commonly referred to as transcranial electrical stimulation, or TES.{{cite journal | vauthors = Ruffini G, Wendling F, Merlet I, Molaee-Ardekani B, Mekonnen A, Salvador R, Soria-Frisch A, Grau C, Dunne S, Miranda PC | display-authors = 6 | title = Transcranial current brain stimulation (tCS): models and technologies | journal = IEEE Transactions on Neural Systems and Rehabilitation Engineering | volume = 21 | issue = 3 | pages = 333–345 | date = May 2013 | pmid = 22949089 | doi = 10.1109/TNSRE.2012.2200046 | s2cid = 19615665 | citeseerx = 10.1.1.352.4406 }}

Determining the safety and effectiveness of tDCS treatment for people with depression is being investigated:

• A systematic review of placebo-controlled trials investigating tDCS treatment for major depressive disorder was published 2020. The meta-analysis collated results across nine eligible studies (572 participants) up until December 2018 to estimate odds ratio (OR) and number needed to treat (NNT) of response and remission, and depression improvement. The results showed statistically superior efficacy of active tDCS compared to sham for nine eligible studies (572 participants), presenting moderate/high certainty of evidence, were included. Active tDCS was significantly superior to sham for response (30.9% vs. 18.9% respectively; OR = 1.96, 95%CI [1.30–2.95], NNT = 9), remission (19.9% vs. 11.7%, OR = 1.94 [1.19–3.16], NNT = 13) and depression improvement (effect size of β = 0.31, [0.15–0.47]).
• A 2016 meta-analysis showed that 34% of people treated with tDCS showed at least 50% symptom reduction (compared to 19% placebo).{{cite journal | vauthors = Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM, Daskalakis ZJ, Bennabi D, Haffen E, Alonzo A, Loo CK | display-authors = 6 | title = Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data | journal = The British Journal of Psychiatry | volume = 208 | issue = 6 | pages = 522–531 | date = June 2016 | pmid = 27056623 | pmc = 4887722 | doi = 10.1192/bjp.bp.115.164715 | doi-access = free }}
• A 2017 study conducted by Brunoni showed 6-weeks of tDCS treatment resulted in reduction of at least half of depression symptoms in 41% of depressed people (vs. 22% placebo and 47% antidepressants).{{cite journal | vauthors = Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA, Veronezi BP, Nogueira BS, Aparicio LV, Razza LB, Chamorro R, Tort LC, Fraguas R, Lotufo PA, Gattaz WF, Fregni F, Benseñor IM | display-authors = 6 | title = Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression | language = EN | journal = The New England Journal of Medicine | volume = 376 | issue = 26 | pages = 2523–2533 | date = June 2017 | pmid = 28657871 | doi = 10.1056/nejmoa1612999 | doi-access = free }}
• In 2015, the British National Institute for Health and Care Excellence (NICE) found tDCS to be safe and to appear effective for depression treatment. Up until 2014, there have been several small randomized clinical trials (RCT) in major depressive disorder (MDD); most found alleviation of depressive symptoms. There have been only two RCTs in treatment-resistant MDD; both were small, and one found an effect and the other did not.{{cite journal | vauthors = Mondino M, Bennabi D, Poulet E, Galvao F, Brunelin J, Haffen E | title = Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders? | journal = The World Journal of Biological Psychiatry | volume = 15 | issue = 4 | pages = 261–275 | date = May 2014 | pmid = 24447054 | doi = 10.3109/15622975.2013.876514 | s2cid = 33184990 }} One meta-analysis of the data focused on reduction in symptoms and found an effect compared to sham treatment, but another that was focused on relapse found no effect compared to sham.

There is mixed evidence about whether tDCS is useful for cognitive enhancement in healthy people. Several reviews have found evidence of small yet significant cognitive improvements.{{cite journal | vauthors = Coffman BA, Clark VP, Parasuraman R | title = Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation | journal = NeuroImage | volume = 85 | issue = Pt 3 | pages = 895–908 | date = January 2014 | pmid = 23933040 | doi = 10.1016/j.neuroimage.2013.07.083 | s2cid = 34389202 }}{{cite journal | vauthors = Dedoncker J, Brunoni AR, Baeken C, Vanderhasselt MA | title = A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters | journal = Brain Stimulation | volume = 9 | issue = 4 | pages = 501–517 | year = 2016 | pmid = 27160468 | doi = 10.1016/j.brs.2016.04.006 | hdl-access = free | s2cid = 98400 | hdl = 1854/LU-7206618 | url = https://biblio.ugent.be/publication/7206618 }}{{cite journal | vauthors = Hill AT, Fitzgerald PB, Hoy KE | title = Effects of Anodal Transcranial Direct Current Stimulation on Working Memory: A Systematic Review and Meta-Analysis of Findings From Healthy and Neuropsychiatric Populations | journal = Brain Stimulation | volume = 9 | issue = 2 | pages = 197–208 | year = 2016 | pmid = 26597929 | doi = 10.1016/j.brs.2015.10.006 | s2cid = 17093486 }}{{cite book | vauthors = Katsoulaki M, Kastrinis A, Tsekoura M | title = GeNeDis 2016 | chapter = The Effects of Anodal Transcranial Direct Current Stimulation on Working Memory | series = Advances in Experimental Medicine and Biology | volume = 987 | pages = 283–289 | year = 2017 | pmid = 28971466 | doi = 10.1007/978-3-319-57379-3_25 | isbn = 978-3319573786 }} Other reviews found no evidence at all, although one of them has been criticized for overlooking within-subject effects{{cite journal | vauthors = Chhatbar PY, Feng W | title = Data Synthesis in Meta-Analysis may Conclude Differently on Cognitive Effect From Transcranial Direct Current Stimulation | journal = Brain Stimulation | volume = 8 | issue = 5 | pages = 974–976 | year = 2015 | pmid = 26115775 | doi = 10.1016/j.brs.2015.06.001 | s2cid = 1539586 }} and evidence from multiple-session tDCS trials. However, the original authors addressed these raised concerns in a further analysis and continued to find no evidence of impact {{cite journal | vauthors = Horvath JC | title = New Quantitative Analyses Following Price & Hamilton's Critique do not Change Original Findings of Horvath et al. | journal = Brain Stimulation | volume = 8 | issue = 3 | pages = 665–666 | year = 2015 | pmid = 26050600 | doi = 10.1016/j.brs.2015.05.001 | s2cid = 38603410 }}

A 2015 review of results from hundreds of tDCS experiments found that there was no statistically conclusive evidence to support any net cognitive effect, positive or negative, of single session tDCS in healthy populations{{snd}}there is no evidence that tDCS is useful for cognitive enhancement. A second study by the same authors found there was little-to-no statistically reliable impact of tDCS on any neurophysiologic outcome.

There is no strong evidence that tDCS is useful for memory deficits in Alzheimer's disease, schizophrenia, non-neuropathic pain. A few clinical trials have been conducted on the use of tDCS to ameliorate memory deficits in Parkinson's disease and Alzheimer's disease and healthy subjects, with mixed results.{{cite journal | vauthors = Bennabi D, Pedron S, Haffen E, Monnin J, Peterschmitt Y, Van Waes V | title = Transcranial direct current stimulation for memory enhancement: from clinical research to animal models | journal = Frontiers in Systems Neuroscience | volume = 8 | pages = 159 | date = Sep 2014 | pmid = 25237299 | pmc = 4154388 | doi = 10.3389/fnsys.2014.00159 | doi-access = free }} Research conducted as of 2013 in schizophrenia, has found that while large effect sizes were initially found for symptom improvement, later and larger studies have found smaller effect sizes (see also section on use of tDCS in psychiatric disorders below). Studies have mostly concentrated on positive symptoms like auditory hallucinations; research on negative symptoms is lacking.{{cite journal | vauthors = Agarwal SM, Shivakumar V, Bose A, Subramaniam A, Nawani H, Chhabra H, Kalmady SV, Narayanaswamy JC, Venkatasubramanian G | display-authors = 6 | title = Transcranial direct current stimulation in schizophrenia | journal = Clinical Psychopharmacology and Neuroscience | volume = 11 | issue = 3 | pages = 118–125 | date = December 2013 | pmid = 24465247 | pmc = 3897759 | doi = 10.9758/cpn.2013.11.3.118 }}

There is no strong evidence that tDCS can help improve upper limb function after stroke.{{cite journal | vauthors = Pollock A, Farmer SE, Brady MC, Langhorne P, Mead GE, Mehrholz J, van Wijck F | title = Interventions for improving upper limb function after stroke | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 11 | pages = CD010820 | date = November 2014 | pmid = 25387001 | pmc = 6469541 | doi = 10.1002/14651858.CD010820.pub2 }} In stroke, research conducted as of 2014, has found that tDCS is not effective for improving upper limb function after stroke.{{cite journal | vauthors = Feng WW, Bowden MG, Kautz S | title = Review of transcranial direct current stimulation in poststroke recovery | journal = Topics in Stroke Rehabilitation | volume = 20 | issue = 1 | pages = 68–77 | date = Jan 2013 | pmid = 23340073 | doi = 10.1310/tsr2001-68 | s2cid = 39688758 }} While some reviews have suggested an effect of tDCS for improving post-stroke aphasia, a 2015 Cochrane review could find no improvement from combining tDCS with conventional treatment.{{cite journal | vauthors = Elsner B, Kugler J, Pohl M, Mehrholz J | title = Transcranial direct current stimulation (tDCS) for improving aphasia in adults with aphasia after stroke | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 5 | pages = CD009760 | date = May 2019 | pmid = 31111960 | pmc = 6528187 | doi = 10.1002/14651858.CD009760.pub4 }}{{cite journal | vauthors = de Aguiar V, Paolazzi CL, Miceli G | title = tDCS in post-stroke aphasia: the role of stimulation parameters, behavioral treatment and patient characteristics | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 63 | pages = 296–316 | date = February 2015 | pmid = 25460496 | doi = 10.1016/j.cortex.2014.08.015 | s2cid = 22631885 }} Research conducted as of 2013 suggests that tDCS may be effective for improve vision deficits following stroke.

Motor Learning and Memory Function

There is evidence that certain tDCS montages can increase learning rates for particular tasks in healthy individuals, namely motor tasks and memory function.{{cite journal | vauthors = Buch ER, Santarnecchi E, Antal A, Born J, Celnik PA, Classen J, Gerloff C, Hallett M, Hummel FC, Nitsche MA, Pascual-Leone A, Paulus WJ, Reis J, Robertson EM, Rothwell JC, Sandrini M, Schambra HM, Wassermann EM, Ziemann U, Cohen LG | display-authors = 6 | title = Effects of tDCS on motor learning and memory formation: A consensus and critical position paper | journal = Clinical Neurophysiology | volume = 128 | issue = 4 | pages = 589–603 | date = April 2017 | pmid = 28231477 | doi = 10.1016/j.clinph.2017.01.004 | url = http://eprints.gla.ac.uk/137645/7/137645.pdf }} However, reproducibility remains to be fully tested across studies and standardization for these kinds of studies has not been implemented fully, though an attempt at formalizing standards was released in 2017.

Research conducted as of 2012 on the use of tDCS to treat pain, found that the research has been of low quality and cannot be used as a basis to recommend use of tDCS to treat pain.{{cite journal | vauthors = Luedtke K, Rushton A, Wright C, Geiss B, Juergens TP, May A | title = Transcranial direct current stimulation for the reduction of clinical and experimentally induced pain: a systematic review and meta-analysis | journal = The Clinical Journal of Pain | volume = 28 | issue = 5 | pages = 452–461 | date = June 2012 | pmid = 22569218 | doi = 10.1097/AJP.0b013e31823853e3 | s2cid = 24612998 }} In chronic pain following spinal cord injury, research is of high quality and has found tDCS to be ineffective.{{cite journal | vauthors = Boldt I, Eriks-Hoogland I, Brinkhof MW, de Bie R, Joggi D, von Elm E | title = Non-pharmacological interventions for chronic pain in people with spinal cord injury | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 11 | pages = CD009177 | date = November 2014 | pmid = 25432061 | doi = 10.1002/14651858.CD009177.pub2 | doi-access = free | pmc = 11329868 }} tDCS has also been studied in addiction.{{cite journal | vauthors = Pedron S, Monnin J, Haffen E, Sechter D, Van Waes V | title = Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption | journal = Neuropsychopharmacology | volume = 39 | issue = 4 | pages = 981–988 | date = March 2014 | pmid = 24154668 | pmc = 3924532 | doi = 10.1038/npp.2013.298 }}{{cite journal | vauthors = Jansen JM, Daams JG, Koeter MW, Veltman DJ, van den Brink W, Goudriaan AE | title = Effects of non-invasive neurostimulation on craving: a meta-analysis | journal = Neuroscience and Biobehavioral Reviews | volume = 37 | issue = 10 Pt 2 | pages = 2472–2480 | date = December 2013 | pmid = 23916527 | doi = 10.1016/j.neubiorev.2013.07.009 | s2cid = 1410164 }} There is some moderate (level B) evidence to indicate that, in addition to treating major depressive disorder, tDCS may also be appropriate to treat fibromyalgia, and craving disorders.{{cite journal | vauthors = Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W | display-authors = 6 | title = Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) | journal = Clinical Neurophysiology | volume = 128 | issue = 1 | pages = 56–92 | date = January 2017 | pmid = 27866120 | doi = 10.1016/j.clinph.2016.10.087 | hdl-access = free | s2cid = 4837447 | hdl = 10067/1420300151162165141 | url = https://repository.uantwerpen.be/docman/irua/211121/142030_2018_01_01.pdf }}

tDCS has been used in neuroscience research, particularly to try to link specific brain regions to specific cognitive tasks{{cite journal | vauthors = Harty S, Robertson IH, Miniussi C, Sheehy OC, Devine CA, McCreery S, O'Connell RG | title = Transcranial direct current stimulation over right dorsolateral prefrontal cortex enhances error awareness in older age | journal = The Journal of Neuroscience | volume = 34 | issue = 10 | pages = 3646–3652 | date = March 2014 | pmid = 24599463 | pmc = 6608991 | doi = 10.1523/JNEUROSCI.5308-13.2014 }} or psychological phenomena.{{cite journal | vauthors = Grimaldi G, Argyropoulos GP, Bastian A, Cortes M, Davis NJ, Edwards DJ, Ferrucci R, Fregni F, Galea JM, Hamada M, Manto M, Miall RC, Morales-Quezada L, Pope PA, Priori A, Rothwell J, Tomlinson SP, Celnik P | display-authors = 6 | title = Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease | journal = The Neuroscientist | volume = 22 | issue = 1 | pages = 83–97 | date = February 2016 | pmid = 25406224 | pmc = 4712385 | doi = 10.1177/1073858414559409 }} The cerebellum has been a focus of research, due to its high concentration of neurons, its location immediately below the skull, and its multiple reciprocal anatomical connections to motor and associative parts of the brain.{{cite journal | vauthors = van Dun K, Bodranghien FC, Mariën P, Manto MU | title = tDCS of the Cerebellum: Where Do We Stand in 2016? Technical Issues and Critical Review of the Literature | journal = Frontiers in Human Neuroscience | volume = 10 | pages = 199 | date = 2016-01-01 | pmid = 27242469 | pmc = 4862979 | doi = 10.3389/fnhum.2016.00199 | doi-access = free }} Most such studies focus on the impact of cerebellar tDCS on motor, cognitive, and affective functions in healthy and patient populations, but some also employ tDCS over the cerebellum to study the functional connectivity of the cerebellum to other areas of the brain.{{cite journal | vauthors = van Dun K, Bodranghien F, Manto M, Mariën P | title = Targeting the Cerebellum by Noninvasive Neurostimulation: a Review | journal = Cerebellum | volume = 16 | issue = 3 | pages = 695–741 | date = June 2017 | pmid = 28032321 | doi = 10.1007/s12311-016-0840-7 | s2cid = 3999098 }}

While growing literature shows the efficacy of transcranial direct current stimulation (tDCS) for treating nervous diseases such as acute depressive episodes, the lack of knowledge about the nature of this treatment at the cell level raises concerns regarding possible adverse effects that would appear long after the treatment has ended.

First, tDCS therapy involves exposure of the brain to an intense electric field, which is several times and even orders of magnitude higher than natural ones in the brain.Grimaldi G, Argyropoulos GP, Boehringer A, Celnik P, Edwards MJ, Ferrucci R, et al. (2014). "Non-invasive cerebellar stimulation--a consensus paper" (PDF). Cerebellum. 13 (1): 121–138. doi:10.1007/s12311-013-0514-7Siebner HR, Hartwigsen G, Kassuba T, Rothwell JC (2009). "How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 45 (9): 1035–1042. doi:10.1016/j.cortex.2009.02.007 While the therapeutic effect is observed in a short period of months, the impact of the electric fields on the brain, specifically on the treated neuronal structures, is a question of further long-term research.

Second, tDCS brain tissue stimulation targets a large area of poorly characterized tissue.Sparing R, Mottaghy FM (2008). "Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction". Methods. 44 (4): 329–337. doi:10.1016/j.ymeth.2007.02.001 Therefore, it is unclear whether electrical fields reach only the neural structures of the brain that need treatment. The radiation can destroy healthy cells which don't need treatment during tDCS therapy.

tDCS is a CE approved treatment for major depressive disorder (MDD) in the UK, EU, Australia, and Mexico. As of 2015, tDCS has not been approved for any use by the US FDA. An FDA briefing document prepared in 2012 stated that "there is no regulation for therapeutic tDCS".{{Cite web|url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM290787.pdf|archive-url=https://web.archive.org/web/20120209220759/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM290787.pdf|url-status=dead|archive-date=February 9, 2012|title=FDA Executive Summary – Petitions to Request Change in Classification for Cranial Electrotherapy Stimulators|website=Food and Drug Administration}}

{{col div|colwidth=40em}}

• Cranial electrotherapy stimulation
• Neurotechnology
• Transcranial alternating current stimulation
• Transcranial random noise stimulation
• Transcranial magnetic stimulation
• Brainwave entrainment
• Non-invasive cerebellar stimulation

{{colend}}

{{reflist|30em|refs=

{{cite journal | vauthors = Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM, Daskalakis ZJ, Bennabi D, Haffen E, Alonzo A, Loo CK | display-authors = 6 | title = Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data | journal = The British Journal of Psychiatry | volume = 208 | issue = 6 | pages = 522–531 | date = June 2016 | pmid = 27056623 | pmc = 4887722 | doi = 10.1192/bjp.bp.115.164715 | quote = Our findings indicates two potential applications for tDCS in the therapeutic arsenal for depression: in primary care settings and as a non-pharmacological, neuromodulatory therapy for depression. }}

{{cite journal | vauthors = Utz KS, Dimova V, Oppenländer K, Kerkhoff G | title = Electrified minds: transcranial direct current stimulation (tDCS) and galvanic vestibular stimulation (GVS) as methods of non-invasive brain stimulation in neuropsychology--a review of current data and future implications | journal = Neuropsychologia | volume = 48 | issue = 10 | pages = 2789–2810 | date = August 2010 | pmid = 20542047 | doi = 10.1016/j.neuropsychologia.2010.06.002 | s2cid = 14538856 }}

{{cite journal | vauthors = Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W | title = Safety criteria for transcranial direct current stimulation (tDCS) in humans | journal = Clinical Neurophysiology | volume = 114 | issue = 11 | pages = 2220–2222; author reply 2222–2223 | date = November 2003 | pmid = 14580622 | doi = 10.1016/S1388-2457(03)00235-9 | s2cid = 46505774 }}

{{cite journal | vauthors = Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus W | title = Level of action of cathodal DC polarisation induced inhibition of the human motor cortex | journal = Clinical Neurophysiology | volume = 114 | issue = 4 | pages = 600–604 | date = April 2003 | pmid = 12686268 | doi = 10.1016/S1388-2457(02)00412-1 | s2cid = 20338096 }}

{{cite journal | vauthors = Liebetanz D, Koch R, Mayenfels S, König F, Paulus W, Nitsche MA | title = Safety limits of cathodal transcranial direct current stimulation in rats | journal = Clinical Neurophysiology | volume = 120 | issue = 6 | pages = 1161–1167 | date = June 2009 | pmid = 19403329 | doi = 10.1016/j.clinph.2009.01.022 | s2cid = 38005569 }}

{{cite journal | vauthors = Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A | display-authors = 6 | title = Transcranial direct current stimulation: State of the art 2008 | journal = Brain Stimulation | volume = 1 | issue = 3 | pages = 206–223 | date = July 2008 | pmid = 20633386 | doi = 10.1016/j.brs.2008.06.004 | s2cid = 16352598 }}

{{cite journal | vauthors = Sparing R, Mottaghy FM | title = Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction | journal = Methods | volume = 44 | issue = 4 | pages = 329–337 | date = April 2008 | pmid = 18374276 | doi = 10.1016/j.ymeth.2007.02.001 }}

{{cite journal | vauthors = Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M | title = Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad | journal = Brain Stimulation | volume = 2 | issue = 4 | pages = 201–7, 207.e1 | date = October 2009 | pmid = 20648973 | pmc = 2790295 | doi = 10.1016/j.brs.2009.03.005 }}

{{cite journal | vauthors = Borckardt JJ, Bikson M, Frohman H, Reeves ST, Datta A, Bansal V, Madan A, Barth K, George MS | display-authors = 6 | title = A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception | journal = The Journal of Pain | volume = 13 | issue = 2 | pages = 112–120 | date = February 2012 | pmid = 22104190 | doi = 10.1016/j.jpain.2011.07.001 | doi-access = free }}

{{cite journal | vauthors = Kuo HI, Bikson M, Datta A, Minhas P, Paulus W, Kuo MF, Nitsche MA | title = Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study | journal = Brain Stimulation | volume = 6 | issue = 4 | pages = 644–648 | date = July 2013 | pmid = 23149292 | doi = 10.1016/j.brs.2012.09.010 | s2cid = 2283411 }}

{{cite journal | vauthors = Nitsche MA, Paulus W | title = Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation | journal = The Journal of Physiology | volume = 527 | issue = Pt 3 | pages = 633–639 | date = September 2000 | pmid = 10990547 | pmc = 2270099 | doi = 10.1111/j.1469-7793.2000.t01-1-00633.x }}

{{cite journal | vauthors = Bikson M, Datta A, Elwassif M | title = Establishing safety limits for transcranial direct current stimulation | journal = Clinical Neurophysiology | volume = 120 | issue = 6 | pages = 1033–1034 | date = June 2009 | pmid = 19394269 | pmc = 2754807 | doi = 10.1016/j.clinph.2009.03.018 }}

{{cite journal | vauthors = Viganò A, D'Elia TS, Sava SL, Auvé M, De Pasqua V, Colosimo A, Di Piero V, Schoenen J, Magis D | display-authors = 6 | title = Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine | journal = The Journal of Headache and Pain | volume = 14 | issue = 1 | pages = 23 | date = March 2013 | pmid = 23566101 | pmc = 3620516 | doi = 10.1186/1129-2377-14-23 | doi-access = free }}

{{cite journal | vauthors = Poreisz C, Boros K, Antal A, Paulus W | title = Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients | journal = Brain Research Bulletin | volume = 72 | issue = 4–6 | pages = 208–214 | date = May 2007 | pmid = 17452283 | doi = 10.1016/j.brainresbull.2007.01.004 | s2cid = 40861513 }}

{{cite journal | vauthors = Horvath JC, Forte JD, Carter O | title = Quantitative Review Finds No Evidence of Cognitive Effects in Healthy Populations From Single-session Transcranial Direct Current Stimulation (tDCS) | journal = Brain Stimulation | volume = 8 | issue = 3 | pages = 535–550 | year = 2015 | pmid = 25701175 | doi = 10.1016/j.brs.2015.01.400 | s2cid = 19833275 }}

{{cite journal | vauthors = Horvath JC, Forte JD, Carter O | title = Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: A systematic review | journal = Neuropsychologia | volume = 66 | pages = 213–236 | date = January 2015 | pmid = 25448853 | doi = 10.1016/j.neuropsychologia.2014.11.021 | s2cid = 27300914 }}

{{cite journal | vauthors = Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CH, Young AH | title = Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis | journal = BMJ | volume = 364 | pages = l1079 | date = March 2019 | pmid = 30917990 | pmc = 6435996 | doi = 10.1136/bmj.l1079 | quote = we found tDCS to be efficacious across outcomes in both pairwise and network meta-analyses. }}

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{{Psychiatry}}

{{DEFAULTSORT:Transcranial Direct Current Stimulation}}

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