Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)
Section snippets
Principles and mechanisms of action of transcranial direct current stimulation
Alterations of neuroplasticity and cortical excitability are important pathophysiological factors in many neuropsychiatric diseases. Thus, to modify cortical activities by using non-invasive brain stimulation (NIBS) might be a valuable therapeutic approach. One of these NIBS approaches is transcranial direct current stimulation (tDCS). Fifty years ago, it has been demonstrated in anesthetized rats that neural activity and cortical excitability could be modified by the application of direct
Clinical applications of tDCS: literature data analysis
For each potential clinical indication of tDCS, a bibliographic search was carried out by several experts independently, using specific keywords that will be specified at the beginning of each section. Each expert then proceeded to a critical reading of all selected publications in order to classify them according to the following criteria, derived from those proposed by the European Federation of Neurological Societies (Brainin et al., 2004). First, the studies were classified (I–IV) according
Pain
The literature review included studies related to ongoing chronic pain, or acute postoperative pain, and therefore excludes publications on the use of tDCS to relieve pain experimentally induced in healthy subjects, reviewed elsewhere (Mylius et al., 2012). A PubMed search [keywords: tDCS AND (pain OR migraine)] identified 269 papers, including 62 original clinical studies covering 1426 patients. In all indications, we first screened literature data for original clinical trials, excluding any
Parkinson’s disease
In advanced Parkinson’s disease (PD), the emergence of fluctuations, dyskinesias, difficulties with gait and postural control, cognitive impairment and non-motor symptoms refractory to conventional therapy poses therapeutic challenges. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in NIBS techniques as alternative therapeutic tool. The rationale for the use of NIBS draws from the concept that reversing
Other movement disorders
Actually, published tDCS studies on movement disorders other than PD are rare and have been recently reviewed (Ferrucci et al., 2016). There are only two sham-controlled crossover studies using repeated tDCS sessions. The first study concerned 8 patients with essential tremor who completed a tDCS protocol for 10 days with two cathodes placed over both cerebellar hemispheres and two anodes positioned over both prefrontal areas (Gironell et al., 2014). In this study, any short- or long-lasting
Motor stroke
The recovery of motor function after stroke is one of the most important issues addressed in neurorehabilitation medicine. The rationale of cortical stimulation following stroke is to promote adaptive neuroplasticity, taking place in the perilesional region as well as in the homologous area of the contralesional hemisphere. Functional magnetic resonance imaging (fMRI) studies have revealed an initial decrease in ipsilesional activity in the first 3 days after stroke followed by an increase in
Aphasia
Aphasia is a highly disabling language disorder frequently caused by a left-lateralized hemispheric stroke (Laska et al., 2001). Even if traditional linguistic-based therapies have been proved to induce an adequate clinical improvement (Basso et al., 2011, Code and Petheram, 2011, Brady et al., 2012), a large percentage of patients are left with some degree of language impairment (Lazar et al., 2010). It has been suggested that one of the key predictors for positive language outcomes is
Multiple sclerosis
Multiple sclerosis (MS) is one of the most common neurological diseases and a serious cause of disability in young adults. Its natural course is characterized by recurrent relapses or progressive functional decline. With disease evolution, patients could accumulate several neurological dysfunctions or disease-related complications including motor deficit, fatigue, tremor, spasticity, sensory disturbances, pain, genital or urinary symptoms, and psychiatric or cognitive disorders. Many of these
Epilepsy
Although NIBS techniques aimed at modifying cortical excitability, the study of their therapeutic potential in epilepsy remains underdeveloped. This is the case for rTMS (Lefaucheur et al., 2014) and even more for tDCS. Actually, a PubMed search (keywords: tDCS AND Epilepsy) identified 65 papers, including only 10 original clinical studies and 147 patients. Moreover, 5 of these studies were case reports of 1–5 patients, while 5 sham-controlled studies with crossover or parallel-arm design
Disorders of consciousness
Disorders of consciousness, such as minimally conscious state (MCS) and vegetative state (VS), are highly challenging clinical conditions for treatment. A PubMed search (keywords: tDCS AND vegetative state OR disorders of consciousness) identified 23 papers, including 4 original clinical studies and 79 patients. These four studies included 10, 30, 25, and 14 patients, respectively (Angelakis et al., 2014, Thibaut et al., 2014, Naro et al., 2015, Naro et al., 2016). The left DLPFC was targeted
Alzheimer’s disease
Since its updating in the early 2000s, tDCS has been widely used in neuropsychological studies to act on cognitive and behavioural features, e.g., attention, memory and working memory, computation, decision-making, and so on, in either healthy humans or patients with various neuropsychiatric diseases (Shin et al., 2015, Hill et al., 2016). Therefore, there are a lot of expectations regarding the therapeutic potential of tDCS to modulate psychological processes in cognitive disorders, such as
Tinnitus
Tinnitus is a phantom perception of a sound in the absence of a corresponding external sound source and occurs in 5–15% of the population (Axelsson and Ringdahl, 1989, Heller, 2003, Gallus et al., 2015). Whereas many patients can habituate to this sound, quality of life is severely disrupted in about 25% of the patients who cannot cope with the tinnitus (Axelsson and Ringdahl, 1989). In these patients, tinnitus is frequently associated with anxiety, depression, cognitive impairment, and sleep
Depression
The rationale for the use of tDCS in the treatment of depressive disorders is based on the knowledge of functional and structural abnormalities in the left and right dorsolateral and ventromedial prefrontal cortex, amygdala and hippocampus in depressed patients (Campbell et al., 2004, Hamilton et al., 2008, Koenigs and Grafman, 2009). The aim of the NIBS techniques is to normalize the interhemispheric imbalance of neuronal activity between the both DLPFC areas, which was highlighted in this
Schizophrenia
Despite advances in psychopharmacology, the majority of treated patients with schizophrenia retain disabling symptoms. The most frequent drug-resistant symptoms are auditory verbal hallucinations (AVH) and various negative symptoms (e.g., avolition, alogia, or emotional withdrawal). Neuroimaging and neurophysiological studies have highlighted that these refractory symptoms may be linked to a fronto-temporal dysconnectivity. Negative symptoms and AVH have been related to a reduced brain activity
Substance abuse, addiction and craving
Addiction to substances such as alcohol, drugs, nicotine, or food, is a major health issue, because of the difficulty to achieve a permanent cure with a high rate of relapses, despite detoxification and pharmacological or psychological interventions (Fant et al., 2009, Heinz et al., 2009). The rationale of using tDCS as a treatment for substance addiction and craving is that the DLPFC, which plays a major role in top-down inhibitory control mechanisms and reward mechanisms, was claimed to be
Other psychiatric disorders
Regarding clinical applications of tDCS in psychiatric disorders other than depression, schizophrenia and addiction, there are only very limited data available in the literature. A PubMed search (keywords: tDCS AND obsessive compulsive disorder) identified 17 papers, including 5 original clinical studies and 12 patients. There were 4 single case reports and only one open-label study performed on 8 patients with the cathode placed over the left orbitofrontal cortex and the anode placed over the
At-home do-it-yourself DCS and neural enhancement
One of the main advantages of tDCS as a therapeutic device is to be a low-cost, small-size, and patient-wearable equipment. Also, it allows distribution of machines for home use, which is not the case for rTMS. Although therapeutic effects may last beyond the time of stimulation when using NIBS techniques because of neural plasticity processes, the treatment of a chronic disease always requires repeated sessions in a maintenance protocol. Considering rTMS, this is resulting in multiple trips
Perspectives of targets other than cortical (cerebellum and spinal cord)
Although this work is intended to be a guideline on the indications of tDCS applied to the cerebral cortex, readers should be informed that research currently develops to explore the possibility of using transcutaneous DC stimulation on other neural targets, such as cerebellum and spinal cord, in order to promote functional neural changes (Priori et al., 2014). This issue will be briefly addressed.
Perspectives of treatment by transcranial electrical stimulation methods other than tDCS (tACS, tRNS)
Although the present work addresses tDCS results, we should also mention that future developments with potential therapeutic application might regard other non-invasive neuromodulation techniques using low-intensity transcranial electrical stimulation. We briefly present these other techniques, namely tACS and tRNS, which are for now the subject of relatively few clinical studies. Taking into account all physical possibilities, an indefinite number of transcranial electrical stimulation
Summary of recommendations
This work presents for the first time a comprehensive evidence-based analysis of the reported clinical efficacy of various tDCS montages that could lead to therapeutic applications in the neurological, otorhinolaryngological, and psychiatric domains. According to this synthesis, there is a sufficient level of evidence to make recommendations for the efficacy of specific tDCS montages in several clinical indications, as summarized in Table 11.
To date, a Level A recommendation has not been
Conflict of interest
Michael A. Nitsche is member of the advisory board of Neuroelectrics, Barcelona, Spain. Simone Rossi have received grants from EBNeuro S.p.A, Florence, Italy and travel support from MagVenture, Farum, Denmark and Magstim Co., Whitland, Carmarthenshire, UK, respectively. Walter Paulus is on the scientific advisory board of EBS technologies, Berlin, Germany. Frank Padberg has received speaker honorarium from Mag&More GmbH, Munich, Germany and equipment support from neuroConn GmbH, Ilmenau,
References (507)
- et al.
Metaplasticity: a new vista across the field of synaptic plasticity
Prog Neurobiol
(1997) - et al.
Transcranial alternating current stimulation reduces symptoms in intractable idiopathic cervical dystonia: a case study
Neurosci Lett
(2013) - et al.
Transcranial direct current stimulation effects in disorders of consciousness
Arch Phys Med Rehabil
(2014) - et al.
Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans
Brain Stimul
(2008) - et al.
Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition
J Pain Symptom Manage
(2010) - et al.
Transcranial direct current stimulation for treatment of refractory childhood focal epilepsy
Brain Stimul
(2013) - et al.
Transcranial direct current stimulation in treatment-resistant obsessive-compulsive disorder: An open-label pilot study
Prog Neuropsychopharmacol Biol Psychiatry
(2016) - et al.
Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram
Clin Neurophysiol
(2015) - et al.
Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials
J Psychiatric Res
(2013) - et al.
Safety of transcranial direct current stimulation: evidence based update 2016
Brain Stimul
(2016)
Spinal direct current stimulation modulates short intracortical inhibition
Neuromodulation
An unexpected target of spinal direct current stimulation: interhemispheric connectivity in humans
J Neurosci Methods
Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease
J Neurol Sci
Go-no-go task performance improvement after anodal transcranial direct DC stimulation of the left dorsolateral prefrontal cortex in major depression
J Affect Disord
Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study
Drug Alcohol Depend
Cumulative priming effects of cortical stimulation on smoking cue-induced craving
Neurosci Lett
Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)
Drug Alcohol Depend
Prolonged visual memory enhancement after direct current stimulation in Alzheimer’s disease
Brain Stimul
Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study
Gastrointest Endosc
Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA)
Clin J Pain
Direct current stimulation of primary motor cortex and cerebellum and botulinum toxin a injections in a person with cervical dystonia
Brain Stimul
Is neuroenhancement by noninvasive brain stimulation a net zero-sum proposition?
Neuroimage
Tremor suppression by rhythmic transcranial current stimulation
Curr Biol
Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia
Brain Stimul
Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings
Prog Neuropsychopharmacol Biol Psychiatry
Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study
Eur Psychiatry
Bifrontal tDCS prevents implicit learning acquisition in antidepressant-free patients with major depressive disorder
Prog Neuropsychopharmacol Biol Psychiatry
Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial
J Affect Disord
Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression
Neuromodulation
Cognitive effects of transcranial direct current stimulation in depression: results from the SELECT-TDCS trial and insights for further clinical trials
J Affect Disord
A meta-analysis of the efficacy of anodal transcranial direct current stimulation for upper limb motor recovery in stroke survivors
J Hand Ther
Combining voxel-based lesion-symptom mapping (VLSM) with A-tDCS language treatment: predicting outcome of recovery in nonfluent chronic aphasia
Brain Stimul
Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke
Clin Neurophysiol
Clinically effective treatment of fibromyalgia pain with high-definition transcranial direct current stimulation: phase ii open-label dose optimization
J Pain
Enhancement of cortical excitability and lower limb motor function in patients with stroke by transcranial direct current stimulation
Brain Stimul
Transcranial direct current stimulation post-stroke upper extremity motor recovery studies exhibit a dose-response relationship
Brain Stimul
Reappraisal of the anatomical landmarks of motor and premotor cortical regions for image-guided brain navigation in TMS practice
Hum Brain Mapp
Neuropathic pain: transcranial electric motor cortex stimulation using high frequency random noise. Case report of a novel treatment
J Pain Res
Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke
Sci Transl Med
Effect of anodal transcranial direct current stimulation on autism: a randomized double-blind crossover trial
Behav Neurol
The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism: a randomized crossover controlled trial
Behav Neurol
Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke
Ann Neurol
Once- to twice-daily, 3-year domiciliary maintenance transcranial direct current stimulation for severe, disabling, clozapine-refractory continuous auditory hallucinations in schizophrenia
J ECT
Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence
Invest Ophthalmol Vis Sci
Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex
Eur J Neurosci
Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine
Cephalalgia
Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain
J Physiol (London)
Efficacy of cathodal transcranial direct current stimulation in drug-resistant epilepsy: a proof of principle
Conf Proc IEEE Eng Med Biol Soc
Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in neuropathic pain due to radiculopathy: a randomized sham controlled comparative study
Pain
Migraine prophylaxis by anodal transcranial direct current stimulation, a randomized, placebo-controlled trial
J Med Assoc Thai
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