Adverse events of tDCS and tACS: A review

Highlights • No serious adverse effects have been reported in experiments using either tDCS or tACS.• Persistent adverse effects of tDCS are mainly skin problems; for tACS, none have been reported.• Further safety investigations are needed.

[1]  O. Lippold,et al.  A Preliminary Account of the Clinical Effects of Polarizing the Brain in Certain Psychiatric Disorders , 1964, British Journal of Psychiatry.

[2]  Y. Ugawa.  Motor cortical plasticity in basal ganglia disorders or movement disorders , 2012 .

[3]  J. Menk,et al.  Safety and Feasibility of Transcranial Direct Current Stimulation in Pediatric Hemiparesis: Randomized Controlled Preliminary Study , 2014, Physical Therapy.

[4]  Abhishek Datta,et al.  Establishing safety limits for transcranial direct current stimulation , 2009, Clinical Neurophysiology.

[5]  A. Antal,et al.  Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans , 2008, Brain Stimulation.

[6]  A. Gharabaghi,et al.  Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study , 2016, Front. Cell. Neurosci..

[7]  F. Fregni,et al.  Hypomanic episode in unipolar depression during transcranial direct current stimulation , 2010, Acta Neuropsychiatrica.

[8]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[9]  J. Calabrese,et al.  Treatment-emergent mania in unipolar and bipolar depression: focus on repetitive transcranial magnetic stimulation. , 2008, The international journal of neuropsychopharmacology.

[10]  Marco Cursi,et al.  Safety and Efficacy of Transcranial Direct Current Stimulation in Acute Experimental Ischemic Stroke , 2013, Stroke.

[11]  F. Fregni,et al.  A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials , 2016, Brain Stimulation.

[12]  Margherita Russo,et al.  Transcranial Alternating Current Stimulation in Patients with Chronic Disorder of Consciousness: A Possible Way to Cut the Diagnostic Gordian Knot? , 2016, Brain Topography.

[13]  J. Brunelin,et al.  Effects of theta-rhythm transcranial alternating current stimulation (4.5 Hz-tACS) in patients with clozapine-resistant negative symptoms of schizophrenia: a case series , 2016, Journal of Neural Transmission.

[14]  Alexander Opitz,et al.  Safety of 5 kHz tACS , 2014, Brain Stimulation.

[15]  J. Rothwell,et al.  Level of action of cathodal DC polarisation induced inhibition of the human motor cortex , 2003, Clinical Neurophysiology.

[16]  A. Brunoni,et al.  Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry. , 2016, Journal of child and adolescent psychopharmacology.

[17]  Mark S. George,et al.  Reducing procedural pain and discomfort associated with transcranial direct current stimulation , 2011, Brain Stimulation.

[18]  W Paulus,et al.  Both the cutaneous sensation and phosphene perception are modulated in a frequency-specific manner during transcranial alternating current stimulation. , 2013, Restorative neurology and neuroscience.

[19]  Michael Siniatchkin,et al.  Ten minutes of 1mA transcranial direct current stimulation was well tolerated by children and adolescents: Self-reports and resting state EEG analysis , 2015, Brain Research Bulletin.

[20]  B. Langguth,et al.  Anodal skin lesions after treatment with transcranial direct current stimulation , 2010, Brain Stimulation.

[21]  K. Hoffmann,et al.  Direct Current Stimulation over V5 Enhances Visuomotor Coordination by Improving Motion Perception in Humans , 2004, Journal of Cognitive Neuroscience.

[22]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[23]  Jordan Grafman,et al.  Recharging cognition with DC brain polarization , 2005, Trends in Cognitive Sciences.

[24]  Géza Gergely Ambrus,et al.  Cutaneous perception thresholds of electrical stimulation methods: Comparison of tDCS and tRNS , 2010, Clinical Neurophysiology.

[25]  F. Fregni,et al.  Safety of repeated transcranial direct current stimulation in impaired skin: a case report. , 2013, The journal of ECT.

[26]  F. Fregni,et al.  The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. , 2013, JAMA psychiatry.

[27]  Dennis J. L. G. Schutter,et al.  Retinal origin of phosphenes to transcranial alternating current stimulation , 2010, Clinical Neurophysiology.

[28]  H. Matsumoto,et al.  Therapeutic effects of non-invasive brain stimulation for dystonia , 2016 .

[29]  Walter Paulus,et al.  Facilitation of visuo‐motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans , 2004, The European journal of neuroscience.

[30]  M. Nitsche,et al.  Facilitation of Implicit Motor Learning by Weak Transcranial Direct Current Stimulation of the Primary Motor Cortex in the Human , 2003, Journal of Cognitive Neuroscience.

[31]  J. Lagopoulos,et al.  Recommendations for the use of tDCS in clinical research , 2010, Acta Neuropsychiatrica.

[32]  L. Merabet,et al.  Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions , 2012, Brain Stimulation.

[33]  O. Lippold,et al.  Mental Changes Resulting from the Passage of Small Direct Currents Through the Human Brain , 1964, British Journal of Psychiatry.

[34]  Caspar M. Schwiedrzik,et al.  Retina or Visual Cortex? The Site of Phosphene Induction by Transcranial Alternating Current Stimulation , 2009, Front. Integr. Neurosci..

[35]  I. Benseñor,et al.  The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase , 2015, Neural plasticity.

[36]  Michael A. Nitsche,et al.  Non-invasive brain stimulation for the treatment of brain diseases in childhood and adolescence: state of the art, current limits and future challenges , 2013, Front. Syst. Neurosci..

[37]  Á. Pascual-Leone,et al.  Skin Lesions Induced by Transcranial Direct Current Stimulation (tDCS) , 2014, Brain Stimulation.

[38]  F. Fregni,et al.  A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. , 2011, The international journal of neuropsychopharmacology.

[39]  M. Nitsche,et al.  Evaluation of Sham Transcranial Direct Current Stimulation for Randomized, Placebo-Controlled Clinical Trials , 2013, Brain Stimulation.

[40]  N Accornero,et al.  Polarization of the human motor cortex through the scalp , 1998, Neuroreport.

[41]  Frank Padberg,et al.  Skin lesions after treatment with transcranial direct current stimulation (tDCS) , 2008, Brain Stimulation.

[42]  Walter Paulus,et al.  Modulation of cortical excitability by weak direct current stimulation--technical, safety and functional aspects. , 2003, Supplements to Clinical neurophysiology.

[43]  Moritz Dannhauer,et al.  Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial , 2016, PloS one.

[44]  Mark S. George,et al.  Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. , 2011, Gastrointestinal endoscopy.

[45]  Margherita Russo,et al.  Does Transcranial Alternating Current Stimulation Induce Cerebellum Plasticity? Feasibility, Safety and Efficacy of a Novel Electrophysiological Approach , 2016, Brain Stimulation.

[46]  Frank Padberg,et al.  The Role of Contact Media at the Skin-electrode Interface During Transcranial Direct Current Stimulation (tDCS) , 2014, Brain Stimulation.

[47]  Yves Vandermeeren,et al.  Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions , 2010, BMC Neuroscience.

[48]  P. Enticott,et al.  Editorial: The safety and efficacy of noninvasive brain stimulation in development and neurodevelopmental disorders , 2015, Front. Hum. Neurosci..

[49]  E. Haffen,et al.  Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram , 2015, Clinical Neurophysiology.

[50]  Marom Bikson,et al.  Reducing Transcranial Direct Current Stimulation‐Induced Erythema With Skin Pretreatment: Considerations for Sham‐Controlled Clinical Trials , 2015, Neuromodulation : journal of the International Neuromodulation Society.

[51]  Leonardo G. Cohen,et al.  Noninvasive brain stimulation in stroke rehabilitation , 2006, NeuroRX.

[52]  N. J. Davis,et al.  “Non-invasive” brain stimulation is not non-invasive , 2013, Front. Syst. Neurosci..

[53]  R. Tuckett.  Itch evoked by electrical stimulation of the skin. , 1982, The Journal of investigative dermatology.

[54]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[55]  A. Priori,et al.  Efficacy and Safety of Transcranial Direct Current Stimulation in Major Depression , 2011, Biological Psychiatry.

[56]  Yasuo Terao,et al.  Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area , 2008, Experimental Brain Research.

[57]  S. Sato,et al.  Safety and cognitive effect of frontal DC brain polarization in healthy individuals , 2005, Neurology.

[58]  L. Rozek,et al.  Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer , 2016, Front. Hum. Neurosci..

[59]  M. Nitsche,et al.  Limited impact of homeostatic plasticity on motor learning in humans , 2008, Neuropsychologia.

[60]  C. Krishnan,et al.  Safety of Noninvasive Brain Stimulation in Children and Adolescents , 2015, Brain Stimulation.

[61]  A. Antal,et al.  Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients , 2007, Brain Research Bulletin.

[62]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[63]  Danique Jeurissen,et al.  Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD) , 2016, Journal of child neurology.

[64]  Walter Paulus,et al.  Transcranial alternating current stimulation in the low kHz range increases motor cortex excitability. , 2011, Restorative neurology and neuroscience.

[65]  S. Tobimatsu,et al.  Phase and Frequency-Dependent Effects of Transcranial Alternating Current Stimulation on Motor Cortical Excitability , 2016, PloS one.

[66]  Gerald V. Smith,et al.  Is Transcranial Electrical Stimulation (TCES) a Safe Intervention for Children with Cerebral Palsy? , 1998 .

[67]  P. Sachdev,et al.  Transcranial direct current stimulation - what is the evidence for its efficacy and safety? , 2009, F1000 medicine reports.

[68]  Alireza Gharabaghi,et al.  Neurosensory Effects of Transcranial Alternating Current Stimulation , 2014, Brain Stimulation.

[69]  S. Rossi,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee , 2015, Clinical Neurophysiology.

[70]  M. Nitsche,et al.  Case Report: Successful Treatment of Therapy-Resistant OCD With Application of Transcranial Alternating Current Stimulation (tACS) , 2016, Brain Stimulation.

[71]  P. Mitchell,et al.  Induction of hypomanic episode with transcranial direct current stimulation. , 2010, The journal of ECT.

[72]  A. Antal,et al.  Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms , 2016, Neural plasticity.

[73]  C. Andrade,et al.  Efficacy and safety of combining clozapine with electrical or magnetic brain stimulation in treatment-refractory schizophrenia , 2016, Expert review of clinical pharmacology.

[74]  C. Gall,et al.  Restoration of vision after optic nerve lesions with noninvasive transorbital alternating current stimulation: a clinical observational study , 2011, Brain Stimulation.

[75]  Alvaro Pascual-Leone,et al.  Cognitive, Mood, and Electroencephalographic Effects of Noninvasive Cortical Stimulation With Weak Electrical Currents , 2011, The journal of ECT.

[76]  M. Nitsche,et al.  Safety limits of cathodal transcranial direct current stimulation in rats , 2009, Clinical Neurophysiology.

[77]  M. Nitsche,et al.  Safety criteria for transcranial direct current stimulation (tDCS) in humans , 2003, Clinical Neurophysiology.

[78]  F. Fregni,et al.  Manic psychosis after sertraline and transcranial direct-current stimulation. , 2011, The Journal of neuropsychiatry and clinical neurosciences.

[79]  J. Lagopoulos,et al.  Feeling the heat: the electrode–skin interface during DCS , 2008, Acta Neuropsychiatrica.

[80]  G. Thickbroom,et al.  Perception of comfort during transcranial DC stimulation: Effect of NaCl solution concentration applied to sponge electrodes , 2007, Clinical Neurophysiology.

[81]  Xiaoli Li,et al.  Skin Burn After Single Session of Transcranial Direct Current Stimulation (tDCS) , 2015, Brain Stimulation.

[82]  M. Nitsche,et al.  Vascular safety of brain plasticity induction via transcranial direct currents , 2015, Neurology.

[83]  D. Baldwin,et al.  Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability , 2015, Neuroscience & Biobehavioral Reviews.

[84]  Perminder Sachdev,et al.  Hypomania Induction in a Patient With Bipolar II Disorder by Transcranial Direct Current Stimulation (tDCS) , 2011, The journal of ECT.

[85]  N. Koutsouleris,et al.  Transcranial direct current stimulation in children and adolescents: a comprehensive review , 2016, Journal of Neural Transmission.

[86]  Géza Gergely Ambrus,et al.  When Size Matters: Large Electrodes Induce Greater Stimulation-related Cutaneous Discomfort Than Smaller Electrodes at Equivalent Current Density , 2014, Brain Stimulation.

[87]  Abhishek Datta,et al.  A Feasibility Study of Bilateral Anodal Stimulation of the Prefrontal Cortex Using High-Definition Electrodes in Healthy Participants , 2015, The Yale journal of biology and medicine.

[88]  A. Bose,et al.  Safety of Transcranial Direct Current Stimulation in Alcohol-Induced Psychotic Disorder with Comorbid Psoriasis , 2016, Indian journal of psychological medicine.

[89]  Sergio P. Rigonatti,et al.  A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury , 2006, PAIN.

[90]  M. Nitsche,et al.  Anticonvulsant Effects of Transcranial Direct‐current Stimulation (tDCS) in the Rat Cortical Ramp Model of Focal Epilepsy , 2006, Epilepsia.

[91]  Lauren L. Richmond,et al.  Repeated Daily Exposure to Direct Current Stimulation Does Not Result in Sustained or Notable Side Effects , 2013, Brain Stimulation.

[92]  Marco Steinhauser,et al.  Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up , 2016, Brain Stimulation.

[93]  Walter Paulus,et al.  Boosting brain excitability by transcranial high frequency stimulation in the ripple range , 2010, The Journal of physiology.

[94]  Axel Thielscher,et al.  Evaluation of a Modified High-Definition Electrode Montage for Transcranial Alternating Current Stimulation (tACS) of Pre-Central Areas , 2016, Brain Stimulation.

[95]  Diamond Urbano,et al.  Randomized Single Blind Sham Controlled Trial of Adjunctive Home-Based tDCS after rTMS for Mal De Debarquement Syndrome: Safety, Efficacy, and Participant Satisfaction Assessment , 2016, Brain Stimulation.

[96]  M. Nitsche,et al.  Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016 , 2016, Brain Stimulation.

[97]  Deanna Greenstein,et al.  Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia , 2011, Brain Stimulation.

[98]  Oliver Speck,et al.  Effects of alternating current stimulation on the healthy and diseased brain , 2015, Front. Neurosci..

[99]  Abhishek Datta,et al.  Transcranial direct current stimulation for major depression: A general system for quantifying transcranial electrotherapy dosage , 2008, Current treatment options in neurology.

[100]  K. Kriegstein,et al.  Contact dermatitis after transcranial direct current stimulation , 2012, Brain Stimulation.

[101]  Felipe Fregni,et al.  Transcranial Direct Current Stimulation in Epilepsy , 2015, Brain Stimulation.

[102]  F. Fregni,et al.  Feasibility of Transcranial Direct Current Stimulation Use in Children Aged 5 to 12 Years , 2014, Journal of child neurology.

[103]  L. Cohen,et al.  Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation , 2006, Clinical Neurophysiology.

[104]  Yi Wu,et al.  Efficacy of transcranial alternating current stimulation over bilateral mastoids (tACSbm) on enhancing recovery of subacute post-stroke patients , 2016, Topics in stroke rehabilitation.

[105]  A. Fedorov,et al.  Repetitive transorbital alternating current stimulation in optic neuropathy. , 2010, NeuroRehabilitation.

[106]  S. Reeves,et al.  A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception. , 2011, The journal of pain : official journal of the American Pain Society.

[107]  W. Paulus,et al.  Neuroscientists Do Not Use Non-invasive Brain Stimulation on Themselves for Neural Enhancement , 2014, Brain Stimulation.

[108]  Donel M. Martin,et al.  Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression , 2015, The journal of ECT.

[109]  P. Turkeltaub,et al.  Differences in the experience of active and sham transcranial direct current stimulation , 2012, Brain Stimulation.

[110]  Carlo Miniussi,et al.  What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects , 2015, Clinical Neurophysiology.

[111]  Akimasa Hirata,et al.  Computational analysis shows why transcranial alternating current stimulation induces retinal phosphenes , 2013, Journal of neural engineering.

[112]  Vincent Walsh,et al.  Frequency-Dependent Electrical Stimulation of the Visual Cortex , 2008, Current Biology.

[113]  D. Schutter,et al.  Transcranial direct current stimulation to the parietal cortex in hemispatial neglect: A feasibility study , 2015, Neuropsychologia.

[114]  N. Wenderoth,et al.  A technical guide to tDCS, and related non-invasive brain stimulation tools , 2016, Clinical Neurophysiology.

[115]  B. Guleyupoglu,et al.  Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine , 2014, Frontiers in Neuroengineering.

[116]  Alvaro Pascual-Leone,et al.  Safety of rTMS to non-motor cortical areas in healthy participants and patients , 2006, Clinical Neurophysiology.

[117]  D. Liebetanz,et al.  MRI study of human brain exposed to weak direct current stimulation of the frontal cortex , 2004, Clinical Neurophysiology.

[118]  Aneta Szymaszek,et al.  Non-invasive alternating current stimulation induces recovery from stroke. , 2010, Restorative neurology and neuroscience.

[119]  Á. Pascual-Leone,et al.  A Controlled Clinical Trial of Cathodal DC Polarization in Patients with Refractory Epilepsy , 2006, Epilepsia.