Il contributo della stimolazione transcranica

alle neuroscienze: una riflessione

SIMPOSIO CONGIUNTO

SNO/SIN–SINC (Società Italiana di Neurofisiologia Clinica)

Massimo Cincotta S.C. di Neurologia, Firenze - Azienda USL Toscana Centro

Discussant Simone Rossi Dip.to di Scienze Mediche Chirurgiche e Neuroscienze - Università di Siena

6-8 aprile 2017 GROSSETO

HOTEL CONFERENCE CENTRE

FATTORIA LA PRINCIPINAS.P. 158 delle Collacchie, 465

58100 Principina Terra (GR)

Sono stati concessi i patrocini di:

Società dei Neurologi,Neurochirurghi eNeuroradiologi Ospedalier i

Meet ing del l e neur oscienze t oscane

Comune di Grosseto

Ordine dei Medici Chirurghi

e degli Odontoiatri

DALLA EPIDEMIOLOGIA AI PERCORSI INTERDISCIPLINARI

Pr o g r aMM

a

6-8 aprile 2017 GROSSETO

HOTEL CONFERENCE CENTRE

FATTORIA LA PRINCIPINAS.P. 158 delle Collacchie, 465

58100 Principina Terra (GR)

Sono stati concessi i patrocini di:

Società dei Neurologi,Neurochirurghi eNeuroradiologi Ospedalier i

Meet ing del l e neur oscienze t oscane

Comune di Grosseto

Ordine dei Medici Chirurghi

e degli Odontoiatri

DALLA EPIDEMIOLOGIA AI PERCORSI INTERDISCIPLINARI

Pr o g r aMM

a

Potenziali evocati motori (MEP)

da stimolazione elettrica transcranica

Stimolazione

corticale

Cenni storici D ’ Arsonval (1896) Electromagnetic fields may also elicit phosphenes

Thompson SP. 1910. A physiological effect of an alternating magnetic field. Proc R Soc Lond B B82:396-399.

Dunlap K. 1911. Visual sensations from the alternating magnetic field. Science 33:68-71.

Magnusson CE & Stevens HC. 1911. Visual sensations created by a magnetic field. Am J Physiol 29:124-136.

Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex. Lancet 1985;1:1106–7.

Coil focale e coil circolare

Principali applicazioni

della stimolazione magnetica transcranica

• Studio della conduzione nervosa cortico-spinale

• Studio dei meccanismi eccitatori ed inibitori corticali

• Interferenza con le funzioni corticali

• Modulazione dei meccanismi eccitatori ed inibitori corticali

• Studio della neuroplasticità

• Studio delle connessioni cortico-corticali

Stimolazione magnetica transcranica

PubMed: transcranial magnetic stimulation

0

200

400

600

800

1000

1200

1400

PubMed: transcranial magnetic stimulation

Potenziali evocati motori

da stimolazione magnetica transcranica:

mielopatia cervicale spondiloartrosica

Valutazione dei fenomeni eccitatori ed inibitori della

corteccia motoria primaria (M1) mediante TMS

• Soglia motoria (RMT, AMT)

• Ampiezza e curva di reclutamento del MEP

• Periodo silente corticale (CSP)

• Periodo silente ipsilaterale (ISP)

• Inibizione intracorticale da impulsi appaiati a breve intervallo interstimolo (SICI)

• Facilitazione intracorticale (ICF)

• Inibizione intracorticale da impulsi appaiati a lungo intervallo interstimolo (LICI)

• Inibizione transcallosale del MEP da impulsi appaiati

• Inibizione afferente a breve latenza (SAI)

• Inibizione afferente a lunga latenza (LAI)

Stimolazione magnetica

transcranica (TMS)

Nature © Macmillan Publishers Ltd 1997

letters to nature

182 NATURE|VOL 389| 11 SEPTEMBER1997

somatosensory information in sighted mammalsoccursat corticalassociation sites2. It is possible that connections between parietaland visual association areasmediate thetransfer of somatosensoryinformation to the occipital cortex in blind subjects22. If so, whatoperations does the occipital cortex perform with the tactileinformation?In our experiment, speech wasnot affected bystimu-lation of anysite, and errorswerenot corrected when subjectsweregiven achanceto restate their choice after theend of stimulation.This indicates that errorswerenot dueto interferencewith speech(output), but todisruption of discrimination processing.TMSovercontralateral sensorimotor cortex and over parietal sites was rela-tively lesseffectivein inducingerrorsthan over mid-occipital areas(Fig. 2). Therefore, arrival of somatosensory information in pri-marysomatosensorycortex (input) wasrelativelysparedbyTMSinblind subjects. Becauseprimary input (somatosensory) and output(speech) werespared, theeffectsof mid-occipital TMSarethoughtto be related to interference with more complex discriminativeoperations performed by the occipital cortex in the blind. Theoccasional induction of complex sensations (phantom or extradots) with occipital TMSsupportsthis interpretation. Stimulationof sensorimotor regions that resulted in jerking of contralateralhand muscles (each TMS train produced 12:206 4:43 motor

evoked potentials in theSVRand 12:406 3:38 in theEBBgroups)did not induce sensations of missing or extra dots in any of thesubjectstested.

In theSVRgroup, therewasasignificant effect of stimulated scalpposition ontheerror rate.Stimulation of theoccipital cortexdidnotaffect identification of embossedRoman lettersor induceabnormalsomatosensory perceptions. This result, in combination with thedecreaseof occipital activity on positron emission tomography insubjectsperformingasimilar task1,suggeststhat sighted individualsdo not normally use the occipital cortex for identification ofembossed Roman letters as the blind do for Braille and Romanletter reading. Stimulation of the contralateral sensorimotorcortex induced more errors than in the control conditionðP# 0:001;OR¼2:95;CI ¼ð1:95;4:48ÞÞ. Because the ability tointerfere with a task is likely to depend on how well learned thetask is, the hand movements induced by stimulation of the con-tralateral sensorimotor cortex may haveexerted amoredisruptiveeffect in theless-trained sighted readersthan in thehighly trainedblind readers. Alternatively, sighted subjectsmay havespent moretimethan blind subjects in somatosensory processing, making thetask moresusceptible to disruption by TMSover thecontralateralsensorimotor cortex.

Thefinding that theoccipital cortex isan important componentof the network involved in Braille reading supports the idea thatperceptionsaredynamicallydeterminedbythecharacteristicsof thesensory inputs rather than only by the brain region that receivesthose inputs, at least in thecaseof early blindness2,7. Theseresultsshowthat cross-modal plasticityasidentified electrophysiologicallyor by neuroimaging techniques in humans may be involved infunctional compensation. M. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Methods

Subjects. StudyprotocolswereapprovedbytheInstitutional ReviewBoardsof

theNational Instituteof Neurological DisordersandStrokeand theUniversity

of Valencia, and TMSwas used under a USFood and Drug Administration

investigational deviceexemption. Subjectsgavetheir written informed consent

for thestudy. Blind subjectshad normal brain magnetic resonanceimagesand

no progressiveneurological disease. Sighted volunteers had normal neurolo-

gical examinationsand visual acuity better than 20/40.

Stimulation technique. Each train of TMSwastriggered bythereadingfinger

crossing a laser beam (Fig. 1b) and had a fixed frequency of 10Hz and a

duration of 3s. TMSwasdeliveredwith amagnetoelectricstimulator (Cadwell

Laboratories, Kennewick, WA) and an 8-shaped23 water-cooled coil, each loop

of which was7cm in diameter. Thecoil washeld tangentially to thescalp with

the intersection of both loops oriented sagittally. The stimulus intensity

(normalized across subjects) was 10% above the minimal output of the

stimulator required to induce a 50-mV electromyographic response from a

relaxed muscle (first dorsal interosseous) involved in theBraille reading task

when thestimuluswasapplied over theprimary motor cortex.

Positions stimulated. SeeFig. 1a. In theblindsubjects(EBB, seeTable1),TMS

wasdelivered randomly to threeoccipital positions(midline, contralateral and

ipsilateral to thereadingfinger, overlyingBrodmann areas17, 18 and 19; Oz,

O1 and O2 of the international 10–20 system of electrode placement), two

parietal positions (contralateral and ipsilateral, approximately overlying

Brodmann area 7; P3 and P4), a midfrontal position (Fz) and to the

contralateral sensorimotor area(overlyingBrodmannareas4,3,1and2)24.Asa

control condition, TMS was also delivered into the air (the sound of the

stimulator was as loud as in actual brain stimulation, but no stimulation

Figure 2 Error rates (mean 6 s:e:) for stimulation of different positions in the four

groups studied. Missing bars indicate that stimulation at that position was not

performed in that specific group (see Methods). Black bars indicate error rates

induced by stimulation of the mid-occipital position, and grey bars the error rates

induced by stimulation of the contralateral sensorimotor cortex. In both groups of

early blind subjects, stimulation of the mid-occipital position induced more errors

in reading Braille and Roman letters than stimulation of any other position,

whereas in the sighted volunteers stimulation of the contralateral primary sen-

sorimotor region induced more errors than stimulation of any other position.

Asterisks indicate scalp positions where significantly more errors occurred than

control (air, marked with arrows). S-M, sensorimotor cortex; contra, contralateral;

ipsi, ipsilateral. Asterisk, P , 0:001.

Table 2 Number of letters read in 3 s

5 Braille letters

EBB

3 Roman letters

SVR

3 Roman letters

EBR

Unstimulated

trials

Stimulated

trials

Unstimulated

trials

Stimulated

trials

Unstimulated

trials

Stimulated

trials.............................................................................................................................................................................

Mean 3.80 3.73 2.38 2.44 2.80 2.86

S.d. 0.83 1.10 0.49 0.62 0.40 0.34.............................................................................................................................................................................

2013

Quartarone et al., 2006

Protocolli di stimolazione transcranica off-line

In the late 1700s to early 1800s,

Giovanni Aldini (Galvani’s

nephew) reported experiments

using galvanization to treat

psychosis and depression

Stimolazione elettrica transcranica (tES)

Guidelines

Evidence-based guidelines on the therapeutic use of transcranial direct

current stimulation (tDCS)

Jean-Pascal Lefaucheur a,b,⇑, Andrea Antal c, Samar S. Ayachea,b, David H. Benninger d, Jérôme Brunelin e,

Filippo Cogiamanian f,g, Maria Cotelli h, Dirk De Ridder i,j, Roberta Ferrucci f,g, Berthold Langguth k,

Paola Marangolo l,m, Veit Myliusn,o, Michael A. Nitschep,q, Frank Padberg r, Ulrich Palm r,

Emmanuel Poulet e,s, Alberto Priori f,g,t, Simone Rossi u, Martin Schecklmann k, Sven Vannestev,w,

Ulf Ziemann x, Luis Garcia-Larrea y,1, Walter Paulusc,1

aDepartment of Physiology, Henri Mondor Hospital, Assistance Publique–Hôpitaux deParis,Créteil, FrancebEA4391, NerveExcitability and Therapeutic Team (ENT), Faculty of Medicine, ParisEst Créteil University, Créteil, FrancecDepartment of Clinical Neurophysiology, University Medical Center, Georg-August University, Göttingen, GermanydDepartment of Clinical Neurosciences, Section of Neurology, CentreHospitalier Universitaire Vaudois, Lausanne, SwitzerlandePsyR2 Team, U1028, INSERM and UMR5292, CNRS, Center for Neuroscience Research of Lyon (CRNL), CH LeVinatier, Lyon-1 University, Bron, Francef Clinica Neurologica III, Dipartimento di Scienzedella Salute, Azienda Ospedaliera Santi Paolo eCarlo,Università degli Studi di Milano, Milano, ItalygIRCCSFondazione OspedaleMaggiorePoliclinico, Milano, ItalyhNeuropsychology Unit, IRCCSFondazione Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italyi Brai2n, Tinnitus Research Initiative Clinic of Antwerp, Sint Augustinus Hospital, Wilrijk, Belgiumj Department of Surgical Sciences, Section of Neurosurgery, Dunedin School of Medicine, University of Otago, Dunedin, New ZealandkDepartment of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germanyl Dipartimento di Studi Umanistici, University Federico II, Naples, Italym IRCCSFondazione Santa Lucia, Rome, ItalynDepartment of Neurology, Section Pain and Neuromodulation, University of Marburg, Marburg, GermanyoDepartment of Neurology, Center for Neurorehabilitation, Valens, SwitzerlandpDepartment of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, GermanyqDepartment of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germanyr Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, GermanysDepartment of Emergency Psychiatry, Edouard Herriot Hospital, HospicesCivilsdeLyon, Lyon, Francet Dipartimento di Fisiopatologia Medico-Chirurgica edei Trapianti, Università degli Studi di Milano, Milano, ItalyuUnit of Neurology and Clinical Neurophysiology, Brain Investigation & Neuromodulation Lab, Department of Neuroscience, and Human Physiology Section, Siena University, Siena,

ItalyvDepartment of Translational Neuroscience, Faculty of Medicine, University of Antwerp, Edegem, BelgiumwLaboratory for Auditory and Integrative Neuroscience, School of Behavioral and Brain Sciences, TheUniversity of Texas, Dallas, TX, USAxDepartment of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard KarlsUniversity, Tübingen, GermanyyNeuroPain Team, U1028, INSERM, Center for Neuroscience Research of Lyon (CRNL), Lyon-1 University, Bron, France

a r t i c l e i n f o

Articlehistory:

Accepted 20 October 2016

Available online 29 October 2016

h i g h l i g h t s

Agroup of European experts reviewed current evidencefor therapeutic efficacy of tDCS.

Level Bevidence (probableefficacy) was found for fibromyalgia, depression and craving.

The therapeutic relevance of tDCSneeds to be further explored in theseand other indications.

http://dx.doi.org/10.1016/j.clinph.2016.10.087

1388-2457/Ó2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Abbreviations: AD, Alzheimer’s disease; ARAT, action research arm test; BDI, Beck Depression Inventory; BI, Barthel Index; DC, direct current; DLPFC, dorsolateral

prefrontal cortex; EEG, electroencephalography; ERP, event-related potentials; FMA, Fugl-Meyer assessment; fMRI, functional magnetic resonance imaging; GABA, gamma-

aminobutyric acid; HDRS, Hamilton Depression Rating Scale; JTT, Jebsen–Taylor hand function test; M1, primary motor cortex; MADRS, Montgomery–Asberg depression

rating scale; MCS, minimally conscious state; MEP, motor evoked potential; NMDA, N-methyl D-aspartate; OMCASS, Orgogozo MCA scale; PANSS, positive and negative

symptomsscale; PD,Parkinson’sdisease; PES, peripheral electrical stimulation; RCT, randomized controlled trial; rTMS, repetitive transcranial magnetic stimulation; SANS,

Scalefor theAssessment of NegativeSymptoms; tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation; TMS, transcranial magnetic

stimulation; tRNS, transcranial random noise stimulation; tsDCS, transcutaneous spinal direct current stimulation; UPDRS, unified Parkinson’s disease rating scale; V1,

primary visual cortex; VAS, visual analogue scale; VRT, virtual reality training; VS, vegetative state.⇑ Correspondingauthor at: ServicePhysiologie,ExplorationsFonctionnelles,Hôpital Henri Mondor,51avenuedeLattredeTassigny,94010Créteil cedex,France. Fax: +331

4981 4660.

E-mail address: jean-pascal.lefaucheur@hmn.aphp.fr (J.-P. Lefaucheur).1 Equal contribution.

Clinical Neurophysiology 128 (2017) 56–92

Contents lists available at ScienceDirect

Clinical Neurophysiology

journal homepage: www.elsevier.com/locate/cl inphKeywords:

Cortex

Indication

Neurological disease

Neuromodulation

Noninvasive brain stimulation

Psychiatric disease

tDCS

Treatment

a b s t r a c t

Agroup of European expertswascommissioned by theEuropean Chapter of theInternational Federation

of Clinical Neurophysiology to gather knowledgeabout thestateof theart of the therapeutic useof tran-

scranial direct current stimulation (tDCS) from studies published up until September 2016, regarding

pain,Parkinson’sdisease,other movement disorders, motor stroke,poststrokeaphasia,multiplesclerosis,

epilepsy, consciousness disorders, Alzheimer’sdisease, tinnitus, depression, schizophrenia, and craving/

addiction. Theevidence-based analysis included only studiesbased on repeated tDCSsessionswith sham

tDCScontrol procedure; 25 patients or more having received active treatment was required for Class I,

while a lower number of 10–24 patients was accepted for Class II studies. Current evidence does not

allow makingany recommendation of Level A (definiteefficacy) for any indication. Level Brecommenda-

tion (probableefficacy) isproposed for: (i) anodal tDCSof the left primary motor cortex (M1) (with right

orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCSof the left dorsolateral prefrontal cortex (DLPFC)

(with right orbitofrontal cathode) in major depressive episodewithout drug resistance; (iii) anodal tDCS

of theright DLPFC(with left DLPFCcathode) in addiction/craving. Level Crecommendation (possibleeffi-

cacy) is proposed for anodal tDCSof the left M1 (or contralateral to pain side, with right orbitofrontal

cathode) in chronic lower limb neuropathicpain secondary to spinal cord lesion. Conversely, Level Brec-

ommendation (probable inefficacy) isconferred on theabsenceof clinical effectsof: (i) anodal tDCSof the

left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCSof theleft DLPFC(with

right orbitofrontal cathode) in drug-resistant major depressiveepisode. It remainstobeclarifiedwhether

the probable or possible therapeutic effects of tDCSare clinically meaningful and how to optimally per-

form tDCSin atherapeutic setting. In addition, theeasy management and low cost of tDCSdevicesallow

at homeuseby thepatient,but thismight raiseethical and legal concernswith regard topotential misuse

or overuse. Wemust becareful toavoid inappropriateapplicationsof thistechniqueby ensuring rigorous

training of the professionals and education of the patients.

Ó2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights

reserved.

Contents

1. Principles and mechanisms of action of transcranial direct current stimulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

2. Clinical applications of tDCS: literature data analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

3. Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

4. Parkinson’s disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

4.1. tDCSeffects on motor symptoms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

4.2. tDCSeffects on nonmotor symptoms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

4.3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

5. Other movement disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

6. Motor stroke. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

7. Aphasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

8. Multiple sclerosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

9. Epilepsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

10. Disorders of consciousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

11. Alzheimer’s disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

12. Tinnitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

13. Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

13.1. Antidepressant effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

13.2. Cognitive effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

14. Schizophrenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

15. Substance abuse, addiction and craving. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

16. Other psychiatric disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

17. At-home do-it-yourself DCSand neural enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

18. Perspectives of targets other than cortical (cerebellum and spinal cord). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

18.1. Cerebellar tDCS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

18.2. Transcutaneous spinal direct current stimulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

19. Perspectives of treatment by transcranial electrical stimulation methods other than tDCS(tACS, tRNS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

20. Summary of recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

Conflict of interest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

J.-P. Lefaucheur et al./Clinical Neurophysiology 128 (2017) 56–92 57

Guidelines

Evidence-based guidelines on the therapeutic use of transcranial direct

current st imulat ion (tDCS)

Jean-Pascal Lefaucheur a,b,⇑, Andrea Antal c, Samar S. Ayache a,b, David H. Benninger d, Jérôme Brunelin e,

Fil ippo Cogiamanian f,g, Maria Cotelli h, Dirk De Ridder i,j, Roberta Ferrucci f,g, Berthold Langguth k,

Paola Marangolo l,m, Veit Mylius n,o, Michael A. Nitsche p,q, Frank Padberg r, Ulrich Palm r,

Emmanuel Poulet e,s, Alberto Priori f,g,t, Simone Rossi u, Mart in Schecklmann k, Sven Vanneste v,w,

Ulf Ziemann x, Luis Garcia-Larrea y,1, Walter Paulusc,1

aDepartment of Physiology, Henri Mondor Hospital, Assistance Publique – Hôpitaux deParis, Créteil, FrancebEA4391, Nerve Excitability and Therapeutic Team (ENT), Faculty of Medicine, Paris Est Créteil University, Créteil, FrancecDepartment of Clinical Neurophysiology, University Medical Center, Georg-August University, Göttingen, GermanydDepartment of Clinical Neurosciences, Section of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, SwitzerlandePsyR2 Team, U 1028, INSERM and UMR5292, CNRS, Center for Neuroscience Research of Lyon (CRNL), CH Le Vinatier, Lyon-1 University, Bron, Francef Clinica Neurologica III, Dipartimento di Scienze della Salute, Azienda Ospedaliera Santi Paolo eCarlo, Università degli Studi di Milano, Milano, Italyg IRCCSFondazione Ospedale Maggiore Policlinico, Milano, ItalyhNeuropsychology Unit, IRCCSFondazione Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italyi Brai2n, Tinnitus Research Initiative Clinic of Antwerp, Sint Augustinus Hospital, Wilrijk, Belgiumj Department of Surgical Sciences, Section of Neurosurgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealandk Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germanyl Dipartimento di Studi Umanistici, University Federico II, Naples, Italym IRCCSFondazione Santa Lucia, Rome, ItalynDepartment of Neurology, Section Pain and Neuromodulation, University of Marburg, Marburg, GermanyoDepartment of Neurology, Center for Neurorehabilitation, Valens, SwitzerlandpDepartment of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, GermanyqDepartment of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germanyr Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, GermanysDepartment of Emergency Psychiatry, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, Francet Dipartimento di Fisiopatologia Medico-Chirurgica edei Trapianti, Università degli Studi di Milano, Milano, ItalyuUnit of Neurology and Clinical Neurophysiology, Brain Investigation & Neuromodulation Lab, Department of Neuroscience, and Human Physiology Section, Siena University, Siena,

Italyv Department of Translational Neuroscience, Faculty of Medicine, University of Antwerp, Edegem, Belgiumw Laboratory for Auditory and Integrative Neuroscience, School of Behavioral and Brain Sciences, TheUniversity of Texas, Dallas, TX, USAx Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germanyy NeuroPain Team, U 1028, INSERM, Center for Neuroscience Research of Lyon (CRNL), Lyon-1 University, Bron, France

a r t i c l e i n f o

Article history:

Accepted 20 October 2016

Available online 29 October 2016

h i g h l i g h t s

A group of European experts reviewed current evidence for therapeutic efficacy of tDCS.

Level Bevidence (probable efficacy) was found for fibromyalgia, depression and craving.

The therapeutic relevance of tDCSneeds to be further explored in these and other indications.

http://dx.doi.org/10.1016/j.clinph.2016.10.087

1388-2457/Ó 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Abbreviations: AD, Alzheimer’s disease; ARAT, action research arm test; BDI, Beck Depression Inventory; BI, Barthel Index; DC, direct current; DLPFC, dorsolateral

prefrontal cortex; EEG, electroencephalography; ERP, event-related potentials; FMA, Fugl-Meyer assessment; fMRI, functional magnetic resonance imaging; GABA, gamma-

aminobutyric acid; HDRS, Hamilton Depression Rating Scale; JTT, Jebsen–Taylor hand function test; M1, primary motor cortex; MADRS, Montgomery–Asberg depression

rating scale; MCS, minimally conscious state; MEP, motor evoked potential; NMDA, N-methyl D-aspartate; OMCASS, Orgogozo MCA scale; PANSS, positive and negative

symptoms scale; PD,Parkinson’s disease; PES, peripheral electrical stimulation; RCT, randomized controlled trial; rTMS, repetitive transcranial magnetic stimulation; SANS,

Scale for the Assessment of Negative Symptoms; tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation; TMS, transcranial magnetic

stimulation; tRNS, transcranial random noise stimulation; tsDCS, transcutaneous spinal direct current stimulation; UPDRS, unified Parkinson’s disease rating scale; V1,

primary visual cortex; VAS, visual analogue scale; VRT, virtual reality training; VS, vegetative state.⇑ Corresponding author at: ServicePhysiologie, ExplorationsFonctionnelles,Hôpital Henri Mondor, 51 avenuedeLattredeTassigny, 94010Créteil cedex, France. Fax: +33 1

4981 4660.

E-mail address: jean-pascal.lefaucheur@hmn.aphp.fr (J.-P. Lefaucheur).1 Equal contribution.

Clinical Neurophysiology 128 (2017) 56–92

Contents lists available at ScienceDirect

Clinical Neurophysiology

journal homepage: www.elsevier.com/locate/cl inph

Recommendation:

Necessary conditions: Given this situation, the IFCN recommends that for any use of tES in the

treatment of a medical indication (at home or in the clinic) this should be done with a medical grade

device or consumer device (CE mark) and under supervision of a medical provider and trained

personnel. In the United States, devices having been approved for Over-The-Counter (Non-

Prescription) by the governing regulatory agency may also be used by law.

Necessary and sufficient conditions: In medical applications, a necessary and sufficient condition is

the use of protocols, which have demonstrated in peer-reviewed clinical trials to be both safe and

efficacious. The manufacturer should have this information in the user manual, based on clinical

evaluations. In non-medical applications, efficacy and safety should also be standard, including

home-use. Many scientific investigations have shown both positive and negative results for

circumscribed cognitive processes in special investigations. As many ‘home-applied’ protocols have

not been formally tested, and many sensitive parameters have not been carefully reproduced,

stimulation may switch positive into negative results.

Thus, the IFCN warns against the use of DIY devices and methods unless they have shown

both efficacy and safety.

Grazie

dell’attenzione!

• The utility of a neurophysiological technique is helping difficult differential diagnosis

• VS/MCS: misdiagnosis in 40% of cases, even in qualified Centers

• TMS/EEG differentiates VS/MCS with a sensitivity of 94.7%

Local and Distant Responses (Cortical Reactivity & Connectivity)

Santarnecchi & Rossi 2016

PLOS One, 2014

Absence of EEG responses expecially in axonal damage

• rTMS is complementary to traditional neuroimaging (causality)

rTMS produces errors

SMA rTMS Trial ～ results

Supplementary motor area stimulation for Parkinson

disease:

a randomized controlled study. Neurology 2013;80:1–6

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rTMS for therapy: The case of Parkinson’s Disease

Problems:

Costs/efficacy

Sustainability