Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.
Andreasen, N.O’Leary, D.Flaum, M.Nopoulos, P.Hypofrontality in schizophrenia: distributed deep TMS for negative symptoms of schizophrenia 5 dysfunctional circuits in neuroleptic-naive patients. Lancet 1997;349:1730–1734.CrossRefGoogle Scholar
Barker, A.T.Jalinous, R.Freeston IL, Non-invasive magnetic stimulation of human motor cortex. Lancet 1985;1:1106–1107.CrossRefGoogle ScholarPubMed
Baron-Cohen, S.Belmonte, M.K.Autism: a window onto the development of the social and analytic brain. Annu Rev Neurosci 2005;28:109–126.CrossRefGoogle ScholarPubMed
Baron-Cohen, S.Swettenham, J.Theory of mind in autism: its relationship to executive function and central coherence. Cohen, D.J.Volkmar, F.R.Handbook of autism and pervasive developmental disorders Second ed. New York: John Wiley & Sons; 1997. p. 880–893.Google Scholar
Baron-Cohen, S.Leslie, A.M.Frith, U.Does the autistic child have a “theory of mind”?. Cognition 1985;21(1):37–46.CrossRefGoogle ScholarPubMed
Bench, C.J.Friston, K.J.Brown, R.G.Scott, L.C.Frackowiak, R.S.Dolan, R.J.The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression. Psychol Med 1992;22:607–615.CrossRefGoogle ScholarPubMed
Bersani, F.S.Capra, E.Minichino, A.Pannese, R.Girardi, N.Marini, I.Factors affecting interindividual differences in clozapine response: a review and case report. Hum Psychopharmacol: Clin Exp 2011;26:177–187.Google ScholarPubMed
Bersani, FSGirardi, NSanna, LMazzarini, Let al.Deep transcranial magnetic stimulation as a therapy for treatment-resistant bipolar depression in acute and maintenance phases: a case report. Neurocase, article in press.Google Scholar
Blumberger, D.Fitzgerald, P.Mulsant, B.Daskalakis Z, Repetitive transcranial magnetic stimulation for refractory symptoms in schizophrenia. Curr Opin Psychiatry 2010;23:85.CrossRefGoogle Scholar
Branston, N.M.Tofts, P.S.Magnetic stimulation of a volume conductor produces a negligible component of induced current perpendicular to the surface. J Physiol (Lond) 1990;423:67.Google Scholar
Broadbent, H.J.van den Eynde, F.Guillaume, S.Hanif, E.L.Stahl, D.David, A.S.Campbell, I.C.Schmidt, U.Blinding success of rTMS applied to the dorsolateral prefrontal cortex in randomised sham-controlled trials: a systematic review. World J Biol Psychiatry. 2011;12(4):240–248.CrossRefGoogle ScholarPubMed
Carrington, S.J.Bailey, A.J.Are there theory of mind regions in the brain? A review of the neuroimaging literature. Hum Brain Mapp 3082009 2313–2335.CrossRefGoogle Scholar
Castelli, F.Frith, C.Happe, F.Frith, U.Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes. Brain 2002;125(Pt 8):1839–1849.CrossRefGoogle ScholarPubMed
Cohen, D.Cuffin, B.N.Developing a more focal magnetic stimulator. Part I: some basic principles. J Clin Neurophysiol 1991;8:102–111.CrossRefGoogle ScholarPubMed
Cohen, L.G.Roth, B.J.Nilsson, J.Effects of coil design on delivery of focal magnetic stimulation. Technical considerations. Electroencephalogr Clin Neurophysiol 1990;75:350–357.CrossRefGoogle ScholarPubMed
Davey, K.R.Riehl, M.E.Suppressing the surface field during transcranial magnetic stimulation. IEEE Trans Biomed Eng 2006;53:190–194.CrossRefGoogle ScholarPubMed
Dell’Osso, B.Mundo, E.D’Urso, N.Pozzoli, S.Buoli, M.Ciabatti, M.Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression. Bipolar Disord 2009;11:76–81.CrossRefGoogle Scholar
Deng, Z.D.Peterchev, A.Lisanby, S.H.Coil design considerations for deep brain transcranial magnetic stimulation (dTMS). Conf Proc IEEE Eng Med Biol Soc 2008;27:5675–5679.Google Scholar
Dierks, T.Linden, D.E.Jandl, M.Formisano, E.Goebel, R.Lanfermann, H.Activation of Heschl's gyrus during auditory hallucinations. Neuron 1999;22:615–621.CrossRefGoogle ScholarPubMed
Dolberg, O.T.Dannon, P.N.Schreiber, S.Grunhaus L, Transcranial magnetic stimulation in patients with bipolar depression: a double-blind, controlled study. Bipolar Disord 2002;4(Suppl 1):94–95.CrossRefGoogle ScholarPubMed
Drevets, W.C.Price, J.L.Simpson, J.R. Jr.Todd, R.D.Reich, T.Vannier, M.Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824–827.CrossRefGoogle ScholarPubMed
Eaton, H.Electric field induced in a spherical volume conductor from arbitrary coils: application to magnetic stimulation and MEG. Med Biol Eng Comput 1992;30:433–440.CrossRefGoogle Scholar
Enticott, P.G.Kennedy, H.A.Zangen, A.Fitzgerald, P.B.Deep repetitive transcranial magnetic stimulation associated with improved social functioning in a young woman with an autism spectrum disorder. J ECT 2011;27:41–43.CrossRefGoogle Scholar
Erfurth, A.Michael, N.Mostert, C.Arolt, V.Mania and rapid transcranial magnetic stimulation. Am J Psychiatry 2000;157:835–836.CrossRefGoogle Scholar
Fitzgerald, P.B.Fountain, S.Daskalakis, Z.J.A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol 2006;117:2584–2596.CrossRefGoogle Scholar
Fregni, F.Merabet, L.Pascual-Leone, A.Marcolin, M.A.Modulation in motor threshold after a severe episode of gastrointestinal distress. J ECT 2004;20:50–51.CrossRefGoogle ScholarPubMed
Freitas, C.Fregni, F.Pascual-Leone, AMeta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia. Schizophr Res 2009;108:11–24.CrossRefGoogle Scholar
Galynker, I.I.Cohen, L.J.Cai, J.Negative symptoms in patients with major depressive disorder: a preliminary report. Neuropsychiatry Neuropsychol Behav Neurol 2000;13:171–176.Google ScholarPubMed
Gentili, C.Ricciardi, E.Gobbini, M.I.Santarelli, M.F.Haxby, J.V.Pietrini, P.Beyond amygdala: default mode network activity differs between patients with social phobia and healthy controls. Brain Res Bull 2009;79(6):409–413.CrossRefGoogle ScholarPubMed
Getz, K.Hermann, B.Seidenberg, M.Bell, B.Dow, C.Jones, J.Negative symptoms in temporal lobe epilepsy. Am J Psychiatry 2002;159:644–651.CrossRefGoogle ScholarPubMed
Harel, E.V.Zangen, A.Roth, Y.Reti, I.Braw, Y.Levkovitz, Y.H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World J Biol Psychiatry 2011;12:119–126.CrossRefGoogle ScholarPubMed
Harel, EVRabany, LDeutsch, LBloch, YZangen, ALevkovitz, Y.H-coil repetitive transcranial magnetic stimulation for treatment-resistant major depressive disorder: an 18-week continuation safety and feasibility study. World J Biol Psychiatry. 2012 Feb 7. [Epub ahead of print].Google ScholarPubMed
Hoffman, R.E.Boutros, N.N.Berman, R.M.Roessler, E.Belger, A.Krystal, J.H.Transcranial magnetic stimulation of left temporo-parietal cortex in three patients reporting hallucinated “voices”. Biol Psychiatry 1999;46:130–132.CrossRefGoogle Scholar
Hoffman, R.E.Hawkins, K.A.Gueorguieva, R.Boutros, N.N.Rachid, F.Carroll, K.Transcranial magnetic stimulation of left temporo-parietal cortex and medication-resistant auditory hallucinations. Arch Gen Psychiatry 2003;60:49–56.CrossRefGoogle Scholar
Isella, V.Melzi, P.Grimaldi, M.Iurlaro, S.Piolti, R.Ferrarese, C.Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease. Mov Disord 2002;17:366–371.CrossRefGoogle ScholarPubMed
Isserles, M.Rosenberg, O.Dannon, P.Levkovitz, Y.Kotler, M.Deutsch, F.Cognitive-emotional reactivation during deep transcranial magnetic stimulation over the prefrontal cortex of depressive patients affects antidepressant outcome. J Affect Disord 2011;128:235–242.CrossRefGoogle ScholarPubMed
Juruena, M.F.Cleare, A.J.Bauer, M.E.Pariante, C.M.Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders. Acta Neuropsychiatrica 2003;15:354–367.CrossRefGoogle ScholarPubMed
Kaland, N.Smith, L.Mortensen, E.L.Response times of children and adolescents with Asperger syndrome on an ‘advanced’ test of theory of mind. J Autism Dev Disord 2007;37(2):197–209.CrossRefGoogle ScholarPubMed
Kana, R.K.Keller, T.A.Cherkassky, V.L.Minshew, N.J.Just, M.A.Atypical frontal-posterior synchronisation of theory of mind regions in autism during mental state attribution. Soc Neurosci 2009;4(2):135–152.CrossRefGoogle Scholar
Krause, L.Enticott, P.G.Zangen, A.Fitzgerald, P.B.The role of medial prefrontal cortex in theory of mind: a deep rTMS study. Behav Brain Res 2012;228(1):87–90.CrossRefGoogle ScholarPubMed
La Pia, S.Monoamine's role in depression and possible consequences for the clinical management of the core symptoms of major depression. Riv Psichiatr 2009;44(1):1–14.Google ScholarPubMed
Lennox, B.R.Park, S.B.Medley, I.Morris, P.G.Jones, P.B.The functional anatomy of auditory hallucinations in schizophrenia. Psychiatry Res 2000;100:13–20.CrossRefGoogle Scholar
Lepine, J.P.Briley, M.The increasing burden of depression. Neuropsychiatr Dis Treat 2011;7(Suppl 1):3–7.Google Scholar
Levkovitz, Y.Roth, Y.Vadim Harel, E.Braw, Y.Sheer, A.Zangen, A.A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation. Clin Neurophysiol 2007;118:2730–2744.CrossRefGoogle ScholarPubMed
Levkovitz, Y.Harel, E.V.Roth, Y.Braw, Y.Most, D.Katz, L.N.Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients. Brain Stimul 2009;2(4):188–200.CrossRefGoogle ScholarPubMed
Levkovitz, Y.Rabany, L.Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Int J Neuropsychopharmacol 2011;14(7):991–996.CrossRefGoogle ScholarPubMed
Levkovitz, Y.Sheer, A.Differential effects of deep TMS of the prefrontal cortex on apathy and depression. Brain Stimul 2011;4(4):266–274.CrossRefGoogle ScholarPubMed
Lukoyanov, N.V.Sa, M.J.Madeira, M.D.Paula-Barbosa, M.M.Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizures. Exp Brain Res 2004;154:192–200.CrossRefGoogle ScholarPubMed
Málly J (ed), The Repetitive Transcranial Magnetic Stimulation in the Treatment and Rehabilitation of Central Nervous Diseases, Eurobridge Co, Budapest. 2009.Google Scholar
Marcolin, M.A.Padberg, F.Transcranial Brain stimulation for treatment in mental disorders. Adv Biol Psychiatr Basel Karger 2007;23:204–225.Google Scholar
Matsuda, H.Gyobu, T.Ii, M.Hisada, K.Iodine-123 iodoamphetamine brain scan in a patient with auditory hallucination. J Nucl Med 1988;29:558–560.Google Scholar
McGuire, P.K.Shah, G.M.Murray, R.M.Increased blood flow in Broca's area during auditory hallucinations in schizophrenia. Lancet 1993;342:703–706.CrossRefGoogle Scholar
Minichino, A.Bersani, F.S.Capra, E.Bonanno, C.Pannese, R.Salviati, M.ECT, rTMS and deepTMS in pharmaco-resistant drug-free patients with unipolar depression: a comparative review. Neuropsychiatric Dis Treatment 2012;8:55–64.Google Scholar
Nahas, Z.Kozel, F.A.Li, X.Anderson, B.George, M.S.Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Bipolar Disord 2003;5:40–47.CrossRefGoogle ScholarPubMed
Nestler, E.J.Carlezon, W.A. Jr.The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 2006;59:1151–1159.CrossRefGoogle ScholarPubMed
Paulus, W.Classen, J.State of the art: pharmacologic effects on cortical excitability measures tested by transcranial magnetic stimulation. Brain Stimul 2008;1(3):151–163.CrossRefGoogle ScholarPubMed
Pini, S.Preve, M.Approach to bipolar spectrum and subthreshold mood disorders. Riv Psichiatr 2011;46(4):233–241.Google ScholarPubMed
Pisani, F.Spina, E.Antidepressant drugs and seizure susceptibility: from in vitro data to clinical practice. Epilepsia 1999;40(Suppl 10):S48–S56.CrossRefGoogle ScholarPubMed
Pompili, M.Iliceto, P.Higher hopelessness and suicide risk predict lower self-deception among psychiatric patients and non-clinical individuals. Riv Psichiatr 2011;46(1):24–30.Google ScholarPubMed
Rami-Gonzalez, L.Bernado, M.Boget, T.Salamero, M.Gil-Verona, J.A.Junque, C.Subtypes of memory dysfunction associated with ECT: characteristics and neurobiological bases. J ECT 2001;17:129–135.CrossRefGoogle ScholarPubMed
Reichman, W.E.Coyne, A.C.Amirneni, S.Molino, B.J.Egan, S.Negative symptoms in Alzheimer's disease. Am J Psychiatry 1996;153:424–426.Google ScholarPubMed
Reid, M.A.Stoeckel, L.E.White, D.M.Avsar, K.B.Bolding, M.S.Akella, N.S.Assessments of function and biochemistry of the anterior cingulate cortex in schizophrenia. Biol Psychiatry 2010;68:625–633.CrossRefGoogle Scholar
Rosenberg, O.Shoenfeld, N.Zangen, A.Kotler, M.Dannon, P.N.Deep TMS in a resistant major depressive disorder: a brief report. Depress Anxiety 2010;27:465–469.CrossRefGoogle Scholar
Rosenberg, O.Zangen, A.Stryjer, R.Kotler, M.Dannon, P.N.Response to deep TMS in depressive patients with previous electroconvulsive treatment. Brain Stimul 2010;3:211–217.CrossRefGoogle ScholarPubMed
Rosenberg, O.Isserles, M.Levkovitz, Y.Kotler, M.Zangen, A.Dannon, P.N.Effectiveness of a second deep TMS in depression: a brief report. Neuropsychopharmacol Biol Psychiatry 2011;35(4):1041–1044.CrossRefGoogle ScholarPubMed
Rosenberg, O.Roth, Y.Kotler, M.Zangen, A.Dannon, P.Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study. Ann Gen Psychiatry 2011;10:3.CrossRefGoogle ScholarPubMed
Roth, Y.Zangen, A.Hallett, M.A coil design for transcranial magnetic stimulation of deep brain regions. J Clin Neurophysiol 2002;19:361–370.CrossRefGoogle ScholarPubMed
Roth, Y.Amir, A.Levkovitz, Y.Zangen A, Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24:31–38.CrossRefGoogle ScholarPubMed
Schneider, P.Scherg, M.Dosch, H.G.Specht, H.J.Gutschalk, A.Rupp, A.Morphology of Heschl's gyrus reflects enhanced activation in the auditory cortex of musicians. Nat Neurosci 2002;5:688–694.CrossRefGoogle ScholarPubMed
Schultz, R.T.Robins, D.L.Functional neuroimaging studies of autism spectrum disorders. In: Volkmar, F.R.Paul, R.Klin, A.Cohen, D.Handbook of autism and pervasive developmental disorders 3rd ed Hoboken, NJ: Wiley; 2005.515–533.Google Scholar
Shergill, S.S.Murray, R.M.McGuire, P.K.Auditory hallucinations: a review of psychological treatments. Schizophr Res 1998;32:137–150.CrossRefGoogle ScholarPubMed
Sommer, M.Dieterich, A.Ruther, E.Paulus, W.Wiltfang, J.Increased transcranial magnetic motor threshold after ECT. A case report. Eur Arch Psychiatry Clin Neurosci 2002;252:250–252.Google ScholarPubMed
Stanford, A.D.Sharif, Z.Corcoran, C.Urban, N.Malaspina, D.Lisanby, S.H.rTMS strategies for the study and treatment of schizophrenia: a review. Int J Neuropsychopharmacol 2008;11:563–576.CrossRefGoogle Scholar
Stanford, A.Sharif, Z.Corcoran, C.Urban, N.rTMS strategies for the study and treatment of schizophrenia: a review. Int J Neuropsychopharmacol 2008;11:563–576.CrossRefGoogle Scholar
Tamas, R.L.Menkes, D.El-Mallakh, R.S.Stimulating research: a prospective, randomized, double-blind, sham-controlled study of slow transcranial magnetic stimulation in depressed bipolar patients. J Neuropsychiatry Clin Neurosci 2007;19:198–199.CrossRefGoogle ScholarPubMed
Tharayil, B.S.Gangadhar, B.N.Thirthalli, J.Anand, L.Seizure with single-pulse transcranial magnetic stimulation in a 35-yearold otherwise-healthy patient with bipolar disorder. J ECT 2005;21:188–189.CrossRefGoogle Scholar
Von Werne Baes, C.de Carvalho Tofoli, S.M.Martins, C.M.S.Juruena, M.F.Assessment of the hypothalamic -pituitary -adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress - a systematic review. Acta Neuropsychiatrica 2012;24:4–15.CrossRefGoogle ScholarPubMed
Walter, H.Adenzato, M.Ciaramidaro, A.Enrici, I.Pia, L.Bara, B.G.Understanding intentions in social interaction: the role of the anterior paracingulate cortex. J Cogn Neurosci 2004;16:1854–1863.CrossRefGoogle ScholarPubMed
Weissman, M.M.Leaf, P.J.Tischler, G.L.Affective disorders in five United States communities. Psychol Med 1988;18:141–153.CrossRefGoogle ScholarPubMed
Zambello, F.Vaona, A.ECT. A critical review of meta-analyses. Riv Psichiatr 2009;44(5):337–340.Google ScholarPubMed
Zangen, A.Roth, Y.Voller, B.Hallett, M.Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 2005;116:775–779.CrossRefGoogle ScholarPubMed