We reviewed novel brain stimulation approaches that modify neuroplasticity and are used in the treatment and study of schizophrenia. We searched PubMed and Scholars Portal using search terms related to schizophrenia, brain stimulation, and neuroplasticity. Various brain stimulation approaches simulating a range of experimental protocols that induce synaptic long-term potentiation or depression have been developed. By far, repetitive transcranial magnetic stimulation (rTMS) has been the most widely used in the field of schizophrenia. Its application has been associated with mixed results in treating treatment-resistant symptoms and cognitive deficits associated with schizophrenia. Compared to the other approaches, rTMS is probably the least similar to plasticity-inducing cellular paradigms. Other approaches, such as paired associative stimulation, theta-burst stimulation, and transcranial direct current stimulation, are in their incipient stages in the study and treatment of schizophrenia, with promising early results. Numerous brain stimulation approaches have been developed to treat resistant dimensions of schizophrenia. Notwithstanding some promising reports, optimization of the methods and large randomized controlled trials are still needed.
CarpenterWB. Principles of mental physiology. London (GB): H S King and Company; 1874.
2.
JamesW.The principles of psychology. New York (NY): Holt; 1890.
3.
KonorskiJ.Conditioned reflexes and neuron organization. Cambridge (GB): Cambridge University Press; 1948.
4.
HebbDO. The organization of behavior. New York (NY): John Wiley & Sons, Ltd; 1949.
5.
BlissTVLomoT.Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973;232:331–356.
6.
MalenkaRCBearMF. LTP and LTD: An embarrassment of riches. Neuron. 2004;44:5–21.
7.
DudekSMBearMF. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-Methyl-d-Aspartate receptor blockade. Proc Natl Acad Sci U S A. 1992;89:4363–4367.
8.
BlissTVPCollingridgeGL. A synaptic model of memory—long-term potentiation in the hippocampus. Nature. 1993;361:31–39.
9.
BuzsakiG.Hippocampal sharp waves: Their origin and significance. Brain Res. 1986;398:242–252.
10.
OttoTEichenbaumH.Neuronal-activity in the hippocampus during delayed nonmatch to sample performance in rats—evidence for hippocampal processing in recognition memory. Hippocampus. 1992;2:323–334.
11.
YlinenABraginANadasdyZ, Sharp wave-associated high-frequency oscillation (200-Hz) in the intact hippocampus—network and intracellular mechanisms. J Neurosci. 1995;15:30–46.
12.
LarsonJWongDLynchG.Patterned stimulation at the theta-frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986;368:347–350.
13.
MarkramHLubkeJFrotscherM, Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science. 1997;275:213–215.
14.
TerzuoloCABullockTH. Measurement of imposed voltage gradient adequate to modulate neuronal firing. Proc Natl Acad Sci U S A. 1956;42:687–694.
15.
ArtolaABrocherSSingerW.Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual-cortex. Nature. 1990;347:69–72.
16.
MalenkaRCNicollRA. Neuroscience—long-term potentiation—a decade of progress?Science. 1999;285:1870–1874.
17.
FritschBReisJMartinowichK, Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning. Neuron. 2010;66:198–204.
18.
Pascual-LeoneAVallssoleJWassermannEM, Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain. 1994;117:847–858.
19.
PellGSRothYZangenA.Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: Influence of timing and geometrical parameters and underlying mechanisms. Prog Neurobiol. 2011;93:59–98.
20.
HoogendamJMRamakersGMDi LazzaroV.Physiology of repetitive transcranial magnetic stimulation of the human brain. Brain Stimul. 2010;3:95–118.
21.
ChenRClassenJGerloffC, Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997;48:1398–1403.
22.
FitzgeraldPBBrownTLDaskalakisZJ, Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability. Clin Neurophysiol. 2002;113:1136–1141.
23.
FitzgeraldPBBrownTLMarstonNAU, Reduced plastic brain responses in schizophrenia: A transcranial magnetic stimulation study. Schizophr Res. 2004;71:17–26.
24.
OxleyTFitzgeraldPBBrownTL, Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia. Biol Psychiatry. 2004;56:628–633.
25.
WaslingPHanseEGustafssonB.Long-term depression in the developing hippocampus: Low induction threshold and synapse nonspecificity. J Neurosci. 2002;22:1823–1830.
26.
WagnerJJAlgerBE. GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus. J Neurosci. 1995;15:1577–1586.
27.
SteelePMMaukMD. Inhibitory control of LTP and LTD: Stability of synapse strength. J Neurophysiol. 1999;81:1559–1566.
28.
TougeTGerschlagerWBrownP, Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses?Clin Neurophysiol. 2001;112:2138–2145.
29.
AlemanASommerIEKahnRS. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: A meta-analysis. J Clin Psychiatry. 2007;68:416–421.
30.
SlotemaCWBlomJDHoekHW, Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010;71:873–884.
31.
FitzgeraldPBBenitezJDaskalakisJZ, A double-blind sham-controlled trial of repetitive transcranial magnetic stimulation in the treatment of refractory auditory hallucinations. J Clin Psychopharmacol. 2005;25:358–362.
32.
RosaMOGattazWFRosaMA, Effects of repetitive transcranial magnetic stimulation on auditory hallucinations refractory to clozapine. J Clin Psychiatry. 2007;68:1528–1532.
33.
SabaGVerdonCMKalalouK, Transcranial magnetic stimulation in the treatment of schizophrenic symptoms: A double blind sham controlled study. J Psychiatr Res. 2006;40:147–152.
34.
SlotemaCWBlomJDde WeijerAD, Can low-frequency repetitive transcranial magnetic stimulation really relieve medication-resistant auditory verbal hallucinations? Negative results from a large randomized controlled trial. Biol Psychiatry. 2011;69:450–456.
35.
DollfusSLarmurier-MontagneARazafimandimbyA, Treatment of auditory hallucinations by combining high-frequency repetitive transcranial magnetic stimulation and functional magnetic resonance imaging. Schizophr Res. 2008;102:348–351.
36.
Montagne-LarmurierAEtardORazafimandimbyA, Two-day treatment of auditory hallucinations by high frequency rTMS guided by cerebral imaging: A 6 month follow-up pilot study. Schizophr Res. 2009;113:77–83.
37.
JinYKempASHuangY, Alpha EEG guided TMS in schizophrenia. Brain Stimul. 2012;5(4):560–568.
38.
SachdevPLooCMitchellP, Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: A pilot investigation. Psychiatry Clin Neurosci. 2005;59:354–357.
39.
JinYPotkinSGKempAS, Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alpha TMS) on the negative symptoms of schizophrenia. Schizophr Bull2006;32:556–61.
40.
PrikrylRKasparekTSkotakovaS, Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study. Schizophr Res. 2007;95:151–157.
41.
HoliMMEronenMToivonenK, Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia. Schizophr Bull. 2004;30:429–434.
42.
MoggAPurvisRErantiS, Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: A randomized controlled pilot study. Schizophr Res. 2007;93:221–228.
43.
NovakTHoracekJMohrP, The double-blind sham-controlled study of high-frequency rTMS (20Hz) for negative symptoms in schizophrenia: Negative results. Neuroendocrinol Lett. 2006;27:209–213.
44.
FitzgeraldPBHerringSHoyK, A study of the effectiveness of bilateral transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia. Brain Stimul. 2008;1:27–32.
45.
BarrMSFarzanFTranLC, Arandomized controlled trial of sequentially bilateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of negative symptoms in schizophrenia. Brain Stimul. 2012;5(3):337–346.
46.
FitzgeraldPBBenitezJOxleyT, A study of the effects of lorazepam and dextromethorphan on the response to cortical 1Hz repetitive transcranial magnetic stimulation. Neuroreport. 2005;16:1525–1528.
47.
Di LazzaroVDileoneMPilatoF, Modulation of motor cortex neuronal networks by rTMS: Comparison of local and remote effects of six different protocols of stimulation. J Neurophysiol. 2011;105:2150–2156.
48.
HuangYZEdwardsMJRounisE, Theta burst stimulation of the human motor cortex. Neuron. 2005;45:201–206.
49.
PouletEBrunelinJBen MakhloufW, A case report of cTBS for the treatment of auditory hallucinations in a patient with schizophrenia. Brain Stimul. 2009;2:118–119.
50.
SidhoumiDBrahaSBouazizN, Evaluation of the therapeutic effect of theta burst stimulation on drug-resistant auditory hallucinations in a schizophrenic patient and its impact on cognitive function and neuronal excitability: A case study. Clin Neurophysiol. 2010;121(5):802.
51.
EberleMCWildgruberDWasserkaB, Relief from chronic intractable auditory hallucinations after long-term bilateral theta burst stimulation. Am J Psychiatry. 2010;167(11):1410.
52.
BorJBrunelinJRivetA, Effects of theta burst stimulation on glutamate levels in a patient with negative symptoms of schizophrenia. Schizophr Res. 2009;111:196–197.
53.
Demirtas-TatlidedeAFreitasCCromerJR, Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010;124:91–100.
54.
BrunelinJSzekelyDCostesN, Theta burst stimulation in the negative symptoms of schizophrenia and striatal dopamine release. An iTBS-[(11)C]raclopride PET case study. Schizophr Res. 2011;131:264–265.
55.
StefanKKuneschECohenLG, Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000;123:572–584.
56.
FlorianJMullerMOrekhovY, Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation. Eur J Neurosci. 2007;25:3461–3468.
57.
ZiemannUPaulusWNitscheMA, Consensus: Motor cortex plasticity protocols. Brain Stimul. 2008;1:164–182.
58.
FrantsevaMVFitzgeraldPBChenR, Evidence for impaired long-term potentiation in schizophrenia and its relationship to motor skill leaning. Cereb Cortex. 2008;18:990–996.
59.
RajjiTKLiuSKFrantsevaMV, Exploring the effect of inducing long-term potentiation in the human motor cortex on motor learning. Brain Stimul. 2011;4:137–144.
60.
RussmannHLamyJCShamimEA, Associative plasticity in intracortical inhibitory circuits in human motor cortex. Clin Neurophysiol. 2009;120:1204–1212.
61.
NitscheMAPaulusW.Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000;527(Pt 3):633–639.
62.
NitscheMAFrickeKHenschkeU, Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J Physiol. 2003;553(Pt 1):293–301.
63.
HasanANitscheMAReinB, Dysfunctional long-term potentiation-like plasticity in schizophrenia revealed by transcranial direct current stimulation. Behav Brain Res. 2011;224:15–22.
64.
HasanANitscheMAHerrmannM, Impaired long-term depression in schizophrenia: A cathodal tDCS pilot study. Brain Stimul. 2012;5(4):475–483.
65.
LiuSKFitzgeraldPBDaigleM, The relationship between cortical inhibition, antipsychotic treatment, and the symptoms of schizophrenia. Biol Psychiatry. 2009;65:503–509.
66.
BrunelinJMondinoMHaesebaertF, Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. Brain Stimul. 2012;5(3):431–4322.
67.
Hôpital le Vinatier; Poulet E, principal investigatorTranscranial direct current stimulation (tDCS) and hallucinations in schizophrenia [Internet]. Bethesda (MD): US National Institutes of Health; 2009 [updated 2011 Feb 1; cited 2013 Jan 4]. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00870909.
68.
VercammenARushbyJALooC, Transcranial direct current stimulation influences probabilistic association learning in schizophrenia. Schizophr Res. 2011;131:198–205.
69.
MattaiAAMillerRWeisingerB, Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia. Brain Stimul. 2011;4(4):275–280.
