Elsevier

Schizophrenia Research

Volume 71, Issue 1, 1 November 2004, Pages 1-16
Schizophrenia Research

Transcranial Magnetic Stimulation in the investigation and treatment of schizophrenia: a review

https://doi.org/10.1016/j.schres.2003.10.006Get rights and content

Abstract

Transcranial Magnetic Stimulation (TMS) is a non-invasive method of stimulating the brain that is increasingly being used in neuropsychiatric research and clinical psychiatry. This review examines the role of TMS in schizophrenia research as a diagnostic and a therapeutic resource. After a brief overview of TMS, we describe the application of TMS to schizophrenia in studies of cortical excitability and inhibition, and we discuss the potential confounding role of neuroleptic medications. Based on these studies, it appears that some impairment of cortical inhibition may be present in schizophrenic subjects. We then review attempts to employ TMS for treating different symptoms of schizophrenia. Some encouraging results have been obtained, such as the reduction of auditory hallucinations after slow TMS over auditory cortex and an improvement of psychotic symptoms after high frequency TMS over left prefrontal cortex. However, these results need to be confirmed using better placebo conditions. Future studies are likely to employ TMS in combination with functional brain imaging to examine the effects produced by the stimulated area on activity in other brain regions. Such studies may reveal impaired effective connectivity between specific brain areas, which could identify these regions as targets for selective stimulation with therapeutic doses of TMS.

Introduction

Transcranial Magnetic Stimulation (TMS), introduced almost two decades ago (Barker et al., 1985), is a non-invasive method of stimulating the brain. It is increasingly being used as a tool in basic neuroscience to study the function of the nervous system, and it has also entered the field of clinical psychiatry as a potential treatment option for a variety of mental illnesses (Burt et al., 2002). Comprehensive reviews of the role of TMS in basic neuroscience and neuropsychiatry have recently been published Burt et al., 2002, Fitzgerald et al., 2002a, George et al., 1999, Hallett, 2000, Lisanby et al., 2000, Lisanby et al., 2002. In this paper, we focus on TMS as a neurophysiological tool in schizophrenia research and as a therapeutic resource for the treatment of schizophrenia. After a brief introduction about TMS, we describe the application of TMS for studying cortical excitability and assessing inhibitory mechanisms. The neurophysiological and clinical studies using TMS in schizophrenia are then reviewed.

Section snippets

Transcranial Magnetic Stimulation

TMS is based on Faraday's principle of electromagnetic induction. A rapidly changing magnetic field (2 T) is generated by passing a very brief (0.2–0.9 milliseconds (ms)) high-current alternating electric pulse through an insulated coil made of wire. When the coil is placed against the scalp the magnetic field passes readily through the skull and induces a weak electrical current in the superficial cortex of the brain lasting exactly as long as the current pulse in the coil (Barker, 2002). The

Studying cortical excitability and inhibitory mechanisms with TMS

Researchers have utilized TMS of the motor cortex to study neuronal excitability, and cortical inhibitory mechanisms, both in patients and healthy subjects (Fitzgerald et al., 2002a). This has mainly been achieved by examining EMG recorded motor evoked potentials (MEPs). Here we briefly review several key TMS paradigms that are useful for evaluating cortical excitability and inhibition.

Motor threshold and MEP

A MEP is a synchronous muscle response evoked by a TMS pulse stimulating the motor cortex. It is a marker of cortical excitability and its size reflects the number of motor neurons that are activated by a TMS pulse. The latency from the time of motor cortex TMS to the onset of a MEP is a measure of corticospinal conduction time. The threshold for inducing MEPs with TMS is called motor threshold. Motor threshold has been defined as the lowest stimulation intensity over the motor cortex needed to

Neurophysiological studies using TMS in patients with schizophrenia

Some histopathological and pharmacological studies have suggested that the pathophysiology of schizophrenia may involve dysfunction of excitatory (Selemon and Goldman-Rakic, 1999) and/or inhibitory neural function (Olney and Farber, 1995). In a number of recent studies, TMS of motor cortex has been used to evaluate both cortical excitability and inhibitory mechanisms in patients with schizophrenia. This research is still in its early days and most of the studies are limited to small sample

Treatment of schizophrenia with TMS

Since the mid 1990s, it has been suggested that TMS may play a role in the treatment of several neurological and psychiatric disorders (Pridmore and Belmaker, 1999). Indeed, there is increasing evidence suggesting that both slow and high frequency TMS trains applied to the left or right prefrontal cortex have antidepressant effects, although the effect sizes are variable between studies and few studies have shown high rates of strong response or remission (Burt et al., 2002). There is less data

TMS of prefrontal cortex

The first two studies of TMS aimed at treating patients with schizophrenia were open trials using slow repetitive stimulation of the prefrontal cortex with circular coils Feinsod et al., 1998, Geller et al., 1997. Transient improvement in mood was described in 2 of 10 schizophrenia patients treated with 15 TMS pulses over each side of the prefrontal cortex (Geller et al., 1997). Feinsod et al. (1998) treated 10 patients with right prefrontal TMS at 1 Hz in two 1-min daily sessions for 10 days.

TMS of temporoparietal cortex to treat auditory hallucinations

Recent studies have provided interesting findings on the effectiveness of TMS applied to one particular brain area to specifically treat auditory hallucinations d'Alfonso et al., 2002, Hoffman et al., 1999, Hoffman et al., 2000, Hoffman et al., 2003. A previous study suggested that auditory hallucinations may stem from abnormalities in brain areas that are involved in the perception of speech. Silbersweig et al. (1995) performed PET scans on six patients with schizophrenia who were

Conclusions and future directions

The application of TMS in basic neurophysiological and neuropsychiatric research has been rapidly expanding since its introduction in 1985. TMS is a noninvasive method that can be employed to study motor cortex excitability and cortical inhibitory mechanisms. A growing number of studies using TMS-based paradigms support the notion that cortical inhibition may be deficient in patients with schizophrenia. However, the use of TMS as a diagnostic tool for psychiatric disorders is still in its

Acknowledgements

This work was supported by a grant from the families of Donald and Patricia Cheney and Jack and Patricia Lane. The authors would also like to thank two anonymous reviewers for helpful suggestions.

References (92)

  • C.D. Frith et al.

    Explaining the symptoms of schizophrenia: abnormalities in the awareness of action

    Brain Res. Rev

    (2000)
  • P. Fuhr et al.

    Spinal motor neuron excitability during the silent period after cortical stimulation

    Electroencephalogr. Clin. Neurophysiol

    (1991)
  • V. Geller et al.

    Slow magnetic stimulation of prefrontal cortex in depression and schizophrenia

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (1997)
  • N. Grisaru et al.

    Effect of transcranial magnetic stimulation in posttraumatic stress disorder: a preliminary study

    Biol. Psychiatry

    (1998)
  • R.E. Hoffman et al.

    Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated “voices”

    Biol. Psychiatry

    (1999)
  • R.E. Hoffman et al.

    Transcranial magnetic stimulation and auditory hallucinations in schizophrenia

    Lancet

    (2000)
  • T.A. Kimbrell et al.

    Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers

    Psychiatry Res. Neuroimaging

    (2002)
  • S. Komssi et al.

    Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation

    Clin. Neurophysiol

    (2002)
  • S.H. Lisanby et al.

    Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials

    Biol. Psychiatry

    (2001)
  • R.W. McCarley et al.

    Event-related potentials in schizophrenia: their biological and clinical correlates and a new model of schizophrenic pathophysiology

    Schizophr. Res

    (1991)
  • Z. Nahas et al.

    Unilateral left prefrontal transcranial magnetic stimulation (TMS) produces intensity-dependent bilateral effects as measured by interleaved BOLD fMRI

    Biol. Psychiatry

    (2001)
  • A. Pascual-Leone et al.

    Motor cortical excitability in schizophrenia

    Biol. Psychiatry

    (2002)
  • P.M. Rossini et al.

    Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee

    Electroencephalogr. Clin. Neurophysiol

    (1994)
  • L.D. Selemon et al.

    The reduced neuropil hypothesis: a circuit based model of schizophrenia

    Biol. Psychiatry

    (1999)
  • G. Tononi et al.

    Schizophrenia and the mechanisms of conscious integration

    Brain Res. Rev

    (2000)
  • W.J. Triggs et al.

    Physiological motor asymmetry in human handedness: evidence from transcranial magnetic stimulation

    Brain Res

    (1994)
  • E.M. Wassermann

    Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996

    Electroencephalogr. Clin. Neurophysiol

    (1998)
  • E.M. Wassermann et al.

    Crossed reduction of human motor excitability by 1 Hz transcranial magnetic stimulation

    Neurosci. Lett

    (1998)
  • T. Wu et al.

    Lasting influence of repetitive transcranial magnetic stimulation on intracortical excitability in human subjects

    Neurosci. Lett

    (2000)
  • U. Ziemann et al.

    Changes in human motor cortex excitability induced by dopaminergic and anti-dopaminergic drugs

    Electroencephalogr. Clin. Neurophysiol

    (1997)
  • A.T. Barker

    The history and basic principles of magnetic nerve stimulation

  • D.E. Bohning et al.

    Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial magnetic stimulation

    Invest. Radiol

    (1998)
  • D.E. Bohning et al.

    Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement

    Invest. Radiol

    (2000)
  • D.E. Bohning et al.

    BOLD-f MRI response to single-pulse transcranial magnetic stimulation (TMS)

    J. Magn. Reson. Imaging

    (2000)
  • B. Boroojerdi et al.

    Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation

    Br. J. Psychiatry

    (1999)
  • J.P. Brasil-Neto et al.

    Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity

    J. Clin. Neurophysiol

    (1992)
  • T. Burt et al.

    Neuropsychiatric applications of transcranial magnetic stimulation: a meta-analysis

    Int. J. Neuropsychopharmacol

    (2002)
  • R. Chen et al.

    Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation

    Neurology

    (1997)
  • P. Cicinelli et al.

    Interhemispheric differences of hand muscle representation in human motor cortex

    Muscle Nerve

    (1997)
  • E. Cohen et al.

    Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: a pilot study

    J. Neurol. Neurosurg. Psychiatry

    (1999)
  • A.A. d'Alfonso et al.

    Transcranial magnetic stimulation of left auditory cortex in patients with schizophrenia: effects on hallucinations and neurocognition

    J. Neuropsychiatry Clin. Neurosci

    (2002)
  • Z.J. Daskalakis et al.

    Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation

    Arch. Gen. Psychiatry

    (2002)
  • N.J. Davey et al.

    Effects of antipsychotic medication on electromyographic responses to transcranial magnetic stimulation of the motor cortex in schizophrenia

    J. Neurol. Neurosurg. Psychiatry

    (1997)
  • V. Di Lazzaro et al.

    Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

    Exp. Brain Res

    (2002)
  • M. Feinsod et al.

    Preliminary evidence for a beneficial effect of low-frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia

    Depress. Anxiety

    (1998)
  • A. Ferbert et al.

    Interhemispheric inhibition of the human motor cortex

    J. Physiol

    (1992)
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