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