Transcranial magnetic stimulation —
New brain imaging tool

R. J. Ilmoniemi^1,2,3
1BioMag Laboratory, Engineering Centre, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Finland;
²Helsinki Brain Research Center, Helsinki, Finland; ³Nexstim Ltd., Elimäenkatu 22 B, FIN-00510 Helsinki, Finland

Abstract: Recent advances in targeting TMS on the basis of 3D MRI images and in combining it with EEG, PET, and fMRI are transforming TMS into a new brain imaging modality. With MRI-based targeting of the stimuli and the ability to measure cortical responses evoked by TMS, one can perform precisely controlled studies on cortical reactivity and connectivity. The new techniques will find applications in cognitive, neurological and psychiatric studies and in therapy.

INTRODUCTION

The brain can be stimulated non-invasively by magnetic field pulses that induce a flow of current in the tissue. This technique, called transcranial magnetic stimulation (TMS), has grown dramatically in popularity since its initial demonstration by Barker et al. in 1985 [1].

Initially, most TMS experiments were limited to the stimulation of the motor cortex, because the only effects of the stimulation that could be reliably observed were those reflected in muscular activity. In the past few years, however, it has been demonstrated that one can observe the cortical effects of TMS also directly, e.g., by means of electro­encephalography (EEG), positron emission tomo­graphy (PET), or functional magnetic resonance imaging (fMRI).

These developments, together with the possibility to target the stimuli on the basis of 3D MRI, are transforming TMS to a completely new brain mapping modality, which is based on observing brain activity after neurons have been triggered into action in a controlled fashion.

METHODS

With TMS, one can 1) measure cortical excitability, 2) study the integrity, efficacy, and timing of area-to-area connections, 3) find cortical areas that are im­por­tant for specific tasks, or 4) treat patients.

The field strength of up to several tesla required in TMS is produced by a strong current in a coil placed over the scalp. The effect in the brain is due to the induced electric current and the consequent depolarization of cell membranes.

The field strengths in TMS are lower than or equal to the field in a typical modern MRI scanner; there is no reason to believe that the direct effect of the magnetic field of a brief pulse would be any more harmful than a static one, which itself appears to pose no danger. Power dissipation due to the TMS-induced electrical currents is also low: the total dissipated power in the brain during 20-Hz repetitive TMS (rTMS) is less than 1 mW, i.e., several orders of magnitude less than the brain’s metabolic power. After over a decade of intense scrutiny, TMS seems to be a rather safe technique [2].

The focality of stimulation depends on the type of coil and on its distance from the head, small coils pressed against the scalp generally producing the most confined stimulation. In early magnetic stimulators, only circular coils were used; better focus can be obtained with the figure-of-eight coil [3]. In the future, we may see arrays of coils, which allow further improved focusing as well as electronic targeting [4,5].

In traditional TMS studies, the coil is placed over the head by using external landmarks or by trial and error until the desired response (e.g., thumb twitch) is generated. In contrast, one can now use navigated TMS, where the coil is positioned on the basis of MRI so that one can define in advance which anatomical feature of the brain is stimulated.

Navigated TMS allows precise definition of the induced electric field strength instead of choosing a percentage of the maximum stimulator output or percentage of the motor threshold. The improved control of stimulus parameters will improve reliability and safety.

TMS combined with multichannel EEG allows one to monitor the spreading of neuronal activation after stimulation [6]. The main advantage of concurrent TMS and EEG is the possibility to study cortical excitability and functional connectivity on a millisecond scale [7].

Paus et al. [8] combined TMS and PET, introducing a new technique that permits the mapping of neural connec­tions in the living human brain. While stimulating a selected cortical area, they simultaneously measured changes in cerebral blood flow. They found significant correlations between cerebral blood flow and the number of TMS pulse trains, demonstrating functional connectivity from the left frontal eye field to visual areas in the superior parietal and medial parieto-occipital cortex.

The use of TMS within an MRI equipment is not straightforward because of the magnetic forces between the two systems and because the TMS coil may distort the MRI images. Nevertheless, it has been shown that TMS-evoked brain activation can be measured by using fMRI [9, 10].

RESULTS

A powerful TMS paradigm was introduced by Amassian et al. [11]: a subject’s performance in a character identifica­tion task was impaired when single magnetic pulses were administered between 60 and 140 ms after the onset of the visual stimulus; a temporary functional lesion had been created. This technique has been subsequently used in a variety of experiments. For example, Pascual-Leone et al. [12] showed that by applying rTMS to language areas in the dominant hemisphere, speech production can be arrested.

Ziemann et al. [13] studied effects of epileptic drugs on motor cortex excitability using TMS. Kähkönen et al. [14] used TMS with high-resolution EEG to see how ethanol affects TMS-evoked cortical activity. Stimulating the motor cortex in the left hemisphere, they observed alcohol-induced changes not only in the stimulated area, but also in the frontal cortex, including the contralateral hemisphere. It thus appeared that ethanol had changed the functional connectivity between motor and prefrontal cortices.

TMS is used increasingly for depression therapy. George et al. [15] treated medication-resistant depressed patients by applying rTMS to the left dorsolateral prefrontal cortex, where neuronal activity appears to be lowered in depression. Several other authors [16] have subsequently reported positive results on depressed patients, giving hope that rTMS may replace the inconvenient electroconvulsive therapy (ECT) at least in some cases of drug-resistant depression.

rTMS has also been an experimental treatment for pa­tients with obsessive-compulsive disorders [17], post-trau­matic stress [18], schizophrenia and Parkinson's disease [19]. However, the physiological mechanisms and the conclusive demonstration of the efficacy of rTMS in therapy still requires extensive clinical trials.

DISCUSSION

In its 16 years of existence, TMS has evolved into a valuable technique for both clinicians and basic researchers. It is a unique and powerful tool providing a means to examine cortical excitability and connectivity in normal and abnormal human brain in vivo. On the other hand, rTMS has shown promise as an alternative treatment in several psychiatric disorders, in particular in depression. In cognitive neuroscience, the excellent temporal resolution of TMS is invaluable in determining brain–behaviour relations with, e.g., temporary lesion studies. Advances in precise, navigated targeting of TMS, improved techniques for the recording of TMS-evoked activity, integration with MRI and other imaging techniques, and new experimental paradigms and clinical applications promise a bright future for TMS. One can say that a new brain imaging tool has emerged.

Acknowledgments: Supported by the Academy of Finland and Helsinki University Central Hospital Research Funds.

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