CCNi

Centre for Cognitive Neuroimaging

Articles

Transcranial magnetic stimulation (TMS) is a non-invasive technique to stimulate a restricted part of the cortex. Developed in the 1980s, it has been used first for clinical diagnostic but rapidly growing interest has shown potentials for TMS as a therapeutic tool in Psychiatry, as well as an investigative tool in Cognitive Neuroscience.

How does TMS work?
TMS is based on the laws of electromagnetic induction: a current passing through a coil of wire generates a magnetic field perpendicular to the current direction in the coil. A rapid change of this magnetic field elicits in turn a transient electric field. This electric field affects the membrane potential of the nearby neurons, which may lead to depolarization and neuron discharging or interfere with the ongoing action potentials. Commercially available stimulators offer the possibility to generate peak of magnetic field up to 2.5 tesla, with frequencies up to 30 Hz. Since the magnetic field decreases rapidly (1/distance2) only the most external parts of the brain can be targeted with TMS.

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Time course and order of amplitudes of the events occurring
during a TMS pulse. (from Jalinous, 1998, Magstim Company)


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Example of a figure-of-eight TMS coil. Two coils are juxtaposed with the currents being discharged in opposite directions. The induced electric fields add up so that the peak of the electric field is located at the junction between the two coils. (a, b ,c) photograph and in plane and transversal X-Ray of the coil. (c,d) Induced field two centimetres above the coil.

What are the applications in cognitive neuroscience?
TMS has proven a very useful tool to help us understand the functioning of the normal and pathological human brain. The principal uses of TMS in cognitive neuroscience include:
1) Probing cortical excitability by directly measuring the response to single-pulse TMS applied over primary cortices.  In this case the evoked response, for example, motor evoked potentials for the motor cortex or phosphene intensity for the visual cortex, as well as the TMS intensity threshold necessary to elicit those responses can be used as dependent variables.
2) Interfering briefly with the ongoing cortical activity with single pulse or short trains of high frequency repetitive TMS.  In this case TMS is applied while the participant is engaged in a behavioural task. Changes in performance in trials with TMS as compared to trials without TMS demonstrate the stimulated region was necessary for the processing involved in the task at the moment of stimulation.
3) Inducing long-term (minutes) changes in cortical excitability and connectivity with several minutes of low frequency repetitive TMS. Here participants participate in behavioural, cognitive or brain imaging tests before
and after the administration of, typically, 10-15 minutes of TMS.

How can the brain area of interest be targeted precisely?
In order to make inferences about brain-behaviour relationships, it is crucial to localize precisely the area stimulated by TMS. This is achieved by identifying this area on the high-resolution magnetic resonance image (MRI) of the participant. Then, by using frameless stereotaxy the investigator can position the TMS coil over the scalp so that the peak of electric field is localized on the desired area.

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Frameless stereotaxy: In the first step (left), easily identifiable landmarks are marked on the MRI with a cursor and simultaneously on the head of the subject with a position tracking device. By using a set of four landmarks, dedicated software can register the subject’s head to his/her MRI. In the second step (right), the camera tracks a reflecting device attached to the coil relatively to the reference, and the software displays the position of the electric field on the cortical surface.

How does TMS complement other methods in cognitive neuroscience?
Transcranial magnetic stimulation presents the advantage of a precise timing (for single pulse) and relatively good localisation. The main disadvantage is the impossibility to stimulate deep brain structures directly.
Most brain imaging techniques allow the investigators to identify brain areas that are active during a given motor, perceptual or cognitive process. They cannot tell us, however, whether those areas are necessary for the process. By interfering with the normal functioning of a brain area, TMS enables inferences about a causal link between this area and behaviour.Second, because of the limited duration of the interference it induces, TMS can be used to investigate when a brain area is making its critical contribution to behaviour.
Thus TMS offers a very important complement to brain mapping techniques such as functional MRI or PET. This is illustrated by the growing number of studies employing a two-step approach: 1) identify brain regions activated during a given task with brain imaging; 2) target those areas with TMS to assess and trace the timing of their importance for this behaviour. In addition, TMS combined directly with PET, fMRI or EEG allows the researchers to study cortical excitability and connectivity as well as plasticity, independently of behaviour. While a controlled stimulation is applied over a given area, brain activity can then be assessed both locally and in remote brain regions

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Combining TMS with other methodologies: example of frontal eye field  (FEF) stimulation. A) The FEF can be first localized with fMRI when alternating periods of saccades (S) with periods of rest (R), either in individuals or group or with meta-analysis of a corpus of study (e.g. Grosbras et al Hum Brain Mapp 2005). B) The location identified on the brain anatomy can then be used as a target for TMS thanks to frameless stereotaxy. C) TMS applied 50 ms before the expected onset of a saccade (blue dotted line) delays the saccade. Traces reflect electrooculor (EOG) activity during auditory cued saccades without TMS (blue) or with TMS (red). Stimulating a control site show that this effect is specific to FEF stimulation (Grosbras et al, J Cogn Neurosci,, 2002). D) TMS applied over the FEF induces electroencephalographic potential as well as synchronization in parieto-occipital cortices (Grosbras, unpublished). E) The amount of TMS applied over the FEF is positively correlated with blood flow locally in the FEF

Is TMS safe?
As functional MRI, TMS is a new investigative technique. Therefore the scope for appreciating safety is limited to research done in the last 20 years. As for MRI, safety guidelines have to be respected. Within those guidelines, TMS is considered a safe technique.
Single pulse TMS has no reported harmful side effects. In some susceptible individuals it can induce headaches. Those are easily treated with mild analgesic. Contra-indications for single-pulse TMS are: pace maker, aneurysm clip, heart/vascular clip, prosthetic valve, intracranial metal prosthesis. Pregnant women and young children are also excluded from research studies, although they might be subject to TMS for clinical or therapeutic purposes.
Repetitive TMS potentially has the power to induce seizures (7 reported cases between 1990 and 1996). Therefore further precautions have to be taken. In addition to those for single-pulse TMS, exclusion criteria for repetitive TMS include: personal or familial history of epilepsy, medications which reduce the threshold for seizure, high alcohol or drug consumption.
In addition, in an international workshop held in 1996, safety guidelines have been established for the parameters of repetitive TMS, which are widely accepted by the scientific community. Since then no cases of seizure have been reported.


Selected references

Cowey A. The Ferrier Lecture 2004 : What can transcranial magnetic stimulation tell us about how the brain works? Philos Trans R Soc Lond B Biol Sci. 2005 Jun 29;360(1458):1185-205.

Paus T, Jech R, Thompson CJ, Comeau R, Peters T, Evans AC. Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex. J Neurosci. 1997 May 1;17(9):3178-84.

Virtanen J, Ruohonen J, Naatanen R, Ilmoniemi RJ. Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation. Med Biol Eng Comput. 1999 May;37(3):322-6.

Walsh V, Rushworth M., A primer of magnetic stimulation as a tool for neuropsychology.
Neuropsychologia. 1999 Feb;37(2):125-35. Review.

Wassermann EM. 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. EEG Clin. Neurophysiol. 108:1-16, 1998.