Special Article

Basic Principle of Transcranial Magnetic Stimulation

Paradee Auvichayapat MD*,
Narong Auvichayapat MD**

* Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
** Division of Child Neurology, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

Background: Transcranial Magnetic Stimulation (TMS) is a new neurophysiological technique based on the
principle of electromagnetic induction. When a pulse of current passes through a coil, it becomes a magnetic
field and penetrates the scalp and skull, and reach the brain painlessly.
Objective: Review TMS stimulator, types of stimulation, mechanism of action, and its application.
Material and Method: There are three types of TMS stimulation: 1) Single pulse; used in studying of
motor threshold and phosphene threshold. 2) Paired pulse; used in the study of intracortical inhibitory and
facilitatory mechanisms. 3) Repetitive stimulation; changes corticospinal/corticocortical pathway.
Results: The mechanisms increases activity of synapse, changes the secretion of neurotransmitter, and causes
neuronal plasticity or long-term potentiation. Repetitive stimulation is used in fundamental basic science
for brain mapping. It is a new therapeutic method for neuro-psychiatic disorders that does not respond to
medications.
Conclusion: TMS study is rapidly increasing and accepted as a noninvasive technique. The most favorable
treating outcomes are depression and Parkinson disease. Other neuro-psychiatic therapeutic outcomes are
ongoing.

Keywords: Transcranial Magnetic Stimulation, TMS, Neurophysiologic technique, neuro-psychiatic disorders

J Med Assoc Thai 2009; 92 (11): 1560-6

Full text. e-Journal: http://www.mat.or.th/journal

Transcranial magnetic stimulation (TMS) is used for researches, diagnosis, and treatments in
a new neurophysiological technique that has an neurophysiology, neurology, and psychiatry.
interesting role in scientific and medical researches. The authors’ objective was to review TMS
TMS was first introduced by Barker A et al in 1985. stimulator, types of stimulation, mechanism of action,
They provided the information of TMS as a non- and its applications.
invasive, painless method and safe tool(1).
TMS is based on the principle of electro- TMS stimulator
magnetic induction discovered by Faraday in 1838. There are three essential components: storage
When a pulse of current passes through a coil, it capacitors, stimulating coil, and timing mechanism. The
becomes a magnetic field and penetrates the scalp capacitor produces discharge currents of 5,000 amps
and skull into the brain. At the stimulation site, TMS or more and is connected to the coil via an electronic
prefers to activate pyramidal cell indirectly by trans- switch(1). Ninety percent of the discharge occurs
synaptic instead of activating directly at their axon within the first 100 millisecond then it flows through
hillock(1). Motor evoked potentials (MEPs) from first the coil. The capacitor can generate mono or biphasic
interosseous muscle are detected by electromyography TMS waveform depending on each capacitor design(1).
(EMG) (Fig. 1). Nowadays, TMS has been increasingly The difference between monophasic and biphasic
TMS is increasingly noticed in many researches(2). The
Correspondence to: Paradee Auvichayapat, Department of
Physiology, Faculty of Medicine, Khon Kaen University, Khon
monophasic pulse has one sharp initial quarter cycle
Kaen 40002, Thailand. Mobile: 089-6222624. E-mail: whereas the biphasic pulse contributes the induced
aparad@kku.ac.th effect in the second and the third quarter cycle. The

1560 J Med Assoc Thai Vol. 92 No. 11 2009

studies on repetitive TMS (rTMS) effects found that
biphasic pulse wave might play an important role than
monophasic one(2).
The stimulating coil consists of one or more
tightly wound and well-insulated copper windings
together with temperature sensors and safety switches.
The intensity of the stimulation can be controlled by
changing the intensity of current flowing in the coil,
thus changing the magnitude of the induced magnetic
field and of the secondarily induced electrical field. Fig. 1 Principle of transcranial magnetic stimulation,
transcranial magnetic stimulator circuit (left)
The focus point of the magnetic field depends on the
releasing electrical current through the stimulating
shape of the stimulation coil. The two most commonly coil and produces a perpendicular magnetic field
used coils are a figure-of-eight shape or butterfly coil to the structures beneath the coil. The detectable
and a circular coil. The figure-of-eight coil is two round muscle contraction or motor evoked potential is
coils that are placed side by side, so that the currents quantitatively measured by electromyography
flow in the same direction at the junction point. The (EMG) apparatus
magnetic fields will add together and be maximized at
the junction point. This coil allows focal stimulation at
a limited and clearly definable location, so that the
figure-of-eight coil is more often used than the round
coil in researches and clinical applications. The
circular coil induces a more widely distributed magnetic
field allowing for bihemispheric stimulation, which is
particularly desirable in the study of central motor
conduction times. In addition to its intensity and focus
point, operators can also control the frequency of
Fig. 2 Types of TMS stimulations, single pulse provides
the delivered stimuli, which will critically determine the one response. Paired pulse is two pulses stimulation
effects of TMS on the targeted region of the brain. separated by interstimulus interval (ISI). Repetitive
Anatomically precise localization of stimulation can be stimulation uses trains of pulse separated by
achieved by using a frameless stereotactic system intertrain interval (ITI)
(Fig. 2)(3).

Type of TMS stimulation phosphene thresholds in patients with migraine and

Single pulse TMS (sTMS) found that they were significantly lower than control(6,7).
When stimulating the primary motor cortex of Apart from the motor or phosphene threshold,
dominant hemisphere by single-pulse. Motor evoked sTMS is used in studying the amplitude and latency of
potentials (MEPs) induce small hand muscle and cause MEPs and silent period(8).
motor threshold (4), which are believed to reflect In many studies, the parameters of sTMS are
membrane excitability of corticospinal neurons and different. Sommer M, et al found that motor threshold
interneurons projecting onto these neurons in the motor at rest or voluntary contraction of biphasic pulse was
cortex, as well as the excitability of motor neurons in significantly lower than monophasic pulse. They also
the spinal cord, neuromuscular junctions, and muscle. found that the orientation of pulse was important in
Motor threshold defined as the lowest intensity required some parameters. Monophasic pulse had an anteriorly
to elicit MEPs of more than 50 μV peak-to-peak longer silent period than monophasic posteriorly
amplitude in at least 50% of successive trials, in resting oriented pulses. They concluded that inhibitory
or activated (slightly contracted) target muscles(5). interneurons were best activated by posteriorly oriented
sTMS applied over the occipital lobe can pulses(9).
elicit phosphene in many individuals. Analogous to
the motor threshold, a “phosphene threshold” can be Paired pulse TMS (pTMS)
determined and used to study the occipital cortex pTMS refers to double stimulation of the same
and the visual pathways. Many studies investigated TMS coil at the same region. This method studies

J Med Assoc Thai Vol. 92 No. 11 2009 1561

intracortical inhibitory and facilitatory mechanisms by The stimulation of the different TMS coil
combining a sub-threshold conditioning stimulus with can also examine the central motor conduction time
a supra-threshold test stimulus at inter-stimulus through (CMCT); calculate by the different of MEP latency of
the same coil. The size of a test MEP depends on the motor cortex and spinal root(13). This technique was
stimulus intensity and the inter-stimulus interval. The performed by giving a first stimulus to motor cortex
inhibitory effects are found at short inter-stimulus and a second stimulus to the spinal root. Many
intervals of 1-4 ms and conditioning stimuli of 60-80% studies found that CMCT was prolonged in multiple
of the resting motor threshold and the inhibition is sclerosis, amyotrophic lateral sclerosis, stroke,
common, about 20-40% of the test MEPs(10). secondary Parkinsonism, secondary dystonia, and
The facilitatory effects of the conditioning brain injury(14).
TMS pulse on the test MEPs can be observed at the It seemed to show that pTMS is one of the
intervals of 7-20 ms. The magnitude of the facilitation interesting tools for neurophysiologic diagnosis.
is varied among individuals, from 120% to 300% of
the test MEPs, depending on the amplitude of the Repetitive TMS (rTMS)
test MEPs and the degree of contraction of the target rTMS is a train of TMS pulses of the same
muscle, a critical variable to control in pTMS studies. intensity applied to a stimulation site at a given
In many studies, pTMS has been used to investigate frequency. Lower frequencies of rTMS, in 1 Hz range,
the effects of neuropsychological drugs on the can suppress excitability of the motor cortex, while
human motor cortex. These studies found that it high frequencies, 1 Hz or more, stimulation trains seem
might be useful for selecting the best-suited drug to temporary increase in cortical excitability(15). While
for neuropsychiatric patients such as epilepsy or these effects vary among individuals, the effect of
psychosis(11). pTMS has been used to study the patho- low frequency rTMS is robust and long lasting and
physiology of various neurological and psychiatric can be applied to the motor cortex and to other cortical
diseases. These results are interesting but seem to be regions to study brain-behavior relations. The higher
rather non-specific. For example, essentially the same the stimulation frequency and intensity, the greater
abnormalities in the paired-pulse curve can be seen the breaking of cortical function during the train of
in dystonia and idiopathic Parkinson’s disease. stimulation. rTMS is a very widespread technique
Furthermore, disorders without clear motor-cortex used in fundamental basic science and therapeutic in
pathology, such as schizophrenia, depression, or neuropsychiatric diseases.
obsessive-compulsive disorder have been found to be
associated with changes in the TMS paired-pulse curve. Mechanism of action of rTMS
However, longitudinal studies of the paired pulse Repetitive transcranial magnetic stimulation
responses may be a prognostic factor for neurological could be a therapeutic tool in the specialty of neuronal
and psychiatric diseases and should be done. disorders, in particular by creating long-lasting
Paired pulse stimulation can also be referred changes in the excitability of synapses within the
to double stimuli of the different TMS coil at the brain as a way to modulate symptoms.
different region. The applications are to examine inter- There were experiments in animals and in brain
hemispheric interactions and transcallosal conduction slices from animals to investigate the mechanisms
times by giving a first conditioning supra-threshold of synaptic plasticity by different applications of
stimulus to one motor cortex and after a short interval electrical stimulation delivered through microelectrodes.
(4-30 ms) a second, test, TMS pulse is applied to the These studies have identified two main types of post-
other motor cortex. Ferbert A, showed that 7-15 ms synaptic, long-term plasticity: long-term potentiation
after suprathreshold TMS of one motor cortex the (LTP) and long-term depression (LTD). The types of
cortical excitability of the opposite motor cortex is stimulation that most consistently produce LTP in
decreased(12). This inter-hemispheric interaction is animal studies are high frequency stimulation (100
influenced by the intensity of the conditioning TMS: pulses at 100 Hz every 10 s for ten trials), which are
the stronger the conditioning TMS, the greater and typically given in an intermittent way, whereas longer
longer the induced inter-hemispheric inhibition. periods of lower frequency stimulation (1-5 Hz pulses
Patients with cortical myoclonus show no such given continuously for 20-30 min) are applied to
interactions, which indicate affected transcallosal or produce LTD. Theta burst stimulation is a pattern of
cortical inhibitory interneurons. stimulation based on the firing arrangement that

1562 J Med Assoc Thai Vol. 92 No. 11 2009

occurs in hippocampal neurons. It was an effective is in line with the frequency-dependent effects of
way of inducing LTP in animal studies by giving high- rTMS on the motor cortical excitability(27).
frequency (50-100 Hz) bursts of 3-4 pulses repeated at Pascual-Leone A et al first reported that
about 4-7 Hz of the theta frequency. The mechanisms submotor-threshold rTMS at high frequency (5 Hz) to
of transcranial magnetic stimulation in animals can the motor cortex improved contralateral hand function
reproduce the patterns of LTP and LDP in the brains of in five patients with Parkinson’s disease(28). There are
conscious human beings(16). two rationales for trials of this method in Parkinson’s
disease: firstly, the increasing cortical excitability to
TMS for basic neurophysiologic science thalamocortical drive, which is believed to lack in
Several studies in humans that combined this disease; and secondly, modifying catecholamine
rTMS and functional neuroimaging techniques such metabolism subcortically through cortical stimulation.
as fMRI and PET have detected the suppression after The mild benefits were reproduced by the other groups.
1 Hz rTMS of the motor cortex stimulation while Strafella AP et al found that rTMS of the prefrontal
increased cerebral blood flow and metabolism in cortex could increase dopamine in the caudate
the stimulated motor cortex 10-20 Hz(17). Similar nucleus(29). Fregni F et al performed the systematic
phenomena have been observed after TMS to other review and meta-analysis of rTMS for Parkinson’s
cortical areas, such as frontal eye field and dorsolateral disease. They evaluated the effects of either 12 studies
prefrontal cortex. Many studies found that the of TMS on motor function in Parkinson’s patients
combination of TMS and neuroimaging could be most using the motor subscale of the Unified Parkinson’s
helpful in the investigation of functional connectivity Disease Rating Scale (UPDRS). They found that rTMS,
between regions in the living human brain called across applied stimulation sites and parameters, can
brain mapping. Furthermore, the combination of rTMS exert a significant, albeit modest, positive effect on the
with tracer PET or magnetic resonance spectroscopy motor function of patients with Parkinson’s disease(30).
may become a novel tool to investigate neurochemical Strafella AP et al studied that whether sham rTMS, in
functional anatomy in health and disease. patients with Parkinson’s disease, induced changes in
striatal [11C] raclopride binding potentials as measured
TMS for therapeutic application with positron emission tomography (PET). They found
rTMS is widely used for therapeutic that the placebo rTMS-induced changes in brain
purposes. The lasting modulation of cortical activity dopaminergic neurotransmission similar to the one
by rTMS is not limited to motor cortical areas. There is activated by other placebo and active dopaminergic
also evidence that these long-lasting effects of rTMS drugs it seemed to support the notion of a shared
can be induced in areas outside the motor cortex(18) neuronal network(31).
and be associated with measurable behavioral effects, After physiological studies of task-specific
including visual(19), prefrontal(20), parietal cortex(21), as dystonia suggested that hyperexcitability of the motor
well as the cerebellum(22). cortex or a failure of intracortical inhibition, rTMS of
Treatment of depression is the most thoroughly the motor cortex at 1 Hz has been used to treat the
studied of the potential clinical applications of rTMS. patients with writer’s cramp. The improvement of
Lasting beneficial effects have been seen in about deficient intracortical inhibition and handwriting
40% of patients with medication-resistant depression lasted at the most 3 hours after application of a 30 min
in the recent studies(23,24). Both high frequency rTMS train of TMS resulted in clinical benefits in only two
of the left dorsolateral prefrontal cortex and low of 16 patients studied. In tics disorder, a similarly
frequency stimulation of the right side can improve abnormal increment of cortical excitability is
depression(25) Lam RW et al performed meta-analysis reported(32) and 1 Hz rTMS of the motor cortex can
of published randomized controlled trials rTMS for reduce the frequency of tics(33). These effects are
treatment-resistant depression in 24 studies, involving transient, but the data support the concept of
1092 patients(26). The data showed that active rTMS impaired inhibitory mechanisms in the motor cortex.
appeared to provide significant benefits in short-term Several other studies have tried to use low-frequency
treatment studies. Kimbrell TA et al suggested that rTMS to treat other diseases, for example cortical
decreasing cerebral metabolism might respond better myoclonus(34) and intractable seizures(35), and showed
to high frequency and those with hyper metabolism successful reduction in the frequency of seizures or
may respond better to low frequency stimulation, which abnormal movements, but in very few patients. Similar

J Med Assoc Thai Vol. 92 No. 11 2009 1563

logic might be applicable to schizophrenia, intractable Krisanaprakornkit and the members of Noninvasive
neurogenic pain, or spasticity, which the suppression Brain Stimulation (NIBS) Research Group of Thailand
of abnormally increased cortical excitability might for their guidance and very valuable suggestions.
achieve desirable symptomatic relief. This study was supported by the Group
The outcome after stroke may be favorably Research Fund of the Faculty of Medicine of
influenced by rTMS suppressing maladaptive cortical Khon Kaen University, Thailand.
plasticity and improving adaptive cortical activity
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หลักพืน้ ฐานของการกระตุน้ ด้วยคลืน่ แม่เหล็กไฟฟ้าผ่านกะโหลกศีรษะ

ภารดี เอือ้ วิชญาแพทย์, ณรงค์ เอือ้ วิชญาแพทย์

การกระตุ ้ น ด้ ว ยคลื ่ น แม่ เ หล็ ก ไฟฟ้ า ผ่ า นกะโหลกศี ร ษะ เป็ น เทคนิ ค ใหม่ ท างประสาทสรี ร วิ ท ยา
หลั ก การทำงานของเครื ่ อ งกระตุ ้ น แม่ เ หล็ ก ไฟฟ้ า คื อ การส่ ง กระแสไฟฟ้ า ผ่ า นขดลวด ทำให้ เ กิ ด สนามแม่ เ หล็ ก
คลื่นแม่เหล็กไฟฟ้าที่เกิดขึ้นจะผ่านเข้าสู่เนื้อเยื่อประสาทได้โดยผู้ถูกทดสอบไม่รู้สึกเจ็บปวด
ชนิดของการกระตุ้นด้วยคลื่นแม่เหล็กไฟฟ้าผ่านกะโหลกศีรษะมี 3 ชนิด คือ 1) การกระตุ้นครั้งเดียว
มีประโยชน์เพือ่ ใช้หา threshold ของสมองส่วนต่างๆ ได้แก่ motor cortex และ occipital cortex 2) การกระตุน้ คลืน่ คู่
เป็นการตรวจกลไก intracortical inhibition และ facilitation ซึ่งเป็นนวัตกรรมใหม่เพื่อใช้ศึกษาพยาธิสรีรวิทยาของ
โรคทางระบบประสาทและโรคทางจิตเวชหลายโรค 3) การกระตุ้นซ้ำ ๆ จะสามารถเพิ่มหรือลด corticospinal หรือ
corticocortical pathway โดยกลไกที่ยังไม่ทราบแน่ชัดนัก แต่เชื่อกันว่าทำให้มีการเปลี่ยนแปลงผลของจุดประสาน
ประสาท ต่อ long term potentiation (LTP) ทำให้เกิดการปรับเปลี่ยนการทำงานของระบบประสาทในระยะยาว
การกระตุ้นซ้ำ ๆ ถูกนำไปใช้ในการศึกษาแผนที่สมอง และเป็นวิธีรักษาโรคทางระบบประสาทและจิตเวชแบบใหม่
ที่การรักษาด้วยยาไม่ได้ผล
การกระตุ้นด้วยคลื่นแม่เหล็กไฟฟ้าผ่านกะโหลกศีรษะได้รับความสนใจมากขึ้นเรื่อย ๆ และเป็นที่ยอมรับว่า
เป็นเทคนิคใหม่ทางประสาทสรีรวิทยาทีไ่ ม่กอ่ ให้เกิดอันตราย สามารถรักษาโรคซึมเศร้า และโรคพาร์กนิ สันได้ผลดีมาก
ส่วนการรักษาโรคทางระบบประสาทและจิตเวชอื่น ๆ กำลังอยู่ในระหว่างการศึกษา

1566 J Med Assoc Thai Vol. 92 No. 11 2009