Transcranial Magnetic Stimulation

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Introduction[edit | edit source]

Transcranial Magnetic Stimulation (TMS) is a focal, noninvasive form of brain stimulation based on principles of electromagnetic induction. The device is placed on the scalp and either single (sTMS) or repeated (rTMS) magnetic pulses are delivered. The frequency, intensity, duration and interval times of pulses can be varied[1].

There is a sufficient body of evidence to accept:

  • Level A (definite efficacy) for the analgesic effect of highfrequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC)[2]
  • Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency(LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke[2].
  • Level C (possible efficacy) for the effect of LF rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations[2]

Historical Background[edit | edit source]

Throughout history, brain stimulation techniques such as TMS have proved to be powerful tools for investigating neurophysiology as well as for mapping and modulating neural circuitry[1]. First emerging as a potential tool for noninvasive neuronal stimulation in the early 20th century[3], repetitive transcranial magnetic stimulation (rTMS) has undergone multiple stages of development.

In 1985 Anthony Barker invented the first modern-day TMS device as a way to study electrophysiology[4]. Barker’s original research was based on single-pulse TMS where a single stimulus was delivered to a specific brain region. These studies demonstrated that TMS could induce muscle movements in the hand when applied to the primary motor cortex (M1).

Expanding on this, the technology developed to allow a device to deliver multiple stimuli over a short period of time, to have lasting effects on cortical excitability that persisted beyond the actual stimulus delivery.

Given the ability of this treatment to modulate cortical activity in a focal way, focus was soon placed on the use of this technique to potentially ameliorate neuropsychiatric disorders, with the earliest studies attempting to treat depression.

In 1995, George et al.[5] used rTMS to target specific prefrontal brain regions thought to be involved in the etiology or pathophysiology of major depression in an open-label study. Although most of the research has supported the antidepressant properties of rTMS, the degree of clinical benefit has been variable and, in some cases, marginal. However, a clear trend toward more robust effects has been seen as both stimulation technique (e.g., dose, coil placement, and course duration) and research quality (e.g., better sham stimulation and larger sample sizes) improve. rTMS has become a recognized, accepted, and clinically available therapeutic intervention. Infact since these first studies, numerous clinical trials of rTMS for the treatment of depression (and other psychiatric disorders) have been conducted[6][7][8].

In October 2008, an rTMS device was approved for use by the US Food and Drug Administration (FDA) for patients with major depression who have not responded to at least one antidepressant medication in their present episode.

With the advent of more advanced structural and functional neuroimaging over the past several decades, the specifics of this network have become better understood [9]

Functioning[edit | edit source]

The equipment consists of a high current pulse generator able to produce a discharge current of several thousand amperes that flows through a stimulating coil, generating a brief magnetic pulse with field strengths up to several Teslas. This magnetic pulse, by the principles of electromagnetism, produces secondary electric fields in the opposite direction to the field generated by the coil[10][11][12][13]. If the coil is placed on the head of a subject, the magnetic field thus created undergoes little attenuation by extracerebral tissues (scalp, cranial bone, meninges, and cerebrospinal fluid layer) and is able to induce an electrical field sufficient to depolarize superficial axons and to activate neural networks in the cortex.

The extent of action of the current density generated into the brain depends on many physical and biological parameters, such as the type and orientation of coil, the distance between the coil and the brain, the magnetic pulse waveform, the intensity, frequency and pattern of stimulation, and the respective orientation into the brain of the current lines and the excitable neural elements.

Type of TMS[edit | edit source]

  1. Single-pulse TMS can be used to simply stimulate a given area while recording the output and is commonly used in research where an area such as the motor cortex is stimulated and a motor response can be recorded from muscles of the body via electromyography[12][13].
  2. Paired-pulse TMS can be used to assess the effect of a preceding stimulus on a secondary stimulus. While this technique is also primarily used in research, it allows for the assessment of one brain region on another. For example, a TMS pulse delivered to the motor cortex of one hemisphere of the brain 10ms prior to a TMS pulse delivered over the opposite motor cortex results in an inhibitory effect in motor output to the arms, showing firing patterns that allow for unimanual control of the upper limbs[14][15][16].
  3. Repetitive TMS (rTMS) techniques involve stringing a large number of consecutive TMS pulses together in rapid succession. This method is used both in research and clinically as it can produce changes in cortical activity that last beyond the duration of the TMS protocol. With some reports demonstrating excitability changes persisting for a number of hours. The rate of pulse delivery appears to dictate the effect of the rTMS protocol, whereas those that deliver pulses at rates of >5Hz (high frequency rTMS) tend to produce excitatory effects and those delivered at rates of < 1Hz (low frequency rTMS) tend to produce inhibitory effects in the brain. These rTMS techniques have been approved as a treatment modality for those with non-responsive major depression disorder (MDD) in Canada. While the use of rTMS has not yet been approved for clinical use in the treatment of movement disorders such as stroke, spinal cord injury, and PD, the scientific literature suggests that it may provide some benefit to both motor and cognitive symptoms in these populations[17][18][19][20].

TMS for Depression[edit | edit source]

Some of the most commonly implicated brain regions include the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex, orbitofrontal cortex, cingulate gyrus (including dorsal anterior, perigenual, subgenual, and posterior subdivisions), insular cortex, medial temporal lobe regions (hippocampus, parahippocampus, and amygdala), parietal cortex, thalamus, midbrain structures (including dorsal and ventral striatum, hypothalamus), and brain stem regions. Abnormalities in these various regions have been identified in depressed patients versus healthy controls.

Resources[edit | edit source]

  1. ↑ 1.0 1.1 Holtzheimer, P., & McDonald, W. (Eds.), A Clinical Guide to Transcranial Magnetic Stimulation. Oxford, UK: Oxford University Press. Retrieved 16 Jan. 2022,
  2. ↑ 2.0 2.1 2.2 Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, et al. "Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)". Clinical Neurophysiology. 2014; 125 (11): 2150–2206.
  3. ↑ Thompson, S. P. . A physiological effect of an alternating magnetic field. Proceedings of the Royal Society B: Biological Sciences, 1910; 82(557): 396–398.
  4. ↑ Barker, A. T., Freeston, I. L., Jalinous, R., Merton, P. A., & Morton, H. B.. Magnetic stimulation of the human brain. Journal Physiology, 1985; 369: 1–3.
  5. ↑ George, M. S., Wassermann, E. M., Williams, W. A., Callahan, A., Ketter, T. A., Basser, P.,… Post, R. M. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport,1995; 6(14): 1853–1856.
  6. ↑ Hoflich, G, Kasper, S, Hufnagel, A, Ruhrmann, S, & Moller, HJ. Application of transcranial magnetic stimulation in treatment of drug-resistant major depression—A report of two cases. Human Psychopharmacology, 1993; 8: 361–365.
  7. ↑ Kolbinger, HM, Hoflich, G, Hufnagel, A, & et al. Transcranial magnetic stimulation (TMS) in the treatment of major depression - a pilot study. Human Psychopharmacology, 1995; 10: 305–310.
  8. ↑ Pascual-Leone, A., Rubio, B., Pallardo, F., & Catala, M. D. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet, 1996; 348(9022): 233–237.
  9. ↑ Drevets, W. C., Price, J. L., & Furey, M. L. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure Function, 2008; 213(1-2): 93–118.
  10. ↑ Barker AT, Jalinous R, Freeston IL. NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX. The Lancet. 1985;325:1106-1107.
  11. ↑ Hallett M. Transcranial magnetic stimulation and the human brain. Nature. 2000;406:147-150.
  12. ↑ 12.0 12.1 Hallett M. Transcranial Magnetic Stimulation: A Primer. Neuron. 2007;55:187-199.
  13. ↑ 13.0 13.1 Siebner H, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity. Experimental Brain Research. 2003;148:1-16.
  14. ↑ Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. Experimental Brain Research. 2004;154:1-10.
  15. ↑ Ni Z, Gunraj C, Nelson AJ, et al. Two Phases of Interhemispheric Inhibition between Motor Related Cortical Areas and the Primary Motor Cortex in Human. Cerebral Cortex. 2009;19:1654-1665.
  16. ↑ Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, Marsden CD. Interhemispheric inhibition of the human motor cortex. The Journal of Physiology. 1992;453:525-546
  17. ↑ Huang Y-Z, Edwards MJ, Rounis E, Bhatia KP, and Rothwell JC. Theta Burst Stimulation of the Human Motor Cortex. Neuron, 2005; 45: 201-206.
  18. ↑ ↑ Le Q, Qu Y, Tao Y, Zhu S. Effects of repetitive transcranial magnetic stimulation on hand function recovery and excitability of the motor cortex after stroke: a meta-analysis. American journal of physical medicine & rehabilitation. 2014 May 1;93(5):422-30.
  19. ↑ Tazoe T, Perez MA. Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury. Archives of physical medicine and rehabilitation. 2015 Apr 1;96(4):S145-55.
  20. ↑ Goodwill A, Lum J, Hendy A, et al. Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's: a systematic review and meta-analysis. SCIENTIFIC REPORTS. 2017;7.
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