Transcranial Magnetic Stimulation: Difference between revisions

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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<ref name=":0" />. First emerging as a potential tool for noninvasive neuronal stimulation in the early 20th century<ref>Thompson, S. P. . A physiological effect of an alternating magnetic field. Proceedings of the Royal Society B: Biological Sciences, 1910; 82(557): 396–398.</ref>, repetitive transcranial magnetic stimulation (rTMS) has undergone multiple stages of development.  
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<ref name=":0" />. First emerging as a potential tool for noninvasive neuronal stimulation in the early 20th century<ref>Thompson, S. P. . A physiological effect of an alternating magnetic field. Proceedings of the Royal Society B: Biological Sciences, 1910; 82(557): 396–398.</ref>, 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<ref>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.</ref>. 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).
In 1985 Anthony Barker invented the first modern-day TMS device as a way to study electrophysiology<ref>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.</ref>. Barker’s original research was based on single-pulse TMS where a single stimulus was delivered to a specific brain region. The easiest muscles to activate are those in the hand and distal upper limb due, in part, to the convenient location of the hand motor area in the central convexity of the brain and, in part, to physiology; these muscles have the purest component of corticospinal innervation from the opposite hemisphere.  These studies demonstrated infact 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.
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.
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In 1995, George et al.<ref>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<sub>;</sub> 6(14): 1853–1856.
In 1995, George et al.<ref>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<sub>;</sub> 6(14): 1853–1856.


</ref> 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<ref>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.</ref><ref>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.</ref><ref>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.</ref>.
</ref> 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, rTMS has been explored as a therapeutic intervention for neuropsychiatric disorders such as treatment-resistant depressionnumerous clinical trials of rTMS for the treatment of depression (and other psychiatric disorders) have been conducted<ref>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.</ref><ref>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.</ref><ref>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.</ref>.


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.
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.
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== Functioning ==
== Functioning ==
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<ref>Barker AT, Jalinous R, Freeston IL. NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX. The Lancet. 1985;325:1106-1107.</ref><ref>Hallett M. Transcranial magnetic stimulation and the human brain. ''Nature''. 2000;406:147-150.</ref><ref name=":2">Hallett M. Transcranial Magnetic Stimulation: A Primer. ''Neuron''. 2007;55:187-199.</ref><ref name=":3">Siebner H, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity. ''Experimental Brain Research''. 2003;148:1-16.</ref>. 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 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<ref>Barker AT, Jalinous R, Freeston IL. NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX. The Lancet. 1985;325:1106-1107.</ref><ref name=":4">Hallett M. Transcranial magnetic stimulation and the human brain. ''Nature''. 2000;406:147-150.</ref><ref name=":2">Hallett M. Transcranial Magnetic Stimulation: A Primer. ''Neuron''. 2007;55:187-199.</ref><ref name=":3">Siebner H, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity. ''Experimental Brain Research''. 2003;148:1-16.</ref>. 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.
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.
The simplest and most easily quantified measure of muscle contraction is motor threshold, that is, the intensity of stimulation that produces the smallest reproducible activation of the tested muscle. Reduced motor threshold is considered to represent a state of greater cortical excitability, and higher threshold a state of lower excitability
=== Frequency ===
Changes in motor-evoked potentials suggest that rTMS alters cortical excitability in a frequency-dependent manner<ref name=":4" />. Whereas high-frequency stimulation (10 Hz) increases cortical excitability, lowfrequency stimulation (1-5 Hz) decreases cortical excitability. The mechanisms by which these neuroadaptations occur remain unclear, but some have speculated that rTMS induces a Hebbian plasticity that resembles long-term potentiation (LTP) or long-term depression (LTD).
=== Coils ===
Since TMS was first introduced, researchers and engineers have proposed a striking variety of coil configurations, all intended to optimally focus the induced electric current within the brain. The use of larger coils stimulate wider and deeper volumes of the underlying brain. However this may be a disadvantage if the target can be precisely localized. Recently study<ref>Deng, Z.-D., Lisanby, S. L., & Peterchev, A. V. Electric field depth— focality tradeoff in transcranial magnetic stimulation: comparison of 50 coil designs. Brain Stimulation, 2013; 6: 1–13.</ref> reported that the final output of these varied designs could be reduced to two fundamental arrangements: a round coil and a double (figure-8) coil.
* Round coils do have advantages, including simple construction, straightforward heat dissipation, stable head  contact, and relatively good penetration beneath the scalp surface. However, the near impossibility of aiming the coils toward a single brain region limits their utility in most applications<ref name=":0" />.
* The double coil consists of two round coils placed side by side to form a shape variously described as a figure-8, which somewhat improves efficiency and penetration.<ref>Lontis, E. R., Voigt, M., & Struijk, J. J. Focality assessment in transcranial magnetic stimulation with double and cone coils. Journal of Clinical Neurophysiology, 2006; 23: 463–472.</ref>
* A recent technological advance in TMS is the H-shaped coil, which stimulates deeper than conventional figure-8 coils. Recent studies have addressed the safety of these coils in small groups of patients with bipolar depression.<ref>Harel, E., Zangen, A., Roth, Y., Reti, I., Braw, Y., & Levkovitz, Y. Hcoil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World Journal of Biological Psychiatry, 2011; 12:119–126.</ref>
=== Intensity ===
Stimulation intensity is usually expressed as a percentage of rest motor threshold (RMT), which is the minimum intensity required to elicit an electromyographic (EMG) response (motor-evoked potential [MEP]) of at least 50 μV, with a probability of 50% in a hand muscle at rest<ref>Rossini, P. M., Barker, A. T., Berardelli, A., Caramia, M. D., Caruso, G., Cracco, R. Q. Tomberg, C. Noninvasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalography and Clinical Neurophysiology, 1994; 91: 79–92.</ref>. RMT can also be determined by observing clinical motor responses (finger movement) rather than recording MEP.


=== Type of TMS ===
=== Type of TMS ===
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# '''Paired-pulse TMS''' can be used to assess the effect of a preceding stimulus on a secondary stimulus.<span class="reference" id="cite_ref-12"></span> 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<ref>Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. ''Experimental Brain Research''. 2004;154:1-10.</ref><ref>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.</ref><ref>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</ref>.
# '''Paired-pulse TMS''' can be used to assess the effect of a preceding stimulus on a secondary stimulus.<span class="reference" id="cite_ref-12"></span> 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<ref>Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. ''Experimental Brain Research''. 2004;154:1-10.</ref><ref>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.</ref><ref>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</ref>.
# '''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.<span class="reference" id="cite_ref-:1_2-4"></span><span class="reference" id="cite_ref-:7_10-1"></span><span class="reference" id="cite_ref-15"></span> With some reports demonstrating excitability changes persisting for a number of hours<span class="reference" id="cite_ref-16"></span>. 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.<span class="reference" id="cite_ref-:6_8-1"></span><span class="reference" id="cite_ref-:7_10-2"></span> These rTMS techniques have been approved as a treatment modality for those with non-responsive major depression disorder (MDD) in Canada. <span class="reference" id="cite_ref-:9_5-1"></span>While the use of rTMS has not yet been approved for clinical use in the treatment of movement disorders such as [[stroke]], [[Overview of spinal cord injuries|spinal cord injury]], and PD, the scientific literature suggests that it may provide some benefit to both motor and cognitive symptoms in these populations<ref>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.</ref><ref>↑ 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.</ref><ref>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.</ref><ref>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.</ref>.
# '''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.<span class="reference" id="cite_ref-:1_2-4"></span><span class="reference" id="cite_ref-:7_10-1"></span><span class="reference" id="cite_ref-15"></span> With some reports demonstrating excitability changes persisting for a number of hours<span class="reference" id="cite_ref-16"></span>. 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.<span class="reference" id="cite_ref-:6_8-1"></span><span class="reference" id="cite_ref-:7_10-2"></span> These rTMS techniques have been approved as a treatment modality for those with non-responsive major depression disorder (MDD) in Canada. <span class="reference" id="cite_ref-:9_5-1"></span>While the use of rTMS has not yet been approved for clinical use in the treatment of movement disorders such as [[stroke]], [[Overview of spinal cord injuries|spinal cord injury]], and PD, the scientific literature suggests that it may provide some benefit to both motor and cognitive symptoms in these populations<ref>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.</ref><ref>↑ 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.</ref><ref>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.</ref><ref>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.</ref>.
== Contraindications ==
The only absolute contraindication of TMS is the presence of ferromagnetic material or implanted devices in close contact with the coil (less than 2 cm) because of the risk of displacement or malfunction.
Relative contraindications that require specific justification or indication for rTMS.are:
* cochlear implants or other intracranially implanted hardware,
* implanted cortical stimulation or DBS systems are present,
* cortical TMS may be considered in cases of cardiac pacemaker or vagus nerve or spinal cord stimulation if material thicker than 10 cm is placed over the implanted generator,
* pregnant women,
* children (aged >2 years),
* patients with hearing disorders require specific justification or indication for rTMS,
* personal history of epilepsy,
* focal cerebral lesion,
* drug intake or removal that lowers the seizure threshold,
* sleep deprivation


== TMS for Depression ==
== TMS for Depression ==

Revision as of 11:18, 17 January 2022

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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. The easiest muscles to activate are those in the hand and distal upper limb due, in part, to the convenient location of the hand motor area in the central convexity of the brain and, in part, to physiology; these muscles have the purest component of corticospinal innervation from the opposite hemisphere. These studies demonstrated infact 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, rTMS has been explored as a therapeutic intervention for neuropsychiatric disorders such as treatment-resistant depressionnumerous 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.

The simplest and most easily quantified measure of muscle contraction is motor threshold, that is, the intensity of stimulation that produces the smallest reproducible activation of the tested muscle. Reduced motor threshold is considered to represent a state of greater cortical excitability, and higher threshold a state of lower excitability

Frequency[edit | edit source]

Changes in motor-evoked potentials suggest that rTMS alters cortical excitability in a frequency-dependent manner[11]. Whereas high-frequency stimulation (10 Hz) increases cortical excitability, lowfrequency stimulation (1-5 Hz) decreases cortical excitability. The mechanisms by which these neuroadaptations occur remain unclear, but some have speculated that rTMS induces a Hebbian plasticity that resembles long-term potentiation (LTP) or long-term depression (LTD).

Coils[edit | edit source]

Since TMS was first introduced, researchers and engineers have proposed a striking variety of coil configurations, all intended to optimally focus the induced electric current within the brain. The use of larger coils stimulate wider and deeper volumes of the underlying brain. However this may be a disadvantage if the target can be precisely localized. Recently study[14] reported that the final output of these varied designs could be reduced to two fundamental arrangements: a round coil and a double (figure-8) coil.

  • Round coils do have advantages, including simple construction, straightforward heat dissipation, stable head contact, and relatively good penetration beneath the scalp surface. However, the near impossibility of aiming the coils toward a single brain region limits their utility in most applications[1].
  • The double coil consists of two round coils placed side by side to form a shape variously described as a figure-8, which somewhat improves efficiency and penetration.[15]
  • A recent technological advance in TMS is the H-shaped coil, which stimulates deeper than conventional figure-8 coils. Recent studies have addressed the safety of these coils in small groups of patients with bipolar depression.[16]

Intensity[edit | edit source]

Stimulation intensity is usually expressed as a percentage of rest motor threshold (RMT), which is the minimum intensity required to elicit an electromyographic (EMG) response (motor-evoked potential [MEP]) of at least 50 μV, with a probability of 50% in a hand muscle at rest[17]. RMT can also be determined by observing clinical motor responses (finger movement) rather than recording MEP.

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[18][19][20].
  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[21][22][23][24].

Contraindications[edit | edit source]

The only absolute contraindication of TMS is the presence of ferromagnetic material or implanted devices in close contact with the coil (less than 2 cm) because of the risk of displacement or malfunction.

Relative contraindications that require specific justification or indication for rTMS.are:

  • cochlear implants or other intracranially implanted hardware,
  • implanted cortical stimulation or DBS systems are present,
  • cortical TMS may be considered in cases of cardiac pacemaker or vagus nerve or spinal cord stimulation if material thicker than 10 cm is placed over the implanted generator,
  • pregnant women,
  • children (aged >2 years),
  • patients with hearing disorders require specific justification or indication for rTMS,
  • personal history of epilepsy,
  • focal cerebral lesion,
  • drug intake or removal that lowers the seizure threshold,
  • sleep deprivation

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 1.2 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. ↑ 11.0 11.1 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. ↑ Deng, Z.-D., Lisanby, S. L., & Peterchev, A. V. Electric field depth— focality tradeoff in transcranial magnetic stimulation: comparison of 50 coil designs. Brain Stimulation, 2013; 6: 1–13.
  15. ↑ Lontis, E. R., Voigt, M., & Struijk, J. J. Focality assessment in transcranial magnetic stimulation with double and cone coils. Journal of Clinical Neurophysiology, 2006; 23: 463–472.
  16. ↑ Harel, E., Zangen, A., Roth, Y., Reti, I., Braw, Y., & Levkovitz, Y. Hcoil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World Journal of Biological Psychiatry, 2011; 12:119–126.
  17. ↑ Rossini, P. M., Barker, A. T., Berardelli, A., Caramia, M. D., Caruso, G., Cracco, R. Q. Tomberg, C. Noninvasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalography and Clinical Neurophysiology, 1994; 91: 79–92.
  18. ↑ Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. Experimental Brain Research. 2004;154:1-10.
  19. ↑ 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.
  20. ↑ 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
  21. ↑ 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.
  22. ↑ ↑ 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.
  23. ↑ 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.
  24. ↑ 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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