Repetitive Transcranial Magnetic Stimulation

Introduction

Transcranial Magnetic Stimulation (TMS) is a form of localized non-invasive brain stimulation based on the principles of electromagnetic induction. The device is placed on the scalp and delivers single (sTMS) or repetitive (rTMS) magnetic pulses. Frequency Intensity Duration and Interval The number of pulses can vary [1].

The exact mechanism of action is unknown, with current evidence suggesting a role in causing long-term depression and excitation of neurons in certain brain regions.

There is sufficient evidence to accept:

• Level A (definite efficacy) for:

1. Efficacy of the analgesic effect of high-frequency (HF) rTMS in the contralateral primary motor cortex (M1)
2. Efficacy of HF rTMS in the left dorsolateral prefrontal cortex (DLPFC) in depression[2].
3. Efficacy of rTMS in the treatment of unipolar depression for both HF rTMS in the left DLPFC and LF rTMS in the right DLPFC.

• A Level B recommendation (probably more efficient) is suggested

1. antidepressant effect of low-frequency (LF) rTMS in the right DLPFC
2. for negative symptoms of depression HF-rTMS of the left DLPFC
3. for chronic motor stroke disease LF-rTMS with contralesional M1 [2].

• Level C (possibly more effective) for the effect of LF rTMS of the left temporoparietal cortex on auditory and auditory hallucinations[2].

Transcranial Magnetic System[3]

Historical Background

Throughout history, brain stimulation techniques such as TMS have proven to be powerful tools for investigating neurophysiology as well as for mapping and modulating neuronal mechanisms[1 ]. First appearing as a potential mechanism for noninvasive nerve stimulation in the early 20th century[4] generally transcranial magnetic stimulation (rTMS) has gone through several stages of development.

In 1985 Anthony Barker developed the first modern TMS device as a means of studying electrophysiology[5]. Barker’s original study was based on a single TMS pulse in which a single stimulus is delivered to a specific region of the brain. The easiest muscles to be mobilized are the brachial and distal muscles the upper limb is due partly to the convenient location of the functional area of the hand in the central spiral of the brain and partly to anatomy; these neurons have the purest corticospinal innervation from the contralateral side. These studies proved infact that TMS can stimulate nerves movement of the hand when applied to the main muscle of the body (M1).

Extending this the technology was designed to allow a device to deliver multiple stimuli in a short period of time to have a sustained effect on cortical excitability that lasted beyond the stimulus delivery itself.

Because of the ability of this treatment to alter cortical function in a focused manner, the use of this technique to potentially improve neurodegenerative disorders soon received attention through the first studies a they tried to cure the depression.

In 1995, George et al.[6] used rTMS to target specific brain regions thought to be involved in the etiology or pathology of major depression in an open-label study. Although most studies have supported the antidepressant effect of rTMS, its clinical benefits have has been variable and in some cases peripheral. However a clear trend toward more robust effects has been observed as both stimulation method (e.g. dose coil placement and course duration) and experimental characteristics (e.g. better sham stimulation and larger sample sizes) improve. rTMS has become accepted acceptable and clinical treatment. Infact since these early studies rTMS has been investigated as a therapeutic intervention for neuropsychiatric diseases such as treatment-resistant depressionnumerous clinical trials of rTMS to treat depression (among others). mental health) has been[7][8][9].

In October 2008, an rTMS device was approved as a U.S. Pat. It is not used by the Food and Drug Administration (FDA) for patients with major depression who have not received at least one antidepressant in their current condition.

With the advent of more advanced structural and functional neuroimaging over the past few decades, the details of this network have become better understood [10]

Functioning

The device consists of a high-current pulse generator capable of producing a discharge current of thousands of amperes, which flows through a stimulating coil to generate brief magnetic pulses with field strengths of up to several Teslas. This magnetic pulse uses the principle of electromagnetism Generate a secondary electric field opposite to the direction of the field generated by the coil [11][12][13][14]. If the coil is placed on the subject’s head, the resulting magnetic field is hardly attenuated by tissues outside the brain (scalp cranium meninges and cerebrospinal fluid) layer) and is capable of inducing electric fields sufficient to depolarize superficial axons and activate neural networks in the cortex.

The extent to which the current density generated into the brain is affected depends on many physical and biological parameters, such as the type and orientation of the coil, the distance between the coil and the brain, the shape of the magnetic pulse, the intensity frequency and stimulation pattern, and Current wires and excitable neural components enter the brain separately.

The simplest and most quantifiable measurement of muscle contraction is the motor threshold, which is the stimulus intensity that produces minimal reproducible activation of the test muscle. Lowered motor thresholds are thought to represent higher cortical excitability and A higher threshold is a state of lower excitability

Type of TMS

1. Single-pulse TMS can be used to simply stimulate a given area while recording the output, and is often used in studies where areas such as the motor cortex are stimulated and motor responses can be recorded from body muscles via electromyography [13] [14].
2. Double-pulse TMS can be used to assess the effect of a previous stimulus on a secondary stimulus. Although this technique is also primarily used in research, it allows the assessment of the influence of one brain region on another. For example, TMS pulses sent to the motor cortex of one hemisphere of the brain Ten milliseconds before the delivery of TMS pulses to the opposite motor cortex results in an inhibitory effect on the motor output of the arm, showing a firing pattern that allows one-handed control of the upper limb [15][16][17].
3. Repetitive TMS (rTMS) techniques involve stringing together a large number of consecutive TMS pulses in rapid succession. This method is used in research and in the clinic because it can generate changes in cortical activity that persist beyond the duration of the TMS protocol. with some reports Shows excitability changes lasting for hours. The rate of pulse delivery appears to determine the effect of rTMS protocols, with those delivering pulses at rates >5 Hz (high frequency rTMS) tending to produce excitatory effects, whereas those delivering pulses at rates <1 Hz (low frequency rTMS) tend to produce excitatory effect Frequency rTMS) tends to produce inhibitory effects in the brain. These rTMS techniques have been approved as a treatment modality for unresponsive major depressive disorder (MDD) patients in Canada. Although the use of rTMS has not been approved clinically for the treatment of exercise Stroke, spinal cord injury, and diseases such as PD, the scientific literature suggests that it may provide some benefit on motor and cognitive symptoms in these populations [18][19][20][21].

Frequency

• Changes in motor-evoked potentials indicated that rTMS altered cortical excitability in a frequency-dependent manner [12]. From the results obtained in different studies based on MEP measurements in healthy subjects, some form of consensus seems to consider low frequency (LF) stimuli (≤1Hz) as “Inhibitory” and high frequency (HF) stimulation (≥5 Hz) as “excitatory”. The mechanisms by which these neuroadaptations occur remain unclear, but some have speculated that rTMS induces Hebbian plasticity similar to long-term potentiation (LTP) or long-term depression (Limited).
• HF rTMS may actually be the result of reduced γ-aminobutyric acid (GABA)-mediated intracortical inhibition (and thus inhibition of inhibition), rather than a direct enhancement of motor cortex excitability. For high frequency TMS, a cooling system is required to prevent the TMS from overheating Electromagnet that repeatedly stimulates.
• LF rTMS may enhance net inhibitory corticospinal control through GABA-B transmission.
• One of the most popular protocols is “theta burst stimulation” training delivered as continuous (cTBS) or intermittent (iTBS), with the former protocol being “inhibitory” and the latter being “excitatory” [22].
• However, this dichotomy is not entirely clear, and it has been suggested that HF and LF rTMS may have mixed excitatory and inhibitory effects [23]. Even when effects on the motor cortex appear specific, e.g. doubling the stimulus duration can reverse the outcome from inhibition to excitation, and vice versa [24].

Coils

Since the TMS was first introduced, researchers and engineers have proposed a wide variety of coil configurations, all of which are designed to optimally focus the induced currents within the brain. Using larger coils stimulates a wider and deeper brain volume. However this may be a Not good if the target can be pinpointed. A recent study [25] reported that the final output of these different designs can be reduced to two basic arrangements: circular coils and dual (figure-eight) coils.

• The circular coil does have the advantages of simple structure, direct heat dissipation, stable head contact, and relatively good penetration under the scalp surface. However, targeting coils to individual brain regions is nearly impossible, which limits their usefulness for most applications [1].

  Transcranial Magnetic Stimulation Coil System [26]

• A double coil consists of two circular coils placed side by side, forming a shape variously described as a figure 8, which increases efficiency and penetration somewhat. [27]
• The latest technological advancement in TMS is the H-coil, which stimulates deeper than traditional figure-of-eight coils. Recent studies have addressed the safety of these coils in people with bipolar depression. [28]

Intensity

Stimulus intensity is usually expressed as a percentage of resting motor threshold (RMT), the minimum intensity required to elicit an electromyographic (EMG) response (motor evoked potential [MEP]) of at least 50 μV with probability 50% of the hand muscles at rest [29]. RMT can also Determined by observing clinical motor responses (finger movements) rather than recording MEPs.

Contraindications

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

Related countermeasures that require specific reasoning or indication of rTMS.are:

• cochlear implants or other atrial fixation devices
• implanted cortical stimulation or DBS systems are available
• cortical TMS may be considered in cases of coma or stimulation of the vagus nerve or spinal cord if objects greater than 10 cm in diameter are placed on the implanted generator
• pregnant women,
• children (aged >2 years),
• patients with auditory problems require specific estimation or determination of the rTMS sensitivity
• personal history of epilepsy,
• focal cerebral lesion,
• taking or withdrawing drugs that relieve seizures
• sleep deprivation

TMS for Depression

Commonly involved brain regions include 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 system (including dorsal and posterior striatum hypothalamus) and brain stem regions. Abnormalities in these areas have been observed in patients with schizophrenia compared with healthy controls. They found a correlation brain metabolic activity and effectiveness of TMS. This was confirmed by the results of TMS treatment in nonresponders who exhibited hypoperfusion in the facial nerve.

Repeated stimulation of the left DLPFC reduces depressive symptoms while repeated stimulation of the right DLPFC helps relieve symptoms of both depression and anxiety. Infact this result correlates with and could be the decrease in synaptic strength seen in schizophrenia attributed to the fact that fast rTMS (> 10 Hz) excites neurons whereas slow rTMS (< 1 Hz) has the opposite effect. [30] .

Studies show that while daily TMS over the DLPFC increases cortical activity and decreases activity in peripheral areas. The neurophysiological response to TMS is particularly important because repetitive stimuli enhance synaptic plasticity to persist even after the stimulation has ceased. Many randomized clinical trials have shown that daily TMS of the left prefrontal cortex is effective in treating symptoms of depressive mood[31][32] .

One study showed prolonged benefit from TMS with or without pharmacotherapy after 6 months.[33][34] TMS demonstrates long-term statistical and clinical significance with strong benefits as well at 12-month follow-up. However all these effects were observed in a pragmatic regimen of continuation antidepressant medication and repeated TMS therapy for symptom relapse.[35]

TMS for Neurological Disease

The most recent guidelines for TMS in rheumatoid arthritis suggest the following:[2]

• Despite the amount of published work, the data in the literature are still too limited to date to support any recommendation regarding the therapeutic use of rTMS in:

1. cerebellar ataxia,
2. myoclonia,
3. Huntington’s disease,
4. Amyotrophic lateral sclerosis,
5. Multiple sclerosis,
6. Alzheimer’s disease
7. Tinnitus a single session of LF rTMS or repeated sessions of rTMS when delivered to the opposite ear canal seems to warrant a Level C recommendation.[36]
8. Anxiety disorders

• In contrast, there is more concrete information about:

1. Parkinson’s Disease; for more information, please see RTMS Treatment For Parkinson’s
2. dystonia (especially writer’s epilepsy) .
3. essential tremor,
4. Tourette’s syndrome.
5. Epilepsy

• Stroke patients:

1. There are some indications of motor potential improvement in the epileptic patient: the increased excitability of HF rTMS in the ipsilesional M1 or the decreased excitability of LF rTMS in the contralesional M1 at Levels B or C recommendation. It should be emphasized that the therapeutic value of the modality of it remains to be determined which stimulus relates to the recovery phase of stroke (acute or subacute vs. chronic).
2. There is also a potential efficacy (Level C recommendation) for repeated applications of cTBS trains to the posterior parietal cortex of the contralesional left hemisphere in hemispatial neglect. For more information, please see Unilateral Neglect.
3. Promising results are expected to be confirmed soon for the use of LF rTMS in the pars triangularis of the IFG of the contralesional right hemisphere in non-fluent Broca’s aphasia

• Schizophrenia: the efficacy of HF rTMS of the left DLPFC in schizophrenia is confirmed by Level A recommendation.
• unipolar or bipolar depression: efficacy of rTMS in unipolar depression with a Level A recommendation (“efficacy”) for both HF rTMS in the left DLPFC and LF rTMS in the right DLPFC.

Transcranial Magnetic Stimulation: A New Approach to the Treatment of Psychiatric Disorders[37]

TMS for Neuropathic Pain

Many areas of the brain including the hypothalamus amygdala thalamus somatosensory cortex insula anterior cingulate cortex and prefrontal cortex are associated with the experience of pain. Additionally some patients with chronic pain do not respond to conventional treatments including injections and anesthesia and corticosteroids and behavioral therapy. rTMS is postulated to induce changes in the activity of cortical and subcortical brain systems related to pain modulation and activation of orbitofrontal cortices medial thalamus anterior cingulate and periaqueductal matter whitish. In particular rTMS is known to modulate neural activities in the periaqueductal gray matter related to pain processing[38].

• Most studies directed the coils of rTMS to the posteroanterior zone of the motor cortex (M1). Patients achieved optimal results with 10 sessions of HF rTMS over M1.
• Good results were obtained with a coil directed to the right DLPFC. Infact stimulation of the appropriate DLPFC was also effective in precipitating the onset of pain.
• No results in patients with chronic neuropathic pain after stroke or spinal cord injury who received deep stimulation time of the anterior cingulated cortex (ACC) or posterior superior insula (PSI). compared with sham rTMS

TMS for Migraine

Studies have reported that the mechanisms of migraine likely involve neural and neurological causes including brain cell hyperexcitability sensitization of the trigeminovascular pathway genetics and environmental factors As shown above RTMS has the potential to it will provide the functionality of cortical structures involved in pain relief or reducing cortical excitability. Plasma β endorphin levels were also found to be lower in patients with migraine than in patients without migraine and HF rTMS increased β endorphin levels[41][42].

HF rTMS was applied to the left M1 and left DLPFC with positive results for headaches during the 4-week study after treatment[43][44].