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Medical treatments using Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a technique used in clinical practice to induce neuronal changes in a patient. The law of electromagnetic induction is the basis of functioning of TMS, where action potentials in cortical neurons are triggered with the help of an ionic current induced by a magnetic field. This magnetic field is generated when an electric current is passed to the cortex through the skull of a patient via a coil placed above the patient’s head which generates a magnetic pulse. The first successful development of a magnetic stimulator took place in 1984 when Anthony Baker and colleagues recorded the aroused action and nerve potentials by delivering short field pulses to the brain [1]. However, it was in 1896 when d’Arsonval placed a coil on a volunteer’s head and induced current at 42 Hz to record the first physiological effect producing phosphenes as a result of magnetic field [1,2]. Nonetheless, TMS has been continuously used since then for medical purposes. Its ability to effect neuronal excitability has been the centre of attraction, where a frequency between 5 and 20 Hz (high) increases excitability of the cortex and frequency of about 1 Hz (low) decreases cortical excitability [1,2,3]. Primarily, TMS is used in the form of continuous trains also known as repetitive TMS (rTMS), to reinstate or uphold functions of the brain in patients with psychological or neurological disorders [1,2,3]. However, it can also be used as a single pulse or paired pulse TMS to observe and record muscle activity on electromyography as a result of motor evoked potential (MEP) [2,3]. TMS can be segregated based on aspects of stimulation such as amplitude, duration, and frequency. Following the recommended safety guidelines, painless rTMS is a reasonably safe clinical practice with mild side effects. TMS is known for its use in the diagnosis of Amyotrophic Lateral Sclerosis (ALS) by detecting impaired inhibition of the cortex along with long-tract and motor neuron degeneration [4]. Moreover, TMS is also helpful for treating stroke by applying TMS pulses to a selected area of the motor cortex and measuring amplitude of MEPs. As a result, cortical representation of a muscle can be mapped which can be used to observe reorganization in the cortex due to behavioural motor training exercises [5]. The induced MEPs can also be used to record neuroplastic changes by measuring excitation and inhibition within and between the cortex [6,7,8]. Besides, a study by Kim et al demonstrated the enhanced accuracy and speed of movement of patients with hemiparesis [9]. In the study, the investigating team applied 10 Hz rTMS to patients practicing sequential finger motor task by using numbers between 1 to 4 to reproduce their 7-digit sequences [9]. It was found that the patients in receipt of active rTMS showed improvement in their movements against patients who did not receive rTMS [9]. This highlights the neuroplastic and therapeutic effects of TMS, a significant support for medical treatments. Additionally, transcranial magnetic stimulation fundamentally helps determine the relationship between behaviour and focal brain activity as well as simplifies the significance of functional neuroimaging results. Comprehensively, TMS has seen rapid development to aid cognitive neuroscience to examine plasticity development, and physiological questions of attention, language, memory and/or vision. A study showed the improved performance in face-name memory task for subjects with impaired memory by the application of 5 Hz rTMS to the prefrontal cortex [13]. During the activity, these subjects also showed active prefrontal and occipital regions after comparing with prejunctional magnetic resonance imaging (fMRI) [13]. These findings highlight that rTMS can allow the addition of a neural network to help enhance performances for memory-related functional activities of the brain [13]. For patients suffering with Alzheimer’s disease (AD), the induction of 0.6 s trains of high rTMS (20 Hz) delivered to the dorsolateral prefrontal cortex improved performance of a picture-naming task assigned to the patients [13]. The application of similarly high rTMS also improves the functioning of language neuronal network via stimulation of cortex, as recorded by the enhanced performance of a sentence comprehension task [13]. Further, TMS can allow medical professionals to distinguish severe neurological disorders such as normal and abnormal aging, subcortical vascular and frontotemporal dementia, and Alzheimer’s disease and mild cognitive impairment (MCI). Therefore, it is safe to say that TMS helps cognition by significantly enhancing incremental validity of neurodiagnostic evaluation [8]. For patients suffering from migraine, TMS enables examining the visual and motor cortex excitability. Studies have shown increased motor threshold (MT) for some patients, while also reporting reduced spasm for muscles of the hand and face [7,8]. Similarly, for patients suffering from idiopathic generalised epilepsy (IGE), cortical excitability can be observed using TMS via reduced MT [8,9]. The repetitive TMS treatment for older adults with mood disorders and depression, when delivered to the prefrontal cortex is effective and well-tolerable without causing severe adverse effects [9]. All these aspects are evident to claim that transcranial magnetic stimulation is a beneficial technique of medical treatments. It is a non-invasive method of therapy that does not require anaesthesia and is usually well tolerated by the patients [10]. It does not limit the patients within the treatment centre as they are free to continue normal daily routines, due to the therapy being outpatient [11]. TMS is highly useful for patients struggling with medication due its efficacy, as well as an excellent alternative form of treatment for patients previously responsive to Electroconvulsive Therapy (ECT) [9,10,11]. A highly concerning aspect for TMS is the potential damage to the head or brain, but TMS overcomes this challenge as no recorded evidence of significant memory impairment or severe brain damage has surfaced [12]. However, TMS does have a few minor drawbacks which are less frequent and unusual in patients. These may include red skin at the placement site of coil, facial twitching, mild discomfort, or anxiety for some patients during the treatment, possible headache, and the time required for complete procedure to end [14]. To highlight its limitations, it can be said that the coil does not completely shape the magnetic field and thus limits the penetration depth. The electric field induced on a spherical head model must always be lower inside the volume and higher on the outer surface. This suggests that stimulations must be stronger for superficial regions in order to achieve non-invasive stimulation of deeper brain regions, which is a complex task [13,14]. As a result, TMS treatment primarily focuses on target regions lying on the superficial cortex and not deep-brain structures which makes it is necessary to enhance the spatial profile of stimulation by proposing novel geometries of the coil [13,14]. Hence, there lies a challenge for researchers to bridge the gap between stimulation depth and focality and reach deeper brain regions while keeping the superficial regions intact. The focality of commonly used coil in TMS makes it difficult to isolate representative areas in the motor cortex and access deep regions of the brain [6-10]. Besides, variability is another challenge given that a subject’s response for two sequentially occurring pulses is irregular, where the inconsistent outcomes continue across patients resulting in inefficiency and uncertainty of the therapy [6-10]. Additionally, the stimulation site is close to the peripheral muscles when a high voltage is applied via the coil which prevents from recording stimulation artifacts [7-11]. Considering these aspects, efforts must be directed towards developing transcranial magnetic stimulation which can begin with the development of a suitable hardware size for portable or home use. Current design necessitates application of high voltage to achieve desired stimulation which can be reduced with a compact and economical machine, with a potential to reduce costs and patient burdens [11,12]. Also, frequent use of TMS combined with neuronavigational systems has the potential of precise targeting of the required regions for cortical stimulation [6-12]. Future research could also focus on determining optimal intensity and interstimulus interval (ISI) with the use of stimulus response curves [13,14]. Such customised strategies could potentially enable to record sensitive measures with the assessment of multiple ISIs. Another promising approach could be the application of neuroimaging to achieve reduced response variability during TMS. It could potentially enable the measurement of neural dynamics to simplify the understanding of stimulation areas of TMS [14]. Lastly, TMS research focusing on the combination of clinical techniques such as electrical stimulation, physical therapy, and/or Magnetic Resonance Imaging with TMS could prove to be a trending aspect with its ability to activate neural mechanisms and supplement changes in excitability []. TMS related research is an increasingly attractive aspect in cognition with the rapid advances in neuromodulation field. The ability of a TMS system to disrupt or alter the neural circuits of a brain may very well determine the future of cognition research with the aid of accurate localisation of coil using robotic systems, enhanced integrated systems, advanced coil designs, and optimised stimulation protocols. References 1.	Luber B, McClintock SM, Lisanby SH. Applications of transcranial magnetic stimulation and magnetic seizure therapy in the study and treatment of disorders related to cerebral aging. Dialogues Clin Neurosci. 2013 Mar;15(1):87-98. doi: 10.31887/DCNS.2013.15.1/bluber. PMID: 23576892; PMCID: PMC3622472 2.	 Luber B., Peterchev A., Nguyen T., Sporn A., Lisanby SH. Application of TMS in psychophysiological studies. In: Cacioppo LG, Tassinary GG. Berntson JT, eds. Handbook of Psychophysiology. 3rd ed. New York, NY: Cambridge University Press. 2007 3.	Peinemann A., Reimer B., Loer C., Quartarone A., Munchau A., Conrad B., Siebner HR. 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Mansur CG., Fregni F., Boggio PS., et al A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology. 2005;64:1802–1804 9.	Kim YH., You SH., Ko MH., et al Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke. 2006;37:1471–1476 10.	 Takeuchi N., Chuma T., Matsuo Y., Watanabe I., Ikoma K. Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke. 2005;36:2681–2686. 11.	Emara TH., Moustafa RR., Elnahas NM. Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke. Eur J Neurol. 2010;17:1203–1209. 12.	Pepin JL., Bogacz D., De Pasqua V., Delwaide PJ. Motor cortex inhibition is not impaired in patients with Alzheimer's disease: evidence from paired transcranial magnetic stimulation. 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