Parkinson’s is a progressive neurodegenerative disease caused by the degeneration of dopamine-producing cells in the Substantia Nigra Pars Compacta. The resulting dopamine depletion causes neurological symptoms characterized by resting tremor bradykinesia rigidity mobilization difficulties and balance of payments. In addition to physical symptoms, Parkinson’s disease is also accompanied by non-neurological symptoms including mania depression depression depression autonomic features and sleep disorders. Parkinson’s disease affects all racial and ethnic groups and is estimated to affect 6-10 million people the world is plagued by the disease. The incidence of Parkinson’s disease ranges from 10–18 cases per 100 000 person-years and increases rapidly with age affecting approximately 2-3% of the population over 65 years of age. The clinical diagnosis of Parkinson’s disease is based on presence Typical Parkinsonian neurological symptoms including bradykinesia include rigidity and resting tremor. Current treatments for Parkinson’s disease only treat the symptoms of the disease and are essentially drugs that slow or stop the underlying neurodegeneration. In any case reported that most patients develop complications after five years including dyskinesia and neurological changes. New treatments for Parkinson’s disease have emerged in recent decades including Transcranial Magnetic Stimulation (TMS) which has generated interest as a potential treatment intervention.
Transcranial Magnetic Stimulation
Transcranial magnetic stimulation (TMS) was developed by Barker and colleagues in 1985 which allowed non-invasive stimulation of parts of the human brain. Since then, this technology has evolved and found a place in both clinical research and treatment of various populations such as those experiencing attention or movement disorders . This modality consists of several conductive wires wound together in a circular coil in a rigid plastic housing. By passing a momentary pulse of electricity through these coil windings, a magnetic field is produced directly for coil that passes unimpeded through the scalp and scalp when placed on the head. This magnetic pulse, driven by the principles of electromagnetism, generates a secondary electric field in the direction opposite to the voltage produced by the coil. It is these secondary fields that effect on any conductive material or tissue in the direction of the magnetic field. In this case, the lymphatic vessels are the nerves in the cerebral cortex. Using the above procedure, TMS can be used to stimulate or stimulate areas of the cortex to examine the activity of different brain areas and their interaction.
Types of TMS
- Single-pulse TMS can be used to simply stimulate an area while recording results and is commonly used in studies where an area is stimulated such as the motor cortex and motor responses can be recorded from body muscles using electromyography ].  .
- Paired-pulse TMS can be used to measure the effect of a first stimulus on a second stimulus. While this method is also used primarily in research it allows one area of the brain to be considered over another. For example the delivery of a TMS pulse to the motor cortex of one hemisphere brain 10ms before a TMS pulse delivered across the contralateral motor cortex produces an inhibitory effect on motor output to the arm indicating a firing pattern that allows unimanual control of the upper limbs .
- Repetitive TMS (rTMS) techniques involve wiring a number of consecutive TMS pulses in rapid succession. This technique is used both experimentally and clinically because it can produce changes in cortical function that last longer than the duration of the TMS protocol. With some reports which shows a change in excitation that lasts for a number of hours. The nature of the pulse delivery appears to determine the effect of the rTMS protocol as those delivering pulses at rates of >5Hz (high frequency rTMS) are more likely to produce excitatory effects and those delivered at rates < 1Hz (low frequency rTMS) often produces inhibitory effects in the brain.. These rTMS techniques have been approved as a treatment modality for patients with major depressive disorder (MDD) in Canada. While the use of rTMS has not yet been approved for clinical use in. treatment of movement disorders such as lumbar spinal cord injury and PD scientific literature suggests that it may provide some benefit to both physical and cognitive symptoms in this population.[19 ]
Potential Benefits of RTMS for Individuals with Parkinson’s disease
Recent studies have shown positive effects of rTMS on motor function in patients with PD. Most studies have assessed motor outcomes in Parkinson’s such as the UPDRS III in addition to various physical tasks such as walking or hand function using rTMS treatment.      The cumulative results of such studies reveal that repetitive rTMS delivered to motor areas of the cortex (both primary and supplementary) tends to improve motor scores on the UPDRS III on it after regular sessions (from daily to one time weekly) treatment  and some observations of continued improvement up to one month after cessation of treatment. The observed benefits were almost always seen with bradykinesia or dyskinesia scores. Changes in gait have also been shown the results of rTMS treatment such that walking speed improved after a single session of typical rTMS as assessed by the Timed Up and Go test. Further gait speed improvements were reported along with decreased bradykinesia after rTMS treatment twice weekly during the period in one month that lasted for at least one month after participants.Notably, one study examined the frequency of rTMS delivery to the central nervous system and changes in After functional MRI activity. This group demonstrated a reduction in bradykinesia after 12 years several weeks of weekly rTMS treatment and improvement rates correlated with increased activity in the caudate nucleus of the basal ganglia during motor tasks suggesting that prolonged stimulation can induce plastic changes in brain subcortical structures. Hence the implementation repeated rTMS appears to confer benefits on motor symptoms in Parkinson’s disease as measured by the UPDRS III and gait index.
The benefits of rTMS on motor function in Parkinson’s disease are further supported by recent meta-analyses summarizing randomized controlled trials completed to date. Specifically gait performance (SMD = 0.70 ) and UPDRS III score (SMD = 0.37) improved with rTMS treatment compared with sham stimulation whereas improvements in hand function were unaffected by rTMS. A meta-analysis found that the change in UPDRS III scores with rTMS treatment was -6.42 points corresponding to a clinically significant change. These changes appear to depend on the location of the rTMS stimulus whereby both high-frequency rTMS over the primary motor cortex and low-frequency rTMS over the supplementary motor area resulted in motor enhancement. These effects of rTMS treatment showed no significant effects of medication or disease severity. This suggests that rTMS may be an effective treatment of internal symptoms regardless of medication or disease severity. Furthermore some recent evidence had shown that rTMS can improve cool walking in people with Parkinson’s disease by normalizing brain connectivity.
A study by Moisello et al. (2015) found that increased rTMS over the primary motor cortex enhanced visuo-motor skill retention (target reaching using proprioceptive cues) and memory consolidation in patients with PD. It has also been shown that patients with Parkinson’s receiving typical rTMS showed enhanced performance on the Stroop and Hooper and Wisconsin Tests suggesting that rTMS may help Parkinson’s with dual tasks and attention. However, rTMS does not appear to have a clear effect on other executive functions (e.g. visuospatial abilities psychomotor speed) compared to sham stimulation although very few studies have been conducted in this area to date. In a recent systematic review, there was conflicting evidence for the effectiveness of rTMS as used for patients with Parkinson’s disease and dementia. However, one study on a subgroup of Parkinson’s patients reported a significant benefit of rTMS manifested by a significant reduction in scores on the Hamilton Rating Scale for Depression and the Montgomery‐Asberg Depression Rating Scale but not the Beck Depression Inventory compared to sham treatment. So rTMS may provide some cognitive and psychological benefits but the resulting changes are likely small and not clinically significant.
- ↑ Jump up to:1.0 1.1 1.2 1.3 Kalia L, Lang A. Parkinson’s. LANCET. 2015; 386:896-912.
- ↑ Jump up to:2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Chou Y, Hickey PT, Sundman M, Song AW, Chen N. Effects of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Parkinson Disease: A Systematic Review and Meta-analysis. JAMA Neurology. 2015; 72:432-440.
- ↑ Jump up to:3.0 3.1 Williams-Gray CH, Worth PF. Parkinson’s. Medicine. 2016;44:542-546.
- ↑ Jump up to:4.0 4.1 Barker AT, Jalinous R, Freeston IL. NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX. The Lancet. 1985;325:1106-1107.
- ↑ Jump up to:5.0 5.1 Downar J, Blumberger D, Daskalakis Z. Repetitive transcranial magnetic stimulation: an emerging treatment for medication-resistant depression. CANADIAN MEDICAL ASSOCIATION JOURNAL. 2016;188:1175-1177.
- ↑ Jump up to:6.0 6.1 Ni Z, Chen R. Transcranial magnetic stimulation to understand pathophysiology and as potential treatment for neurodegenerative diseases. Translational neurodegeneration. 2015 Dec;4(1):22.
- ↑ Jump up to:7.0 7.1 Hallett M. Transcranial magnetic stimulation and the human brain. Nature. 2000;406:147-150.
- ↑ Jump up to:8.0 8.1 Hallett M. Transcranial Magnetic Stimulation: A Primer. Neuron. 2007;55:187-199.
- ↑ Jump up to:9.0 9.1 9.2 Siebner H, Rothwell J. Transcranial magnetic stimulation: new insights into representational cortical plasticity. Experimental Brain Research. 2003;148:1-16.
- ↑ Jump up to:10.0 10.1 10.2 Rossini PM, Burke D, Chen R, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clinical Neurophysiology. 2015;126:1071-1107
- ↑ Alyssa Hindle.Transcranial Magnetic Stimulation Demonstration. Available fromhttps://www.youtube.com/watch?time_continue=1&v=qkNbYHu_STU&feature=emb_logo
- ↑ Chen R. Interactions between inhibitory and excitatory circuits in the human motor cortex. Experimental Brain Research. 2004;154:1-10.
- ↑ 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.
- ↑ 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
- ↑ Chung SW, Rogasch NC, Hoy KE, Fitzgerald PB. Measuring Brain Stimulation Induced Changes in Cortical Properties Using TMS-EEG. Brain Stimulation. 2015;8:1010-1020.
- ↑ Huang Y-Z, Edwards MJ, Rounis E, Bhatia KP, and Rothwell JC. Theta Burst Stimulation of the Human Motor Cortex. Neuron 45: 201-206, 2005.
- ↑ 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.
- ↑ 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.
- ↑ Jump up to:19.0 19.1 19.2 19.3 19.4 19.5 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.
- ↑ TMS Center – Southeastern Psychiatric AssociatesRepetitive Trancranial Magnetic Stimulation (rTMS) Physiology by Magstim Available from https://www.youtube.com/watch?v=NmciYGTXOBo&feature=emb_logo
- ↑ Jump up to:21.0 21.1 Ikeguchi M, Touge T, Nishiyama Y, Takeuchi H, Kuriyama S, Ohkawa M. Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson’s. Journal of the neurological sciences. 2003 May 15;209(1):41-6.
- ↑ Jump up to:22.0 22.1 Khedr EM, Rothwell JC, Shawky OA, Ahmed MA, Hamdy A. Effect of daily repetitive transcranial magnetic stimulation on motor performance in Parkinson’s. Movement Disorders. 2006 Dec 1;21(12):2201-5.
- ↑ Jump up to:23.0 23.1 23.2 Lomarev MP, Kanchana S, Bara‐Jimenez W, Iyer M, Wassermann EM, Hallett M. Placebo‐controlled study of rTMS for the treatment of Parkinson’s. Movement Disorders. 2006 Mar 1;21(3):325-31.
- ↑ Jump up to:24.0 24.1 Hamada M, Ugawa Y, Tsuji S. High‐frequency rTMS over the supplementary motor area for treatment of Parkinson’s. Movement Disorders. 2008 Aug 15;23(11):1524-31.
- ↑ Jump up to:25.0 25.1 Filipović SR, Rothwell JC, van de Warrenburg BP, Bhatia K. Repetitive transcranial magnetic stimulation for levodopa‐induced dyskinesias in Parkinson’s. Movement Disorders. 2009 Jan 30;24(2):246-53.
- ↑ Jump up to:26.0 26.1 Maruo T, Hosomi K, Shimokawa T, Kishima H, Oshino S, Morris S, Kageyama Y, Yokoe M, Yoshimine T, Saitoh Y. High-frequency repetitive transcranial magnetic stimulation over the primary foot motor area in Parkinson’s. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 2013 Nov 1;6(6):884-91.
- ↑ Jump up to:27.0 27.1 Lee SY, Kim MS, Chang WH, Cho JW, Youn JY, Kim YH. Effects of repetitive transcranial magnetic stimulation on freezing of gait in patients with Parkinsonism. Restorative neurology and neuroscience. 2014 Jan 1;32(6):743-53.
- ↑ Jump up to:28.0 28.1 28.2 28.3 González-García N, Armony JL, Soto J, Trejo D, Alegría MA, Drucker-Colín R. Effects of rTMS on Parkinson’s disease: a longitudinal fMRI study. Journal of neurology. 2011 Jul 1;258(7):1268-80.
- ↑ Shulman LM, Gruber-Baldini AL, Anderson KE, Fishman PS, Reich SG, Weiner WJ. The clinically important difference on the unified Parkinson’s rating scale. Archives of neurology. 2010 Jan 1;67(1):64-70.
- ↑ Mi TM, Garg S, Ba F, Liu AP, Liang PP, Gao LL, Jia Q, Xu EH, Li KC, Chan P, McKeown MJ. Repetitive transcranial magnetic stimulation improves Parkinson’s freezing of gait via normalizing brain connectivity. NPJ Parkinson’s disease. 2020 Jul 17;6(1):1-9.
- ↑ Moisello C, Blanco D, Fontanesi C, et al. TMS Enhances Retention of a Motor Skill in Parkinson’s. Brain Stimulation. 2015;8:224-230.
- ↑ Boggio PS, Fregni F, Bermpohl F, et al. Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson’s and concurrent depression. Movement Disorders. 2005;20:1178-1184.
- ↑ Starkstein S, Brockman S. Management of Depression in Parkinson’s: A Systematic Review. Movement Disorders Clinical Practice. 2017 Jul 1.
- ↑ Shin HW, Youn YC, Chung SJ, Sohn YH. Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson’s disease. Journal of neurology. 2016 Jul 1;263(7):1442-8.