Mariam Khakoo-Georgopoulos,
MB BS(Lond.), MRCP(UK), FRCR, CCST-Radiotherapy,
MRCP(London), Scientific Advisor,
Anaplasi Medical Rehabilitation Center,
Athens, Greece.
.
World Brain Day, July 22nd, 2025, is dedicated to promoting brain health from conception to old age. Among its five key messages for action are ‘Education: Empowering healthcare professionals, caregivers, and the public with the latest scientific knowledge’ and ‘Access: Equal access to Neurological Care and Disability Management’ [1]. In this spirit, it is pertinent to explain neuromodulation, one of the latest methods of restoring brain health, using neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS), which is offered to patients at Anaplasi Medical Rehabilitation Center.
The human brain is estimated to contain close to 100 billion neurons, and each neuron talks to thousands of other neurons by sending signals across specialized connections called synapses. It has been calculated that there are a staggering 164 trillion synapses in the neocortex alone [2]. Notwithstanding its many connections, each neuron can only perform one action. It decides whether to act (fire) or not, depending on information received from its many connections. This takes the form of chemicals called neurotransmitters, which pass between neurons across synapses.
The neuron evaluates the signals, which either encourage (excitatory influences) or dissuade it from firing (inhibitory influences). When the sum of excitatory influences is large enough, the neuron fires, meaning that an electrical signal passes through the cell. This results in the neuron releasing neurotransmitters not only to other neurons but in some instances to instigate muscle contraction, hormone release, or other functions. Since neurons are arranged in large interconnecting networks, the action of one neuron affects thousands of others.
The more a neuronal network is used, the stronger it becomes. When we learn to walk in infancy, we repeat a successful pattern of neuronal firing, strengthening our walking network until we walk without thinking. However, even this automatic movement can be influenced by our mood. Unconsciously, we walk faster when we’re happy and slower when we’re sad, all depending on which other networks are influencing our walking network.
Unfortunately, when we become ill, especially with neurological or psychological problems, our brains don’t function as desired. It is the responsibility of healthcare professionals to restore them to health, as much as possible. Neural networks can be influenced, in other words, modulated, using pharmaceuticals that change the amount or type of neurotransmitters present. Giving medicines to rebalance the neurotransmitters in the brain, called pharmaceutical neuromodulation, can help in many conditions, but may cause unwanted effects in other parts of the brain or body.
Neuromodulation can be achieved more precisely using focused repetitive magnetic stimulation, rTMS. In its simplest form, a pulse of magnetism produces an electric current in the brain using the same principles of physics as a generator producing electricity. With an advanced magnetic coil configuration, the pulse from transcranial magnetic stimulation, TMS, stimulates the brain more deeply and more precisely than a simple electric current applied to the scalp. Using neuronavigated TMS, nTMS, with an MRI image, enables the exact location of the stimulus on the individual patient’s brain to be seen in real time, thus allowing the stimulus to be reliably repeated in the same location.
Scientific studies have shown that when the brain is stimulated at different frequencies, different neuronal networks are influenced. At a low frequency, an inhibitory neurotransmitter, GABA, is produced, while at a high frequency, glutamine, a neurotransmitter causing excitation, is released. A special rhythm, theta burst stimulation, mimics the brainwaves from the deep brain region of the hippocampus and can be regulated to either produce stimulation or inhibition [3] [4].
In this way, neuronavigated rTMS produces a precise, repeatable method of neuromodulation. As rTMS takes place over several sessions, it is important to be sure that the same area of the cerebral cortex is stimulated each time, and the most accurate method is with a neuronavigated system.
In medical terms, rTMS is a relatively new therapy, and it has been explored in a number of neurological conditions. To date, international guidelines recommend rTMS for the following [5]:
- Acute paralysis of the hand from motor stroke.
- Drug-resistant unipolar depression.
- Neuropathic pain.
Additional studies are currently investigating the effects in stroke aphasia, chronic stroke, motor neuron disease, and other neurological and psychiatric illnesses [6].
Since 2016, Anaplasi Medical Rehabilitation Center has been one of the few rehabilitation centers in the world to offer neuronavigated rTMS. Owing to its non-invasive nature, our patients have found it to be an easily tolerated treatment with some remarkable results.
In addition to the established protocols for hand paralysis after stroke, we are offering our patients hand stimulation with a robotic glove at the same time as neuronavigated rTMS is taking place, and then immediate hand therapy as part of their rehabilitation program. As noted before, a person’s mood can greatly influence their motor skills. At Anaplasi, we provide each patient with a personal rehabilitation program that includes mental and social support so they can be sure of the best rehabilitation outcome.
At ANAPLASI
“We do the maximum possible, not the minimum necessary.”
“We care for our patients as we would care for our own family.”
Bibliography
[1] “World Brain Day 2025.” Accessed: Jul. 11, 2025. [Online]. Available: https://wfneurology.org/world-brain-day-2025
[2] Y. Tang, J. R. Nyengaard, D. M. De Groot, and H. J. Gundersen, “Total regional and global number of synapses in the human brain neocortex,” Synap. N. Y. N, vol. 41, no. 3, pp. 258–273, Sep. 2001, doi: 10.1002/syn.1083.
[3] G. Castrillon, N. Sollmann, K. Kurcyus, A. Razi, S. M. Krieg, and V. Riedl, “The physiological effects of noninvasive brain stimulation fundamentally differ across the human cortex,” Sci. Adv., vol. 6, no. 5, p. eaay2739, Jan. 2020, doi: 10.1126/sciadv.aay2739.
[4] W. Klomjai, R. Katz, and A. Lackmy-Vallée, “Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS),” Ann. Phys. Rehabil. Med., vol. 58, no. 4, pp. 208–213, Sep. 2015, doi: 10.1016/j.rehab.2015.05.005.
[5] J.-P. Lefaucheur et al., “Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018),” Clin. Neurophysiol., vol. 131, no. 2, pp. 474–528, Feb. 2020, doi: 10.1016/j.clinph.2019.11.002.
[6] M. Khakoo-Georgopoulos, C. E. Georgopoulos, P. Lioumis, K. Zikopoulos, G. Baygeris, “A Controlled Study Of Low Frequency Repetitive Transcranial Magnetic Stimulation In Upper Limb Rehabilitation Of Chronic Stroke Patients,” presented at the European Congress of NeuroRehabilitation 2021 jointly with 27. Jahrestagung der Deutschen Gesellschaft für Neurorehabilitation, Digital, Dec. 08, 2021.
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