Non-invasive brain stimulation

What NIBS procedures are available?

The best known NIBS methods include procedures such as Transcranial Pulse Stimulation (TPS), Transcranial Magnetic Stimulation (TMS), Repetitive Transcranial Magnetic Stimulation (rTMS), Transcranial Focused Ultrasound (tFUS) and Transcranial Direct Current Stimulation (tDCS).

These differ in aspects such as where they are applied, the treatment protocol, and the physical mechanism that they use to modulate the neuronal activity in the brain: TMS and rTMS are based on magnetic fields to stimulate the brain, tFUS uses focused ultrasound waves for precise deep brain stimulation, tDCS uses electrical currents to alter neuronal excitability, and TPS applies acoustic shock waves to reach deeper brain structures and stimulate neuronal processes.

Transcranial pulse stimulation

Transcranial pulse stimulation (TPS) is a procedure that uses shock waves (acoustic pulse waves) to emit physical energy into localised areas of tissue. Pulse waves are generated through a handpiece placed onto the scalp, which emit energy to specific regions of the brain. These have a focus zone in the shape of an extended ellipse measuring 3 to 6 cm and emit clinically effective energy waves that penetrate down as far as 8 cm.

The advantage of this method is the manual and highly controlled application of pulses in the target regions and the compact treatment protocol, which consists of just six sessions within a two-week period. A session generally lasts around 30 minutes and is carried out as an outpatient procedure. Shaving of the scalp is not required.

TPS using the NEUROLITH® system, which gained the CE mark in 2018, is an accompanying treatment option for patients with Alzheimer’s disease.

Current studies have indicated good safety levels[10] and potential neuroplastic[11] and morphological[2] changes as a result of TPS, as well as an improvement in overall cognitive performance and function in patients with Alzheimer’s disease[12]. In addition, more recent clinical trials have demonstrated a significant improvement in depression symptoms in patients with Alzheimer’s disease[13, 14]. Other research projects are ongoing to clarify the long-term effects, mechanisms of action and biological effects of TPS.

Transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are non-invasive procedures, which are used in neurology and psychiatry to treat a range of disorders. Magnetic stimulation of the brain involves the use of magnetic fields to stimulate neurons in specific brain regions[1, 2]. This enables areas of the brain to be influenced in a targeted way and neuronal activity to be altered.

With TMS, a short magnetic pulse is generated over the scalp, which penetrates the tissue into the brain. This procedure is used in clinical practice to treat depression, pain disorders or certain types of movement disorders[3, 4], for example. It is also often used for research purposes to investigate the function of certain brain areas. The penetration depth is usually 2 to 3 cm, while the deep TMS method extends down to 5 cm [5] [6].

Repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is an extension of the TMS technique. This involves the application of repeated magnetic pulses to influence the neuronal activity over a longer period. The aim of repeated application over several sessions is to bring about long-term changes in neuronal activity and connectivity. rTMS is primarily used to treat severe forms of depression that do not respond to conventional therapies[7]. Research and clinical trials are also being carried out to study potential areas of application, such as anxiety disorders, schizophrenia and rehabilitation after a stroke[8].

Both TMS and rTMS influence brain activity in a targeted way without the need for surgery or permanent implants. They are considered safe, and unlike invasive methods, they carry a lower risk of side effects[2], while the exact action and optimal use continue to be the subject of scientific research[1].

Different treatment protocols are used depending on the area of application. However, TMS and rTMS treatments generally involve 20 to 30 sessions lasting 15 to 40 minutes. The sessions usually take place on 5 days per week over a period of 4 to 6 weeks.

Transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is another non-invasive brain stimulation technique, which is used to modulate neuronal activity. This method uses weak electrical currents to influence neuronal excitability and plasticity in specific brain regions. tDCS works with pairs of electrodes, each consisting of an anode and a cathode, which are placed on a specific area of the scalp to deliver a continuous, low current flow through certain parts of the brain (from one electrode to the other).

The tDCS method works on the assumption that the application of weak direct current can alter the resting membrane potential of neurons, leading to increased or reduced neuronal activity. The anode is intended to increase neuronal activity under the electrode (excitatory action), while the cathode reduces it (inhibitory action)[9].

tDCS is being studied and used in a wide range of applications, including to improve cognitive functions such as learning, memory and concentration, to treat depression, in pain management, and to support rehabilitation after strokes[8]. A particular advantage of tDCS is its simplicity and safety, which makes the method of interest for use in clinical and research environments.

While tDCS has demonstrated promising results in various studies, the exact effectiveness and optimal application (such as the strength of current, duration and placement of electrodes) in many areas are still the subject of ongoing research. An individual patient’s response to tDCS may vary, and it is recommended that this technique is used only under the instruction or on the recommendation of a specialist.

A typical tDCS treatment protocol for depression or to improve cognitive symptoms involves 10 to 20 sessions lasting 20 to 30 minutes each, which are held daily or almost daily over a period of 2 to 4 weeks.

Transcranial focused ultrasound

Transcranial focused ultrasound (tFUS) is an advanced, non-invasive technology that uses ultrasound waves to stimulate deep brain regions in a targeted way. Unlike other brain stimulation methods, tFUS makes high-precision focused application possible, enabling specific brain regions to be influenced without surgery.

This method involves the transmission of focused ultrasound waves through the skull, which are concentrated on a precise point in the brain. This focused energy point can modulate neuronal activity, either by stimulating the cells or inhibiting their activity, depending on the ultrasound setting. A key advantage of tFUS is its ability to reach deeper brain structures that are difficult for other non-invasive methods (such as TMS or tDCS) to access.

tFUS is being investigated in clinical research for a range of potential applications, including the treatment of neurological and psychiatric disorders, such as Parkinson’s disease, Alzheimer’s disease, severe depression and chronic pain. What is more, research is being conducted into the possibility of using tFUS to improve cognitive function or to modulate states of consciousness.

The safety and effectiveness of tFUS continues to be researched, with the aim of establishing the technology as a precise and effective treatment method for a variety of brain disorders.

As research into tFUS is still ongoing, there are no standardised treatment protocols. Early results have shown that a treatment could take the form of multiple sessions over several weeks. A session may last from 30 minutes to several hours.

Magnetic stimulation of the brain

As signals in the brain are primarily transmitted by electrical impulses that are supported by chemical processes, it is possible to influence brain function using different external procedures that generate weak electrical fields. For this reason, NIBS procedures are a promising, gentle treatment option to complement existing drug-based care for disorders that primarily affect the brain. These procedures can often be carried out on an outpatient basis and do not require any surgery or administration of additional drugs. This means they do not influence any ongoing therapies and are ideal as a patient-friendly, accompanying treatment option.
During the last 20 years, the number of studies into NIBS has risen dramatically[15], reflecting the increasing relevance of the technology, which has shown good levels of tolerance for neurological and mental disorders[16]. More recent studies have been more closely concerned with which procedures are effective with which treatment protocol and for which conditions. Although further research is required in order to prove and define the effectiveness of these procedures in more detail, these innovative approaches hold the potential for broader application in the future to improve patients’ quality of life.

References

1. Jannati, A., et al., Assessing the mechanisms of brain plasticity by transcranial magnetic stimulation. Neuropsychopharmacology, 2023. 48(1): p. 191-208.
2. Rossi, S., et al., Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol, 2021. 132(1): p. 269-306.
3. McClintock, S.M., et al., Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. J Clin Psychiatry, 2018. 79(1).
4. Mutz, J., et al., Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. BMJ, 2019. 364: p. l1079.
5. Samoudi, A.M., et al., Deep Transcranial Magnetic Stimulation: Improved Coil Design and Assessment of the Induced Fields Using MIDA Model. Biomed Res Int, 2018. 2018: p. 7061420.
6. Kedzior, K.K., et al., Deep transcranial magnetic stimulation (DTMS) in the treatment of major depression: An exploratory systematic review and meta-analysis. J Affect Disord, 2015. 187: p. 73-83.
7. Ontario, H., Repetitive Transcranial Magnetic Stimulation for People With Treatment-Resistant Depression: A Health Technology Assessment. Ont Health Technol Assess Ser, 2021. 21(4): p. 1-232.
8. Fregni, F., et al., Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. Int J Neuropsychopharmacol, 2021. 24(4): p. 256-313.
9. Nitsche, M.A., et al., [Modulation of cortical excitability by transcranial direct current stimulation]. Nervenarzt, 2002. 73(4): p. 332-5.
10. Beisteiner, R., et al., Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Adv Sci (Weinh), 2020. 7(3): p. 1902583.
11. Chen, X., et al., Transcranial pulse stimulation in Alzheimer's disease. CNS Neurosci Ther, 2024. 30(2): p. e14372.
12. Menardi, A., et al., Toward noninvasive brain stimulation 2.0 in Alzheimer's disease. Ageing Res Rev, 2022. 75: p. 101555.
13. Matt, E., G. Dorl, and R. Beisteiner, Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment. Alzheimers Dement (N Y), 2022. 8(1): p. e12245.
14. Cheung, T., et al., Evaluating the efficacy and safety of transcranial pulse stimulation on adolescents with attention deficit hyperactivity disorder: Study protocol of a pilot randomized, double-blind, sham-controlled trial. Front Neurol, 2023. 14: p. 1076086.
15. Huang, Y.Z., et al., Plasticity induced by non-invasive transcranial brain stimulation: A position paper. Clin Neurophysiol, 2017. 128(11): p. 2318-2329.
16. Oberman, L.M. and P.G. Enticott, Editorial: The safety and efficacy of noninvasive brain stimulation in development and neurodevelopmental disorders. Front Hum Neurosci, 2015. 9: p. 544