Non-Invasive Brain Stimulation: Back to the Basics of Safety for More Effective Use

Over 2 decades have already passed since non-invasive brain stimulation (NIBS) was first applied to patients with various neurological disorders [1]. Building on advances in engineering and our understanding of clinical neurophysiology, we now have effective tools that can non-invasively strengthen or weaken the activities of specific areas or networks of the human brain. These tools include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and more recently, transcranial focused ultrasound (tFUS). These tools are often collectively referred to as NIBS.

Many reports have described positive effects of rTMS on various conditions, including pain; psychiatric disorders such as substance abuse, schizophrenia, and depression; motor deficit and language disorders after stroke; and tinnitus [2]. Although it is uncommon for NIBS to be the mainstay treatment for various diseases, it has been thought that NIBS can play an adjuvant treatment role. However, this idea was challenged after a large-scale clinical trial of rTMS on upper limb motor deficits after stroke showed negative results [3]. Active discussion continues on how to apply NIBS more effectively in various conditions [2]. In order to enhance the effectiveness of NIBS, it may be necessary to consider increasing stimulation intensity, stimulation duration, or the number of treatment sessions. In this regard, having a safety guideline for the use of NIBS on the human brain becomes even more important.

In this issue, 3 excellent review articles are published on the safety of NIBS techniques.

Kim and Paik [4] reviewed the safety of rTMS in neurological disorders such as stroke or traumatic brain injury. They suggest that rTMS can be used relatively safely in clinical settings and for research if the current guideline for rTMS parameters is followed. However, the use of a checklist beforehand is highly recommended to ensure the absence of contraindications.

Ko [5] reviewed the safety of tDCS in clinical practice and research. In this review, he proposes that tDCS, which is currently used in clinical practice, is safe because it uses a weak intensity of less than 5% of the current threshold that can cause irreversible brain changes. Future research seems to be required on how to increase stimulation intensity to achieve sufficient clinical effects without increasing significant adverse effects.

As a newly emerging NIBS technique, tFUS is attracting considerable attention in the field of neurorehabilitation. In particular, it is considered highly advantageous that tFUS can stimulate much deeper brain structures (such as the thalamus) than rTMS or tDCS can, while maintaining excellent spatial resolution [6]. However, since the action potential of a nerve is essentially an electrical phenomenon, more studies on the neurobiological mechanism of tFUS would appear to be necessary than is the case for rTMS or tDCS. Lee et al. [7] present a broader perspective and an extensive review on the state-of-the-art evidence for the safety of tFUS. I expect that their excellent review will serve as a landmark article on the safety of this emerging neuromodulation technique.

The applications of NIBS in the field of neurorehabilitation continue to expand. For further development, it is essential to show solid evidence of the effects of NIBS on specific diseases, which may require higher stimulation intensity. Therefore, re-examining the basics of safety would be the first step towards using NIBS more effectively. I hope the articles published in this issue will spark future clinical and preclinical studies.