Non-invasive brain stimulation (NIBS)

Non-invasive brain stimulation (NIBS) involve the application of energy forces such as electromagnetic or electrical stimulation to the scalp to alter the activity of neurons in targeted brain regions. Current theories^1–3 suggest that NIBS influences synaptic activity, resulting in changes to network connectivity, rebalancing of Excitatory /Inhibitory signaling (E/I) ratio, and induction of plasticity through mechanisms such as polarity-dependent long-term potentiation (LTP)-like and long-term depression (LTD)-like changes, which are neural mechanisms closely associated with cognitive functions. Among the various NIBS techniques, the most commonly used in research and clinical settings are repetitive transcranial magnetic stimulation (rTMS)² and transcranial electrical stimulation (tES)⁴. The latter can be further divided into various modalities⁴, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), and transcranial pulsed current stimulation (tPCS), each distinguished by its unique current waveform employed to stimulate the cortex.

Specifically, rTMS generates a rapidly changing magnetic field through a coil placed on the scalp, which in turn induces electric currents in the targeted brain areas. The resultant electric field in the brain may be strong enough to cause neuronal firing, leading to neuronal activation and plasticity changes. In contrast, tES directly applies low intensity electrical current (<2mA) to specific areas of the brain via surface electrodes that are placed on the scalp which can modulate neuronal spike timing ^4,5, resting membrane potential in the cortex underlying the area of the electrodes and may also influence interconnected brain regions distant from the site of the electrodes through trans-synaptic activation⁶. Unlike rTMS, tES effects are not known to directly elicit action potentials⁷. The overall therapeutic effects of tES are due to the resultant online (during stimulation) changes in neuronal membrane excitability and spontaneous firing rates across the stimulated brain areas⁸, which may also induce long-term potentiation (LTP)-like and long-term depression (LTD)-like effects that mediates neuroplasticity changes⁹ as offline effects (post stimulation). tES has been increasingly investigated for the treatment of neurological and psychiatric disorders such as Sleep Disorders¹⁰ , Depression^11,12, ADHD¹³, Anxiety¹⁴ , Obsessive compulsive disorder¹⁵ , Mental Fatigue¹⁶ , Autism Spectrum Disorder¹⁷¹⁸, Stroke¹⁹, Mild cognitive impairment and Alzheimer’s Disease^20,21, Parkinson Disease²², Cerebral Palsy²³ and more .

References :

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13. Salehinejad MA, Nejati V, Mosayebi-Samani M, et al. Transcranial Direct Current Stimulation in ADHD: A Systematic Review of Efficacy, Safety, and Protocol-induced Electrical Field Modeling Results. Neurosci Bull. 2020;36(10):1191-1212. doi:10.1007/s12264-020-00501-x

14. Freire RC, Cabrera-Abreu C, Milev R. Neurostimulation in Anxiety Disorders, Post-traumatic Stress Disorder, and Obsessive-Compulsive Disorder. In: 2020:331-346. doi:10.1007/978-981-32-9705-0_18

15. Silva R de MF da, Brunoni AR, Goerigk S, et al. Efficacy and safety of transcranial direct current stimulation as an add-on treatment for obsessive-compulsive disorder: a randomized, sham-controlled trial. Neuropsychopharmacology. 2021;46(5):1028-1034. doi:10.1038/s41386-020-00928-w

16. Shen Y, Liu J, Zhang X, Wu Q, Lou H. Experimental study of transcranial pulsed current stimulation on relieving athlete’s mental fatigue. Front Psychol. 2022;13. doi:10.3389/fpsyg.2022.957582

17. Liu Z, Zhong S, Ho RCM, et al. Transcranial Pulsed Current Stimulation and Social Functioning in Children With Autism. JAMA Netw Open. 2025;8(4):e255776. doi:10.1001/jamanetworkopen.2025.5776

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19. Bai X, Guo Z, He L, Ren L, McClure MA, Mu Q. Different Therapeutic Effects of Transcranial Direct Current Stimulation on Upper and Lower Limb Recovery of Stroke Patients with Motor Dysfunction: A Meta-Analysis. Neural Plast.Hindawi Limited. 2019;2019. doi:10.1155/2019/1372138

20. Chen J, Wang Z, Chen Q, Fu Y, Zheng K. Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Brain Sci. 2022;12(5):562. doi:10.3390/brainsci12050562

21. Li S, Tang Y, Zhou Y, Ni Y. Effects of Transcranial Direct Current Stimulation on Cognitive Function in Older Adults with and without Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Gerontology. 2024;70(5):544-560. doi:10.1159/000537848

22. Alon G, Yungher DA, Shulman LM, Rogers MW. Safety and immediate effect of noninvasive transcranial pulsed current stimulation on gait and balance in parkinson disease. Neurorehabil Neural Repair. 2012;26(9):1089-1095. doi:10.1177/1545968312448233

23. Liu Z, Dong S, Zhong S, et al. The effect of combined transcranial pulsed current stimulation and transcutaneous electrical nerve stimulation on lower limb spasticity in children with spastic cerebral palsy: a randomized and controlled clinical study. BMC Pediatr. 2021;21(1). doi:10.1186/s12887-021-02615-1