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Brain Sciences
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Noninvasive Neuromodulation Applications in Research and Clinics
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Noninvasive Neuromodulation Applications in Research and Clinics

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurotechnology and Neuroimaging".

Deadline for manuscript submissions: closed (15 October 2025) | Viewed by 12767

Special Issue Editors

Dr. Mehran Emadi Andani

E-Mail Website
Guest Editor
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37131 Verona, Italy
Interests: cognitive neuroscience; human motor control and movement analysis; system identification and pattern recognition; signal processing; biological system modeling; artificial intelligence
Special Issues, Collections and Topics in MDPI journals
Dr. Fatemeh B. Yavari

E-Mail Website
Guest Editor
Leibniz Research Centre for Working Environment and Human Factors, Ardeystrasse 67, 44139 Dortmund, Germany
Interests: non invasive brain stimulation; basic neuroscience; fear extinction learning; neuromodulation; tDCS and TMS; computational modeling

Special Issue Information

Dear Colleagues,

Noninvasive transcranial brain stimulation (TBS) has emerged as a powerful tool in both research and clinical settings. Techniques such as Transcranial Magnetic Stimulation (TMS, rTMS, iTBS, and cTBS), Transcranial Electrical Stimulation (tDCS, tACS, and tRNS), Transcranial Focused Ultrasound Stimulation (tFUS), and Transcranial Vagus Nerve Stimulation (tVNS) enable researchers to modulate neural activity and investigate brain function with precision. Additionally, Virtual Reality (VR) can be considered a noninvasive brain stimulator, creating immersive environments that significantly influence sensory, motor, and cognitive processes. TBS and VR are valued for their ability to noninvasively alter brain activity, providing insights into brain–behavior relationships and enhancing various cognitive and motor functions. For example, TMS and tDCS have been shown to enhance motor learning and neuroplasticity, making them valuable in educational and rehabilitation settings. Furthermore, tFUS offers a novel approach to target deep brain structures with high spatial precision, while tVNS provides a noninvasive means to modulate autonomic functions and mood states. The safety and versatility of these techniques make them attractive for diverse applications, offering innovative approaches that improve outcomes in research, education, and clinical practice with minimal side effects. As research continues to advance, the potential for TBS and VR to revolutionize our understanding and enhancement of brain function grows ever more promising.

Dr. Mehran Emadi Andani
Dr. Fatemeh B. Yavari
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • transcranial brain stimulation (TBS)
  • transcranial magnetic stimulation (TMS, rTMS, iTBS, and cTBS)
  • transcranial electrical stimulation (tDCS, tACS, and tRNS)
  • transcranial focused ultrasound stimulation (tFUS)
  • transcranial vagus nerve stimulation (tVNS)
  • virtual reality effect on the brain states
  • TBS applications in neuromotor disease (Parkinson’s disease and Huntington’s disease)
  • TBS applications in mental disease (Alzheimer disease and Dementia)
  • TBS application on functional brain mapping (TMS brain mapping)
  • clinical application of brain stimulation in motor symptoms in PD patients (tremor, gait, bradykinesia, postural instability, rigidity, handwriting, etc.)
  • clinical application of brain stimulation in non-motor symptoms (cognitive, psychosis, neuropsychiatric, etc.)
  • safety of brain stimulation

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Published Papers (5 papers)

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Research

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15 pages, 1033 KB  
Article
Transcranial Pulse Stimulation in Alzheimer’s: Long-Term Feasibility and a Multifocal Treatment Approach
by Celine Cont-Richter, Nathalie Stute, Anastasia Galli, Christina Schulte and Lars Wojtecki
Brain Sci. 2025, 15(8), 830; https://doi.org/10.3390/brainsci15080830 - 1 Aug 2025
Cited by 1 | Viewed by 2371
Abstract
Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and [...] Read more.
Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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12 pages, 1694 KB  
Article
The Relationship Between Soleus H-Reflex Following Standing GVS and Postural Control Responses on Firm and Foam Surfaces: An Exploratory Study
by Tsubasa Mitsutake, Takanori Taniguchi, Hisato Nakazono, Tomoyuki Shiozaki, Hisayoshi Yoshizuka and Maiko Sakamoto
Brain Sci. 2025, 15(2), 115; https://doi.org/10.3390/brainsci15020115 - 25 Jan 2025
Viewed by 1868
Abstract
Background: The vestibular postural control system affects standing stability on an unstable surface. However, it is unclear whether maintaining a standing position on different surfaces alters lateral vestibulospinal tract (LVST) excitability and body control responses following vestibular stimulation. This study aimed to [...] Read more.
Background: The vestibular postural control system affects standing stability on an unstable surface. However, it is unclear whether maintaining a standing position on different surfaces alters lateral vestibulospinal tract (LVST) excitability and body control responses following vestibular stimulation. This study aimed to investigate the relationship between the soleus H-reflex following galvanic vestibular stimulation (GVSH), a measure of LVST, and post-stimulus body movement responses while standing with eyes closed on different surfaces. Methods: Twelve healthy volunteers (mean age 20.4 ± 0.5 years, 7 females) performed eyes-closed standing GVSH on firm and foam surfaces. Body control responses in each condition were evaluated using an inertial measurement unit to monitor neck and pelvic movements, along with surface electromyography to assess muscle activity in the tibialis anterior and soleus muscles. Body responses to the GVS were averaged over up to a second after tibial nerve stimulation. Results: We observed a significant negative correlation between the H-wave amplitude of the GVSH on the firm surface and the tibialis anterior muscle activity following stimulation (r = −0.666, p = 0.018). No significant differences were observed during the eyes-closed standing GVSH on either firm or foam surfaces (p = 0.568). Conclusions: Postural maintenance in response to vestibular stimulation may contribute to body stability by regulating tibialis anterior muscle contraction via the LVST. Our findings may help elucidate the neural activity of vestibular function-related standing postural control responses. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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Review

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29 pages, 1401 KB  
Review
Using Low-Intensity Focused Ultrasound to Treat Depression and Anxiety Disorders: A Review of Current Evidence
by Ao Du, Manli Huang, Zheng Wang, Hetong Zhou, Huilong Duan, Shaohua Hu and Yinfei Zheng
Brain Sci. 2025, 15(10), 1129; https://doi.org/10.3390/brainsci15101129 - 21 Oct 2025
Viewed by 570
Abstract
Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, [...] Read more.
Background: Depression and anxiety disorders impact millions globally. In recent years, low-intensity focused ultrasound (LIFU), characterized by its high precision, deep penetration, and non-invasive nature, has garnered significant interest in neuroscience and clinical practice. To enhance understanding of its effects on mood, therapeutic availability in treatment of depression/anxiety disorders, and potential mechanisms, a systematic review of studies investigating the emotional impact of LIFU on depressive/anxious-like animal models, healthy volunteers, and patients with depression or anxiety disorders has been undertaken. Methods: Relevant papers published before 15 July 2025 were searched across four databases: Web of Science, PubMed, Science Direct, and Embase. A total of 28 papers which met the inclusion and exclusion criteria are included in this review. Results: Our findings indicate that LIFU reversed the depressive/anxious-like behaviors in the animal models and showed antidepressant/anti-anxiety effects among the state-of-art clinical studies. For example, immobility time in FST or TST is reduced in depressive animal models, and HRSD/BAI scales are improved in human studies. Key molecules such as BDNF/5-HT are found restored in animal models, and FC between key brain areas related to depression/anxiety is modulated after LIFU treatment. Notably, no brain tissue damage was observed in animal studies, and only mild adverse effects (such as dizziness and vomiting) were noted in a few human studies. Conclusions: The studies using LIFU to treat depression and anxiety remain in the preliminary stage. The mechanisms underlying LIFU’s mood effects—such as activation or inhibition of specific brain regions or neural circuits, anti-inflammatory effects, alterations in functional connectivity, synaptic plasticity, neurotransmitter levels, and BDNF—remain incompletely understood and warrant further investigation. Nevertheless, the LIFU technique holds promise for regulating both cortical and subcortical brain areas implicated in depression/anxiety disorders as a precise neuromodulation tool. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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26 pages, 2058 KB  
Review
Neuromodulation Interventions for Language Deficits in Alzheimer’s Disease: Update on Current Practice and Future Developments
by Fei Chen, Yuyan Nie and Chen Kuang
Brain Sci. 2025, 15(7), 754; https://doi.org/10.3390/brainsci15070754 - 16 Jul 2025
Viewed by 1131
Abstract
Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have [...] Read more.
Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have emerged as promising interventions. This study employs bibliometric analysis to evaluate global research trends in neuromodulation treatments for AD-related language impairments. A total of 88 publications from the Web of Science Core Collection (2006–2024) were analyzed using bibliometric methods. Key indicators such as publication trends, citation patterns, collaboration networks, and research themes were examined to map the intellectual landscape of this field. The analysis identified 580 authors across 65 journals, with an average of 34.82 citations per article. Nearly half of the publications were produced after 2021, indicating rapid recent growth. The findings highlight a predominant focus on non-invasive neuromodulation methods, particularly rTMS and tDCS, within neurosciences and neurology. While research activity is increasing, significant challenges persist, including ethical concerns, operational constraints, and the translational gap between research and clinical applications. This study provides insights into the current research landscape and future directions for neuromodulation in AD-related language impairments. The results emphasize the need for novel neuromodulation techniques and interdisciplinary collaboration to enhance therapeutic efficacy and clinical integration. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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26 pages, 1809 KB  
Review
Brain Stimulation Techniques in Research and Clinical Practice: A Comprehensive Review of Applications and Therapeutic Potential in Parkinson’s Disease
by Ata Jahangir Moshayedi, Tahmineh Mokhtari and Mehran Emadi Andani
Brain Sci. 2025, 15(1), 20; https://doi.org/10.3390/brainsci15010020 - 27 Dec 2024
Cited by 2 | Viewed by 5690
Abstract
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods [...] Read more.
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), transcranial focused ultrasound stimulation (tFUS), and transcutaneous vagus nerve stimulation (tVNS), as well as invasive approaches like deep brain stimulation (DBS). We explore the efficacy and safety profiles of these techniques in alleviating both motor impairments, such as bradykinesia and rigidity, and non-motor symptoms, including cognitive decline, depression, and impulse control disorders. Current findings indicate that while non-invasive techniques present a favorable safety profile and are effective for milder symptoms, invasive methods like DBS provide significant relief for severe cases that are unresponsive to other treatments. Future research is needed to optimize stimulation parameters, establish robust clinical protocols, and expand the application of these technologies across various stages of PD. This review underscores the potential of brain stimulation as a vital therapeutic tool in managing PD, paving the way for enhanced treatment strategies and improved patient outcomes. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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