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Brain Sciences
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Advances in Non-Invasive Brain Stimulation
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Advances in Non-Invasive Brain Stimulation

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

Deadline for manuscript submissions: closed (31 October 2025) | Viewed by 20019

Special Issue Editors

Dr. Mariagiovanna Cantone

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Guest Editor
Neurology Unit, University Hospital Policlinico “G. Rodolico-San Marco”, Catania, Italy
Interests: transcranial magnetic stimulation; noninvasive brain stimulation; neuroplasticity; metaplasticity; motor cortex; stroke; vascular dementia; vascular cognitive impairment; vascular depression
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giuseppe Lanza

E-Mail Website
Guest Editor
1. Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, Troina, Italy
2. Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy
Interests: translational neurophysiology; neuroimaging; neurodegenerative diseases; cognitive neuroscience; neuroplasticity; neuromodulation; sleep disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

From the pioneering application of transcranial magnetic stimulation, many different, innovative methods of non-invasive brain stimulation (NIBS) have attracted both clinicians and researchers.

NIBS techniques were first developed for the assessment and modulation of synaptic plasticity; however, when they were integrated with other neurophysiological methods (e.g., electroencephalography—EEG) or structural and functional imaging, NIBS techniques were found to enable the exploration of connectivity and more advanced neuroplastic phenomena across both motor and non-motor areas.

As such, NIBS techniques are emerging as some of the most innovative and translational tools for the assessment and treatment of several neuropsychiatric disorders worldwide, including depression, dementia, and stroke. In the near future, interventions aiming to enhance neuroplasticity should receive further attention; such progress could enable the inclusion of other neurological disorders, such as sleep disorders or metabolic and rare diseases with insidious central nervous system involvement.

This Special Issue aims to encourage and collect original research, review articles, and case series addressing recent evidence on clinical applications of NIBS techniques in humans and, at the same time, to highlight current challenges and technical issues in the “cutting-edge” topic of NIBS research. In this exciting scenario, special attention should be paid to innovative NIBS protocols, the link to genetic patterns, and the interaction with drugs acting on multiple neurotransmission pathways.

You may choose our Joint Special Issue in Life.

Dr. Mariagiovanna Cantone
Dr. Giuseppe Lanza
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

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

  • translational neuroscience
  • clinical neurophysiology
  • neurodegeneration
  • neural plasticity
  • neurosonology
  • sleep disorders
  • cognitive decline
  • non-invasive brain stimulation
  • nutraceuticals
  • neurogenetics
  • transcranial magnetic stimulation
  • dementia
  • vascular cognitive impairment
  • stroke
  • depression
  • metaplasticity
  • motor cortex
  • motor learning
  • neurotrophins
  • transcranial-focused ultrasound

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Published Papers (3 papers)

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Research

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19 pages, 616 KB  
Article
Green Light and Transcranial Direct Current Stimulation in Migraine Patients: A Preliminary Randomized Control Trial
by Amna Mahmood, Mirza Obaid Baig, Sumaiyah Obaid, Turki Abualait and Shahid Bashir
Brain Sci. 2025, 15(11), 1209; https://doi.org/10.3390/brainsci15111209 - 9 Nov 2025
Viewed by 3870
Abstract
Background: Migraine is a complex neurological condition characterized by a range of symptoms, such as intense to severe headaches, sensitivity to light and sound, and feelings of nausea and vomiting. The most common complaints regarding acute treatment are that medication causes adverse effects, [...] Read more.
Background: Migraine is a complex neurological condition characterized by a range of symptoms, such as intense to severe headaches, sensitivity to light and sound, and feelings of nausea and vomiting. The most common complaints regarding acute treatment are that medication causes adverse effects, that pain returns, or that pain relief is either too slow or inconsistent. Certain non-pharmacological methods, such as non-invasive neuromodulators, might be beneficial for alleviating migraines and require evidence for clinical judgment. Objective: The objective of the study was to determine the effects and compare the effects of green light and transcranial direct current stimulation on migraine frequency, intensity, impact, and quality of life. Methods: A randomized controlled trial was conducted with 69 migraine patients of both genders aged over 18 years, experiencing headache attacks lasting more than 4 h, characterized by pulsating and unilateral pain with an intensity of 5 or higher on the numeric pain scale. Active tDCS, sham tDCS, and green light, along with prescribed medications, were applied to Groups A, B, and C, respectively, for four weeks. The outcomes were measured at baseline, week 2, and week 4 for primary outcomes, including a structured headache diary, numeric pain scale, multidimensional pain inventory, and migraine-specific quality of life version 2.1 as a secondary variable. Results: Significant results were found for the NPS and MSQ with a p-value < 0.05 between and within the groups. There was a substantial reduction in pain intensity and improved quality of life in all three groups. Group A and Group C had p-values < 0.05 for most of the subscales of MPI, showing decreased pain interference, enhanced support, improved emotional function, and increased participation in everyday activities. Medication dependency in Group A was reduced to four weeks with 22 (95.7%) with ‘no medication’ use. The number of migraine attacks in Group A at four weeks reduced to ‘no attack’ for 7 (30.4%) participants, showing a reduction in both the number of attacks and their duration to 1–5 h in 12 (52.2%) participants. Conclusions: Both tDCS and green light therapy were found to be effective non-pharmacological therapies for reducing pain intensity, frequency, impact, and drug usage and for improving the quality of life of migraine patients. However, tDCS showed an advantage in terms of reducing pain intensity and its impact on daily living, while green light therapy showed a slightly greater improvement in quality of life. Full article
(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)
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16 pages, 1423 KB  
Article
Frontal Transcranial Direct Current Stimulation in Moderate to Severe Depression: Clinical and Neurophysiological Findings from a Pilot Study
by Florin Zamfirache, Gabriela Prundaru, Cristina Dumitru and Beatrice Mihaela Radu
Brain Sci. 2025, 15(6), 540; https://doi.org/10.3390/brainsci15060540 - 22 May 2025
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Abstract
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the [...] Read more.
Background/Objectives: Transcranial Direct Current Stimulation (tDCS) has proven to be a promising intervention for major depressive disorder (MDD). Even so, the specific neurophysiological mechanisms underlying its therapeutic effects, particularly regarding frontal EEG markers, remain insufficiently understood. This pilot study investigated both the clinical efficacy and neurophysiological impact of frontal tDCS in individuals with mild to severe depression, with particular focus on mood changes and alterations in Frontal Alpha Asymmetry (FAA), Beta Symmetry, and Theta/Alpha Ratios at the F3 and F4 electrode sites. Methods: A total of thirty–one participants were enrolled and completed a standardized Flow Neuroscience tDCS protocol targeting the dorsolateral prefrontal cortex using a bilateral F3/F4 montage. The intervention included an active phase of five stimulations per week for three weeks, followed by a Strengthening Phase with two stimulations per week. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), while neurophysiological changes were evaluated via standardized quantitative EEG (QEEG) recordings obtained before and after the treatment course. Among the participants, fourteen individuals had a baseline MADRS score of ≥20, indicating moderate to severe depressive symptoms. Results: Following tDCS treatment, significant reductions in MADRS scores were observed across the cohort, with clinical response rates notably higher in the moderate/severe group (71.4%) compared to the mild depression group (20.0%). Neurophysiological effects were modest: no significant changes were detected in FAA or Beta Symmetry measures. However, a substantial reduction in the Theta/Alpha Ratio at F4 was found in participants with moderate to severe depression (p = 0.018, Cohen’s d = −0.72), suggesting enhanced frontal cortical activation associated with clinical improvement. Conclusions: These findings indicate that frontal tDCS is effective in reducing depressive symptoms, particularly in cases of moderate to severe depression. While improvements in FAA and Beta Symmetry were not significant, changes in the Theta/Alpha Ratio at F4 point toward dynamic neurophysiological reorganization potentially linked to therapeutic outcomes. The Theta/Alpha Ratio may serve as a promising biomarker for tracking tDCS response, whereas other EEG metrics might represent more stable trait characteristics. Future research should prioritize individualized stimulation protocols and incorporate more sensitive neurophysiological assessments, including functional connectivity analyses and task-evoked EEG paradigms, to understand the mechanisms underlying clinical improvements. Full article
(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)
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Review

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23 pages, 3425 KB  
Review
Engineering and Technological Advancements in Repetitive Transcranial Magnetic Stimulation (rTMS): A Five-Year Review
by Abigail Tubbs and Enrique Alvarez Vazquez
Brain Sci. 2024, 14(11), 1092; https://doi.org/10.3390/brainsci14111092 - 30 Oct 2024
Cited by 14 | Viewed by 11672
Abstract
In the past five years, repetitive transcranial magnetic stimulation (rTMS) has evolved significantly, driven by advancements in device design, treatment protocols, software integration, and brain-computer interfaces (BCIs). This review evaluates how these innovations enhance the safety, efficacy, and accessibility of rTMS while identifying [...] Read more.
In the past five years, repetitive transcranial magnetic stimulation (rTMS) has evolved significantly, driven by advancements in device design, treatment protocols, software integration, and brain-computer interfaces (BCIs). This review evaluates how these innovations enhance the safety, efficacy, and accessibility of rTMS while identifying key challenges such as protocol standardization and ethical considerations. A structured review of peer-reviewed studies from 2019 to 2024 focused on technological and clinical advancements in rTMS, including AI-driven personalized treatments, portable devices, and integrated BCIs. AI algorithms have optimized patient-specific protocols, while portable devices have expanded access. Enhanced coil designs and BCI integration offer more precise and adaptive neuromodulation. However, challenges remain in standardizing protocols, addressing device complexity, and ensuring equitable access. While recent innovations improve rTMS’s clinical utility, gaps in long-term efficacy and ethical concerns persist. Future research must prioritize standardization, accessibility, and robust ethical frameworks to ensure rTMS’s sustainable impact. Full article
(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)
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