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Non-invasive Neuromodulation: Past, Present and Future

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 23874

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Dr. Andrés Molero-Chamizo

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Guest Editor

Department of Clinical and Experimental Psychology, University of Huelva, 21071 Huelva, Spain
Interests: cognitive neuroscience; neural systems; neuromodulation; neuroplasticity; non-invasive brain stimulation
Special Issues, Collections and Topics in MDPI journals

Dr. Guadalupe Nathzidy Rivera-Urbina

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Guest Editor

Psychology Center, Faculty of Administrative Sciences, Autonomous University of Baja California, Ensenada 22890, Baja California, Mexico
Interests: behavioral neuroscience, brain plasticity; clinical neuropsychology, cognitive neuroscience; neuromodulation; neurophysiology

Special Issue Information

Dear Colleagues,

Over the last three decades there has been a continuous increase of different neuromodulation methods and techniques aimed to modulate nervous system activity and functions. In some cases, non-invasive approaches offer not great different results compared with more invasive methods, in both clinical and basic research. The effectiveness of neuromodulation depends on several factors, some known, and others not well known. The specific technique (repetitive, single or double transcranial magnetic stimulation, theta burst stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcranial pulsed current stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, transcutaneous spinal cord stimulation, etc.), stimulation parameters (intensity, duration, focality, and target location), protocols (repetition or number of sessions, task-related stimulation, and implementation of follow-up period), baseline differences, inter-individual differences (responders vs. non responders), outcome measures, brain anatomy, clinical condition evaluated, comorbidities, age, sham susceptibility, etc., are some of the variables determining differences between studies. It is important to control these determinants to minimize the heterogeneity of results in non-invasive neuromodulation studies. In this Special Issue, recent advances in non-invasive neuromodulation are presented, including brain and spinal magnetic and electric stimulation, in both basic and clinical research, with a focus on the potential factors mediating the effectiveness and safety of different protocols. Complementary procedures for recording the effect of neurostimulation on the nervous system and for brain monitoring (event-related potentials, EEG, neuroimaging, neuronavigation, etc.), and recent methods for calculating the parameters of the simulated electrical flow induced in the nervous system and adjacent tissues (current intensity and density, as well as the direction and distribution of the electrical field), will also be covered in this Special Issue.

Dr. Andrés Molero-Chamizo
Dr. Guadalupe Nathzidy Rivera-Urbina
Guest Editors

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Keywords

behavior and neurostimulation
clinical neurostimulation
cognition and brain stimulation
electric neurostimulation
functional brain and spinal stimulation
neuro-induced electric field modeling
neurostimulation-induced plasticity
non-invasive neuromodulation approaches
transcranial magnetic stimulation

Published Papers (10 papers)

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Research

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15 pages, 2237 KiB

Open AccessArticle

Transcranial Focal Electric Stimulation Avoids P-Glycoprotein Over-Expression during Electrical Amygdala Kindling and Delays Epileptogenesis in Rats

by Daniel Fonseca-Barriendos, José Luis Castañeda-Cabral, Frida Martínez-Cuevas, Walter Besio, Alejandro Valdés-Cruz and Luisa Rocha

Life 2023, 13(6), 1294; https://doi.org/10.3390/life13061294 - 31 May 2023

Viewed by 1294

Abstract

Recent evidence suggests that P-glycoprotein (P-gp) overexpression mediates hyperexcitability and is associated with epileptogenesis. Transcranial focal electrical stimulation (TFS) delays epileptogenesis and inhibits P-gp overexpression after a generalized seizure. Here, first we measured P-gp expression during epileptogenesis and second, we assessed if TFS antiepileptogenic effect was related with P-gp overexpression avoidance. Male Wistar rats were implanted in right basolateral amygdala and stimulated daily for electrical amygdala kindling (EAK), P-gp expression was assessed during epileptogenesis in relevant brain areas. Stage I group showed 85% increase in P-gp in ipsilateral hippocampus (p < 0.001). Stage III group presented 58% and 57% increase in P-gp in both hippocampi (p < 0.05). Kindled group had 92% and 90% increase in P-gp in both hippocampi (p < 0.01), and 93% and 143% increase in both neocortices (p < 0.01). For the second experiment, TFS was administrated daily after each EAK stimulation for 20 days and P-gp concentration was assessed. No changes were found in the TFS group (p > 0.05). Kindled group showed 132% and 138% increase in P-gp in both hippocampi (p < 0.001) and 51% and 92% increase in both cortices (p < 0.001). Kindled + TFS group presented no changes (p > 0.05). Our experiments revealed that progression of EAK is associated with increased P-gp expression. These changes are structure-specific and dependent on seizure severity. EAK-induced P-gp overexpression would be associated with neuronal hyperexcitability and thus, epileptogenesis. P-gp could be a novel therapeutical target to avoid epileptogenesis. In accordance with this, TFS inhibited P-gp overexpression and interfered with EAK. An important limitation of the present study is that P-gp neuronal expression was not evaluated under the different experimental conditions. Future studies should be carried out to determine P-gp neuronal overexpression in hyperexcitable networks during epileptogenesis. The TFS-induced lessening of P-gp overexpression could be a novel therapeutical strategy to avoid epileptogenesis in high-risk patients. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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13 pages, 634 KiB

Open AccessArticle

Exploring the Potential of Transcranial Direct Current Stimulation for Relieving Central Post-Stroke Pain: A Randomized Controlled Pilot Study

by Ji-Soo Baik, Jung-Hyun Yang, Sung-Hwa Ko, So-Jung Lee and Yong-Il Shin

Life 2023, 13(5), 1172; https://doi.org/10.3390/life13051172 - 12 May 2023

Cited by 3 | Viewed by 1765

Abstract

The potential of transcranial direct current stimulation (tDCS) as a non-invasive brain stimulation technique for treating pain has been studied. However, its effectiveness in patients with central post-stroke pain (CPSP) and the impact of lesion location remain unclear. This study investigated tDCS’s pain reduction effects in patients with CPSP. Twenty-two patients with CPSP were randomized into the tDCS or sham groups. The tDCS group received stimulation of the primary motor cortex (M1) for 20 min, five times weekly, for two weeks, and underwent evaluations at baseline, immediately after the intervention, and one week after the intervention. The tDCS group had no significant improvement compared to the sham group in pain, depression, and quality of life. Nevertheless, significant changes were identified within the tDCS group, and the pain trends appeared to be influenced by the lesion location. These findings provide important insights into the use of tDCS in patients with CPSP, which could inform further research and development of pain treatment options. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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13 pages, 1418 KiB

Open AccessArticle

Anodal Transcranial Direct Current Stimulation over the Right Dorsolateral Prefrontal Cortex Boosts Decision Making and Functional Impulsivity in Female Sports Referees

by Shahrouz Ghayebzadeh, Shirin Zardoshtian, Ehsan Amiri, Louis-Solal Giboin and Daniel Gomes da Silva Machado

Life 2023, 13(5), 1131; https://doi.org/10.3390/life13051131 - 5 May 2023

Viewed by 1800

Abstract

We investigated the effect of anodal transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (rDLPFC) on the sensitive decision making of female team sports referees. Twenty-four female referees voluntarily participated in this randomized, double-blind, crossover, and sham-controlled study. In three different sessions, participants received either anodal (a-tDCS; anode (+) over F4, cathode (−) over the supraorbital region (SO)), cathodal (c-tDCS; −F4/+SO), or sham tDCS (sh-tDCS) in a randomized and counterbalanced order. a-tDCS and c-tDCS were applied with 2 mA for 20 min. In sh-tDCS, the current was turned off after 30 s. Before and after tDCS, participants performed the computerized Iowa Gambling Task (IGT) and Go/No Go impulsivity (IMP) tests. Only a-tDCS improved IGT and IMP scores from pre to post. The delta (Δ = post–pre) analysis showed a significantly higher ΔIGT in a-tDCS compared to c-tDCS (p = 0.02). The ΔIMP was also significantly higher in a-tDCS compared to sh-tDCS (p = 0.01). Finally, the reaction time decreased significantly more in a-tDCS (p = 0.02) and sh-tDCS (p = 0.03) than in c-tDCS. The results suggest that the a-tDCS improved factors related to sensitive decision making in female team sports referees. a-tDCS might be used as an ergogenic aid to enhance decision performance in female team sports referees. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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10 pages, 506 KiB

Open AccessArticle

First Use of Non-Invasive Spinal Cord Stimulation in Motor Rehabilitation of Children with Spinal Muscular Atrophy

by Anton Novikov, Maria Maldova, Natalia Shandybina, Ivan Shalmiev, Elena Shoshina, Natalia Epoyan and Tatiana Moshonkina

Life 2023, 13(2), 449; https://doi.org/10.3390/life13020449 - 5 Feb 2023

Cited by 2 | Viewed by 2600

Abstract

Spinal muscular atrophy (SMA) is characterized by the degeneration of spinal alpha motorneurons. Nusinersen demonstrated good efficacy in the early disease phases. The feasibility of transcutaneous spinal cord stimulation (tSCS) in motor rehabilitation of patients with spinal cord injury has been demonstrated. We hypothesize that tSCS may activate intact and restored by nusinersen motorneurons and slow down the decline in motor activity, and may contribute to the development of motor skills in children with SMA. A case series is presented. Five children (6–13 years old) with SMA type II or III participated in the study. They were treated with nusinersen for ~2 years. Application of tSCS was carried out during physical therapy for 30–40 min per day in the course of 10–14 days. Outcome measures were goniometry of joints with contracture, forced vital capacity (FVC), RULM and HFMSE scales. The participants tolerated the stimulation well. The reduction of the contracture was ≥5 deg. RULM and HFMSE increased by ~1–2 points. Predicted FVC increased by 1–7% in three participants. Each participant expanded their range of active movements and/or learned new motor skills. Spinal cord stimulation may be an effective rehabilitation method in patients treated with nusinersen. More research is needed. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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8 pages, 2167 KiB

Open AccessCommunication

Transcutaneous Spinal Cord Stimulation Attenuates Blood Pressure Drops in Orthostasis

by Natalia N. Beliaeva, Tatiana R. Moshonkina, Oleg V. Mamontov, Elena N. Zharova, Heber Ivan Condori Leandro, Nigar Z. Gasimova and Evgeny N. Mikhaylov

Life 2023, 13(1), 26; https://doi.org/10.3390/life13010026 - 22 Dec 2022

Viewed by 2100

Abstract

Orthostatic hypotension is a complex medical problem with various underlying pathogenic mechanisms and limited modalities for its correction. Since transcutaneous spinal cord stimulation (t-SCS) leads to immediate blood pressure (BP) elevation in a supine position, we suggested that t-SCS may attenuate blood pressure drops in orthostasis. We aimed to evaluate the hemodynamic effects of t-SCS during tilt testing in a feasibility study in three patients with documented orthostatic hypotension. Four sessions on two different days of tilt testing on and off t-SCS were performed on each patient. While tilting with t-SCS off showed typical significant BP drops in every patient, active t-SCS resulted in systemic vascular resistance (SVR) elevation in all patients and significantly higher values of systolic and diastolic BP in two patients. T-SCS requires further investigation on a larger patient population. However, our preliminary results demonstrate its ability for SVR and BP elevation in subjects with severe orthostatic hypotension. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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15 pages, 2151 KiB

Open AccessArticle

Transcutaneous Auricular Vagus Nerve Stimulation Improves Inflammation but Does Not Interfere with Cardiac Modulation and Clinical Symptoms of Individuals with COVID-19: A Randomized Clinical Trial

by Fernanda Ishida Corrêa, Paulo Henrique Leite Souza, Laura Uehara, Raphael Mendes Ritti-Dias, Gustavo Oliveira da Silva, Wellington Segheto, Kevin Pacheco-Barrios, Felipe Fregni and João Carlos Ferrari Corrêa

Life 2022, 12(10), 1644; https://doi.org/10.3390/life12101644 - 19 Oct 2022

Cited by 9 | Viewed by 3189

Abstract

Transcranial auricular vagus nerve stimulation (taVNS) has shown effectiveness in reducing inflammation and depression. Thus, this study evaluated its effect on inflammation, cardiac autonomic modulation, and clinical symptoms in individuals affected by COVID-19. Methods: There were 52 randomized participants hospitalized with COVID-19 diagnosis who were to receive active (a-taVNS) or sham taVNS (s-taVNS) for 90 min twice a day for seven consecutive days. Interleukin 6 (IL-6), 10 (IL-10), cortisol, C-reactive protein (CRP), heart rate variability (HRV), and clinical symptoms were assessed before and after seven days of treatment. There were also seven- and fourteen-day follow-ups for clinical symptoms, including anxiety and depression levels, as well as a six-month follow-up for memory and attention levels. Results: There was significant reduction in CRP −23.9%, (95% CI −46.3 to −1.4) and IL-6 −37.7%, (95% CI −57.6 to −17.7) for the a-taVNS group. There were no changes in IL-10, cortisol levels, or in HRV results (p > 0.05) in both groups. There were no changes regarding clinical symptoms, except for a significant decrease in depression level (−2.85, 95% CI −5.44 to −0.27) in the a-taVNS group. Conclusion: taVNS showed effects on CRP, IL-6, and depression levels; however, it did not affect other clinical symptoms. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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Review

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18 pages, 770 KiB

Open AccessReview

Transcranial Electrical Stimulation for Associative Memory Enhancement: State-of-the-Art from Basic to Clinical Research

by Jovana Bjekić, Milica Manojlović and Saša R. Filipović

Life 2023, 13(5), 1125; https://doi.org/10.3390/life13051125 - 2 May 2023

Cited by 2 | Viewed by 2911

Abstract

Associative memory (AM) is the ability to bind new information into complex memory representations. Noninvasive brain stimulation (NIBS), especially transcranial electric stimulation (tES), has gained increased interest in research of associative memory (AM) and its impairments. To provide an overview of the current state of knowledge, we conducted a systematic review following PRISMA guidelines covering basic and clinical research. Out of 374 identified records, 41 studies were analyzed—twenty-nine in healthy young adults, six in the aging population, three comparing older and younger adults, as well as two studies on people with MCI, and one in people with Alzheimer’s dementia. Studies using transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS) as well as oscillatory (otDCS) and high-definition protocols (HD-tDCS, HD-tACS) have been included. The results showed methodological heterogeneity in terms of study design, stimulation type, and parameters, as well as outcome measures. Overall, the results show that tES is a promising method for AM enhancement, especially if the stimulation is applied over the parietal cortex and the effects are assessed in cued recall paradigms. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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Other

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14 pages, 838 KiB

Open AccessBrief Report

The Effect of Multi-Session Prefrontal Cortical Stimulation on Aggression: A Randomized, Double-Blind, Parallel-Group Trial

by Olivia Choy, Gary Tan and Yen Cong Wong

Life 2023, 13(8), 1729; https://doi.org/10.3390/life13081729 - 11 Aug 2023

Cited by 1 | Viewed by 1798

Abstract

Findings from brain imaging studies investigating the neural underpinnings of antisocial behavior have implicated the prefrontal cortex in the regulation of aggressive reactions. However, relatively few studies have examined the role of the prefrontal cortex on aggression in an experimental way. This study examines whether upregulating the prefrontal cortex using repeated transcranial direct current stimulation (tDCS) reduces aggressive behavior. In a double-blind, parallel-group, randomized controlled trial, 88 healthy adults (42 males, 46 females) were assigned to one session of anodal tDCS over the ventromedial prefrontal cortex (n = 47) or sham stimulation (n = 41) per day for three consecutive days and assessed using a behavioral measure of aggression. Levels of aggressive responses post-intervention did not significantly differ between the active and sham stimulation groups. However, a significant interaction effect between the stimulation group and gender was observed, whereby males, but not females, exhibited reduced aggression after prefrontal stimulation. To the authors’ knowledge, this is the first study to examine the effect of multi-session prefrontal tDCS on aggressive behavior in healthy adults. Results highlight that there are differences in responsivity to tDCS in modifying aggressive behavior. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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31 pages, 1048 KiB

Open AccessSystematic Review

Non-Invasive Brain Stimulation for the Modulation of Aggressive Behavior—A Systematic Review of Randomized Sham-Controlled Studies

by Antony Casula, Bianca M. Milazzo, Gabriella Martino, Alessandro Sergi, Chiara Lucifora, Francesco Tomaiuolo, Angelo Quartarone, Michael A. Nitsche and Carmelo M. Vicario

Life 2023, 13(5), 1220; https://doi.org/10.3390/life13051220 - 20 May 2023

Cited by 4 | Viewed by 2807

Abstract

Intro: Aggressive behavior represents a significant public health issue, with relevant social, political, and security implications. Non-invasive brain stimulation (NIBS) techniques may modulate aggressive behavior through stimulation of the prefrontal cortex. Aims: To review research on the effectiveness of NIBS to alter aggression, discuss the main findings and potential limitations, consider the specifics of the techniques and protocols employed, and discuss clinical implications. Methods: A systematic review of the literature available in the PubMed database was carried out, and 17 randomized sham-controlled studies investigating the effectiveness of NIBS techniques on aggression were included. Exclusion criteria included reviews, meta-analyses, and articles not referring to the subject of interest or not addressing cognitive and emotional modulation aims. Conclusions: The reviewed data provide promising evidence for the beneficial effects of tDCS, conventional rTMS, and cTBS on aggression in healthy adults, forensic, and clinical samples. The specific stimulation target is a key factor for the success of stimulation on aggression modulation. rTMS and cTBS showed opposite effects on aggression compared with tDCS. However, due to the heterogeneity of stimulation protocols, experimental designs, and samples, we cannot exclude other factors that may play a confounding role. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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10 pages, 2112 KiB

Open AccessCase Report

Twenty-Three Months Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex for Refractory Trigeminal Neuralgia: A Single-Case Study

by Sascha Freigang, Shane Fresnoza, Christian Lehner, Dominyka Jasinskaitė, Kariem Mahdy Ali, Karla Zaar and Michael Mokry

Life 2023, 13(1), 126; https://doi.org/10.3390/life13010126 - 2 Jan 2023

Cited by 1 | Viewed by 1991

Abstract

Treatment refractory or recurrent trigeminal neuralgia (TN) is a severe chronic pain illness. Single-session repetitive transcranial magnetic stimulation (rTMS) has been shown to elicit analgesic effects in several craniofacial pain syndromes, including TN. However, the safety and long-term effect of multi-session rTMS for TN have yet to be fully explored. In this study, we present a case of a patient with medical treatment-refractory TN after microvascular decompression. The patient volunteered to undergo 73 sessions of 10 Hz rTMS over 23 months. Neurovagination was used for precise localization and stimulation of the hand and face representation at the left motor cortex. The numeric pain intensity scores derived using the visual analog scale served as a daily index of treatment efficacy. The patient experienced a significant weekly reduction in pain scores, cumulating in 70.89% overall pain relief. The medication dosages were reduced and then discontinued toward the end of the intervention period. No severe adverse events were reported. From our results, we can conclude that the longitudinal multi-session application of rTMS over the hand and face area of M1 is a safe and effective method for producing long-lasting pain relief in TN. Using rTMS may thus prove helpful as an adjunct to conventional methods for treating pain in TN. Full article

(This article belongs to the Special Issue Non-invasive Neuromodulation: Past, Present and Future)

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