Emerging Trends in Brain Stimulation

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 18766

Special Issue Editors


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Guest Editor
Institute of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil
Interests: neuroscience; brain stimulation; neuroimaging

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Guest Editor
Department of Psychiatry and Psychology, Division of Child and Adolescent Psychiatry, Mayo Clinic, Rochester, MN 55905, USA
Interests: brain stimulation; neurobiology

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Guest Editor
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Interests: brain stimulation

Special Issue Information

Dear Colleagues,

This is an exciting time in the field of brain stimulation. Transcranial magnetic stimulation (TMS) and its variants rapidly expand clinical indications and efficacy, while novel and portable transcranial electric stimulation (tES) devices are being increasingly used and researched in clinical trials. The mechanisms of action of these techniques are progressively being unveiled, which allows researchers to use multimodal methods to provide a better prediction of response. In addition, magnetic seizure therapy is being evaluated as an alternative intervention for electroconvulsive therapy, reducing cognitive side effects while maintaining clinical efficacy. This Special Issue invites researchers in the field to submit their recent findings that fall under the scope of these emerging trends. We welcome both original and review work, as well as manuscripts describing clinical findings, mechanisms of action, translational research, modelling, bioengineering, and animal studies.

Dr. Andre Russowsky Brunoni
Dr. Paul E. Croarkin
Dr. Lais Boralli Razza
Guest Editors

Manuscript Submission Information

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Keywords

  • transcranial magnetic stimulation
  • transcranial electric stimulation
  • psychiatry, neurology
  • neuroimaging
  • electroconvulsive therapy
  • neuromodulation
  • depression
  • pain
  • stroke

Published Papers (9 papers)

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15 pages, 1166 KiB  
Article
Exploring Motor Network Connectivity in State-Dependent Transcranial Magnetic Stimulation: A Proof-of-Concept Study
by Laura Marzetti, Alessio Basti, Roberto Guidotti, Antonello Baldassarre, Johanna Metsomaa, Christoph Zrenner, Antea D’Andrea, Saeed Makkinayeri, Giulia Pieramico, Risto J. Ilmoniemi, Ulf Ziemann, Gian Luca Romani and Vittorio Pizzella
Biomedicines 2024, 12(5), 955; https://doi.org/10.3390/biomedicines12050955 - 25 Apr 2024
Viewed by 516
Abstract
State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This [...] Read more.
State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor μ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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15 pages, 9794 KiB  
Article
Optimizing TMS Coil Placement Approaches for Targeting the Dorsolateral Prefrontal Cortex in Depressed Adolescents: An Electric Field Modeling Study
by Zhi-De Deng, Pei L. Robins, Moritz Dannhauer, Laura M. Haugen, John D. Port and Paul E. Croarkin
Biomedicines 2023, 11(8), 2320; https://doi.org/10.3390/biomedicines11082320 - 21 Aug 2023
Cited by 5 | Viewed by 2139
Abstract
High-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) shows promise as a treatment for treatment-resistant depression in adolescents. Conventional rTMS coil placement strategies include the 5 cm, the Beam F3, and the magnetic resonance imaging (MRI) neuronavigation [...] Read more.
High-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) shows promise as a treatment for treatment-resistant depression in adolescents. Conventional rTMS coil placement strategies include the 5 cm, the Beam F3, and the magnetic resonance imaging (MRI) neuronavigation methods. The purpose of this study was to use electric field (E-field) models to compare the three targeting approaches to a computational E-field optimization coil placement method in depressed adolescents. Ten depressed adolescents (4 females, age: 15.9±1.1) participated in an open-label rTMS treatment study and were offered MRI-guided rTMS five times per week over 6–8 weeks. Head models were generated based on individual MRI images, and E-fields were simulated for the four targeting approaches. Results showed a significant difference in the induced E-fields at the L-DLPFC between the four targeting methods (χ2=24.7, p<0.001). Post hoc pairwise comparisons showed that there was a significant difference between any two of the targeting methods (Holm adjusted p<0.05), with the 5 cm rule producing the weakest E-field (46.0±17.4V/m), followed by the F3 method (87.4±35.4V/m), followed by MRI-guided (112.1±14.6V/m), and followed by the computational approach (130.1±18.1V/m). Variance analysis showed that there was a significant difference in sample variance between the groups (K2=8.0, p<0.05), with F3 having the largest variance. Participants who completed the full course of treatment had median E-fields correlated with depression symptom improvement (r=0.77, p<0.05). E-field models revealed limitations of scalp-based methods compared to MRI guidance, suggesting computational optimization could enhance dose delivery to the target. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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16 pages, 1881 KiB  
Article
Neuronavigated Cerebellar 50 Hz tACS: Attenuation of Stimulation Effects by Motor Sequence Learning
by Rebecca Herzog, Christina Bolte, Jan-Ole Radecke, Kathinka von Möller, Rebekka Lencer, Elinor Tzvi, Alexander Münchau, Tobias Bäumer and Anne Weissbach
Biomedicines 2023, 11(8), 2218; https://doi.org/10.3390/biomedicines11082218 - 8 Aug 2023
Cited by 4 | Viewed by 1224
Abstract
Cerebellar transcranial alternating current stimulation (tACS) is an emerging non-invasive technique that induces electric fields to modulate cerebellar function. Although the effect of cortical tACS seems to be state-dependent, the impact of concurrent motor activation and the duration of stimulation on the effects [...] Read more.
Cerebellar transcranial alternating current stimulation (tACS) is an emerging non-invasive technique that induces electric fields to modulate cerebellar function. Although the effect of cortical tACS seems to be state-dependent, the impact of concurrent motor activation and the duration of stimulation on the effects of cerebellar tACS has not yet been examined. In our study, 20 healthy subjects received neuronavigated 50 Hz cerebellar tACS for 40 s or 20 min, each during performance using a motor sequence learning task (MSL) and at rest. We measured the motor evoked potential (MEP) before and at two time points after tACS application to assess corticospinal excitability. Additionally, we investigated the online effect of tACS on MSL. Individual electric field simulations were computed to evaluate the distribution of electric fields, showing a focal electric field in the right cerebellar hemisphere with the highest intensities in lobe VIIb, VIII and IX. Corticospinal excitability was only increased after tACS was applied for 40 s or 20 min at rest, and motor activation during tACS (MSL) cancelled this effect. In addition, performance was better (shorter reaction times) for the learned sequences after 20 min of tACS, indicating more pronounced learning under 20 min of tACS compared to tACS applied only in the first 40 s. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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25 pages, 1625 KiB  
Article
Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study
by Krisztián Iszak, Simon Mathies Gronemann, Stefanie Meyer, Alexander Hunold, Jana Zschüntzsch, Mathias Bähr, Walter Paulus and Andrea Antal
Biomedicines 2023, 11(7), 1813; https://doi.org/10.3390/biomedicines11071813 - 24 Jun 2023
Cited by 2 | Viewed by 7159
Abstract
Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking [...] Read more.
Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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18 pages, 2351 KiB  
Article
Rhythmic TMS as a Feasible Tool to Uncover the Oscillatory Signatures of Audiovisual Integration
by Riccardo Bertaccini, Giuseppe Ippolito, Luca Tarasi, Agnese Zazio, Antonietta Stango, Marta Bortoletto and Vincenzo Romei
Biomedicines 2023, 11(6), 1746; https://doi.org/10.3390/biomedicines11061746 - 17 Jun 2023
Cited by 3 | Viewed by 1142
Abstract
Multisensory integration is quintessential to adaptive behavior, with clinical populations showing significant impairments in this domain, most notably hallucinatory reports. Interestingly, altered cross-modal interactions have also been reported in healthy individuals when engaged in tasks such as the Sound-Induced Flash-Illusion (SIFI). The temporal [...] Read more.
Multisensory integration is quintessential to adaptive behavior, with clinical populations showing significant impairments in this domain, most notably hallucinatory reports. Interestingly, altered cross-modal interactions have also been reported in healthy individuals when engaged in tasks such as the Sound-Induced Flash-Illusion (SIFI). The temporal dynamics of the SIFI have been recently tied to the speed of occipital alpha rhythms (IAF), with faster oscillations entailing reduced temporal windows within which the illusion is experienced. In this regard, entrainment-based protocols have not yet implemented rhythmic transcranial magnetic stimulation (rhTMS) to causally test for this relationship. It thus remains to be evaluated whether rhTMS-induced acoustic and somatosensory sensations may not specifically interfere with the illusion. Here, we addressed this issue by asking 27 volunteers to perform a SIFI paradigm under different Sham and active rhTMS protocols, delivered over the occipital pole at the IAF. Although TMS has been proven to act upon brain tissues excitability, results show that the SIFI occurred for both Sham and active rhTMS, with the illusory rate not being significantly different between baseline and stimulation conditions. This aligns with the discrete sampling hypothesis, for which alpha amplitude modulation, known to reflect changes in cortical excitability, should not account for changes in the illusory rate. Moreover, these findings highlight the viability of rhTMS-based interventions as a means to probe the neuroelectric signatures of illusory and hallucinatory audiovisual experiences, in healthy and neuropsychiatric populations. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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14 pages, 1298 KiB  
Article
Neurophysiological Markers of Premotor–Motor Network Plasticity Predict Motor Performance in Young and Older Adults
by Sonia Turrini, Naomi Bevacqua, Antonio Cataneo, Emilio Chiappini, Francesca Fiori, Simone Battaglia, Vincenzo Romei and Alessio Avenanti
Biomedicines 2023, 11(5), 1464; https://doi.org/10.3390/biomedicines11051464 - 17 May 2023
Cited by 14 | Viewed by 2035
Abstract
Aging is commonly associated with a decline in motor control and neural plasticity. Tuning cortico–cortical interactions between premotor and motor areas is essential for controlling fine manual movements. However, whether plasticity in premotor–motor circuits predicts hand motor abilities in young and elderly humans [...] Read more.
Aging is commonly associated with a decline in motor control and neural plasticity. Tuning cortico–cortical interactions between premotor and motor areas is essential for controlling fine manual movements. However, whether plasticity in premotor–motor circuits predicts hand motor abilities in young and elderly humans remains unclear. Here, we administered transcranial magnetic stimulation (TMS) over the ventral premotor cortex (PMv) and primary motor cortex (M1) using the cortico–cortical paired-associative stimulation (ccPAS) protocol to manipulate the strength of PMv-to-M1 connectivity in 14 young and 14 elderly healthy adults. We assessed changes in motor-evoked potentials (MEPs) during ccPAS as an index of PMv-M1 network plasticity. We tested whether the magnitude of MEP changes might predict interindividual differences in performance in two motor tasks that rely on premotor-motor circuits, i.e., the nine-hole pegboard test and a choice reaction task. Results show lower motor performance and decreased PMv-M1 network plasticity in elderly adults. Critically, the slope of MEP changes during ccPAS accurately predicted performance at the two tasks across age groups, with larger slopes (i.e., MEP increase) predicting better motor performance at baseline in both young and elderly participants. These findings suggest that physiological indices of PMv-M1 plasticity could provide a neurophysiological marker of fine motor control across age-groups. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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9 pages, 560 KiB  
Article
Long-Interval Intracortical Inhibition and the Cortical Silent Period in Youth
by Kelly B. Ahern, Juan F. Garzon, Deniz Yuruk, Maria Saliba, Can Ozger, Jennifer L. Vande Voort and Paul E. Croarkin
Biomedicines 2023, 11(2), 409; https://doi.org/10.3390/biomedicines11020409 - 30 Jan 2023
Viewed by 1432
Abstract
Background: The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABAB)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths. Methods: We analyzed data from three [...] Read more.
Background: The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABAB)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths. Methods: We analyzed data from three previous studies of youth who underwent CSP and LICI measurements with transcranial magnetic stimulation and electromyography. We assessed CSP and LICI association using Spearman rank correlation tests and multiple linear regression analyses adjusted for demographic and clinical covariates. Results: The sample included 16 healthy participants and 45 participants with depression. The general mean (SD) age was 15.5 (1.7), 14.3 (1.7) for healthy participants, and 15.9 (1.6) years for participants with depression. Measures were nonnormally distributed (Shapiro–Wilk, p < 0.001). CSP and LICI were not correlated at 100-millisecond (ρ = −0.2421, p = 0.06), 150-millisecond (ρ = −0.1612, p = 0.21), or 200-millisecond (ρ = −0.0507, p = 0.70) interstimulus intervals using Spearman rank correlation test. No correlations were found in the multiple regression analysis (p = 0.35). Conclusions: Although previous studies suggest that cortical silent period and long-interval intracortical inhibition measure GABAB receptor-mediated activity, these biomarkers were not associated in our sample of youths. Future studies should focus on the specific physiologic and pharmacodynamic properties assessed by CSP and LICI in younger populations. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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20 pages, 639 KiB  
Systematic Review
Neurobiological Effects of Transcranial Direct Current Stimulation over the Inferior Frontal Gyrus: A Systematic Review on Cognitive Enhancement in Healthy and Neurological Adults
by Raffaele Di Fuccio, Anna Lardone, Mariagiovanna De Luca, Leila Ali, Pierpaolo Limone and Paola Marangolo
Biomedicines 2024, 12(6), 1146; https://doi.org/10.3390/biomedicines12061146 - 22 May 2024
Viewed by 133
Abstract
The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes [...] Read more.
The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
17 pages, 671 KiB  
Study Protocol
Magnetic Waves vs. Electric Shocks: A Non-Inferiority Study of Magnetic Seizure Therapy and Electroconvulsive Therapy in Treatment-Resistant Depression
by Helena Bellini, Eric Cretaz, Adriana Munhoz Carneiro, Pedro Henrique Rodrigues da Silva, Leonardo Afonso dos Santos, José Gallucci-Neto and André Russowsky Brunoni
Biomedicines 2023, 11(8), 2150; https://doi.org/10.3390/biomedicines11082150 - 30 Jul 2023
Cited by 2 | Viewed by 1659
Abstract
Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) [...] Read more.
Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) has emerged as a promising alternative, offering comparable antidepressant efficacy with better cognitive outcomes. However, the clinical outcomes and cognitive effects of MST require further investigation. This double-blinded, randomized, non-inferiority study aims to compare the efficacy, tolerability, cognitive adverse effects, and neurophysiological biomarkers of MST with bilateral ECT (BT ECT) in patients with TRD. This study will employ multimodal nuclear magnetic resonance imaging (MRI) and serum neurotrophic markers to gain insight into the neurobiological basis of seizure therapy. Additionally, neurophysiological biomarkers will be evaluated as secondary outcomes to predict the antidepressant and cognitive effects of both techniques. The study design, recruitment methods, ethical considerations, eligibility criteria, interventions, and blinding procedures are described. The expected outcomes will advance the field by offering a potential alternative to ECT with improved cognitive outcomes and a better understanding of the underlying pathophysiology of depression and antidepressant therapies. Full article
(This article belongs to the Special Issue Emerging Trends in Brain Stimulation)
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