Neuromodulation of Cortical Networks in Neurological and Neuropsychiatric Disorders: Potential Clinical Indications and the Biophysiological Impact of Stimulation

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Systems Neuroscience".

Deadline for manuscript submissions: closed (23 February 2024) | Viewed by 13073

Special Issue Editors


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Guest Editor
Laboratory for Human and Experimental Neurophysiology, Department of Neuroscience, University of Split School of Medicine, 21000 Split, Croatia
Interests: transcranial magnetic stimulation; intraoperative neurophysiologic monitoring IONM and mapping; brain mapping; neurophysiology of neurological disorders; speech and language pathologies; cognition

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Guest Editor
Signal Processing, Analysis, and Advanced Diagnostics Research and Education Laboratory (SPAADREL), Faculty of Maritime Studies, University of Split, 21000 Split, Croatia
Interests: time–frequency analysis; biomedical signal processing; applied statistical signal pro-cessing; digital signal processing

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Guest Editor
Piedmont Neuroscience Center, Oakland, CA 94610, USA
Interests: neuromodulation and other novel therapies for refractory neuropsychiatric conditions

Special Issue Information

Dear Colleagues,

Individuals with neurological and neuropsychiatric disorders face a variety of difficulties that can significantly impact their daily lives. Neuromodulation of cortical networks following electrical and magnetic stimulation techniques has been proposed as a therapeutic tool to assist in treating their condition. Stimulating cortical networks can enhance neuroplasticity, act as a neuro-rehabilitative tool, or recalibrate aberrant neural pathways. The question is how brain stimulation results in lasting changes in cortical excitability, how brain dynamics evolve during stimulation, how we can quantify the excitability changes in human cortical networks, and how these changes translate into improved clinical outcomes. Uncertainty about these questions hinders the development of personalized brain stimulation therapies.

The aim of the current Special Issue is to gather the latest high-quality research on the use of neuromodulation following electrical and magnetic stimulation in neurological and neuropsychiatric disorders, focusing on movement disorders, spinal cord injury, epilepsy, stroke, aphasia, chronic pain, tinnitus, migraine, depression, anxiety, hallucinations, addiction, and memory disorders. 

Authors are invited to submit original research articles, reviews, or protocol papers outlining new and promising techniques and stimulation protocols. We are keeping our outlook broad and welcome submissions on the application of electrical and magnetic stimulation techniques in any neurological and neuropsychiatric population. This will enable us to put together a collection of work that will provide insight into the potential wide-ranging applicability of neuromodulation following electrical and magnetic stimulation in neurology and neuropsychiatry.

Dr. Maja Rogić Vidaković
Dr. Joško Šoda
Dr. Joshua E. Kuluva
Guest Editors

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Keywords

  • neuromodulation
  • electrical stimulation
  • magnetic stimulation
  • neurology
  • neuropsychiatry
  • neurorehabilitation

Published Papers (10 papers)

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Research

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15 pages, 1692 KiB  
Article
Different Effect Sizes of Motor Skill Training Combined with Repetitive Transcranial versus Trans-Spinal Magnetic Stimulation in Healthy Subjects
by Farsin Hamzei, Alexander Ritter, Kristin Pohl, Peggy Stäps and Eric Wieduwild
Brain Sci. 2024, 14(2), 165; https://doi.org/10.3390/brainsci14020165 - 06 Feb 2024
Viewed by 848
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is used to enhance motor training (MT) performance. The use of rTMS is limited under certain conditions, such as after a stroke with severe damage to the corticospinal tract. This raises the question as to whether repetitive trans-spinal [...] Read more.
Repetitive transcranial magnetic stimulation (rTMS) is used to enhance motor training (MT) performance. The use of rTMS is limited under certain conditions, such as after a stroke with severe damage to the corticospinal tract. This raises the question as to whether repetitive trans-spinal magnetic stimulation (rSMS) can also be used to improve MT. A direct comparison of the effect size between rTMS and rSMS on the same MT is still lacking. Before conducting the study in patients, we determined the effect sizes of different stimulation approaches combined with the same motor training in healthy subjects. Two experiments (E1 and E2) with 96 subjects investigated the effect size of combining magnetic stimulation with the same MT. In E1, high-frequency rTMS, rSMS, and spinal sham stimulation (sham-spinal) were applied once in combination with MT, while one group only received the same MT (without stimulation). In E2, rTMS, rSMS, and sham-spinal were applied in combination with MT over several days. In all subjects, motor tests and motor-evoked potentials were evaluated before and after the intervention period. rTMS had the greatest effect on MT, followed by rSMS and then sham-spinal. Daily stimulation resulted in additional training gains. This study suggests that rSMS increases excitability and also enhances MT performance. This current study provides a basis for further research to discover whether patients who cannot be treated effectively with rTMS would benefit from rSMS. Full article
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26 pages, 7822 KiB  
Article
Transcranial Direct Current Stimulation (tDCS) Ameliorates Stress-Induced Sleep Disruption via Activating Infralimbic-Ventrolateral Preoptic Projections
by Yu-Jie Su, Pei-Lu Yi and Fang-Chia Chang
Brain Sci. 2024, 14(1), 105; https://doi.org/10.3390/brainsci14010105 - 22 Jan 2024
Viewed by 1115
Abstract
Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and [...] Read more.
Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutamatergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 min, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 h post-stimulation, persisting up to 16–24 h. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS’s sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS’s effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy. Full article
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11 pages, 787 KiB  
Article
A Comparison of Neuropsychological Outcomes following Responsive Neurostimulation and Anterior Temporal Lobectomy in Drug-Resistant Epilepsy
by Carly M. O’Donnell, Christopher Todd Anderson, Anthony J. Oleksy and Sara J. Swanson
Brain Sci. 2023, 13(12), 1628; https://doi.org/10.3390/brainsci13121628 - 24 Nov 2023
Viewed by 1415
Abstract
Neuropsychological outcomes following temporal lobe resection for drug-resistant epilepsy (DRE) are well established. For instance, left anterior temporal lobectomy (LATL) is associated with a greater risk for cognitive morbidity compared to right (RATL). However, the impact of neuromodulatory devices, specifically responsive neurostimulation (RNS), [...] Read more.
Neuropsychological outcomes following temporal lobe resection for drug-resistant epilepsy (DRE) are well established. For instance, left anterior temporal lobectomy (LATL) is associated with a greater risk for cognitive morbidity compared to right (RATL). However, the impact of neuromodulatory devices, specifically responsive neurostimulation (RNS), remains an area of active interest. There are currently no head-to-head comparisons of neuropsychological outcomes after surgical resection and neuromodulation. This study reports on a cohort of 21 DRE patients with the RNS System who received comprehensive pre- and post-implantation neuropsychological testing. We compared both cognitive and seizure outcomes in the RNS group to those of 307 DRE patients who underwent LATL (n = 138) or RATL (n = 169). RNS patients had higher seizure rates pre-intervention. While fewer in the RNS group achieved Class I Engel outcomes compared to the ATL cohorts, RNS patients also showed seizure frequency declines from pre- to post-intervention that were similar to those who underwent resective surgery. Moreover, the RNS and RATL groups were similar in their neuropsychological outcomes, showing no significant cognitive decline post-intervention. In contrast, the LATL group notably declined in object naming and verbal list learning. Direct comparisons like this study may be used to guide clinicians in shared decision making to tailor management plans for patients’ overall treatment goals. Full article
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12 pages, 1807 KiB  
Article
Role of Vagus Nerve Stimulation in Refractory and Super Refractory Status Epilepticus: A Pediatric Case Series
by Giulia Melinda Furlanis, Jacopo Favaro, Nicola Bresolin, Daniele Grioni, Valentina Baro, Alberto D’Amico, Stefano Sartori, Luca Denaro and Andrea Landi
Brain Sci. 2023, 13(11), 1589; https://doi.org/10.3390/brainsci13111589 - 14 Nov 2023
Viewed by 1068
Abstract
Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few [...] Read more.
Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE. Methods: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up. Results: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE. Discussion and Conclusions: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS’s potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights. Full article
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17 pages, 2193 KiB  
Article
Association between Mood and Sensation Seeking Following rTMS
by Ulrike Kumpf, Aldo Soldini, Gerrit Burkhardt, Lucia Bulubas, Esther Dechantsreiter, Julia Eder, Frank Padberg and Ulrich Palm
Brain Sci. 2023, 13(9), 1265; https://doi.org/10.3390/brainsci13091265 - 30 Aug 2023
Viewed by 709
Abstract
Previous studies investigating mood changes in healthy subjects after prefrontal repetitive transcranial magnetic stimulation (rTMS) have shown largely inconsistent results. This may be due to methodological issues, considerable inter-individual variation in prefrontal connectivity or other factors, e.g., personality traits. This pilot study investigates [...] Read more.
Previous studies investigating mood changes in healthy subjects after prefrontal repetitive transcranial magnetic stimulation (rTMS) have shown largely inconsistent results. This may be due to methodological issues, considerable inter-individual variation in prefrontal connectivity or other factors, e.g., personality traits. This pilot study investigates whether mood changes after rTMS are affected by personality parameters. In a randomized cross-over design, 17 healthy volunteers received three sessions of 1 Hz rTMS to Fz, F3 and T3 (10/20 system). The T3 electrode site served as the control condition with the coil angled 45° to the scalp. Subjective mood was rated at baseline and after each condition. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI) and the Sensation Seeking Scale (SSS). For all conditions, a significant association between mood changes towards a deterioration in mood and SSS scores was observed. There were no differences between conditions and no correlations between mood changes and NEO-FFI. The data show that sensation-seeking personality has an impact on subjective mood changes following prefrontal rTMS in all conditions. Future studies investigating the effects of rTMS on emotional paradigms should include individual measures of sensation-seeking personality. The pre-selection of subjects according to personality criteria may reduce the variability in results. Full article
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16 pages, 2485 KiB  
Article
Excitatory Dorsal Lateral Prefrontal Cortex Transcranial Magnetic Stimulation Increases Social Anxiety
by Anthony Minervini, Adriana LaVarco, Samantha Zorns, Ruth Propper, Christos Suriano and Julian Paul Keenan
Brain Sci. 2023, 13(7), 989; https://doi.org/10.3390/brainsci13070989 - 24 Jun 2023
Cited by 4 | Viewed by 1321
Abstract
Social exclusion refers to the experience of rejection by one or more people during a social event and can induce pain-related sensations. Cyberball, a computer program, is one of the most common tools for analyzing social exclusion. Regions of the brain that underlie [...] Read more.
Social exclusion refers to the experience of rejection by one or more people during a social event and can induce pain-related sensations. Cyberball, a computer program, is one of the most common tools for analyzing social exclusion. Regions of the brain that underlie social pain include networks linked to the dorsal lateral prefrontal cortex (DLPFC). Specifically, self-directed negative socially induced exclusion is associated with changes in DLPFC activity. Direct manipulation of this area may provide a better understanding of how the DLPFC can influence the perception of social exclusion and determine a causal role of the DLPFC. Transcranial magnetic stimulation (TMS) was applied to both the left and right DLPFC to gauge different reactions to the Cyberball experience. It was found that there were elevated exclusion indices following right DLPFC rTMS; participants consistently felt more excluded when the right DLPFC was excited. This may relate to greater feelings of social pain when the right DLPFC is manipulated. These data demonstrate that direct manipulation of the DLPFC results in changes in responses to social exclusion. Full article
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Review

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13 pages, 1309 KiB  
Review
Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach
by Maja Rogić Vidaković, Joško Šoda, Joshua Elan Kuluva, Braco Bošković, Krešimir Dolić and Ivana Gunjača
Brain Sci. 2023, 13(11), 1591; https://doi.org/10.3390/brainsci13111591 - 15 Nov 2023
Viewed by 1076
Abstract
Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study’s [...] Read more.
Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study’s aims are to (1) describe transcranial magnetic stimulation (TMS) methodology for studying the functional integrity of the corticospinal tract by stimulating the primary motor cortex (M1) for laryngeal muscle representation and recording motor evoked potentials (MEPs) from laryngeal muscles; (2) evaluate the results of TMS studies investigating the cortical silent period (cSP) in LD; and (3) present the standard treatments of LD, as well as the results of new theoretical views and treatment approaches like repetitive TMS and laryngeal vibration over the laryngeal muscles as the recent research attempts in treatment of LD. Neurophysiological findings point to a shortened duration of cSP in adductor LD and altered cSP duration in abductor LD individuals. Future TMS studies could further investigate the role of cSP in relation to standard laryngological measures and treatment options. A better understanding of the neurophysiological mechanisms might give new perspectives for the treatment of LD. Full article
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Other

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27 pages, 881 KiB  
Systematic Review
Novel Approaches for the Treatment of Post-Traumatic Stress Disorder: A Systematic Review of Non-Invasive Brain Stimulation Interventions and Insights from Clinical Trials
by Daniele Saccenti, Leandro Lodi, Andrea Stefano Moro, Simona Scaini, Barbara Forresi, Jacopo Lamanna and Mattia Ferro
Brain Sci. 2024, 14(3), 210; https://doi.org/10.3390/brainsci14030210 - 24 Feb 2024
Viewed by 1064
Abstract
First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could [...] Read more.
First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms’ severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects’ clinical conditions. Full article
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10 pages, 3550 KiB  
Case Report
Effects of Transcranial Direct Current Stimulation on Clinical Features of Dizziness and Cortical Activation in a Patient with Vestibular Migraine
by Sang Seok Yeo, Chang Ju Kim, Seong Ho Yun, Sung Min Son and Yoon Jae Kim
Brain Sci. 2024, 14(2), 187; https://doi.org/10.3390/brainsci14020187 - 19 Feb 2024
Viewed by 1055
Abstract
Background: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects [...] Read more.
Background: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects of tDCS on dizziness and cortical activation in a patient with VM. Methods: We recruited a male patient aged 31 years with no dizziness. The patient watched a video to induce dizziness using a virtual reality device. The study applied the intervention using tDCS for 4 weeks and measured 4 assessments: functional near-infrared spectroscopy (fNIRS), quantitative electroencephalography (qEEG), dizziness handicap inventory, and visual vertigo analog scale. Results: We showed the activation in the middle temporal gyrus and inferior temporal gyrus (ITG) of the left hemisphere and in the superior temporal gyrus and ITG of the right hemisphere in the pre-intervention. After the intervention, the activation of these areas decreased. In the results of qEEG, excessive activation of C3, P3, and T5 in the left hemisphere and C4 in the right hemisphere before intervention disappeared after the intervention. Conclusions: This study indicated that tDCS-based intervention could be considered a viable approach to treating patients with vestibular dysfunction and dizziness caused by VM. Full article
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28 pages, 2269 KiB  
Systematic Review
Betting on Non-Invasive Brain Stimulation to Treat Gambling Disorder: A Systematic Review and Meta-Analysis
by Lilia Del Mauro, Alessandra Vergallito, Gaia Gattavara, Lucrezia Juris, Alessia Gallucci, Anna Vedani, Laura Cappelletti, Pietro Maria Farneti and Leonor J. Romero Lauro
Brain Sci. 2023, 13(4), 698; https://doi.org/10.3390/brainsci13040698 - 21 Apr 2023
Cited by 2 | Viewed by 2345
Abstract
Gambling disorder (GD) is a behavioral addiction that severely impacts individuals’ functioning, leading to high socioeconomic costs. Non-invasive brain stimulation (NiBS) has received attention for treating psychiatric and neurological conditions in recent decades, but there is no recommendation for its use for GD. [...] Read more.
Gambling disorder (GD) is a behavioral addiction that severely impacts individuals’ functioning, leading to high socioeconomic costs. Non-invasive brain stimulation (NiBS) has received attention for treating psychiatric and neurological conditions in recent decades, but there is no recommendation for its use for GD. Therefore, this study aimed to systematically review and analyze the available literature to determine the effectiveness of NiBS in treating GD. Following the PRISMA guidelines, we screened four electronic databases up to July 2022 and selected relevant English-written original articles. We included ten papers in the systematic review and seven in the meta-analysis. As only two studies employed a sham-controlled design, the pre–post standardized mean change (SMCC) was computed as effect size only for real stimulation. The results showed a significant effect of NiBS in reducing craving scores (SMCC = −0.69; 95% CI = [−1.2, −0.2], p = 0.010). Moreover, considering the GD’s frequent comorbidity with mood disorders, we ran an exploratory analysis of the effects of NiBS on depressive symptoms, which showed significant decreases in post-treatment scores (SMCC = −0.71; 95% CI = [−1.1, −0.3], p < 0.001). These results provide initial evidence for developing NiBS as a feasible therapy for GD symptoms but further comprehensive research is needed to validate these findings. The limitations of the available literature are critically discussed. Full article
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