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Neuromodulation: From Theories to Therapies

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

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 13228

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Dr. Hatice Kumru

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Guest Editor

1. Fundación Institut Guttmann, Institut Universitari de Neurorrehabilitació Adscrit a la UAB, 08916 Badalona, Spain
2. Universitat Autónoma de Barcelona, 08193 Barcelona, Spain
3. Fundació Institut d’Investigació en Ciéncies de la Salut Germans Trias i Pujol, 08916 Badalona, Spain
Interests: neuromodulation; brain stimulation; neurology; psychiatric disorders; neurorehabilitation; spinal cord stimulation

Special Issue Information

Dear Colleagues,

Neuromodulation is the alteration of neuronal and synaptic properties by neurons, neuronal substances, or via the targeted delivery of an electromagnetic or chemical stimulus, etc., to specific neurological sites in the body to normalize or modulate nervous tissue function. Neuromodulation, whether electrical or magnetic, at the brain- or at the spinal cord-level, employs the body's natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters or other chemical messengers that can modulate the excitability and firing patterns of neural circuits. The end effect is a "normalization" and/or "modulation" of neural network function from its perturbed state. Neuromodulation is an increasingly accepted treatment for neurological and psychiatric disorders, and its significance in the field of neurorehabilitation is growing and evolving.

Dr. Hatice Kumru
Guest Editor

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Keywords

neuromodulation
electromagnetic stimulation
brain stimulation
spinal cord stimulation
neurological disorders
psychiatric disorders
neurorehabilitation

Published Papers (6 papers)

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Research

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16 pages, 9686 KiB

Open AccessArticle

Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization

by Enrique Germany Morrison, Venethia Danthine, Roberto Santalucia, Andrés Torres, Inci Cakiroglu, Antoine Nonclercq and Riëm El Tahry

Biomedicines 2024, 12(3), 557; https://doi.org/10.3390/biomedicines12030557 - 01 Mar 2024

Viewed by 780

Abstract

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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17 pages, 2131 KiB

Open AccessArticle

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS Modulates Theta-Band EEG Source-Based Large-Scale Functional Network Connectivity in Patients with Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Clinical Trial

by Ta-Chuan Yeh, Cathy Chia-Yu Huang, Yong-An Chung, Sonya Youngju Park, Jooyeon Jamie Im, Yen-Yue Lin, Chin-Chao Ma, Nian-Sheng Tzeng and Hsin-An Chang

Biomedicines 2023, 11(2), 630; https://doi.org/10.3390/biomedicines11020630 - 20 Feb 2023

Cited by 2 | Viewed by 2043

Abstract

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5–7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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17 pages, 1759 KiB

Open AccessArticle

Transcutaneous Cervical Spinal Cord Stimulation Combined with Robotic Exoskeleton Rehabilitation for the Upper Limbs in Subjects with Cervical SCI: Clinical Trial

by Loreto García-Alén, Hatice Kumru, Yolanda Castillo-Escario, Jesús Benito-Penalva, Josep Medina-Casanovas, Yury P. Gerasimenko, Victor Reggie Edgerton, Guillermo García-Alías and Joan Vidal

Biomedicines 2023, 11(2), 589; https://doi.org/10.3390/biomedicines11020589 - 16 Feb 2023

Cited by 2 | Viewed by 2432

Abstract

(1) Background: Restoring arm and hand function is a priority for individuals with cervical spinal cord injury (cSCI) for independence and quality of life. Transcutaneous spinal cord stimulation (tSCS) promotes the upper extremity (UE) motor function when applied at the cervical region. The aim of the study was to determine the effects of cervical tSCS, combined with an exoskeleton, on motor strength and functionality of UE in subjects with cSCI. (2) Methods: twenty-two subjects participated in the randomized mix of parallel-group and crossover clinical trial, consisting of an intervention group (n = 15; tSCS exoskeleton) and a control group (n = 14; exoskeleton). The assessment was carried out at baseline, after the last session, and two weeks after the last session. We assessed graded redefined assessment of strength, sensibility, and prehension (GRASSP), box and block test (BBT), spinal cord independence measure III (SCIM-III), maximal voluntary contraction (MVC), ASIA impairment scale (AIS), and WhoQol-Bref; (3) Results: GRASSP, BBT, SCIM III, cylindrical grip force and AIS motor score showed significant improvement in both groups (p ≤ 0.05), however, it was significantly higher in the intervention group than the control group for GRASSP strength, and GRASSP prehension ability (p ≤ 0.05); (4) Conclusion: our findings show potential advantages of the combination of cervical tSCS with an exoskeleton to optimize the outcome for UE. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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13 pages, 1594 KiB

Open AccessArticle

Contralateral Selectivity of Upper-Limb Motor Pools via Targeted Stimulation of the Cervical Spinal Cord

by Neil Fleming, Clare Taylor, Mark Etzelmueller, Conor Gill, Clodagh O'Keeffe, Nicholas Mahony and Richard B. Reilly

Biomedicines 2023, 11(2), 332; https://doi.org/10.3390/biomedicines11020332 - 24 Jan 2023

Viewed by 1694

Abstract

Transcutaneous spinal cord stimulation (tSCS) at the cervical level may facilitate improved upper-limb function in those with incomplete tetraplegia. While clinical trials are ongoing, there is still much debate regarding the transmission pathway as well as appropriate stimulation parameters. This study aimed to explore the extent to which cervical tSCS can induce mono-synaptic reflexes in discrete upper-limb motor pools and examine the effects of altering stimulus location and intensity. Methods: Fourteen participants with intact nervous systems completed two laboratory visits, during which posterior root-muscle reflexes (PRMRs) were evoked via a 3 × 3 cathode matrix applied over the cervical spine. An incremental recruitment curve at the C7 vertebral level was initially performed to attain resting motor threshold (RMT) in each muscle. Paired pulses (1 ms square monophasic with inter-pulse interval of 50 ms) were subsequently delivered at a frequency of 0.25 Hz at two intensities (RMT and RMT + 20%) across all nine cathode positions. Evoked responses to the 1st (PRMR₁) and 2nd (PRMR₂) stimuli were recorded in four upper-limb muscles. Results: A significant effect of the spinal level was observed in all muscles for PRMR₁, with greater responses being recorded caudally. Contralateral stimulation significantly increased PRMR₁ in Biceps Brachii (p < 0.05, F = 4.9, η2 = 0.29), Flexor Carpi Radialis (p < 0.05, F = 4.9, η2 = 0.28) and Abductor Pollicis Brevis (p < 0.01, F = 8.9, η2 = 0.89). Post-activation depression (PAD) was also significantly increased with contralateral stimulation in Biceps Brachii (p = 0.001, F = 9.3, η2 = 0.44), Triceps Brachii (p < 0.05, F = 5.4, η2 = 0.31) and Flexor Carpi Radialis (p < 0.001, F = 17.4, η2 = 0.59). Conclusions: A level of unilateral motor pool selectivity may be attained by altering stimulus intensity and location during cervical tSCS. Optimising these parameters may improve the efficacy of this neuromodulation method in clinical cohorts. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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14 pages, 2905 KiB

Open AccessArticle

Transcranial Magnetic Stimulation Following a Paired Associative Stimulation Protocol Based on a Video Game Neuromodulates Cortical Excitability and Motor Behavior

by Arantzazu San Agustín, Guillermo Asín-Prieto, Juan C. Moreno, Antonio Oliviero and José L. Pons

Biomedicines 2022, 10(10), 2632; https://doi.org/10.3390/biomedicines10102632 - 19 Oct 2022

Cited by 1 | Viewed by 1513

Abstract

Transcranial Magnetic Stimulation (TMS) can be used to modulate cortico-spinal excitability following a paired associative stimulation (PAS) protocol. Movement-related cortical stimulation (MRCS) is a PAS protocol based on the synchronization of a single-pulse TMS with a movement task. However, plasticity and motor performance potentiation due to MRCS has been related exclusively to single-movement tasks. In order to unveil the effects of an MRCS protocol in complex movements, we applied PAS synchronized with a movement-related dynamic task (MRDT) with a customized video game. In 22 healthy subjects, we measured the reaction time (RT), trajectory error (TE), and the number of collected and avoided items when playing the custom video game to evaluate the task motor performance. Moreover, we assessed the recruitment curve of Motor Evoked Potentials (MEPs) with five different intensities to evaluate the motor corticospinal excitability. MEPs were recorded in Abductor Pollicis Brevis (APB) and Abductor Digiti Minimi (ADM), before, right after, and 30 min after the PAS intervention, in an active versus sham experimental design. The MRCS PAS intervention resulted in RT reduction, and motor corticospinal excitability was modulated, reflected as significant MEP amplitude change at 110% RMT intensity in ADM and at 130% RMT intensity in APB. RTs and ADM MEP amplitudes correlated positively in specific time and intensity assessments. We conclude that the proposed PAS protocol facilitated RT performance in a complex task. This phenomenon might be useful to develop neurorehabilitation strategies with complex movements, similar to activities of daily living. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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Review

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37 pages, 1638 KiB

Open AccessReview

Alternative Pharmacological Strategies for the Treatment of Alzheimer’s Disease: Focus on Neuromodulator Function

by Grace Cunliffe, Yi Tang Lim, Woori Chae and Sangyong Jung

Biomedicines 2022, 10(12), 3064; https://doi.org/10.3390/biomedicines10123064 - 28 Nov 2022

Cited by 1 | Viewed by 3794

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder, comprising 70% of dementia diagnoses worldwide and affecting 1 in 9 people over the age of 65. However, the majority of its treatments, which predominantly target the cholinergic system, remain insufficient at reversing pathology and act simply to slow the inevitable progression of the disease. The most recent neurotransmitter-targeting drug for AD was approved in 2003, strongly suggesting that targeting neurotransmitter systems alone is unlikely to be sufficient, and that research into alternate treatment avenues is urgently required. Neuromodulators are substances released by neurons which influence neurotransmitter release and signal transmission across synapses. Neuromodulators including neuropeptides, hormones, neurotrophins, ATP and metal ions display altered function in AD, which underlies aberrant neuronal activity and pathology. However, research into how the manipulation of neuromodulators may be useful in the treatment of AD is relatively understudied. Combining neuromodulator targeting with more novel methods of drug delivery, such as the use of multi-targeted directed ligands, combinatorial drugs and encapsulated nanoparticle delivery systems, may help to overcome limitations of conventional treatments. These include difficulty crossing the blood-brain-barrier and the exertion of effects on a single target only. This review aims to highlight the ways in which neuromodulator functions are altered in AD and investigate how future therapies targeting such substances, which act upstream to classical neurotransmitter systems, may be of potential therapeutic benefit in the sustained search for more effective treatments. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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