Static Magnetic Field Stimulation Research Articles

Static magnetic field-induced IL-6 secretion in periodontal ligament stem cells accelerates orthodontic tooth movement

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.

4D-printed dual-responsive bioscaffolds for treating critical-sized irregular bone defects

Currently, treating irregular bone defects with a critical size is still challenging as material implantation in the complex defects with irregular shapes, effective osteogenesis and sufficient vascularization cannot be easily achieved simultaneously via a simple strategy. Herein, a dual-responsive bone tissue engineering scaffold is developed using a 4D printing strategy by intergrating a single type of multifunctional magnetic nanoparticles, Fe3O4@SiO2, with printing inks made of bioceramics and biopolymers. Minimally invasive implantation, fluent navigation of scaffolds as well as the precise boundary matching between scaffolds and the irregular defects are achieved through near-infrared (NIR) irradiation-based temperature responsive shape recovery and static magnetic field (SMF) stimulation. Moreover, improved bone regeneration in critical-sized bone defects is successfully achieved through the activation of PI3K/AKT pathway which significantly promotes osteogenic differentiation and vascularization. Besides, NIR-based photothermal stimulation upregulates the expression of heat shock protein (HSP90) and further promotes the osteogenesis and vascularization. The in vivo study also confirms that our scaffold can precisely fit the bone defect, and induce satisfactory osteogenesis and angiogenesis. This work provides a facile strategy to simultaneously-realize easy scaffold implantation in irregular bone defects and improves osteogenesis and angiogenesis by integrating a single type of multifunctional nanoparticles with scaffold matrices.

Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study

Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation technique that is portable and easy to use. Long-term, home-based treatments with tSMS of the supplementary motor area (SMA) are promising for movement disorders and other brain diseases. The aim of the present work was to investigate the potential of SMA-tSMS for reducing corticospinal excitability. We completed an open pilot study in which twenty right-handed healthy subjects (8 females; age: 31.3 ± 5.4 years) completed two 30-min sessions (at least one week apart) of SMA-tSMS. We assessed corticospinal excitability by applying transcranial magnetic stimulation (TMS) over the primary motor cortex, recording 30 motor evoked potentials (MEPs) from either the left or right first dorsal interosseous (FDI, ‘hotspot’ muscle) and extensor carpi radialis (ECR, ‘offspot’ muscle) in each session before and after (up to 30 min) tSMS. We observed moderate-to-extreme level of Bayesian evidence for a reduction of MEP amplitude after 30 min of tSMS over SMA compared to baseline. Thus, tSMS applied over SMA may reduce corticospinal excitability. These findings, if confirmed with double-blind, placebo-controlled experiments, support the potential of targeting the SMA for neuromodulating a large motor network in future therapeutic applications of tSMS.

Tackling social anxiety with targeted brain stimulation: investigating the effects of transcranial static magnetic field stimulation on self-focused attention.

Previous studies suggested that self-focused attention (SFA), implicated in social anxiety disorder (SAD), correlates with heightened activity in the right frontopolar area (rFPA), which is the right prefrontal cortex just behind the forehead. Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation method capable of temporarily suppressing brain function beneath the magnet. We explored whether tSMS on individuals with tendencies toward SAD elicited (1) suppressing rFPA activation during the resting-state and (2) reducing SFA during a subsequent speech task. Twenty-three university students with social anxiety performed two speech tasks. Between tasks, the tSMS group received neodymium magnet stimulation while the sham group received fake magnet stimulation on the rFPA for 20 min. Resting-state rFPA activities was measured using functional near-infrared spectroscopy (fNIRS), while SFA (body sensations and observer perspective), field perspective, and detached mindfulness (DM) perspective were assessed via questionnaires during both speech tasks. The observer perspective means SFA to self-imagery from others' viewpoint, while the field and DM perspectives mean appropriately focusing on the external environment. The results indicated that tSMS intervention decreased rFPA activity from pre- to post-intervention rest. Then, tSMS reduced SFA to bodily sensations and increased DM perspective from pre- to post-intervention speech, especially in those with high levels of social anxiety. Furthermore, tSMS enhanced the field perspective regardless of social anxiety tendency. The results suggest that tSMS may suppress overactivity in rFPA, reduce SFA to body sensation, and increase adaptive attention in highly socially anxious individuals. Our study suggests the possibility of the clinical application of tSMS for treating SAD.

Static Magnetic Field Stimulation Enhances Shunting Inhibition via a SLC26 Family Cl- Channel, Inducing Intrinsic Plasticity.

Magnetic fields are being used for detailed anatomical and functional examination of the human brain. In addition, evidence for their efficacy in treatment of brain dysfunctions is accumulating. Transcranial static magnetic field stimulation (tSMS) is a recently developed technique for noninvasively modifying brain functions. In tSMS, a strong and small magnet when placed over the skull can temporarily suppress brain functions. Its modulatory effects persist beyond the time of stimulation. However, the neurophysiological mechanisms underlying tSMS-induced plasticity remain unclear. Here, using acute motor cortical slice preparation obtained from male C57BL/6N mice, we show that tSMS alters the intrinsic electrical properties of neurons by altering the activity of chloride (Cl-) channels in neurons. Exposure of mouse pyramidal neurons to a static magnetic field (SMF) at a strength similar to human tSMS temporarily decreased their excitability and induced transient neuronal swelling. The effects of SMF were blocked by DIDS and GlyH-101, but not by NPPB, consistent with the pharmacological profile of SLC26A11, a transporter protein with Cl- channel activity. Whole-cell voltage-clamp recordings of the GlyH-101-sensitive Cl- current component showed significant enhancement of the component at both subthreshold and depolarized membrane potentials after SMF application, resulting in shunting inhibition and reduced repetitive action potential (AP) firing at the respective potentials. Thus, this study provides the first neurophysiological evidence for the inhibitory effect of tSMS on neuronal activity and advances our mechanistic understanding of noninvasive human neuromodulation.

Transcranial static magnetic field stimulation over hMT+ inhibits visual motion discriminability

Visuomotor performance acting on a moving target is fundamentally based on visual motion discriminability, and its neural basis is presumed to be human MT (hMT+), a motion vision center of the dorsal visual pathway. In this study, we investigated whether and how the accuracy and speed of motion discrimination are affected by applying transcranial static magnetic field stimulation (tSMS) to hMT+, which reduces cortical excitability. Sixteen participants performed a motion direction discrimination (MDD) task using a random dot kinematogram before (Pre-test) and during (During-test) application of the tSMS over left hMT+. The correct rate of the MDD task was significantly lower in the During-test compared to the Pre-test, an effect not seen with the sham condition. The inhibition effects were observed only for the right visual field corresponding to hMT+ in the stimulated hemisphere. On the other hand, no modulatory effect of tSMS was observed in the reaction time. We, therefore, demonstrated the inhibitory effect of tSMS on the left hMT+ impairs the accuracy but not the speed of motion information processing in the contralateral visual field.

Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis.

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the β-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.

Noninvasive modulation of human corticostriatal activity

Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.

The Supplementary Motor Area and Automatic Cognitive Control: Lack of Evidence from Two Neuromodulation Techniques.

The SMA is fundamental in planning voluntary movements and execution of some cognitive control operations. Specifically, the SMA has been known to play a dominant role in controlling goal-directed actions as well as those that are highly predicted (i.e., automatic). Yet, the essential contribution of SMA in goal-directed or automatic control of behavior is scarce. Our objective was to test the possible direct role of SMA in automatic and voluntary response inhibition. We separately applied two noninvasive brain stimulation (NIBS) inhibitory techniques over SMA: either continuous theta-burst stimulation using repetitive transcranial magnetic stimulation or transcranial static magnetic field stimulation. Each NIBS technique was performed in a randomized, crossover, sham-controlled design. Before applying NIBS, participants practiced a go/no-go learning task where associations between stimulus and stopping behaviors were created (initiation and inhibition). After applying each NIBS, participants performed a go/no-go task with reversed associations (automatic control) and the stop signal task (voluntary control). Learning associations between stimuli and response initiation/inhibition was achieved by participants and therefore automatized during training. However, no significant differences between real and sham NIBS were found in either automatic (go/no-go learning task) or voluntary inhibition (stop signal task), with Bayesian statistics providing moderate evidence of absence. In conclusion, our results are compatible with a nondirect involvement of SMA in automatic control of behavior. Further studies are needed to prove a noncausal link between prior neuroimaging findings relative to SMA controlling functions and the observed behavior.

Effects of transcranial static magnetic field stimulation over the left dorsolateral prefrontal cortex on random number generation

ObjectiveFocal application of transcranial static magnetic field stimulation (tSMS) is a neuromodulation technique, with predominantly inhibitory effects when applied to the motor, somatosensory or visual cortex. Whether this approach can also transiently interact with dorsolateral prefrontal cortex (DLPFC) function remains unclear. The suppression of habitual or competitive responses is one of the core executive functions linked to DLPFC function. This study aimed to assess the impact of tSMS on the prefrontal contributions to inhibitory control and response selection by means of a RNG task. MethodsWe applied 20 min of tSMS over the left DLPFC of healthy subjects, using a real/sham cross-over design, during performance of a RNG task. We used an index of randomness calculated with the measures of entropy and correlation to assess the impact of stimulation on DLPFC function. ResultsThe randomness index of the sequences generated during the tSMS intervention was significantly higher compared to those produced in the sham condition. ConclusionsOur results indicate that application of tSMS transiently modulates specific functional brain networks in DLPFC, which indicate a potential use of tSMS for treatment of neuropsychiatric disorders. SignificanceThis study provides evidence for the capacity of tSMS for modulating DLPFC function.

Effect size for the reduction of corticospinal excitability induced by transcranial static magnetic field stimulation

Effect size for the reduction of corticospinal excitability induced by transcranial static magnetic field stimulation

The effects of unilateral and bilateral transcranial static magnetic field stimulation over the premotor cortex on simple and choice reaction times

The effects of unilateral and bilateral transcranial static magnetic field stimulation over the premotor cortex on simple and choice reaction times

280 mT static magnetic field promotes the growth of postpartum condylar cartilage

ABSTRACT Purpose Functional appliances made of permanent magnets have been used in jaw orthopedic treatment. However, whether the static magnetic field (SMF) generated by permanent magnets promotes the developmental sequence of condylar cartilage and thus promotes the growth of the mandible remains to be studied. The aim of this study was to investigate the effects of 280 mT SMF on postnatal condylar chondrogenesis and endochondral ossification and the roles of FLRT3, FGF2 and BMP2 signaling in this chondrodevelopmental sequences. Methods Forty-eight rats were assigned to two groups (control and SMF). The condyles were collected at the specified time points. The histomorphological changes in the condyle were observed by histological staining. The expression of proteins related to the proliferation and differentiation of the condylar cartilage and the changes in subchondral bone microstructure were analyzed by immunohistochemical staining and micro-CT scanning. FLRT3, FGF2, and BMP2 expression was detected by immunofluorescence staining. Results Under SMF stimulation, the cartilage of young rats grew longitudinally and laterally, and the thickness of the cartilage became thinner as it grew. The SMF promoted the proliferation and differentiation of condylar chondrocytes and endochondral ossification and increased subchondral bone mineral density, and BMP2 signaling was involved. Moreover, under SMF loading, the increased expression of FGF2 and FLRT3 were involved in regulating cartilage morphogenesis and growth. In late development, the decreased expression of FGF2/FLRT3 and the increased expression of BMP2 promoted endochondral ossification. The SMF accelerated this opposite expression trend. Conclusion FGF2/FLRT3 and BMP2 signals are involved in the regulatory effect of SMF exposure on chondrogenesis and endochondral ossification, which provides a theoretical basis for the clinical use of magnetic appliances to promote condylar growth.

Triple tSMS system (“SHIN jiba”) for non-invasive deep brain stimulation: a validation study in healthy subjects

BackgroundTranscranial static magnetic field stimulation (tSMS) using a small and strong neodymium (NdFeB) magnet can temporarily suppress brain functions below the magnet. It is a promising non-invasive brain stimulation modality because of its competitive advantages such as safety, simplicity, and low-cost. However, current tSMS is insufficient to effectively stimulate deep brain areas due to attenuation of the magnetic field with the distance from the magnet. The aim of this study was to develop a brand-new tSMS system for non-invasive deep brain stimulation.MethodsWe designed and fabricated a triple tSMS system with three cylindrical NdFeB magnets placed close to each other. We compared the strength of magnetic field produced by the triple tSMS system with that by the current tSMS. Furthermore, to confirm its function, we stimulated the primary motor area in 17 healthy subjects with the triple tSMS for 20 min and assessed the cortical excitability using the motor evoked potential (MEP) obtained by transcranial magnetic stimulation.ResultsOur triple tSMS system produced the magnetic field sufficient for neuromodulation up to 80 mm depth from the magnet surface, which was 30 mm deeper than the current tSMS system. In the stimulation experiment, the triple tSMS significantly reduced the MEP amplitude, demonstrating a successful inhibition of the M1 excitability in healthy subjects.ConclusionOur triple tSMS system has an ability to produce an effective magnetic field in deep areas and to modulate the brain functions. It can be used for non-invasive deep brain stimulation.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Blood-brain barrier crossing using magnetic stimulated nanoparticles

Due to the low permeability and high selectivity of the blood-brain barrier (BBB), existing brain therapeutic technologies are limited by the inefficient BBB crossing of conventional drugs. Magnetic nanoparticles (MNPs) have shown great potential as nano-carriers for efficient BBB crossing under the external static magnetic field (SMF). To quantify the impact of SMF on MNPs' in vivo dynamics towards BBB crossing, we developed a physiologically based pharmacokinetic (PBPK) model for intraperitoneal (IP) injected superparamagnetic iron oxide nanoparticles coated by gold and conjugated with poly (ethylene glycol) (PEG) (SPIO-Au-PEG NPs) in mice. Unlike most reported PBPK models that ignore brain permeability, we first obtained the brain permeabilities with and without SMF by determining the concentration of SPIO-Au-PEG NPs in the cerebral blood and brain tissue. This concentration in the brain was simulated by the advection-diffusion equations and was numerically solved in COMSOL Multiphysics. The results from the PBPK model after incorporating the brain permeability showed a good agreement (regression coefficient R2 = 0.848) with the in vivo results, verifying the capability of using the proposed PBPK model to predict the in vivo biodistribution of SPIO-Au-PEG NPs under the exposure to SMF. Furthermore, the in vivo results revealed that the distribution coefficient from blood to brain under the exposure to SMF (4.01%) is slightly better than the control group (3.68%). In addition, the modification of SPIO-Au-PEG NPs with insulin (SPIO-Au-PEG-insulin) showed an improvement of the brain bioavailability by 24.47% in comparison to the non-insulin group. With the SMF stimulation, the brain bioavailability of SPIO-Au-PEG-insulin was further improved by 3.91% compared to the group without SMF. The PBPK model and in vivo validation in this paper lay a solid foundation for future study on non-invasive targeted drug delivery to the brain.

Electrically-magnetically bifunctional PMMA composite with improved physicochemical properties and promoting BMSC growth under electrical and magnetic stimulation

Electric and magnetic stimulation play a unique role in promoting bone regeneration. Here, a novel type of electrically-magnetically bifunctional polymethyl methacrylate (PMMA) composite that integrates stimulus-responsive, cytocompatiablity and osteostimulation properties were developed by incorporating activated carbon nanotubes (ACNTs) into PMMA matrix. The maximum hyperthermal temperature of polymerization (Tmax), physicochemical properties and cytocompatibility of the PMMA composites were evaluated. The results showed that the ACNTs-doped PMMA composite exhibited a dramatic reduced Tmax, effectively alleviating the adverse effect of the strongly exothermic polymerization of PMMA, an enhanced compressive strength, a reduced elastic modulus being close to human spongy bone, certain conductivity and magnetic character. The cell culture indicated that the PMMA composite with 6 wt% ACNTs had better cell viability under the 10 mA of electrical stimulation (ES), 60 mT of static magnetic field stimulation (SMF), and these combination. This electrically-magnetically bifunctional PMMA composite with excellent stimulus-responsive, mechanical properties and cytocompatiablity has great practical potential for bone tissue engineering.

Static Magnetic Fields Enhance the Chondrogenesis of Mandibular Bone Marrow Mesenchymal Stem Cells in Coculture Systems.

Objectives Combining the advantages of static magnetic fields (SMF) and coculture systems, we investigated the effect of moderate-intensity SMF on the chondrogenesis and proliferation of mandibular bone marrow mesenchymal stem cells (MBMSCs) in the MBMSC/mandibular condylar chondrocyte (MCC) coculture system. The main aim of the present study was to provide an experimental basis for obtaining better cartilage tissue engineering seed cells for the effective repair of condylar cartilage defects in clinical practice. Methods MBMSCs and MCCs were isolated from SD (Sprague Dawley) rats. Flow cytometry, three-lineage differentiation, colony-forming assays, immunocytochemistry, and toluidine blue staining were used for the identification of MBMSCs and MCCs. MBMSCs and MCCs were seeded into the lower and upper Transwell chambers, respectively, at a ratio of 1 : 2, and exposed to a 280 mT SMF. MBMSCs were harvested after 3, 7, or 14 days for analysis. CCK-8 was used to detect cell proliferation, Alcian blue staining was utilized to evaluate glycosaminoglycan (GAG), and western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) detected protein and gene expression levels of SOX9, Col2A1 (Collagen Type II Alpha 1), and Aggrecan (ACAN). Results The proliferation of MBMSCs was significantly enhanced in the experimental group with MBMSCs cocultured with MCCs under SMF stimulation relative to controls (P < 0.05). GAG content was increased, and SOX9, Col2A1, and ACAN were also increased at the mRNA and protein levels (P < 0.05). Conclusions Moderate-intensity SMF improved the chondrogenesis and proliferation of MBMSCs in the coculture system, and it might be a promising approach to repair condylar cartilage defects in the clinical setting.

Distinct hemispherical responsiveness to transcranial static magnetic field stimulation?

Distinct hemispherical responsiveness to transcranial static magnetic field stimulation?

Static Magnetic Stimulation Induces Changes in the Oxidative Status and Cell Viability Parameters in a Primary Culture Model of Astrocytes.

Astrocytes play an important role in the central nervous system function and may contribute to brain plasticity response during static magnetic fields (SMF) brain therapy. However, most studies evaluate SMF stimulation in brain plasticity while few studies evaluate the consequences of SMF at the cellular level. Thus, we here evaluate the effects of SMF at 305 mT (medium-intensity) in a primary culture of healthy/normal cortical astrocytes obtained from neonatal (1 to 2-day-old) Wistar rats. After reaching confluence, cells were daily subjected to SMF stimulation for 5 min, 15 min, 30 min, and 40 min during 7 consecutive days. Oxidative stress parameters, cell cycle, cell viability, and mitochondrial function were analyzed. The antioxidant capacity was reduced in groups stimulated for 5 and 40 min. Although no difference was observed in the enzymatic activity of superoxide dismutase and catalase or the total thiol content, lipid peroxidation was increased in all stimulated groups. The cell cycle was changed after 40 min of SMF stimulation while 15, 30, and 40 min led cells to death by necrosis. Mitochondrial function was reduced after SMF stimulation, although imaging analysis did not reveal substantial changes in the mitochondrial network. Results mainly revealed that SMF compromised healthy astrocytes' oxidative status and viability. This finding reveals how important is to understand the SMF stimulation at the cellular level since this therapeutic approach has been largely used against neurological and psychiatric diseases.