High-frequency Magnetic Stimulation Research Articles

Inhibition of Acute mGluR5-Dependent Depression in Hippocampal CA1 by High-Frequency Magnetic Stimulation.

High-frequency magnetic stimulation (HFMS) applied directly to the hippocampal slice preparation in vitro induces activity-dependent synaptic plasticity and metaplasticity. In addition, changes in synaptic transmission following HFMS involve the activation of N-methyl-D-aspartate and metabotropic glutamate receptors (mGluR). Here, we asked whether a short period of HFMS (5 × 10 delta-burst trains, duration of ~1 min) could alter mGluR5-mediated depression at Schaffer collateral-CA1 synapses in the acute brain slice preparation at 30 min after HFMS. To this end, we obtained field excitatory postsynaptic potential (fEPSP) slopes from Schaffer collateral-CA1 synapses after HFMS or control. First, we demonstrated that activity-dependent plasticity following HFMS depends on the slice orientation towards the magnetic coil indicating specific ion fluxes induced by magnetic fields. Second, we found that the mGluR5-specific agonist (RS)-2-chloro-5-hydroxyphenylglycine reduced the field excitatory postsynaptic potential (fEPSP) slopes in control slices but rather enhanced them in HFMS-treated slices. In contrast, the compound (S)-3,5-dihydroxyphenylglycine acting at both mGluR1 and mGluR5 reduced fEPSP slopes in both control and HFMS-treated slices. Importantly, the mGluR-dependent effects were independent from the slice-to-coil orientation indicating that asynchronous glutamate release could play a role. We conclude that a short period of HFMS inhibits subsequently evoked mGluR5-dependent depression at Schaffer collateral-CA1 synapses. This could be relevant for repetitive transcranial magnetic stimulation in psychiatric disorders such as major depression.

Cellular mechanisms underlying carry-over effects after magnetic stimulation

Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation state right after stimulation. Many theoretical and experimental works have focused on the cellular and molecular basis of the acute neural response to magnetic field. However, effects of magnetic stimulation can still last after the termination of the magnetic stimulation (named “carry-over effects”), which could generate profound effects to the outcome of the stimulation. However, the cellular and molecular mechanisms of carry-over effects are largely unknown, which renders the neural modulation practice using magnetic stimulation unpredictable. Here, we investigated carry-over effects at the cellular level, using the combination of micro-magnetic stimulation (µMS), electrophysiology, and computation modeling. We found that high frequency magnetic stimulation could lead to immediate neural inhibition in ganglion neurons from Aplysia californica, as well as persistent, carry-over inhibition after withdrawing the magnetic stimulus. Carry-over effects were found in the neurons that fired action potentials under a variety of conditions. The carry-over effects were also observed in the neurons when the magnetic field was applied across the ganglion sheath. The state of the neuron, specifically synaptic input and membrane potential fluctuation, plays a significant role in generating the carry-over effects after magnetic stimulation. To elucidate the cellular mechanisms of such carry-over effects under magnetic stimulation, we simulated a single neuron under magnetic stimulation with multi-compartment modeling. The model successfully replicated the carry-over effects in the neuron, and revealed that the carry-over effect was due to the dysfunction of the ion channel dynamics that were responsible for the initiation and sustaining of membrane excitability. A virtual voltage-clamp experiment revealed a compromised Na conductance and enhanced K conductance post magnetic stimulation, rendering the neurons incapable of generating action potentials and, therefore, leading to the carry over effects. Finally, both simulation and experimental results demonstrated that the carry-over effects could be controlled by disturbing the membrane potential during the post-stimulus inhibition period. Delineating the cellular and ion channel mechanisms underlying carry-over effects could provide insights to the clinical outcomes in brain stimulation using TMS and other modalities. This research incentivizes the development of novel neural engineering or pharmacological approaches to better control the carry-over effects for optimized clinical outcomes.

Measurement of maximal muscle contraction force induced by high-frequency magnetic stimulation: a preliminary study on the identification of the optimal stimulation site.

To identify the optimal stimulation site and technique for inducing strong muscle contraction using a high-frequency magnetic stimulator. High-frequency magnetic stimulation was administered to the right vastus lateralis (VL) of eight healthy adults at maximal intensity within the range of tolerable pain. The stimulation sites were as follows: section A, the area between the lateral edge of the base of the patella (LEBP) and the distal one-third of the thigh (point D); section B, the area between point D and the proximal one-third of the thigh (point P). Isometric maximal muscle contraction forces induced by magnetic stimulation (Stim-MCF) were compared between the two sections. The Stim-MCF was significantly higher in section B than in section A. Additionally, the sites susceptible to stimulation were confined to a narrow area near point D in section A and the central part between points D and P in section B. The degree of pain was very low in both sections. The optimal site for magnetic stimulation of the VL was limited to the central part of the thigh. In addition to the superficial proximal sub-branch, the deep proximal sub-branch and/or deeply clustered motor nerve endings may have been stimulated. Our results suggested that moving the probe was a useful way to identify the site that elicited the strongest muscle contraction force.

Efficacy and safety of high-frequency repetitive transcranial magnetic stimulation for post-stroke depression: A systematic review

Objective To evaluate the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke depression (PSD). Methods The Cochrane Library, Medline, EMbase and CBMdisc were electronically searched for reports of randomized and controlled trials (RCTs) of high-frequency rTMS in the treatment of PSD before October 2017. Two researchers screened the reports independently, extracted data and assessed the risk of bias in the included studies. The meta-analysis was performed using version 5.1 of the RevMan software. Results A total of 26 RCTs were included, covering 1810 patients with PSD. The meta-analysis showed that the remission rate [relative risk (RR)=2.15, 95%CI (1.64, 2.83)] and the effectiveness [RR=1.66, 95%CI (1.28, 2.15)] of high-frequency rTMS group were significantly higher than in the control groups. Compared with the control group, the average Hamilton depression rating scale (HAMD) score of the high-frequency rTMS groups was significantly lower than in the control groups. There was no significant difference in withdrawal between the two groups after treatment [RR=0.55, 95%CI (0.18, 1.65)]. The incidence of headaches was significantly higher in the high-frequency rTMS group than among the controls. Conclusion High-frequency rTMS has a good curative effect and better acceptability for PSD patients, but attention should be given to headaches and other adverse reactions. Due to the limited number of studies and their quality, these conclusions still need to be verified in better-quality studies. Key words: High-frequency magnetic stimulation; Transcranial magnetic stimulation; Magnetic stimulation; Depression; Stroke

The impact of high-frequency magnetic stimulation of peripheral nerves: muscle hardness, venous blood flow, and motor function of upper extremity in healthy subjects.

The purpose of this study was to investigate the impact of high-frequency peripheral nerve magnetic stimulation on the upper limb function. Twenty-five healthy adults (16 men and 9 women) participated in this study. The radial nerve of the non-dominant hand was stimulated by high-frequency magnetic stimulation device. A total of 600 impulses were applied at a frequency of 20 Hz and intensity of 1.2 resting motor threshold (rMT). At three time points (before, immediately after, and 15 min after stimulation), muscle hardness of the extensor digitorum muscle on the stimulated side was measured using a mechanical tissue hardness meter and a shear wave imaging device, cephalic venous blood flow on the stimulated side was measured using an ultrasound system, and the Box and Block test (BBT) was performed. Mechanical tissue hardness results did not show any significant differences between before, immediately after, and 15 min after stimulation. Measurements via shear wave imaging showed that muscle hardness significantly decreased both immediately and 15 min after stimulation compared to before stimulation (P < 0.05). Peripheral venous blood flow and BBT score significantly increased both immediately and 15 min after stimulation compared to before stimulation (P < 0.01). High-frequency peripheral nerve magnetic stimulation can achieve effects similar to electrical stimulation in a less invasive manner, and may therefore become an important element in next-generation rehabilitation.

NMDA receptor-dependent metaplasticity by high-frequency magnetic stimulation.

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity.

High-frequency magnetic stimulation induces long-term potentiation in rat hippocampal slices

Recent reports indicate that the exposure of brain tissues to transcranial magnetic stimulation induces persistent changes in neuronal activity and influences hippocampal synaptic plasticity. However, the modulation of synaptic efficiency by magnetic stimulation in vitro is still unclear. In the present study, we investigated whether high-frequency magnetic stimulation (HFMS) can induce long-term potentiation (LTP) in rat hippocampal slices in vitro. During baseline recording and after HFMS, field excitatory postsynaptic potentials (fEPSPs) were recorded within the CA1 stratum radiatum in response to electrical stimulation of the Schaffer collateral inputs. For LTP induction, HFMS was delivered through a circular coil positioned closely above the slices using two different paradigms (A: 10 trains of 20 pulses at 100 Hz with 1 s intervals, 5 repetitions with 10 s intervals; B: 3 trains of 100 pulses at 100 Hz with 20 s intervals). The intensity of the magnetic stimulus was adjusted to 60–75 A/μs. After application of HFMS, electrically evoked CA1 fEPSPs were enhanced showing significant levels of LTP by both paradigms (A: 142 ± 9% of baseline, n = 6; B: 129 ± 7%, n = 8). Furthermore, HFMS-induced LTP induced by paradigm A was prevented by the presence of the selective N-methyl- d-aspartate receptor (NMDAR) blocker D-AP5 (50 μM) in the bath solution (95 ± 6% of the baseline, n = 6; p < 0.01 compared to control condition without D-AP5). Further, the lack of changes in paired-pulse ratio and the afferent fiber volleys exclude presynaptic involvement in HFMS-induced LTP. In summary, we have demonstrated that HFMS can induce NMDAR-dependent LTP in the CA1 region in vitro.

High frequency magnetic stimulation of the sacral nerves in spinal cord injured patients

High frequency magnetic stimulation of the sacral nerves in spinal cord injured patients

High frequency magnetic stimulation of the sacral nerves in spinal cord injured patients

High frequency magnetic stimulation of the sacral nerves in spinal cord injured patients