Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)

Saha, Renata; Faramarzi, Sadegh; Bloom, Robert P.; Benally, Onri J.; Wu, Kai; Girolamo, Arturo Di; Tonini, Denis; Keirstead, Susan A.; Low, Walter C.; Netoff, Theoden I.; Wang, Jianping

doi:10.1088/1741-2552/ac4baf

Cited by 15 publications

(46 citation statements)

References 56 publications

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“…In this work, we present μMS using the Mag netic Pen (MagPen) [21] on the rat sciatic nerve. We measure a dose-response relationship of magnetic stimuli (varying amplitudes and durations) on twitch in the hind limb evoked via the sciatic nerve.…”

Section: Introductionmentioning

confidence: 99%

Micromagnetic Stimulation (μMS) Dose-Response of the Rat Sciatic Nerve

Saha

Sanger

Bloom

et al. 2022

Preprint

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Objective: The objective of this study was to investigate the effects of micromagnetic stimuli strength and frequency from the Magnetic Pen (MagPen) on the rat right sciatic nerve. The nerve s response would be measured by recording muscle activity and movement of the right hind limb. Approach: The MagPen was custom-built such that it can be held over the sciatic nerve in a stable manner. Rat leg muscle twitches were captured on video and movements were extracted using image processing algorithms. EMG recordings were also used to measure muscle activity. Main results: The MagPen prototype when driven by alternating current, generates time-varying magnetic field which as per Faradays Law of Electromagnetic Induction, induces an electric field for neuromodulation. The orientation dependent spatial contour maps for the induced electric field from the MagPen prototype has been numerically simulated. Furthermore, in this in vivo work on μMS, a dose-response relationship has been reported by experimentally studying how the varying amplitude (Range: 25 mVp-p through 6 Vp-p) and frequency (Range: 100 Hz through 5 kHz) of the MagPen stimuli alters the hind limb movement. The primary highlight of this dose-response relationship is that at a higher frequency of the μMS stimuli, significantly smaller amplitudes can trigger hind limb muscle twitch. This frequency-dependent activation can be justified following directly from the Faradays Law as the magnitude of the induced electric field is directly proportional to frequency. Significance: This work reports that μMS can successfully activate the sciatic nerve in a dose-dependent manner. The MagPen probe, unlike electrodes, does not have a direct electrochemical interface with tissues rendering it much safer than an electrode. Magnetic fields create more precise activation than electrodes because they induce smaller volumes of activation. Finally, unique features of μMS such as orientation dependence, directionality and spatial selectivity have been demonstrated.

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Section: Introductionmentioning

confidence: 99%

Micromagnetic Stimulation (μMS) Dose-Response of the Rat Sciatic Nerve

Saha

Sanger

Bloom

et al. 2022

Preprint

Self Cite

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“…This corresponds to a 50–550 μm distance range between the coil edge and the tissue. Experimentally, researchers maintain the distance between the coil edge and the tissue to below 500 μm to ensure a sufficient field intensity for axonal activation [Bonmassar et al, 2012 ; Saha et al, 2022 )]. Figure 7A demonstrates the coil current, induced electric field, and location of axonal activation (+).…”

Section: Resultsmentioning

confidence: 99%

“…This study models the effect of μMS driven by pulsatile stimuli as previously reported experimentally (Bonmassar et al, 2012 ; Lee et al, 2016 ). Several studies in the field also used sine waves as the stimulus for axon stimulation (Lee et al, 2019 ; Saha et al, 2022 ). The induced electric field is the time derivative of the coil waveform.…”

Section: Discussionmentioning

confidence: 99%

“…Golestanirad et al used a small inductor (coil) to activate axons in the dorsal cochlear nucleus (Golestanirad et al, 2018 ). Using a similar induction coil, Saha et al activated the unmyelinated axons of CA3 neurons in the Schaffer collaterals to trigger synaptic transmission in the hippocampus (Saha et al, 2022 ). Lee et al improved the shape design of the micro-coil to activate the apical dendrites of layer V pyramidal neurons (Lee et al, 2016 ; Lee and Fried, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Finding the Location of Axonal Activation by a Miniature Magnetic Coil

2022

Front. Comput. Neurosci.

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Magnetic stimulation for neural activation is widely used in clinical and lab research. In comparison to electric stimulation using an implanted electrode, stimulation with a large magnetic coil is associated with poor spatial specificity and incapability to stimulate deep brain structures. Recent developments in micromagnetic stimulation (μMS) technology mitigates some of these shortcomings. The sub-millimeter coils can be covered with soft, biocompatible material, and chronically implanted. They can provide highly specific neural stimulation in the deep neural structure. Although the μMS technology is expected to provide a precise location of neural stimulation, the exact site of neural activation is difficult to determine. Furthermore, factors that could cause the shifting of the activation site during μMS have not been fully investigated. To estimate the location of axon activation in μMS, we first derived an analytical expression of the activating function, which predicts the location of membrane depolarization in an unmyelinated axon. Then, we developed a multi-compartment, Hodgkin-Huxley (H-H) type of NEURON model of an unmyelinated axon to test the impact of several important coil parameters on the location of axonal activation. The location of axonal activation was dependent on both the parameters of the stimulus and the biophysics properties of the targeted axon during μMS. The activating function analysis predicted that the location of membrane depolarization and activation could shift due to the reversal of the coil current and the change in the coil-axon distance. The NEURON modeling confirmed these predictions. Interestingly, the NEURON simulation further revealed that the intensity of stimulation played a significant role in the activation location. Moderate or strong coil currents activated the axon at different locations, mediated by two distinct ion channel mechanisms. This study reports several experimental factors that could cause a potential shift in the location of neural activation during μMS, which is essential for further development of this novel technology.

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“…According to COMSOL FEM simulation results where the 60 mA, 5 kHz sine input signal is pulsed at 1 kHz with a 50% duty cycle, the linear approximation of the long-term heating rate is y = 1.1 × 10 −7 t + 37, shown in Figure 5 (d-e). The process of inflammation begins after one microcoil is run for 17.46 hours straight, after reaching 44 • C. Additionally, the experimental data from magnetic stimulation of other groups with microcoils of a similar scale and driving current [19], [31]- [33] further enforce that the heat can be managed to operate safely once implanted.…”

Section: B Heating Characterizationmentioning

confidence: 94%

Development and Characterization of a Micromagnetic Alternative to Cochlear Implant Electrode Arrays

Sarreal

Blake

Bhatti

2022

IEEE Trans. Neural Syst. Rehabil. Eng.

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To stimulate the auditory nerve, cochlear implants directly inject electrical current into surrounding tissue via an implanted electrode array. While many cochlear implant users achieve strong speech perception scores, there remains significant variability. Since cochlear implant electrode arrays are surrounded by a conductive fluid, perilymph, a spread of excitation occurs. The functionality of the cochlea is spatially dependent, and a wider area of excitation negatively affects the hearing of the user. Importantly, magnetic fields are unaffected by the material properties of biological components. To utilize the electromagnetic properties of the human ear, a microcoil array was developed. The microcoils are 4-turn solenoids with a 250-µm turn radius and a 31.75-µm wire radius, coated with Parylene-C. The efficient design was implemented to accelerate testing. The obtained results describe stimulation capabilities. Functionality was validated using a frequency response analyzer to measure how the generated electromagnetic power radiates in space. 99.8% power loss was observed over a 100-µm separation between a pair of identical microcoils. Obtained through finite-element modeling, the microcoils can be driven by a 60 mA, 5 kHz, sinusoidal input for 10 minutes before predicted inflammation. Rattay's activating function was calculated to evaluate the magnetic stimulation effect of external fields on target neurons. Combined with the frequency response analysis, magnitude and spatial effects of the generated potential is established. As a result, each microcoil requires a 400-µmwide area for each independent stimulation channel, which is 84% narrower than a commercial cochlear array channel, thereby suggesting greater spatial selectivity.

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Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)

Cited by 15 publications

References 56 publications

Micromagnetic Stimulation (μMS) Dose-Response of the Rat Sciatic Nerve

Micromagnetic Stimulation (μMS) Dose-Response of the Rat Sciatic Nerve

Finding the Location of Axonal Activation by a Miniature Magnetic Coil

Development and Characterization of a Micromagnetic Alternative to Cochlear Implant Electrode Arrays

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