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

Abstract

ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) prototype, Magnetic Pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving the μcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the μcoil to minimize power will be estimated.ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the μcoil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the μcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V/m). The induced electric field profiles generated at different values of current applied to the μcoil can elicit a neuron response, which was validated by numerical modeling. The modeling settings for the μcoil were replicated in experiments on rat hippocampal neurons.Main resultsThe preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due to μMS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs from μMS while after prolonged TTX washout, a partial recovery of the EPSP from μMS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving the μcoil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation.SignificanceThis work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strengthfrequency curve for μMS and its unique features related to orientation dependence of the μcoils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related to μMS experiments were studied including ways to overcome them.

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“…BK Precision 889B; see Table S1 in Supplementary Information S1) at two frequencies (120 Hz and 1 kHz). The frequency of operation for the μcoil in this work was around 60-130 Hz compared to other reported works with MagPen where the frequency of operation for the μcoil was at 1-5 kHz [20,21]. The frequency of operation around 60-130 Hz contributed to the benefit for micromagnetic operation on MFB fibers in the rodent brain as compared to the LCR meter measurements at 1 kHz.…”

“…In this in vivo study, we used the Magnetic Pen (MagPen) as the μcoil implant (μcoil dimension = 1 mm × 0.6 mm × 0.5 mm) [20,21]. The commercially available solenoidal μcoil of model no.…”

“…To ensure complete biocompatibility in addition to an antileakage current and waterproof sealing for the probe, the tip of the MagPen was encapsulated in a 10 μm thick coating of Parylene-C (SCS-Labcoater Parylene-C deposition system). Successful coating for the MagPen prototype was determined once the impedance between the MagPen and a salt bath was > 5MΩ [20,21].…”

“…Since then, attempts have been made by several groups to use similar μcoil prototypes in several experimental settings, both in vitro and in vivo, to showcase the efficacy of micromagnetic neurostimulation [20][21][22][23][24][25]. Furthermore, different designs of μcoils, solenoidal [20], planar [22,26],…”

“…Since the induced electric field that activates the neural tissues are not in direct galvanic contact with the tissues, these μcoils exhibit less implant surface corrosion due to biofouling [21]. The induced electric field is highly directional in nature causing spatially-selective activation of the neural tissue from these μcoils [20]. Furthermore, in a recent numerical study, these μcoils have shown significantly less radio frequency (RF) heating (antenna effect) from a 1.5 Tesla magnetic Resonance Imaging (1.5T-MRI) environment compared to traditional deep brain stimulation (DBS) leads [28].…”