In vitro Magnetic Stimulation: A Simple Stimulation Device to Deliver Defined Low Intensity Electromagnetic Fields

Abstract

Non-invasive brain stimulation (NIBS) by electromagnetic fields appears to benefit human neurological and psychiatric conditions, although the optimal stimulation parameters and underlying mechanisms remain unclear. Although, in vitro studies have begun to elucidate cellular mechanisms, stimulation is delivered by a range of coils (from commercially available human stimulation coils to laboratory-built circuits) so that the electromagnetic fields induced within the tissue to produce the reported effects are ill-defined. Here, we develop a simple in vitro stimulation device with plug-and-play features that allow delivery of a range of stimulation parameters. We chose to test low intensity repetitive magnetic stimulation (LI-rMS) delivered at three frequencies to hindbrain explant cultures containing the olivocerebellar pathway. We used computational modeling to define the parameters of a stimulation circuit and coil that deliver a unidirectional homogeneous magnetic field of known intensity and direction, and therefore a predictable electric field, to the target. We built the coil to be compatible with culture requirements: stimulation within an incubator; a flat surface allowing consistent position and magnetic field direction; location outside the culture plate to maintain sterility and no heating or vibration. Measurements at the explant confirmed the induced magnetic field was homogenous and matched the simulation results. To validate our system we investigated biological effects following LI-rMS at 1 Hz, 10 Hz and biomimetic high frequency, which we have previously shown induces neural circuit reorganization. We found that gene expression was modified by LI-rMS in a frequency-related manner. Four hours after a single 10-min stimulation session, the number of c-fos positive cells increased, indicating that our stimulation activated the tissue. Also, after 14 days of LI-rMS, the expression of genes normally present in the tissue was differentially modified according to the stimulation delivered. Thus we describe a simple magnetic stimulation device that delivers defined stimulation parameters to different neural systems in vitro. Such devices are essential to further understanding of the fundamental effects of magnetic stimulation on biological tissue and optimize therapeutic application of human NIBS.

Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms

“…We used a commercial rat coil (MagVenture) that not only delivers a broader field than our small animal coils (Fig. 1 ) but also differs in shape from the conventional human coils (such as figure-of-eight coils or large circular coils) used in previous studies 49 . We also did not observe an increase in brain BDNF levels following LI-rTMS, consistent with previous work showing that very low-intensity stimulation may be brain region specific: LI-rTMS upregulates BDNF in the visual cortex, midbrain, and cerebellum but not in the retina 50 – 52 , and the lack of upregulation of BDNF in the hippocampus is consistent with our previous study showing no change in hippocampal dendritic spines following LI-rTMS 53 .…”

Electric Field Modeling for Transcranial Magnetic Stimulation and Electroconvulsive Therapy

“…This field strength is an order of magnitude lower compared to those induced by transcranial current stimulation (tCS) [15] and low-field magnetic stimulation (LFMS) [16,17]. The sTMS field strength is comparable to that of low-intensity repetitive magnetic stimulation (LI-rMS) in an in vitro model, which has been shown to alter cellular activation and gene expression in an organotypic hindbrain explant and in a stimulation frequency-specific manner [18]. Thus, the low field strength of sTMS could be biologically active.…”

Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b

“…In clinical experiments, high frequency rTMS is generally used for neuropathic pain (38,39), cognition and motor recovery in patients with Parkinson's disease and Alzheimer's disease (6), and leads to superior improvements over low frequency rTMS. The stimulation intensity is another important parameter; it decreases within the coil distance of 3.5 cm, and 60% of its intensity is maintained at a distance of 1 cm (40). Although transcranial magnetic stimulations should not be uniform on the suspended cell cultures in a dish due to the difference in distance, the electromagnetic field has been shown to be effective in inducing NPc proliferation (29).…”