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.
Highlights
Non-invasive brain stimulation (NIBS), using electric or magnetic fields, is increasingly used in neurological and psychiatric treatment (Pascual-Leone, 2006; Pell et al, 2011)
LFMS forms an additional tool for NIBS therapies (Shafi et al, 2014), the mechanisms underlying the effects of low intensity magnetic stimulation remain ill-defined
This study created a magnetic stimulation device whose design was compatible with long-term stimulation protocols within an incubator, simultaneously delivering defined electromagnetic fields to tissue in multiple culture wells, without either eddy-current cross-interference or disturbing the culture environment
Summary
Non-invasive brain stimulation (NIBS), using electric or magnetic fields, is increasingly used in neurological and psychiatric treatment (Pascual-Leone, 2006; Pell et al, 2011). Newer low- or pulsed-field magnetic stimulation (LFMS, PMF) delivers diffuse low-intensity stimuli (μT-mT range, E ≤ 1 V/m) that are biologically effective: modifying cortical function (Capone et al, 2009; Robertson et al, 2010), brain oscillations (Cook et al, 2004; Modolo et al, 2013) and metabolism (Volkow et al, 2010), as well as neurological dysfunction (Martiny et al, 2010; Rohan et al, 2014) We have combined these two approaches creating a small rodent coil to deliver focal low-intensity magnetic stimulation (LI-rTMS), and found that 2 weeks of LI-rTMS can reorganize neural circuits (Rodger et al, 2012; Makowiecki et al, 2014). LFMS forms an additional tool for NIBS therapies (Shafi et al, 2014), the mechanisms underlying the effects of low intensity magnetic stimulation remain ill-defined
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