Magnetic Strategies for Nervous System Control

Abstract

Magnetic fields pass through tissue undiminished and without producing harmful effects, motivating their use as a wireless, minimally invasive means to control neural activity. Here, we review mechanisms and techniques coupling magnetic fields to changes in electrochemical potentials across neuronal membranes. Biological magnetoreception, although incompletely understood, is discussed as a potential source of inspiration. The emergence of magnetic properties in materials is reviewed to clarify the distinction between biomolecules containing transition metals and ferrite nanoparticles that exhibit significant net moments. We describe recent developments in the use of magnetic nanomaterials as transducers converting magnetic stimuli to forms readily perceived by neurons and discuss opportunities for multiplexed and bidirectional control as well as the challenges posed by delivery to the brain. The variety of magnetic field conditions and mechanisms by which they can be coupled to neuronal signaling cascades highlights the desirability of continued interchange between magnetism physics and neurobiology.

Keywords: magnetic field; magnetic nanoparticles; magnetic stimulation; magnetoreception; neuromodulation.

Figure 1

A palette of artificial magnetic stimuli, categorized according to spatial and temporal characteristics. (a) Nearly uniform fields can be created, for example, using a Helmholtz coil (two current carrying rings separated by a distance equal to their radius). (b) A conical permanent magnet magnetized along its azimuthal axis produces a field at the tip that decays rapidly with distance, resulting in a high magnetic field gradient. Fields with various spatial distributions can also be categorized by how they vary in time. (c) Magnetic fields can remain constant over the timescale of interest. (d) Rotating fields maintain a constant magnitude while changing direction, revolving around some axis. A simple, planar rotation is shown. (e) Alternating magnetic fields sinusoidally change polarity, and are typically generated by applying AC current to a solenoid. If the linear dimensions of the solenoid are much less than the corresponding wavelength of electromagnetic radiation, the field is quasimagnetostatic. (f) Pulsed fields, which exhibit high dB/dt, can be generated by discharging a momentary burst of current through a coil. This approach is often used in TMS pulses.

Figure 2

Lessons offered by hypothesized mechanisms of magnetoreception. (a) Pigeons are an example of organisms that sense the inclination of the Earth’s magnetic field and also possess a “map sense.” They are thought to to detect minute local variations in the magnetic field and remember those variations to help navigate. (b) In the radical pair hypothesis, cryptochrome generates radical pairs when exposed to ultraviolet or blue light, and weak magnetic fields bias the proportion of radical pairs in the triplet or singlet state, altering the generation of downstream products detectable by neurons. (c) Magnetite nanoparticles have been reportedly found in many animals and could perhaps interact with the Earth’s magnetic field strongly enough to produce forces detectable by neurons. A 50 nm magnetite particle is contrasted with the mineralized core of ferritin in terms of interaction energy with the Earth’s magnetic field (50 μT). Thermal energy at room temperature is marked as k_BT, where k_B is the Boltzmann constant and T is temperature.

Figure 3

Electromagnetic induction can be used to control neural activity. (a) Schematic of the electromagnetic induction in the context of TMS. A butterfly coil is held over the head of a human and a pulsed current is applied, resulting in a rapidly increasing magnetic field that induces a current in the brain (from Wagner et al. 2007). (b) Examples of TMS coils, single and butterfly (from magstim.com). (c) Electromagnetic induction could be used to stimulate deep brain structures via implanted millimeter-scale solenoids (from Bonmassar et al. 2012). (d) Implanted devices may be powered using electromagnetic induction. This device may be implanted into an animal and rectifies the induced voltage from an externally applied alternating magnetic field into a DC current that can stimulate neural activity (from Freeman et al. 2017).

Figure 4

Forms of magnetic ordering. (a) Paramagnetism: uncoupled spins are randomly oriented in the absence of applied field, but they asymptotically approach complete alignment with the application of large magnetic fields. (b) In ferromagnetic materials, magnetic moments spontaneously align to give the material a net magnetic moment. In anti-ferromagnetic materials, adjacent magnetic moments align anti-parallel to perfectly cancel, resulting in zero net magnetization. In ferrimagnetic materials, adjacent magnetic moments align anti-parallel but have unequal magnitude, resulting in a net magnetic moment for the material. (c) Single and multi-domain particles: below a critical size determined by the material properties, all moments within a ferromagnetic particle are aligned. At larger sizes, particles develop multiple domains to minimize their magnetostatic energy. For simplicity, the domain wall is illustrated as if it were abrupt; in reality, there would be spins of intermediate orientation between the two opposing domains. (d) Superparamagnetism: an ensemble of singledomain particles of ferromagnetic or ferrimagnetic material has zero net magnetization at zero applied field, but upon the application of moderate magnetic fields, the particle moments align with the applied field.

Figure 5

Strategies for using synthetic nanomaterials for neuronal stimulation with magnetic fields. (a) Forces may be applied to magnetic particles in highly nonuniform fields, and torques may be generated if particles exhibit anisotropy. (b) Magnetoelectric composite nanoparticles couple the strain resulting from magnetostriction of their core to a piezoelectric shell, producing a change in electric polarization. (c) The lag in response of magnetization to an applied alternating magnetic field, which can be graphically represented by hysteresis loops, results in dissipated heat. (d) Force or torque may be used to actuate mechanosensitive ion channels. (e) Magnetoelectric composite particles can, in principle, be used to trigger the response of voltage gated ion channels. (f) Temperature-sensitive channel proteins may be actuated by the heat dissipated by magnetic nanoparticles, whether through nanoscale or bulk effects. (g) Heat may also be used to trigger the release of chemical agonists or antagonists that actuate ion channels.