**6. Writing to the brain**

The brain can be stimulated electrically, chemically and even mechanically. Most brain-machine interface work has been performed with electrical stimulation from invasive focal electrodes, which have advantages of high speed and spatial precision, but can only access a small portion of the brain. Noninvasive electrical stimulation has been performed with transcranial magnetic stimulation, where externally applied changing magnetic fields are used to induce electrical fields and currents in the brain. This technique yields relatively poor spatial resolution (e.g., centimeter scale) at the brain surface, with spatial resolution worsening appreciably in deeper parts of the brain. Externally applied electrical currents have even worse spatial localization capability, since the impedance of various tissues in the head is highly nonuniform. Theoretically, radio-frequency energy could be focused in small regions with high-field MRI, but this technique has not been intentionally used for stimulation [36]. Externally Administered chemical brain modulation is an ancient technique, practiced in pubs daily by millions of people. In a few rare cases, the focal concentration of receptors in certain sections of the brain allows chemical stimulants to target specific regions (e.g., substantia nigra by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin) [37]. Microinfusions of chemicals via brain-implanted catheters have been applied in animal studies for research. Catheters have been implanted in the neuronal sections of human brains to deliver cancer treatment (i.e., convection-enhanced delivery). Externally applied high-intensity-focused ultrasound (HIFU) has been used experimentally to stimulate the brain, although the exact mechanism is not well understood [38]. We hypothesize that magnetic particles may be useful in focal brain stimulation, with focality realized either through noninvasive selective placement of particles (e.g., after magnetically-assisted intranasal administration) in desired locations or with diffusely delivered particles that can be addressed selectively. In the next sections, we list various candidate magnetic particles for brain stimulation, some of which overlap the prior section for brain readout.

## **6.1. Mechanical stimulation with magnetic particles**

Anecdotal surgical data from the placement of deep-brain stimulation leads have shown that mechanical vibration can stimulate neurons [39, 40]. Cultured neuron studies have demonstrated mechanoreceptors that react by opening calcium channels [41]. Invertebrate experiments suggest that externally applied magnetic gradients can wiggle magnetic particles enough to cause nerve stimulation (**Figure 7**) [42].

#### **6.2. Composite piezoelectric/magnetic particles**

With appropriately designed piezomagnetic particles, externally applied magnetic fields can be applied to the particles in order to generate powerful electric fields focally (e.g., strong enough to electroporate cells) [32]. Indirect evidence of global brain stimulation has been collected through electroencephalography of animals [20].

#### **6.3. Electret-based magnetic particles**

for deployment as a contrast agent. The spintronic particles can be used in a reverse mode for stimulation (with radio-frequency energy converted to low-frequency currents) again with

The brain can be stimulated electrically, chemically and even mechanically. Most brain-machine interface work has been performed with electrical stimulation from invasive focal electrodes, which have advantages of high speed and spatial precision, but can only access a small portion of the brain. Noninvasive electrical stimulation has been performed with transcranial magnetic stimulation, where externally applied changing magnetic fields are used to induce electrical fields and currents in the brain. This technique yields relatively poor spatial resolution (e.g., centimeter scale) at the brain surface, with spatial resolution worsening appreciably in deeper parts of the brain. Externally applied electrical currents have even worse spatial localization capability, since the impedance of various tissues in the head is highly nonuniform. Theoretically, radio-frequency energy could be focused in small regions with high-field MRI, but this technique has not been intentionally used for stimulation [36]. Externally Administered chemical brain modulation is an ancient technique, practiced in pubs daily by millions of people. In a few rare cases, the focal concentration of receptors in certain sections of the brain allows chemical stimulants to target specific regions (e.g., substantia nigra by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin) [37]. Microinfusions of chemicals via brain-implanted catheters have been applied in animal studies for research. Catheters have been implanted in the neuronal sections of human brains to deliver cancer treatment (i.e., convection-enhanced delivery). Externally applied high-intensity-focused ultrasound (HIFU) has been used experimentally to stimulate the brain, although the exact mechanism is not well understood [38]. We hypothesize that magnetic particles may be useful in focal brain stimulation, with focality realized either through noninvasive selective placement of particles (e.g., after magnetically-assisted intranasal

the possibility of localization with applied magnetic gradients [35].

**Figure 6.** Voltage-sensitive MRI signal from piezo-magnetic particle.

148 Evolving BCI Therapy - Engaging Brain State Dynamics

**6. Writing to the brain**

Recent innovations in harvesting harvesting from mechanical motion have been driven because of the proliferation of wearable devices. Some of the principles of energy harvesting can be reversed in order to generate electrical currents and voltages. Electrets, which rely on changes in capacitance to generate power, are very efficient vibrational energy harvesters. Liquid crystals have been used as electrets for energy harvesting [43]. Typically, liquid crystals require very high magnetic fields to change their capacitance, but the addition of magnetic

**Figure 7.** Magnetic particle neurostim-ulation visualized with manganese-enhanced MRI (MEMRI). Particles were injected behind the left eye of crawfish and stimulated for 3 min using magnetic wiggling of particles. Increased MEMRI signal is seen in the left brain.

or readout with appropriate RF or magnetic tuning. Many of the particles listed above (e.g., magnetoelectric, electret-based particles) can both read and write electrically and therefore potentially fit the bill for high-speed bidirectionality. Building on the work of deep-brain stimulation, one might expect that the focal stimulation of specific brain nuclei would be the first clinical target for noninvasive or minimally invasive bidirectional BMI. The high temporal and spatial resolution of voltage-sensitive contrast media would likely shed additional light on large-scale brain processes (e.g., attractors [44]) that would be useful in building more eloquent BMIs. System architectures for reading from and writing to the brain would be similar to conventional MRI systems, preferably with the ability to rapidly turn off the static magnetic field in order to manipulate the magnetic particles with high flexibility [12]. Once the particles were placed in the appropriate location, stimulation could be implemented with a wearable coil. Readout with voltage-sensitive contrast media could be

Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution...

, Sahar Jafari<sup>1</sup>

, Christian Koudelka<sup>4</sup>

[1] Kurzweil R. How to Create a Mind. New York City: Viking & Penguin; 2012

[2] Kennedy P. Brain-machine interfaces as a challenge to the "moment of singularity".

, Sagar Chowdhury3

, Pavel Y. Stepanov3

, Jose Algarin<sup>2</sup>

, Pablo S. Villar<sup>5</sup>

, Pulkit Malik3

, Ricardo Araneda5

, Aleksandar Nacev4

, Ilya Krivorotov<sup>6</sup>

, Jose Maria Benlloch Baviera<sup>2</sup>

http://dx.doi.org/10.5772/intechopen.75522

, Danica Sun3

,

, Jens Herberholz<sup>5</sup>

,

,

151

,

,

performed with conventional MRI systems.

, Said Ijanaten4

\*, Lamar O. Mair1

 and Stanley Fricke8 \*Address all correspondence to: inweinberg@gmail.com 1 Neuroparticle Corporation, Rockville, Maryland, USA 2 Polytechnic University of Valencia, Valencia, Spain

, Bradley English3

, Olivia Hale3

3 Weinberg Medical Physics, North Bethesda, Maryland, USA

4 Promaxo Corporation, North Bethesda, Maryland, USA 5 University of Maryland, College Park, Maryland, USA

7 Florida International University, Miami, Florida, USA

Frontiers in Systems Neuroscience. 2014;**8**:213

8 Children's National Medical Center, Washington, DC, USA

6 University of California, Irvine, California, USA

, Benjamin Shapiro5

**Author details**

Irving N. Weinberg1

James Baker-McKee<sup>3</sup>

Ryan Hilaman4

**References**

Sakhrat Khizroev<sup>7</sup>

Jamelle Watson-Daniels<sup>3</sup>

Luz J. Martinez-Miranda<sup>5</sup>

**Figure 8.** Spintronic particle writing to single neuron. Top: neuro-modulation in vital mouse brain slice (red) when spintronic nano-oscillator (STNO) particle is triggered by RF signal. Bottom: neuronal frequency changes in as a function of applied RF pulse.

dopants dramatically reduces the magnetic field strength required to alter capacitance [28]. Therefore, a composite of magnetic particles and liquid crystals (as discussed above) might be able to convert a changing externally applied magnetic field into local electrical stimulation.
