Wireless deep-brain stimulation
A team of researchers at MIT recently showed that it's possible to wirelessly stimulate targeted brain regions, potentially expanding treatment options for disorders of brain function.
Deep-brain stimulation is a neuropsychiatric technique where neural activity is induced in targeted brain areas, usually to relieve symptoms of Parkinson's or, more experimentally, major depression. The current state of the art relies on macroscopic devices that have to be surgically implanted in patients' brains and powered by pulse generators implanted elsewhere (usually near the collarbone). But Ritchie Chen and colleagues have taken the first steps toward a new method using magnetic nanoparticles (MNPs), which can be injected in solution and might remain in the brain for months.
Magnetic nanoparticles are tiny (5-500 nanometers, where a human hair measures around 75,000 nanometers) molecules that interact with magnetic fields. They have a variety of potential medical applications, since they can easily be dissolved in a solution and injected into targeted tissues or regions like little sleeper agents, and the magnetic fields that activate them easily penetrate the body without doing any damage. Magnetic hyperthermia, for example, is a cancer treatment that takes advantage of MNPs' tendency to generate heat in certain magnetic environments, cooking tumor tissue to irreparable damage. In their recent study, Chen et al used magnetothermal excitation to trigger heat-sensitive neural receptors, inducing the same neural effects as old-school deep-brain stimulation without the hassle of invasive implants and external power devices.
The new technique hijacks a protein called TRPV1, which is one of many different molecular gate-keepers that sit embedded in neurons' cell membranes, regulating neural activity by controlling the calcium ions (Ca2+) coming into the cell. Calcium buildup makes the neuron fire, so, if you open the gate, you let in more Ca2+, and you activate the neuron. Under normal circumstances, TRPV1 opens when a molecule called capsaicin comes along and unlocks it. (Other types of receptors need different molecular keys.) But TRPV1 also opens at high temperatures.
To that end, Chen et al use the MNP iron(II,III) oxide (Fe3O4) to warm up the brain—not enough to damage the tissue, but just enough to open the TRPV1 gates. This happens by a process called hysteretic power loss. Basically, when they're exposed to a magnetic field that changes direction at a particular frequency, Fe3O4 molecules spin like wobbly tops. As they slow down, they lose energy, and this energy is released as heat.
So, just to recap the chain of events: you put Fe3O4 in the brain, you put the brain in a magnet, the brain gets warmer, TRPV1 gates open up, Ca2+ enters neurons, neurons fire.
The researchers showed that this actually works in the mouse brain. They injected a solution of Fe3O4 into a specific region, the ventral tegmental area, or VTA. (And it's worth noting that it took some additional chemical sleight of hand to get those molecules into a solution that would be stable and compatible with the chemical environment in the brain). They exposed the mouse to the prescribed magnetic fields using a machine much like a typical lab or hospital MRI. (That M stands for magnetic.) Then they showed that both the temperature and the amount of neural activity in VTA increased as expected. They also showed that the injection of Fe3O4 did less damage to the brain tissue than implanting a traditional deep-brain stimulation device. And, they got the same effects in the magnetic field a month after the initial injection, suggesting that the MNPs can hang around the brain for at least that long.
This is a huge step forward for potential psychiatric treatments... Also, remote-control brains? It's just cool. But along with the usual caveat about how long it takes to perfect, test, approve, and implement new treatments, it comes with certain inconveniences. Probably the biggest one is it requires specialized machinery to generate the appropriate magnetic field conditions—as far as I can tell, manipulating MNPs generally requires extremely strong magnetic fields, which means it takes a lot of bulky, powerful hardware—think of the MRI machine again. Parkinson's patients would basically have to live in there. And in treatment of major depression, stimulation is often controlled by the users as needed, so they'd have to drive to a lab or a clinic every time they needed a dose.
Plus, scientists don't know exactly why deep-brain stimulation works, when it works. Treatments do stimulate regions that are known to malfunction in disease, but these regions are just isolated pieces of complicated neural circuits distributed throughout the brain. At the same time, taking a neuron-level perspective, DBS is quite broad—there are local circuits within each brain region, and many different types of neurons playing different roles. It's basically poking the brain with a big stick; clinicians calibrate the pokes to get the best effects, but it's not yet clear what's really going on inside. (Though, to be fair, it is also unclear exactly why SSRI's work for depression. The chemical mechanism is known, but that plays out on a much faster time scale than the actual relief of symptoms. And though the chemical effects are the same in everyone, the amount of actual relief varies widely from patient to patient.)
I've also seen a bit of evidence suggesting that at least some of the benefits of deep-brain stimulation for Parkinson's patients slowly decline in the long term. I haven't done a thorough search of the literature, but this makes sense given that the brain does tend to adapt to certain kinds of inputs over time—that's how people build tolerance to drugs, or develop chemical addictions.
Still, this study paves the way for future research, and it's a very elegant illustration of a way magnetothermal properties can be finessed into gentle biomedical treatments, rather than just frying the crap out of cancerous tumors.
The paper is here at Science, probably pay-walled, but if you Google the title you’ll also find an open-access download.