Toward A Less Invasive Mode Of Deep Brain Stimulation

Imagine this futuristic tableau: A severely depressed person walks into her doctor's office, sits in a specially designed chair with a coil around her head, and with little more than an IV injection, undergoes deep brain stimulation to treat her deep, dark psychological illness.

Well, that's not going to happen any time soon, but engineers at MIT are working on the building blocks that could make that fictional scenario a reality.

They've developed a method — a proof-of-concept, really — to stimulate brain tissue using external magnetic fields and injected magnetic nanoparticles that resemble small bits of rust. This technique allows for direct stimulation of neurons, which could someday be an effective treatment for a variety of neurological diseases, like Parkinson's, and even further in the future, for severe, treatment-resistant psychiatric disorders like depression, without the need for highly invasive brain implants or external connections. The research is published in the journal Science.

Current treatments have been effective in reducing or eliminating tremors associated with Parkinson's but involve major brain surgery to implant wires that are connected to an outside power source.

Polina Anikeeva, an assistant professor of materials science and engineering at MIT, says the new research suggests a much less invasive possibility. I asked her to describe the research in an accessible way and here's what she said:

First, I want to clearly say that we are still very far away from any clinical or even pre-clinical application, this is a first proof-of-concept study, looking at the possibility of using these materials to stimulate neurons deep in the brain.

What we've done is to give a simple injection of nanomaterials (iron oxide) that look like small bits of rust [but aren't actually rust], deep into the brain. This allows us to deliver stimulus using a magnetic field, which is converted into heat by the little rust particules. Now we have a system where a magnetic field is applied from the outside and with a simple injection of the materials we can deliver the stimulas deep in the brain without the connectors and without the implants. We don't have to be invasive in order to do the stimulation.

These tests, she says, were conducted in culture, with flourescent measurements, and also in mice who had their brains extracted after the stimulation, allowing researchers to look at the expression of factors (proteins) that happen with neural activity; specifically, a protein called C-Fos.

Here's more from Anikeeva:

The magnetic field is applied from the outside using coils shaped like a donut with a hole cut out — more like a halo, but part of the halo is snapped out — and that's where the field escapes. When magnetic fields interact with rust particules, they dissipate heat and that heat can trigger neurol activity.

This method still uses an injection in the brain, but in the future, instead of injecting the particles directly into the brain, doctors might use catheters or IV injection to treat certain types of neurological disorders (Parkinson's, Essential tremor, depression) that are currently treated with deep brain stimulation which is a highly invasive procedure, a major surgery.

In the very far off future, the stimulation coils could be built into a chair or bed in a doctor's office where a patient can receive the therapy — this is very very speculative, many decades from now...

We hope for this method to be used first as a research tool to explore paradigms of neural stimulation in a research setting, and then ultimately at least inform new types of therapies on actual human patients...

Essentially any neurological condition that is currently treated with DBS would in the very distant future be a potential therapeutic target. Psychiatric disorders could also be potential candidates, but as of now even standard DBS is not fully approved yet for those cases, so the timeline would be even longer.

Here's more from the MIT news release:

In their study, the team injected magnetic iron oxide particles just 22 nanometers in diameter into the brain. When exposed to an external alternating magnetic field — which can penetrate deep inside biological tissues — these particles rapidly heat up.

The resulting local temperature increase can then lead to neural activation by triggering heat-sensitive capsaicin receptors — the same proteins that the body uses to detect both actual heat and the “heat” of spicy foods. (Capsaicin is the chemical that gives hot peppers their searing taste.) Anikeeva’s team used viral gene delivery to induce the sensitivity to heat in selected neurons in the brain.

The particles, which have virtually no interaction with biological tissues except when heated, tend to remain where they’re placed, allowing for long-term treatment without the need for further invasive procedures.

“The nanoparticles integrate into the tissue and remain largely intact,” Anikeeva says. “Then, that region can be stimulated at will by externally applying an alternating magnetic field. The goal for us was to figure out whether we could deliver stimuli to the nervous system in a wireless and noninvasive way.”

The new work has proven that the approach is feasible, but much work remains to turn this proof-of-concept into a practical method for brain research or clinical treatment.

The use of magnetic fields and injected particles has been an active area of cancer research; the thought is that this approach could destroy cancer cells by heating them. “The new technique is derived, in part, from that research,” Anikeeva says. “By calibrating the delivered thermal dosage, we can excite neurons without killing them. The magnetic nanoparticles also have been used for decades as contrast agents in MRI scans, so they are considered relatively safe in the human body.”

The team developed ways to make the particles with precisely controlled sizes and shapes, in order to maximize their interaction with the applied alternating magnetic field. They also developed devices to deliver the applied magnetic field: Existing devices for cancer treatment — intended to produce much more intense heating — were far too big and energy-inefficient for this application.

The next step toward making this a practical technology for clinical use in humans “is to understand better how our method works through neural recordings and behavioral experiments, and assess whether there are any other side effects to tissues in the affected area,” Anikeeva says.