Epilepsy was once considered to be a disease of supernatural origin. In ancient Mesopotamia, the seizures associated with the condition were attributed to ‘the hand of sin’ from the god of the Moon. Thankfully, our understanding of the condition has come a long way since then. The electroencephalogram’s advent in the 1920s showed researchers that sudden bursts of electricity in the brain led to seizures, and treatments such as anticonvulsant drugs now help the majority of people with the condition. Others benefit from vagus nerve stimulation, where a small electrical device is implanted under the skin of the chest. It sends impulses to the brain through the vagus nerve in the neck and aims to reduce the number of seizures experienced. For a certain subset of people with the condition who do not respond to conventional treatment, brain implants could be promising. These halt the electrical surge when the very first signals of a seizure are detected. But although medical devices for epilepsy can vastly improve patients’ lives, the technology is still somewhat clunky. The problem is the electronic components of these devices don’t mix well with substances inside the human body. In other words, they’re not biocompatible. Device circuits would be damaged as soon as they came into contact with the water and charged particles inside of us.

Human cells don’t like being exposed to these electric components either. “There are elements needed to make these circuits work that are potentially toxic to the body,” explains neurologist Jennifer Gelinas from Columbia University, whose research focuses on epilepsy surgery and brain monitoring. “That’s why the electronic components are often sealed off in pretty large metallic compartments that are implanted in the chest wall or the skull.”

These titanium cases make the device much safer, but the added bulk is inconvenient for the patient and increases the possibility of damaging the surrounding tissue. Another problem, according to electrical engineer Dion Khodagholy, also at Columbia, is that the materials used for diagnostics can actually dampen body signals, making the measurement less precise.

Banish the bulk

“We need to be able to speak the language of the body,” Khodagholy says, pointing out that while electronic devices communicate using electrons, the human body talks in charged particles called ions. But it’s a catch- 22. We need electronics to interact closely with these ions to get a good understanding of what’s going on under the skin, but traditional electronics can’t survive in ionic environments. Scientists must rethink the materials used in medical devices and find ones that don’t clash with human physiology. And that’s exactly what Khodagholy has teamed up with Gelinas to do. He develops soft materials that don’t have to be cloaked in metal to be implanted in the body, while Gelinas tests out devices made from these materials in animal models.

“We are trying to use unique properties of materials to design and develop novel electronics to efficiently interact with biological substrates, specifically neural networks and the brain,” reveals Khodagholy. “This involves synthesising the material, turning it into an effective device and hopefully coming up with new opportunities that current devices cannot provide for better diagnostics and interventions.”

They’ve already had some success. In 2015, Khodagholy and Gelinas helped develop biocompatible polymer electrodes called NeuroGrids that could replace conventional metal devices used for measuring brain activity. Electrode arrays currently used by doctors are large and rigid, but the NeuroGrid polymer is tiny. It can be made on the same scale as a brain cell, allowing researchers to get a more precise recording of brain activity. The polymer conducts both ions and electrons – making it ideal for brain-machine interaction. It could help doctors better understand the unusual electrical activity responsible for recurrent, unpredictable seizures in epilepsy. The NeuroGrid has now been approved for use intraoperatively during the surgical workup for treating the condition.

More recently, the researchers have built on this work to find a way to stimulate the brain as well as record its activity, which could have applications for multiple neurological conditions, from epilepsy to Parkinson’s disease. They have developed soft, ion-driven semiconductors called e-IGTs, which stands for enhance-mode, internal ion-gated organic electrochemical transistors. “The ions are right in the vicinity of the polymer microstructure, and can be quickly converted to electrons,” explains Khodagholy. “As a result, the transistor is very fast and the whole bulk of the material is engaged.”

After the materials are developed and devices assembled, they are then tested in rodent models. Because the researchers usually study the developing brain, the animals they work with are often just a few days old. “When we’re working with fragile organisms, such as mouse pups, we find a lot of devices can damage the tissue,” reveals Gelinas. “And that’s something we worry about in humans when we’re determining the eligibility of patients for epilepsy surgery. But what’s good about these new devices is they are extremely miniaturised. The recording components are fully conformable so it feels almost like a piece of plastic wrap.”

The device is extremely thin and doesn’t apply much pressure to the delicate tissue. Scientists can place the tech right on the surface of the brain without damaging the surrounding neurons. Khodagholy also wanted to find better materials to record large-scale brain activity during electrode implantation for deep brain stimulation. He has developed a film-like polymer with an electrical function that can be controlled by varying the size and density of the material. It’s called a mixed conducting particulate (MCP) film.

“We thought of making a material that can conduct vertically but not horizontally. In other words, it only conducts in one place,” he explains. “The device is made with completely biocompatible materials, and the surrounding adhesive is made from the same material as crustacean shells – a polysaccharide called chitosan that will be stable in the human body.”

Human touch

The next step will be safety tests in humans. Ultimately, the team hopes its biocompatible devices will not only increase clinicians’ understanding of epilepsy and other neurological disorders, but also lead to better, less invasive treatments.

“We are consistently moving towards being able to have these conformable organic electronic-based devices in a form factor that will allow them to be implanted,” says Gelinas.

But first they need to show they can be safely placed on the surface of the brain and kept there for up to a fortnight – the standard pre-surgical monitoring period – so surgeons can identify the epicentre of unusual electrical activity in epilepsy patients.

“This would be a really crucial step forward to show that the approach is first and foremost safe, but also effective in generating the same type of information that we’re currently getting with our much bulkier and less biocompatible devices,” Gelinas adds.

A shorter route to human use could be getting the particles to interface with the skin for non-invasive diagnostic procedures. The MCP device can record muscle action potentials from the surface of the arm. Preliminary work with human volunteers found that it is feasible to take a thin film of particles, rub it on the skin and gently press an electrode array over the top. The team says they’ve seen impressive recordings of nerves and muscles this way.

“It could open up some interesting avenues in terms of motor control,” says Gelinas. “If these noninvasive interfaces are working out well, there are a lot of other possibilities. We could move to recording the brain from the surface of the scalp rather than from the surface of the brain itself.”

The duo has plenty of collaborators for future projects and Khodagholy is particularly excited about the multidisciplinary nature of the work. Making devices that will eventually help patients with epilepsy and other brain disorders will require experts from materials science, electronics engineering, neuroscience and medicine. “At the beginning, it’s always complicated to understand each other in meetings,” says Khodagholy, “but once it becomes established it’s wonderful. You learn new skills and you can definitely see the impact of the technology you’re developing.”

Brain Musk

It was only a matter of time before Elon Musk found a more literal way of inserting himself into the brains of living beings – porcine ones, specifically. In August 2020, he live-streamed footage of a pig named Gertrude snuffling her way through her pen while computer speakers beeped and blue wavelengths oscillated across a screen. “The beeps you are hearing are real-time signals,” said Musk. “The future’s going to be weird.”

Two months prior to this, Musk’s Neuralink start-up had implanted a coin-sized chip into Gertrude’s brain. One month after that, in July, Neuralink’s chip was designated a breakthrough device by the Food and Drug Administration. The chip, which outside observers have described as ‘beyond state-of-the-art’, detects and stimulates brain activity with 1,024 gold electrodes positioned on incredibly soft and flexible wires, each about one-tenth of the width of a human hair. The wires and gold electrodes are currently research-level technologies, and little is known about how they might perform over time. On the other side, the chip connects via Bluetooth to a smartphone app, which allows users to control and monitor the device. “It’s like a Fitbit in your skull,” Musk quipped on the stream.

Neuralink’s method of implanting the device and its fiddly gossamer wires works similarly to a sewing machine, threading them through a hole drilled in the skull. Impressively, the robot uses a feature called online motion correction to match its sewing needle to the movement of the brain’s blood vessels.

According to Neuralink, the chip’s first clinical trials in humans will focus on restoring movement and feeling to people who have suffered spinal injuries. Over the longer term, Musk has suggested the device could enable “conceptual telepathy”, and lay the foundations for “a good AI symbiosis” – attracting scepticism from academics and more established brain researchers. But money and enthusiasm has achieved a lot already – we couldn’t exactly read her thoughts, but Gertrude looked like she was enjoying herself.