Breakthroughs in Brain Implants

Breakthroughs in Brain Implants

Breakthroughs in Brain Implants 789 444 IEEE Pulse
Author(s): Zara Abrams

Recent advances are spurring the development, testing, and commercialization of implantable devices that hold the potential to treat a variety of neurological conditions

In 2023, brain implants got a big boost. Neuralink, Elon Musk’s startup, began recruiting for its first clinical trial for paralysis patients; Precision Neuroscience received breakthrough designation from the Food and Drug Administration (FDA), allowing it to fast-track its own trials. Meanwhile, scientific advances are revealing promising new applications for such devices, including more comprehensive restoration of speech, sight, hearing, and movement to people who have lost those abilities, as well as help for psychiatric conditions, such as eating disorders and depression.

“These devices are going to give us a profound insight into the human brain, which is really exciting because there is no model for that,” said Bradley Greger, Ph.D., an associate professor in the School of Biological and Health Systems Engineering at Arizona State University who studies how brain implants can be used to restore vision and other functions. “That rigorous scientific understanding, I’m very hopeful, will lead to great impacts in terms of patient care.”

Restoring movement, sight, and speech

Brain implants are already used on a regular basis to help prevent seizures in patients with severe epilepsy, treat movement disorders such as Parkinson’s disease, and manage symptoms of psychiatric conditions, including obsessive-compulsive disorder (OCD). A growing body of evidence shows that they will soon be able to restore movement to people who are paralyzed, speech to people with locked-in syndrome or stroke, and vision to people who have lost it. “This is not in the realm of science fiction,” Greger said. “We know for a fact this will work, but we’re now getting into the fine details of the engineering to make sure these devices are durable and provide sufficient resolution.”

New startups, including Neuralink and Precision Neuroscience, as well as first movers such as Blackrock Neurotech, are increasingly focused on that goal: using very small electrodes to both sense and stimulate the brain at higher resolution (Figure 1). “The brain is an electrical organ and it computes on a pretty fine-grained scale,” said Ben Rapoport, M.D., Ph.D., an assistant professor of neurosurgery at the Icahn School of Medicine at Mount Sinai and co-founder and chief science officer at Precision Neuroscience. “Neurons in the brain collectively ‘vote’, and the integral of their votes is really what drives macroscopic movement,” he said, including rapid, fine-scale movements such as the movements of the lips and tongue to make speech. For that reason, effectively collecting (and delivering) information requires recording and stimulating the brain at the submillimeter level.

Breakthroughs in Brain Implants

Figure 1. The Layer 7 Cortical Interface, Precision Neuroscience’s thin film microelectrode array. (Image courtesy of Kevin Brown.)

“That requires some really elegant engineering on the electrode, but that’s what’s starting to become available now,” Greger said. For the first time, semiconductor manufacturing techniques (Figure 2) are being applied to medicine to create very small electrodes—in the case of Precision’s brain–computer interface (BCI), 50 microns across, or about half the diameter of an eyelash. The implant’s 1024 electrodes are embedded within a thin film that lies on the surface of the cortex, rather than penetrating it (traditional BCIs such as the Utah array, as well as Neuralink’s device, use penetrating electrodes) (Figure 3).

Breakthroughs in Brain Implants

Figure 2. Cleanroom for microfabrication at Precision BioMEMS. (Image courtesy of Kevin Brown.)

“Most of conscious thought and movement happens very close to the brain’s surface, in the neocortex, so it’s possible to maximize the relevant information exchange without actually penetrating into the brain,” said Rapoport, who was also a co-founder of Neuralink. A nonpenetrating BCI offers several advantages. It eliminates the inflammatory response caused by implanting a device inside brain tissue and it can be removed relatively easily. In theory, it can also be scaled up to cover a larger surface area of the cortex—and increase the device’s bandwidth—without causing additional harm. Precision Neuroscience completed its first round of safety and efficacy studies. Additional trials will continue in 2024.

Breakthroughs in Brain Implants

Figure 3. On the Layer 7 Cortical Interface, the smaller dots are sensing electrodes (50 microns in diameter); the larger dots are stimulating electrodes (380 microns in diameter). (Image courtesy of Kevin Brown.)

In September, Neuralink began recruiting for its first clinical trial of patients with paralysis due to spinal cord injury or amyotrophic lateral sclerosis (ALS), receiving approval after an earlier rejection from the FDA. “I’m very excited about the Neuralink trial, because while their technology is penetrating, it’s compliant and very small scale,” Greger said. “Now they’ve got to get through FDA approval—that’s the big hurdle. They need to show they can do this safely.”

Advances in deep brain stimulation

While much of conscious thought occurs near the surface of the cortex, patients with certain neurological conditions can benefit from a device implanted deeper in the brain. Deep brain stimulation (DBS) has proven utility for easing symptoms in a range of conditions, including movement disorders (such as Parkinson’s disease and essential tremor), psychiatric disorders (such as OCD and depression), and epilepsy.

The past few years have ushered in a new era for DBS: NeuroPace’s device can sense and record brain activity, offering troves of data that researchers can use to better understand the pathology that underlies various conditions. “We can see through these devices what’s happening in the brain in real time, which will help us understand what’s happening physiologically with depression, for instance, and attune the treatment to the patient,” Greger said. “That data is starting to come in now and it’s likely to be a game changer.”

For more than two decades, Helen Mayberg, M.D., a professor of neurology and neurosurgery and director of the Nash Family Center for Advanced Circuit Therapeutics at the Icahn School of Medicine at Mount Sinai, has studied how to use DBS to help patients with treatment-resistant depression [1]. Over the years, she and her team gained significant insights about circuitry related to depression and worked to determine the ideal location for implanting a device to treat it (in a part of the brain known as Brodmann area 25).

In their latest study of 10 participants, nine had a robust clinical response after six months and seven achieved remission [2]. They used data from these patients, who were implanted with a prototype system that can both sense brain signals and deliver stimulation, to create a general depression tracking signal. That signal can then be used to pinpoint periods of depression recovery for patients having ongoing DBS treatment.

“We’ve been able to define a robust electrophysiological signal that we can measure from the implanted DBS system. That allows us to adjust therapeutic stimulation as needed,” Mayberg said. “But I’m excited that we also have new imaging evidence that the stimulation may even be inducing structural plasticity—remodeling the specific brain circuits we are targeting.” Separately, in 2022, medical device company Abbott received breakthrough designation from the FDA to begin testing its own DBS system for treatment-resistant depression.

DBS has been used for years to help patients with severe OCD, but a new approach shows promise for providing even more effective treatment. Casey Halpern, M.D., an associate professor of neurosurgery at Penn Medicine, has tested what is known as closed-loop stimulation for OCD in an early “off-label” preclinical trial. In closed-loop stimulation, a device delivers stimulation in response to recordings of brain activity. Existing DBS treatment for OCD is open-loop, meaning it does not sense or respond to electrical activity in the patient’s brain.

In order to pinpoint the activity patterns linked to compulsive behaviors, Halpern and his team built a personalized protocol designed to provoke their first patient’s symptoms. They exposed her to one of her reported triggers, a plate of contaminated seafood, and developed a virtual experience that simulated the same encounter. “We were able to provoke her symptoms in a laboratory setting and capture signals evoked at the moment of handling contaminated seafood, which for this patient was a highly stressful stimulus,” he said. They used that signal to selectively deliver stimulation to reward circuits in the brain when the patient encountered stressful stimuli in daily life, leading to robust reductions in both obsessive thoughts and compulsive behaviors [3].

Halpern studies other compulsive urges, such as uncontrolled eating and addiction, which also affect areas of the brain relating to reward, including a structure called the nucleus accumbens that helps modulate reward-seeking behavior. “There are common circuits in the brain that mediate these different types of dangerous urges, whether that’s the urge to wash your hands or an urge to overeat,” he said. “We think these circuits overlap between these disorders, which may also allow us to expedite the development of a treatment that could work for all of them.” He recently received funding to test DBS for patients with binge eating disorder, observing improved self-control of food intake, and weight loss over the course of six months [4]. The next steps include advancing the work to a larger trial and applying it to other conditions that involve uncontrolled eating, including bulimia.

“These problems have a biological basis and are not simply due to somebody’s lack of self-control,” Halpern said. “But once habits form, they can be very hard to break, so delivering a therapy that retrains neural circuits can be powerful,” especially in the most severe cases.

Leveraging data from brain implants

In addition to the direct benefits they offer patients, BCIs that can sense and record brain activity offer something powerful to neuroscientists: massive amounts of data about how the brain functions in various circumstances (for example, when people with depression are well versus when they are unwell). “Let’s learn as much as possible, then take what we’ve learned and do it in a way that scales to people who don’t need implants,” Mayberg said. “We need the endpoint to be clear, then we can build tools that do that.” Data from BCIs can also inform how to use stimulation for new indications, such as chronic pain, Greger said.

That data can also help researchers find other markers that can be used as indicators of health, such as changes in a person’s facial expression and tone of voice that shift in parallel with brain signals and could be an easy-to-obtain marker for depressive episodes, Mayberg said. Ultimately, she hopes the latest breakthroughs can help dispel fears about brain implants and illustrate their utility and potential. “Instead of fearing that we’re using these devices to make cyborgs or for mind control, everyone needs to remember: There are people who are suffering because their brains cannot be repaired in other ways, and we’re repairing them,” she said.

References

  1. H. S. Mayberg et al., “Deep brain stimulation for treatment-resistant depression,” Neuron, vol. 45, pp. 651–660, Mar. 2005, doi: 10.1016/j.neuron.2005.02.014.
  2. S. Alagapan et al., “Cingulate dynamics track depression recovery with deep brain stimulation,” Nature, vol. 622, pp. 130–138, Sep. 2023, doi: 10.1038/s41586-023-06541-3.
  3. Y. Nho et al., “Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion,” Neuron, vol. 112, no. 1, pp. 73–83, Jan. 2024, doi: 10.1016/j.neuron.2023.09.034.
  4. R. S. Shivacharan et al., “Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating,” Nature Med., vol. 28, pp. 1791–1796, Aug. 2022, doi: 10.1038/s41591-022-01941-w.