Sensors built with a new manufacturing approach are capable of recording activity deep within the brain from large populations of individual neurons–with a resolution of as few as one or two neurons–in humans as well as a range of animal models, according to a study published in the Jan. 17, 2024 issue of the journal Nature Communications. The research team is led by the Integrated Electronics and Biointerfaces Laboratory (IEBL) at the University of California San Diego.
The approach is unique in several ways. It relies on ultra-thin, flexible and customizable probes, made of clinical-grade materials, and equipped with sensors that can record extremely localized brain signals. Because the probes are much smaller than today’s clinical sensors, they can be placed extremely close to one another, allowing for high-resolution sensing in specific areas at unprecedented depths within the brain.
Right now, the probes can record with up to 128 channels, while the state of the art in today’s clinical probes is only 8 to 16 channels. In future, the innovative manufacturing approach the researchers developed can expand the number of channels to thousands per probe, dramatically enhancing physicians’ ability to acquire, analyze and understand brain signals at a higher resolution.
This technology is a first step towards wireless monitoring of patients with treatment-resistant epilepsy for extended periods of time–up to 30 days–as they go about their daily lives. Beyond treatment-resistant epilepsy, the potential applications are much broader, including helping people with Parkinson’s disease, movement disorders, obsessive-compulsive disorder, obesity, treatment-resistant depression, high-impact chronic pain and other disorders.
While the Nature Communications paper reports brain-recording data only, the system has been developed to both record brain activity and provide electrical stimulation to precise locations. In fact, the team is building on previous – and ongoing – work that uses this scalable, thin-film manufacturing approach to create brain-computer interfaces that record activity and deliver therapeutic electrical stimulation to the surface of the brain cortex.
The probes are monolithic, meaning that their individual components are layered on top of one another to create a single, cohesive unit, and do not require manual assembly of additional wires to conduct recordings. The new recording system is both extremely customizable and scalable to manufacture, thanks to thin-film technology derived from the semiconductor and digital-display screen industries. As such, the probes are extremely compact–15 micron thick, or about 1/5th the thickness of a human hair–minimizing the differences between the material properties of the probe and the brain.
“We developed an entirely different manufacturing method for thin-film electrodes that can reach deep brain structures - at a depth that is necessary for therapeutic reasons - enabling reproducible, customizable, and high-throughput production of electrodes but with a high spatial resolution and channel count despite a thinner electrode body. Additionally, the electrode insertion is compatible with existing surgical techniques in the operating room, lowering the barrier for their adoption in clinical procedures,” said UC San Diego electrical engineering professor Shadi Dayeh, the corresponding author on the new paper.
The design, manufacture, experimental testing and analysis of results from this system was performed by a cross-disciplinary team of engineers, surgeons, and medical researchers from UC San Diego; Harvard Medical School and Massachusetts General Hospital; and Oregon Health and Science University.
Dayeh advises two of the three first authors on the paper: UC San Diego postdoctoral researcher Keundong Lee and UC San Diego graduate student researcher Yun Goo Ro. Angelique C. Paulk, also a first author, is a researcher at Massachusetts General Hospital and Harvard Medical School in a group led by neurologist Dr. Sydney Cash.
Toward a 30 day wireless brain-recording system
The kind of system researchers developed is needed in order to identify the very specific regions of the brain that are triggering seizures caused by treatment-resistant epilepsy. To meet this goal, the team is working toward their vision of a brain-monitoring system with sensors both inserted deep within the brain and sensors on the surface of the brain. These sensors will communicate wirelessly with a small computer system in a wireless cap, which a person could wear for extended periods of time. This cap would provide wireless power and the computational infrastructure to capture the brain signals being recorded from a person's brain for 30 days.
“We are currently focused on applying the technology to patients with treatment-resistant epilepsy. The ultimate goal is to advance the system and related required technologies by 2026 to give patients access to a wireless system that allows them to move freely within the hospital environment and then at home, without being tethered to any machinery, while cortical and deep brain structures are monitored continuously for up to 30 days,” Dayeh said.
The system is called the UC San Diego Micro-stereo-electro-encephalography (µSEEG). The technology that is used to create the device can be manufactured at high volume and low cost because it is derived from existing technologies to manufacture digital display screens, an approach that was originally created by the semiconductor industry. This unique manufacturing process also allows for a series of unique features for these depth electrodes (see sidebar).
Experimental subjects
In the new paper, the team reports the functioning of the new system in two human patients. The team also presents data from a series of different animal models including successful recordings from rat barrel cortex in both acute and chronic settings; recording of the somatosensory cortex in an anesthetized pig; and recordings in non-human primates at different depths inside the brain.
The data on the successful functioning of the device in humans were collected, with all proper approvals and consent, during already scheduled tumor-removal surgeries. During an unrelated pause in the surgery, clinicians inserted the new depth probes into brain tissue that was about to be removed.
“In a true test of the translational feasibility of the µSEEG,” the authors write in the Nature Communications paper, referring to the technical term for their device, “we acutely implanted short 64 channel µSEEG electrodes in the middle temporal gyrus in two separate human patient participants undergoing temporal lobe resection for clinical reasons. With each participant, we inserted a single 64 channel short µSEEG device into tissue, which the clinical team determined would be resected.” The recordings lasted 10 minutes and were able to record ongoing spontaneous activity.
