A High-density Microelectrode for Human Neuronal Recordings

Description

Recording of human brain activity at many scales is an important tool in clinical medicine. The ability to record extracellular action potentials, otherwise known as a “single unit activity” (SUA) has provided fundamental insight into the details of neuronal function in humans as well as a variety of nonhuman animals. In humans the techniques for recording extracellular action potentials are relatively limited. Rigid, sharp tipped probes manufactured by several companies are FDA approved and routinely used as part of standard of care during a variety of surgical procedures such as deep brain stimulation (DBS) device implantation to identify areas of neuronal activity and optimize placement of clinical electrodes. The same technique has been used to better understand brain function and its impairment by disease in humans. In addition, a variety of semi- chronically implanted microwire techniques are available. These electrodes are more commonly used in patients with seizure disorders and have allowed insight into network behavior such as in the medial temporal lobe and medial frontal lobe.

However there remains a tremendous gap between the recording capabilities of modern electrodes used in animal research, and what is currently clinically available for human testing. A typical rigid shaft single electrode currently used in clinical care will record anywhere from 1-3 distinctly isolated neurons at a time. In contrast, in state-of-the art animal research, higher density probes such as the Neuropixel electrode [4-6] now routinely allow recording of hundreds or even thousands of neurons in a single brain region. This markedly increased recording capability translates directly into a better understanding of how brain neurons and networks interact to create complex behaviors and disease. Most of the commonly used high-density electrodes are based on a rigid silicon shaft onto which multiple recording contacts (typically made of platinum, Iridium, gold or conductive polymers) are embedded. There are several significant limitations of silicon-based probes in translating them to large brain, and in particular human, applications [7] First, silicon is fragile, making the electrodes prone to fracture, which makes them risky for human applications. Furthermore, the silicon microfabrication process is impractical for making large devices, limiting commercially available probe length to around 20mm, which is too short for most clinical applications in the human brain. Also, the connection between the electrode contacts and the pre-amplifier in the currently available products requires a rigid circuit board that is attached to the electrode, which is difficult to work with and which requires that the pre-amplifiers to be kept very close to the brain. While there are FDA approved version of silicon probes (i.e. the Utah Array used for brain machine interfaces), these applications are limited to short 100mm is required for probing deep brain structures such as the basal ganglia in the human brain, which is routinely done in clinical settings. The DBC electrode can record up to 1024 individual channels simultaneously. The DBC devices have been used successfully in nonhuman primates and have undergone the biocompatibility, cytotoxicity, sterilization, and safety testing expected for use in humans. The results of these tests were all a pass, and the resulting reports are attached to this protocol.