Objective. Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans. Approach. We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities. Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution. Significance. Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

Objective. The force that an electrocorticography (ECoG) array exerts on the brain manifests when it bends to match the curvature of the skull and cerebral cortex. This force can negatively impact both short-term and long-term patient outcomes. Here we provide a mechanical characterization of a novel Liquid Crystal Polymer (LCP) ECoG array prototype to demonstrate that its thinner geometry reduces the force potentially applied to the cortex of the brain. Approach. We built a low-force flexural testing machine to measure ECoG array bending forces, calculate their effective flexural moduli, and approximate the maximum force they could exerted on the human brain. Main Results. The LCP ECoG prototype was found to have a maximal force less than 20% that of any commercially available ECoG arrays that was tested. However, as a material, LCP was measured to be as much as 24x more rigid than silicone, which is traditionally used in ECoG arrays. This suggests that the lower maximal force resulted from the prototype’s thinner profile (2.9x-3.25x). Significance. While decreasing material stiffness can lower the force an ECoG array exhibits, our LCP ECoG array prototype demonstrated that flexible circuit manufacturing techniques can also lower these forces by decreasing ECoG array thickness. Flexural tests of ECoG arrays are necessary to accurately assess these forces, as material properties for polymers and laminates are often scale dependent. As the polymers used are anisotropic, elastic modulus cannot be used to predict ECoG flexural behavior. Accounting for these factors, we used our four-point flexure testing procedure to quantify the forces exerted on the brain by ECoG array bending. With this experimental method, ECoG arrays can be designed to minimize force excerted on the brain, potentially improving both acute and chronic clinical utility.