Foldable three dimensional neural electrode arrays for simultaneous brain interfacing of cortical surface and intracortical multilayers

The brain's complex network of neurons is crucial for cognitive function, memory, and communication. Neural interfaces capable of accurately mapping these circuits are vital for understanding brain function and diagnosing diseases. Electrophysiological approaches, such as electrocorticography (ECOG) for surface recording, multi-shank Utah arrays for intracortical recording, and multi-channel Michigan probes for deep brain recording, offer excellent temporal resolution. However, existing methods have limitations: ECOG provides high-resolution surface signals but lacks intracortical detail, while penetrating probes offer intracortical information but lack surface context. Simultaneous recording from both surface and intracortical areas is crucial for understanding 3D neural transmission, but current technologies face challenges in achieving this. Previous attempts at 3D recording using multi-channel arrays or individually implanted ECOG and penetrating probes suffer from limited spatial coverage or temporal resolution due to signal timing discrepancies. Furthermore, rigid silicon-based probes and ECOG arrays often cause inflammation and neuronal damage due to mechanical mismatch with brain tissue. Flexible electronics offer a solution, providing conformal contact and reducing tissue damage. This study introduces a flexible device with extended recording coverage from the brain's surface to its interior, enabling accurate 3D electrophysiological recording and addressing the limitations of previous technologies.

The introduction extensively reviews existing neural interface technologies, highlighting the advantages and limitations of ECOG arrays, Utah arrays, and Michigan probes. It discusses previous attempts to achieve 3D brain signal recording, noting their shortcomings in terms of spatial coverage, temporal resolution, and biocompatibility. The authors specifically mention studies using multi-shank interfaces, injectable mesh electrodes, and separate ECOG and penetrating probe implants. The literature review emphasizes the need for a flexible, integrated device capable of simultaneous surface and intracortical recording to overcome the limitations of existing technologies and provide a more comprehensive understanding of 3D brain networks.

The study describes the design and fabrication of a foldable and flexible 3D neural electrode array. The device integrates surface ECOG electrodes and penetrating shanks, mimicking the functionalities of ECOG arrays, Utah arrays, and Michigan probes. The fabrication process involves multiple steps: planar patterning of polyimide (PI) substrate, gold (Au)/chromium (Cr) deposition, photolithographic patterning, reactive ion etching (RIE), and a pop-up process to create the 3D structure. The pop-up structure is achieved by partially bonding a pre-stretched elastomer to the device, creating a flexible hinge mechanism. Penetrating shanks are temporarily stiffened with polyethylene glycol (PEG) for implantation, then the PEG dissolves, restoring the flexibility. The recording sites are electroplated with platinum (Pt) black to reduce impedance. The device's mechanical properties, including bending stiffness, are analyzed using finite element analysis (FEA). In vitro experiments assess the device's electrical characteristics (electrochemical impedance spectroscopy, EIS) before and after PEG coating and during PEG dissolution. Biocompatibility is tested using PC12 cells, NIH 3T3 cells, and primary cortical neurons. In vivo experiments involve implanting the device in the mouse barrel cortex and recording electrophysiological signals during unidirectional whisker stimulation. Data analysis includes spike sorting, LFP signal analysis, and 3D heatmap visualization of signal propagation. The study includes detailed descriptions of all fabrication processes, materials used, and experimental setups.

The researchers successfully fabricated a foldable and flexible 3D neural electrode array integrating surface and intracortical electrodes. The pop-up structure and use of PEG enabled successful implantation with minimal tissue damage. In vitro tests demonstrated low impedance and biocompatibility. In vivo experiments showed the device's ability to simultaneously record local field potentials (LFPs) and single-unit activity from both surface and intracortical regions during whisker stimulation. The unidirectional whisker stimulation evoked synchronized single spikes and LFP changes, indicating successful recording of functional neural connectivity across different brain regions. 3D heatmaps visually demonstrated the spatiotemporal propagation of neural signals, showing distinct patterns for different whisker stimulation sequences. These results highlight the device’s effectiveness in measuring 3D neuronal propagation patterns.

The successful integration of surface and intracortical electrodes in a flexible, foldable device offers significant advantages over existing technologies. The findings demonstrate the potential to investigate complex 3D neural circuit dynamics with high spatiotemporal resolution. The simultaneous recording of LFPs and single-unit activity enables detailed analysis of neural information processing. The observation of synchronized spiking activity during whisker stimulation suggests the potential for studying functional connectivity within the brain. The 3D heatmap visualization effectively illustrates signal propagation patterns, providing valuable insights into neural network organization. The device's flexibility and biocompatibility minimize tissue damage and inflammation, improving long-term stability and reducing the risk of adverse effects. These results highlight the device's potential in advancing neuroscience research and clinical applications.

This study successfully demonstrated a novel foldable and flexible 3D neural electrode array capable of simultaneously recording electrophysiological signals from both cortical surface and intracortical multilayers. The device’s unique design, fabrication, and biocompatibility offer a significant advancement in neural interface technology. Future work should focus on increasing the number of recording channels to enhance spatial resolution and investigate the potential for chronic implantation and clinical applications. The device could be a valuable tool in studying brain function and neurologic disorders.

The current design has a limited number of recording channels due to spatial constraints. The long-term stability and biocompatibility of the device need further investigation in chronic in vivo studies. The study was conducted using a specific animal model and brain region; the device's applicability to other brain areas and species requires further validation. The analysis primarily focused on evoked responses during whisker stimulation; spontaneous neural activity requires more detailed investigation.