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1. Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS

   https://doi.org/10.1038/s41928-023-01013-y  

   Taal, Adriaan J.; Uguz, Ilke; Hillebrandt, Sabina; Moon, Chang-Ki; Andino-Pavlovsky, Victoria; Choi, Jaebin; Keum, Changmin; Deisseroth, Karl; Gather, Malte C.; Shepard, Kenneth L. (January 2023, Nature Electronics)

   Abstract The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice. 

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2. High Throughput Neuromorphic Brain Interface with CuO _x Resistive Crossbars for Real-time Spike Sorting

   https://doi.org/10.1109/IEDM19574.2021.9720712  

   Shi, Yuhan; Ananthakrishnan, Akshay; Oh, Sangheon; Liu, Xin; Hota, Gopabandhu; Cauwenberghs, Gert; Kuzum, Duygu (December 2021, IEEE International Electron Devices Meeting)

   Real-time spike sorting with large data throughput is essential for studying neural dynamics and brain-machine interfaces. Neural recordings from high-density multi-electrode arrays that consist of hundreds of electrodes impose stringent demands on spike sorting hardware regarding data transmission bandwidth and computation complexity. That leads to an urgent need for specialized hardware with high throughput, low power, and latency. Here, we present a real-time spike sorting processor that utilizes high-density BEOL-integrable CuO x resistive crossbars to perform in-memory spike segregation. We experimentally demonstrate, for the first time, efficient hardware implementation of spike sorting from in vivo extracellular recordings with high accuracy. Our neuromorphic interface promises substantial performance gains ( ∼1000×less area,∼200×less power,4.8 μs latency for sorting 100 channels) for in vivo real-time spike sorting. 

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3. Synapses without tension fail to fire in an in vitro network of hippocampal neurons

   https://doi.org/10.1073/pnas.2311995120  

   Joy, Md Saddam; Nall, Duncan L.; Emon, Bashar; Lee, Ki Yun; Barishman, Alexandra; Ahmed, Movviz; Rahman, Saeedur; Selvin, Paul R.; Saif, M. Taher (December 2023, Proceedings of the National Academy of Sciences)

   Neurons in the brain communicate with each other at their synapses. It has long been understood that this communication occurs through biochemical processes. Here, we reveal that mechanical tension in neurons is essential for communication. Using in vitro rat hippocampal neurons, we find that 1) neurons become tout/tensed after forming synapses resulting in a contractile neural network, and 2) without this contractility, neurons fail to fire. To measure time evolution of network contractility in 3D (not 2D) extracellular matrix, we developed an ultrasensitive force sensor with 1 nN resolution. We employed Multi-Electrode Array and iGluSnFR, a glutamate sensor, to quantify neuronal firing at the network and at the single synapse scale, respectively. When neuron contractility is relaxed, both techniques show significantly reduced firing. Firing resumes when contractility is restored. This finding highlights the essential contribution of neural contractility in fundamental brain functions and has implications for our understanding of neural physiology. 

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4. Fully desktop fabricated flexible graphene electrocorticography (ECoG) arrays

   https://doi.org/10.1088/1741-2552/acae08  

   Hu, Jia; Hossain, Ridwan Fayaz; Navabi, Zahra S; Tillery, Alana; Laroque, Michael; Donaldson, Preston D; Swisher, Sarah L; Kodandaramaiah, Suhasa B (January 2023, Journal of Neural Engineering)

   Abstract Objective: Flexible Electrocorticography (ECoG) electrode arrays that conform to the cortical surface and record surface field potentials from multiple brain regions provide unique insights into how computations occurring in distributed brain regions mediate behavior. Specialized microfabrication methods are required to produce flexible ECoG devices with high-density electrode arrays. However, these fabrication methods are challenging for scientists without access to cleanroom fabrication equipment. Results: Here we present a fully desktop fabricated flexible graphene ECoG array. First, we synthesized a stable, conductive ink via liquid exfoliation of Graphene in Cyrene. Next, we established a stencil-printing process for patterning the graphene ink via laser-cut stencils on flexible polyimide substrates. Benchtop tests indicate that the graphene electrodes have good conductivity of ∼1.1 × 10 3 S cm −1 , flexibility to maintain their electrical connection under static bending, and electrochemical stability in a 15 d accelerated corrosion test. Chronically implanted graphene ECoG devices remain fully functional for up to 180 d, with average in vivo impedances of 24.72 ± 95.23 kΩ at 1 kHz. The ECoG device can measure spontaneous surface field potentials from mice under awake and anesthetized states and sensory stimulus-evoked responses. Significance: The stencil-printing fabrication process can be used to create Graphene ECoG devices with customized electrode layouts within 24 h using commonly available laboratory equipment. 

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5. A fully transparent, flexible PEDOT:PSS–ITO–Ag–ITO based microelectrode array for ECoG recording

   https://doi.org/10.1039/d0lc01123a  

   Yang, Weiyang; Gong, Yan; Yao, Cheng-You; Shrestha, Maheshwar; Jia, Yaoyao; Qiu, Zhen; Fan, Qi Hua; Weber, Arthur; Li, Wen (March 2021, Lab on a Chip)

   null (Ed.)

   Integrative neural interfaces combining neurophysiology and optogenetics with neural imaging provide numerous opportunities for neuroscientists to study the structure and function of neural circuits in the brain. Such a comprehensive interface demands miniature electrode arrays with high transparency, mechanical flexibility, electrical conductivity, and biocompatibility. Conventional transparent microelectrodes made of a single material, such as indium tin oxide (ITO), ultrathin metals, graphene and poly-(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS), hardly possess the desired combination of those properties. Herein, ultra-flexible, highly conductive and fully transparent microscale electrocorticogram (μECoG) electrode arrays made of a PEDOT:PSS–ITO–Ag–ITO assembly are constructed on thin parylene C films. The PEDOT:PSS–ITO–Ag–ITO assembly achieves a maximum ∼14% enhancement in light transmission over a broad spectrum (350–650 nm), a significant reduction in electrochemical impedance by 91.25%, and an increase in charge storage capacitance by 1229.78 μC cm −2 . Peeling, bending, and Young's modulus tests verify the enhanced mechanical flexibility and robustness of the multilayer assembly. The μECoG electrodes enable electrical recordings with high signal-to-noise ratios (SNRs) (∼35–36 dB) under different color photostimulations, suggesting that the electrodes are resilient to photon-induced artifacts. In vivo animal experiments confirm that our array can successfully record light-evoked ECoG oscillations from the primary visual cortex (V1) of an anesthetized rat. 

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