Data availability
All electrophysiological data relevant to the figures presented in this paper are available via GitHub at https://github.com/klshepard/bisc with a version archived in Zenodo (https://doi.org/10.5281/zenodo.17074065)70. All other relevant data are available from the corresponding authors upon reasonable request.
Code availability
All scripts used for the data analysis are available via GitHub at https://github.com/klshepard/bisc. All other relevant codes are available from the corresponding authors upon reasonable request.
References
Biasiucci, A., Franceschiello, B. & Murray, M. M. Electroencephalography. Curr. Biol. 29, R80–R85 (2019).
Nicolelis, M. A. L., Ghazanfar, A. A., Faggin, B. M., Votaw, S. & Oliveira, L. M. O. Reconstructing the engram: simultaneous, multisite, many single neuron recordings. Neuron 18, 529–537 (1997).
Maynard, E. M., Nordhausen, C. T. & Normann, R. A. The Utah Intracortical Electrode Array: a recording structure for potential brain-computer interfaces. Electroencephalogr. Clin. Neurophysiol. 102, 228–239 (1997).
Polikov, V. S., Tresco, P. A. & Reichert, W. M. Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148, 1–18 (2005).
Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y. & Purcell, E. K. Glial responses to implanted electrodes in the brain. Nat. Biomed. Eng. 1, 862–877 (2017).
Rousche, P. J. & Normann, R. A. Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex. J. Neurosci. Methods 82, 1–15 (1998).
Chestek, C. A. et al. Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex. J. Neural Eng. 8, 045005 (2011).
Volkova, K., Lebedev, M. A., Kaplan, A. & Ossadtchi, A. Decoding movement from electrocorticographic activity: a review. Front. Neuroinform. 13, 74 (2019).
Nurse, E. S. et al. Consistency of long-term subdural electrocorticography in humans. IEEE Trans. Biomed. Eng. 65, 344–352 (2018).
Yan, T. et al. Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces. Front. Neurosci. 17, 1260675 (2023).
Chiang, C.-H. et al. Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates. Sci. Transl. Med. 12, eaay4682 (2020).
Tchoe, Y. et al. Human brain mapping with multithousand-channel PtNRGrids resolves spatiotemporal dynamics. Sci. Transl. Med. 14, eabj1441 (2022).
Kaiju, T. et al. High spatiotemporal resolution ECoG recording of somatosensory evoked potentials with flexible micro-electrode arrays. Front. Neural Circuits 11, 20 (2017).
Wang, P. T. et al. Comparison of decoding resolution of standard and high-density electrocorticogram electrodes. J. Neural Eng. 13, 026016 (2016).
Duraivel, S. et al. High-resolution neural recordings improve the accuracy of speech decoding. Nat. Commun. 14, 6938 (2023).
Khodagholy, D. et al. NeuroGrid: recording action potentials from the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).
Steinmetz, N. A. et al. Neuropixels 2.0: a miniaturized high-density probe for stable, long-term brain recordings. Science 372, eabf4588 (2021).
Carmena, J. M. et al. Learning to control a brain–machine interface for reaching and grasping by primates. PLoS Biol. 1, e42 (2003).
Hochberg, L. R. et al. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012).
Gilletti, A. & Muthuswamy, J. Brain micromotion around implants in the rodent somatosensory cortex. J. Neural Eng. 3, 189 (2006).
Biran, R., Martin, D. C. & Tresco, P. A. The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. J. Biomed. Mater. Res. A 82A, 169–178 (2007).
Schwarz, D. A. et al. Chronic, wireless recordings of large-scale brain activity in freely moving rhesus monkeys. Nat. Methods 11, 670–676 (2014).
Zhou, A. et al. A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates. Nat. Biomed. Eng. 3, 15–26 (2018).
Topalovic, U. et al. A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans. Nat. Neurosci. https://doi.org/10.1038/s41593-023-01260-4 (2023).
Oxley, T. J. et al. Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. Nat. Biotechnol. 34, 320–327 (2016).
Benabid, A. L. et al. An exoskeleton controlled by an epidural wireless brain–machine interface in a tetraplegic patient: a proof-of-concept demonstration. Lancet Neurol. 18, 1112–1122 (2019).
Musk, E. An integrated brain-machine interface platform with thousands of channels. J. Med. Internet Res. 21, e16194 (2019).
Hariz, M. I. Complications of deep brain stimulation surgery. Mov. Disord. 17, S162–S166 (2002).
Jitkritsadakul, O. et al. Systematic review of hardware-related complications of deep brain stimulation: do new indications pose an increased risk? Brain Stimul. 10, 967–976 (2017).
Zeng, N. et al. A wireless, mechanically flexible, 25 μm-thick, 65,536-channel subdural surface recording and stimulating microelectrode array with integrated antennas. In Proc. IEEE Symposium on VLSI Technology and Circuits 1–2 (IEEE, 2023).
Harrison, R. R. & Charles, C. A. low-power, low-noise CMOS amplifier for neural recording applications. IEEE J. Solid-State Circuits 38, 958–965 (2003).
Zhang, M. et al. Wireless compact neural interface for freely moving animal subjects: a review on wireless neural interface SoC designs. IEEE Solid-State Circuits Mag. 15, 20–29 (2023).
Weiland, J. D., Anderson, D. J. & Humayun, M. S. In vitro electrical properties for iridium oxide versus titanium nitride stimulating electrodes. IEEE Trans. Biomed. Eng. 49, 1574–1579 (2002).
Raducanu, B. C. et al. Time multiplexed active neural probe with 1n356 parallel recording sites. Sensors 17, 2388 (2017).
IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields, 3 kHz to 300 GHz (IEEE, 2006).
Thimot, J. & Shepard, K. L. Bioelectronic devices: wirelessly powered implants. Nat. Biomed. Eng. 1, 0051 (2017).
Kim, S., Tathireddy, P., Normann, R. A. & Solzbacher, F. Thermal impact of an active 3-D microelectrode array implanted in the brain. IEEE Trans. Neural Syst. Rehabil. Eng. 15, 493–501 (2007).
Marblestone, A. H. et al. Physical principles for scalable neural recording. Front. Comput. Neurosci. 7, 137 (2013).
Craner, S. L. & Ray, R. H. Somatosensory cortex of the neonatal pig. I. Topographic organization of the primary somatosensory cortex (SI). J. Comp. Neurol. 306, 24–38 (1991).
Okada, Y., Lähteenmäki, A. & Xu, C. Comparison of MEG and EEG on the basis of somatic evoked responses elicited by stimulation of the snout in the juvenile swine. Clin. Neurophysiol. 110, 214–229 (1999).
Sauleau, P., Lapouble, E., Val-Laillet, D. & Malbert, C. H. The pig model in brain imaging and neurosurgery. Animal 3, 1138–1151 (2009).
van der Maaten, L. aurens & Hinton, G. Visualizing data using t-SNE. J. Mach. Learn. Res. 9, 2579 (2008).
Pollmann, E. H. et al. A subdural CMOS optical device for bidirectional neural interfacing. Nat. Electron. 7, 829–841 (2024).
Mitra, P. P. & Pesaran, B. Analysis of dynamic brain imaging data. Biophys. J. 76, 691–708 (1999).
Stavisky, S. D., Kao, J. C., Nuyujukian, P., Ryu, S. I. & Shenoy, K. V. A high performing brain–machine interface driven by low-frequency local field potentials alone and together with spikes. J. Neural Eng. 12, 036009 (2015).
Thomson, D. J. Spectrum estimation and harmonic analysis. Proc. IEEE 70, 1055–1096 (1982).
Wold, S., Sjöström, M. & Eriksson, L. PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst. 58, 109–130 (2001).
Das, A., Zabeh, E., Ermentrout, B. & Jacobs, J. Planar, spiral, and concentric traveling waves distinguish cognitive states in human memory. Preprint at bioRxiv https://doi.org/10.1101/2024.01.26.577456 (2024).
Zabeh, E., Foley, N. C., Jacobs, J. & Gottlieb, J. P. Beta traveling waves in monkey frontal and parietal areas encode recent reward history. Nat. Commun. 14, 5428 (2023).
Deng, J. et al. ImageNet: a large-scale hierarchical image database. In Proc. IEEE Conference on Computer Vision and Pattern Recognition 248–255 (IEEE, 2009).
Willeke, K. F. et al. Deep learning-driven characterization of single cell tuning in primate visual area V4 unveils topological organization. Preprint at bioRxiv https://doi.org/10.1101/2023.05.12.540591 (2023).
Jia, X., Tanabe, S. & Kohn, A. Gamma and the coordination of spiking activity in early visual cortex. Neuron 77, 762–774 (2013).
Woo, S. et al. ConvNeXt V2: co-designing and scaling ConvNets with masked autoencoders. In Proc. IEEE/CVF Conference on Computer Vision and Pattern Recognition 16133–16142 (IEEE, 2023).
Pierzchlewicz, P. et al. Energy guided diffusion for generating neurally exciting images. Adv. Neural Inf. Process. Syst. 36, 32574–32601 (2023).
Cadena, S. A. et al. Diverse task-driven modeling of macaque V4 reveals functional specialization towards semantic tasks. PLOS Comp. Biol. 20, e1012056 (2024).
Walker, E. Y. et al. Inception loops discover what excites neurons most using deep predictive models. Nat. Neurosci. 22, 2060–2065 (2019).
Fu, J. et al. Pattern completion and disruption characterize contextual modulation in mouse visual cortex. Preprint at bioRxiv https://doi.org/10.1101/2023.03.13.532473 (2023).
Franke, K. et al. State-dependent pupil dilation rapidly shifts visual feature selectivity. Nature 610, 128–134 (2022).
Cowley, B. R., Stan, P. L., Pillow, J. W. & Smith, M. A. Compact deep neural network models of visual cortex. Preprint at bioRxiv https://doi.org/10.1101/2023.11.22.568315 (2023).
Bashivan, P., Kar, K. & DiCarlo, J. J. Neural population control via deep image synthesis. Science 364, eaav9436 (2019).
Zhang, H., Watrous, A. J., Patel, A. & Jacobs, J. Theta and alpha oscillations are traveling waves in the human neocortex. Neuron 98, 1269–1281.e1264 (2018).
Das, A. et al. Spontaneous neuronal oscillations in the human insula are hierarchically organized traveling waves. eLife 11, e76702 (2022).
Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006).
Kara, P. & Boyd, J. D. A micro-architecture for binocular disparity and ocular dominance in visual cortex. Nature 458, 627–631 (2009).
Willett, F. R. et al. A high-performance speech neuroprosthesis. Nature 620, 1031–1036 (2023).
Metzger, S. L. et al. A high-performance neuroprosthesis for speech decoding and avatar control. Nature 620, 1037–1046 (2023).
Sokal, N. O. & Sokal, A. D. Class E—a new class of high-efficiency tuned single-ended switching power amplifiers. IEEE J. Solid-State Circuits 10, 168–176 (1975).
Lim, Y., Tang, H., Lim, S. & Park, J. An adaptive impedance-matching network based on a novel capacitor matrix for wireless power transfer. IEEE Trans. Power Electron. 29, 4403–4413 (2014).
Ferro, M. D. & Melosh, N. A. Electronic and ionic materials for neurointerfaces. Adv. Funct. Mater. 28, 1704335 (2018).
Jung, T. et al. klshepard/bisc: bioelectronic interface system to the cortex (a wireless subdural-contained 65,536-electrode, 1,024-channel brain-computer interface). Zenodo https://doi.org/10.5281/zenodo.17074065 (2025).
Calabrese, E. et al. A diffusion tensor MRI atlas of the postmortem rhesus macaque brain. Neuroimage 117, 408–416 (2015).
Bakker, R., Tiesinga, P. & Kötter, R. The Scalable Brain Atlas: instant web-based access to public brain atlases and related content. Neuroinformatics 13, 353–366 (2015).
Acknowledgements
This work was partly supported by the Defense Advanced Research Project Agency (DARPA) under contract number N66001-17-C-4001, the Department of the Defense Congressionally Directed Medical Research Program under contract number HT9425-23-1-0758, the National Science Foundation under grant number 1546296 and the National Institutes of Health under grant number R01DC019498. We acknowledge the use of facilities and instrumentation at the Columbia Nano Initiative, the CUNY ASRC and the UPenn Quattrone Nanofabrication Facility. We also thank Y. Borisenkov, A. Banees and K. Kim at Columbia University for help with chip processing and many helpful discussions.
Ethics declarations
Competing interests
N.Z. is a principal with Kampto Neurotech, LLC, which is commercializing the BISC technology. The BISC technology is patented under US patent 11617890, issued on 4 April 2023, and exclusively licensed to Kampto from Columbia University. The other authors declare no competing interests.
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Extended data
Extended Data Fig. 1 Bench-top in vitro characterization of the BISC implant.
(a) Electrochemical impedance spectroscopy of titanium nitride electrode. (b) Frequency response across different gain configurations from a representative 16×16 recording. Note that gain is programmed through a single back-end amplifier that is shared by all pixels. Error bars indicate standard error (SE), and dashed rectangle marks the effects of boxcar sampling (flat band gains: 53.7 ± 0.20 dB, 57.2 ± 0.21 dB, 60.7 ± 0.20 dB, 64.2 ± 0.19 dB, values: mean ± SD. n = 255, 255, 245, 235). (c) Histogram of normalized channel gain variation for each recording mode (16×16 mode: 100 ± 5.1%, 32×32 mode: 100 ± 4.8%, values: mean ± SD. n = 15,163 and 62,245). (d) Frequency response across different high-pass (HP) filter configurations from a representative 16×16 recording. Error bars indicate SE (3-dB corner: 4.19 ± 2.28 Hz, 13.30 ± 2.37 Hz, 54.42 ± 1.98 Hz, values: mean ± SD. n = 244, 254, 256). (e) Input-referred noise (IRN) spectrum averaged over representative pixels (n = 10) for each recording mode. (f) Histogram of channel IRN for each recording mode, integrated from 10 Hz to 4 kHz (16×16 mode: 7.68 ± 3.11 μVRMS, 32×32 mode: 16.51 ± 6.85 μVRMS, values: mean ± SD. n = 15,163 and 62,245).
Extended Data Fig. 2 BISC recordings over visual cortex with natural images.
(a) We presented static colored natural images, while the monkey maintained fixation (120 ms presentation time per image, 15 images per trial, 1200 ms inter-trial period). Each image (10°×10°) was centered 3° to the right and below the fixation spot. (b) Model architecture: Pre-processed stimuli (184 × 184 pixels) and neuronal responses were used to train a neural predictive model, which takes images as an input and outputs an estimate of the underlying neuronal activity. We passed the images through a ConvNext model, pre-trained on an image classification task to obtain image embeddings, that is a shared feature space. We then computed the neuronal responses by passing the feature activations through a transformer-based readout followed by a non-linearity stage. (c) Explainable variance, a measure of response reliability to natural images, plotted against the model’s predictive performance (correlation between prediction and average neural response to repeated presentations) of all 144 channels (explainable variance 0.24 ± 0.09, and correlation to average 0.69 ± 0.14. values: mean ± SD). Only channels with an explainable variance greater than or equal to 0.1 are included in these analyses. (d) Spatial map of explainable variance across the recording array (same layout as in Fig. 4 and Fig. 5e). (e) Same as (d), but showing the model’s predictive performance (correlation to average neural response). (f) Schematic illustrating optimization of maximally exciting images (MEIs). A random starting image was iteratively optimized to elicit maximal activity for each in-silico channel, revealing the visual features to which that channel is selective. Three example MEIs from areas V1, V2, and V4 are shown. (g) MEIs for all 144 channels across the array which reliably responded to repeated image presentations. MEIs in area V1 are characterized by oriented Gabor filters, while the channels overlying area V2 and V4 exhibit more complex, color opponent feature tuning. Credit: cow image in a,b, Nicolas Vigier, flickr under a Creative Commons license CC0.
Supplementary information
Supplementary Information
Supplementary Discussions 1–10, Figs. 1–26, Tables 1 and 2, and captions for Videos 1–9.
Reporting Summary
Supplementary Video 1
Normalized somatosensory evoked potential (SSEP) recording from a porcine model, trial averaged (n = 100 per location).
Supplementary Video 2
Motor cortex recording from a NHP model performing asynchronous reach-and-grab task.
Supplementary Video 3
Dot-triggered-average responses of all channels without filtering.
Supplementary Video 4
Dot-triggered-average responses of all channels after wavelet transformation (central frequency 8 Hz).
Supplementary Video 5
Dot-triggered-average responses of all channels after wavelet transformation (central frequency 16 Hz).
Supplementary Video 6
Dot-triggered-average responses of all channels after wavelet transformation (central frequency 32 Hz).
Supplementary Video 7
Dot-triggered-average responses of all channels after wavelet transformation (central frequency 64 Hz).
Supplementary Video 8
Dot-triggered-average responses of all channels after wavelet transformation (central frequency 128 Hz).
Supplementary Video 9
Dot-triggered travelling waves used for decoding stimuli location. The travelling waves are computed from the γ-band (30–90 Hz) signals recorded from 32 × 32 spatially dense channels at a pitch of 26.5 μm × 29 μm. The spatiotemporal sequence of these travelling waves, measured within each dot presentation, is used to predict the current location of the dot stimuli presented to the subject.
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Jung, T., Zeng, N., Fabbri, J.D. et al. A wireless subdural-contained brain–computer interface with 65,536 electrodes and 1,024 channels. Nat Electron 8, 1272–1288 (2025). https://doi.org/10.1038/s41928-025-01509-9
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DOI: https://doi.org/10.1038/s41928-025-01509-9