Large-scale high-density brain-wide neural recording in nonhuman primates

Creators: Trautmann, Eric M.; Hesse, Janis K.; Stine, Gabriel M.; Xia, Ruobing; Zhu, Shude; O'Shea, Daniel J.; Karsh, Bill; Colonell, Jennifer; Lanfranchi, Frank F.; Vyas, Saurabh; Zimnik, Andrew; Amematsro, Elom; Steinmann, Natalie A.; Wagenaar, Daniel A.; Pachitariu, Marius; Andrei, Alexandru; Mora Lopez, Carolina; O'Callaghan, John; Putzeys, Jan; Raducanu, Bogdan C.; Welkenhuysen, Marleen; Churchland, Mark; Moore, Tirin; Shadlen, Michael; Shenoy, Krishna; Tsao, Doris; Dutta, Barundeb; Harris, Timothy

Abstract

High-density silicon probes have transformed neuroscience by enabling large-scale neural recordings at single-cell resolution. However, existing technologies have provided limited functionality in nonhuman primates (NHPs) such as macaques. In the present report, we describe the design, fabrication and performance of Neuropixels 1.0 NHP, a high-channel electrode array designed to enable large-scale acute recording throughout large animal brains. The probe features 4,416 recording sites distributed along a 45-mm shank. Experimenters can programmably select 384 recording channels, enabling simultaneous multi-area recording from thousands of neurons with single or multiple probes. This technology substantially increases scalability and recording access relative to existing technologies and enables new classes of experiments that involve electrophysiological mapping of brain areas at single-neuron and single-spike resolution, measurement of spike–spike correlations between cells and simultaneous brain-wide recordings at scale.

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Acknowledgement

We thank the Howard Hughes Medical Institute (HHMI) for their support; they funded the development of the probe. We thank Y. Pavlova, D. Abreu Lopes, S. Cital, C. Duhaney, B. Madeira, M. Ricsch and M. Wechsler for surgical assistance and expert veterinary care and their assistance in the planning and execution of surgeries, animal training and general support, and S. Ryu for surgical expertise. We thank B. Schneeveis and T. Tabachnik for engineering assistance. In addition, we thank Columbia University’s ICM for the quality of care that they provided for our animals, especially during the pandemic and lockdown. We thank W.-l. Sun, for probe testing and software development (HHMI Janelia). This work was supported by the HHMI, the Kavli institute at Columbia University, the Simons Foundation and the Grossman Center for the Statistic of Mind. E.M.T. was supported by the Grossman Center and the Brain and Behavior Research Foundation. S.V. was supported by the NIH National Research Service Award, National Institute of Neurological Disorders and Stroke (F32). N.A.S. and M.S. were supported by the NIH Brain Initiative (grant no. R01NS113113) and AFOSR (grant no. 21RT0878 09/2022–08/2027) and N.A.S. was supported by the NIH/National Institute of Mental Health (grant no. R01MH122513). G.M.S. ws supported by the National Eye Institute (grant nos. T32 EY013933 and F31 EY032791). T.M. was supported by grant nos. EY014924 and NS116623. A.Z. was supported by the American Parkinson Disease Post-Doctoral Fellowship. D.J.O. was supported by the Simons Collaboration on the Global Brain (grant no. 543045). J.K.H., F.F.L. and D.Y.T. were supported by the NIH (grant nos. DP1-NS083063 and EY030650-01), the HHMI, the Simons Foundation, the Human Frontiers in Science Program and the Office of Naval Research. The funders had no role in study design, data collection and analysis or decision to publish the manuscript.

Data Availability

Data to replicate key analyses shown in Figs. 1–6 and 8 are available via Zenodo at https://doi.org/10.5281/zenodo.14744139 (ref. ⁵⁸). Data to replicate the analyses of LIP data shown in Fig. 7 are available via Zenodo at https://zenodo.org/records/7946011 (ref. ⁵⁹).

Code Availability

Code to replicate the analysis shown in Fig. 7 is available via Zenodo at https://zenodo.org/records/7946011 (ref. ⁵⁹).

Contributions

These authors contributed equally: Janis K. Hesse, Gabriel M. Stine, Ruobing Xia, Shude Zhu.

These authors jointly supervised this work: Tirin Moore, Michael Shadlen, Krishna Shenoy, Doris Tsao, Barundeb Dutta, Timothy Harris.

E.M.T., J.K.H., G.M.S., R.X., S.Z., D.J.O., F.F.L., K.S., D.T., M.S., T.M., B.D. and T.H. conceptualized the project. E.M.T., J.K.H., G.M.S., R.X., S.Z., D.J.O., F.F.L., E.A., N.A.S. and D.A.W. were responsible for data preprocessing. E.M.T., J.K.H., G.M.S., R.X., S.Z., D.J.O., A.Z., E.A., N.A.S. and D.A.W. analyzed the data. R.X. and S.Z. collected vision data. E.M.T., S.V., A.Z. and E.A. collected motor data. G.M.S. and N.A.S. collected data on decision-making. J.K.H. and F.F.L. collected data on face patches. D.J.O., B.K., J.C., D.A.W. and M.P. were responsible for software development. A.A., C.M.L., J.O.C., J.P., B.C.R., M.W. and B.D. designed the electronic hardware. E.M.T., J.K.H., G.M.S., R.X., S.Z., D.J.O., F.F.L., A.Z., D.A.W., M.C., D.T., M.S., T.M. and T.H. designed the implants. E.M.T., J.K.H., G.M.S., R.X., S.Z., S.V., A.Z. and D.A.W. were responsible for visualization. E.M.T., J.K.H., G.M.S., R.X., S.Z., D.T. and T.H. wrote the original draft. E.M.T., J.K.H., G.M.S., R.X., S.Z., D.J.O., F.F.L., D.A.W., M.P., C.M.L., M.W., D.T., B.D. and T.H. reviewed and edited the paper. D.A.W., C.M.L., M.C., K.S., D.T., M.S., T.M., B.D. and T.H. supervised. M.C., K.S., D.T., M.S., T.M., B.D. and T.H. acquired funding.

Conflict of Interest

E.M.T. works for Meta Reality Labs, although the work presented in the present article was performed via his roles at Columbia, University of California, Davis and Stanford. K.V.S. previously consulted for Neuralink and CTRL-Labs and served on the scientific advisory boards of MIND-X, Inscopix and Heal. The other authors declare no competing interests.