Chronic, wireless recordings of large-scale brain activity in freely moving rhesus monkeys

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ABSTRACT Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces


(BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants.


This approach allowed us to isolate up to 1,800 neurons (units) per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple


cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5


consecutive years) and recording of a broad range of behaviors, such as social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings


could have a profound impact on basic primate neurophysiology research while providing a framework for the development and testing of clinically relevant neuroprostheses. Access through your


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BEING VIEWED BY OTHERS A STEALTHY NEURAL RECORDER FOR THE STUDY OF BEHAVIOUR IN PRIMATES Article Open access 08 November 2024 A HIGH-DENSITY 1,024-CHANNEL PROBE FOR BRAIN-WIDE RECORDINGS IN


NON-HUMAN PRIMATES Article 24 June 2024 BRAIN-WIDE NEURAL RECORDINGS IN MICE NAVIGATING PHYSICAL SPACES ENABLED BY ROBOTIC NEURAL RECORDING HEADSTAGES Article 07 October 2024 REFERENCES *


Evarts, E.V. Pyramidal tract activity associated with a conditioned hand movement in the monkey. _J. Neurophysiol._ 29, 1011–1027 (1966). Article  CAS  Google Scholar  * Nicolelis, M.A.L.,


Lin, R.C.S., Woodward, D.J. & Chapin, J.K. Induction of immediate spatiotemporal changes in thalamic networks by peripheral block of ascending cutaneous information. _Nature_ 361,


533–536 (1993). Article  CAS  Google Scholar  * Supèr, H. & Roelfsema, P.R. Chronic multiunit recordings in behaving animals: advantages and limitations. _Prog. Brain Res._ 147, 263–282


(2005). Article  Google Scholar  * 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). Article  CAS  Google Scholar  * Nicolelis, M.A.L. Actions from thoughts. _Nature_ 409, 403–407 (2001). Article  CAS  Google Scholar  * Nicolelis,


M.A.L. et al. Chronic, multisite, multielectrode recordings in macaque monkeys. _Proc. Natl. Acad. Sci. USA_ 100, 11041–11046 (2003). Article  CAS  Google Scholar  * Wessberg, J. et al.


Real-time prediction of hand trajectory by ensembles of cortical neurons in primates. _Nature_ 408, 361–365 (2000). Article  CAS  Google Scholar  * Chapin, J.K., Moxon, K.A., Markowitz, R.S.


& Nicolelis, M.A.L. Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex. _Nat. Neurosci._ 2, 664–670 (1999). Article  CAS  Google Scholar  *


Nicolelis, M.A.L. & Lebedev, M.A. Principles of neural ensemble physiology underlying the operation of brain-machine interfaces. _Nat. Rev. Neurosci._ 10, 530–540 (2009). Article  CAS 


Google Scholar  * Azevedo, F.A.C. et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. _J. Comp. Neurol._ 513, 532–541


(2009). Article  Google Scholar  * Marblestone, A.H. et al. Physical principles for scalable neural recording. _Front. Comput. Neurosci._ 7, 137 (2013). Article  Google Scholar  * Chestek,


C.A. et al. HermesC: low-power wireless neural recording system for freely moving primates. _IEEE Trans. Neural Syst. Rehabil. Eng._ 17, 330–338 (2009). Article  Google Scholar  * Bonfanti,


A. et al. A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal. _Conf. Proc. IEEE Eng. Med. Biol. Soc._ 2010, 1555–1560


(2010). CAS  PubMed  Google Scholar  * Rizk, M. et al. A fully implantable 96-channe 96-channel neural data acquisition system. _J. Neural Eng._ 6, 026002 (2009). Article  Google Scholar  *


Borton, D.A., Yin, M., Aceros, J. & Nurmikko, A. An implantable wireless neural interface for recording cortical circuit dynamics in moving primates. _J. Neural Eng._ 10, 026010 (2013).


Article  Google Scholar  * Lebedev, M.A. & Nicolelis, M.A.L. Brain-machine interfaces: past, present and future. _Trends Neurosci._ 29, 536–546 (2006). Article  CAS  Google Scholar  *


Lebedev, M.A. et al. Future developments in brain-machine interface research. _Clinics (Sao Paulo)_ 66 (suppl. 1), 25–32 (2011). Article  Google Scholar  * Lebedev, M.A. & Nicolelis,


M.A.L. Toward a whole-body neuroprosthetic. _Prog. Brain Res._ 194, 47–60 (2011). Article  Google Scholar  * Lebedev, M.A. et al. Cortical ensemble adaptation to represent velocity of an


artificial actuator controlled by a brain-machine interface. _J. Neurosci._ 25, 4681–4693 (2005). Article  CAS  Google Scholar  * Lebedev, M.A., O'Doherty, J.E. & Nicolelis, M.A.L.


Decoding of temporal intervals from cortical ensemble activity. _J. Neurophysiol._ 99, 166–186 (2008). Article  Google Scholar  * Zacksenhouse, M. & Nemets, S. in _Methods for Neural


Ensemble Recordings_ 2nd edn. (ed. Nicolelis, M.A.L.) Ch. 4 (CRC Press, 2008). * O'Doherty, J.E. et al. Active tactile exploration enabled by a brain-machine-brain interface. _Nature_


479, 228–231 (2011). Article  CAS  Google Scholar  * Shokur, S. et al. Expanding the primate body schema in sensorimotor cortex by virtual touches of an avatar. _Proc. Natl. Acad. Sci. USA_


110, 15121–15126 (2013). Article  CAS  Google Scholar  * Ifft, P.J., Shokur, S., Li, Z., Lebedev, M.A. & Nicolelis, M.A.L. A brain-machine interface enables bimanual arm movements in


monkeys. _Sci. Transl. Med._ 5, 210ra154 (2013). Article  Google Scholar  * Lu, C.W., Patil, P.G. & Chestek, C.A. Current challenges to the clinical translation of brain machine


interface technology. _Int. Rev. Neurobiol._ 107, 137–160 (2012). Article  Google Scholar  * Patil, P.G., Carmena, J.M., Nicolelis, M.A.L. & Turner, D.A. Ensemble recordings of human


subcortical neurons as a source of motor control signals for a brain-machine interface. _Neurosurgery_ 55, 27–35, discussion 35–38 (2004). Article  Google Scholar  * Hanson, T.L., Fuller,


A.M., Lebedev, M.A., Turner, D.A. & Nicolelis, M.A.L. Subcortical neuronal ensembles: an analysis of motor task association, tremor, oscillations, and synchrony in human patients. _J.


Neurosci._ 32, 8620–8632 (2012). Article  CAS  Google Scholar  * Carmena, J.M. et al. Learning to control a brain-machine interface for reaching and grasping by primates. _PLoS Biol._ 1, E42


(2003). Article  Google Scholar  * Li, Z. et al. Unscented Kalman filter for brain-machine interfaces. _PLoS ONE_ 4, e6243 (2009). Article  Google Scholar  * Nicolelis, M.A.L. Brain-machine


interfaces to restore motor function and probe neural circuits. _Nat. Rev. Neurosci._ 4, 417–422 (2003). Article  CAS  Google Scholar  * Nicolelis, M.A.L., Lehew, G.C. & Krupa, D.J.


Miniaturized high-density multichannel electrode array for long-term neuronal recordings. US patent 6,993,392 (2006). * 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). Article  CAS  Google Scholar  *


Freire, M.A.M. et al. Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants. _PLoS ONE_ 6, e27554 (2011). Article  CAS  Google Scholar  *


Ochsner, K.N. & Lieberman, M.D. The emergence of social cognitive neuroscience. _Am. Psychol._ 56, 717–734 (2001). Article  CAS  Google Scholar  * Mattout, J. Brain-computer interfaces:


a neuroscience paradigm of social interaction? A matter of perspective. _Front. Hum. Neurosci._ 6, 114 (2012). Article  Google Scholar  * O'Doherty, J.E., Lebedev, M.A., Li, Z. &


Nicolelis, M.A.L. Virtual active touch using randomly patterned intracortical microstimulation. _IEEE Trans. Neural Syst. Rehabil. Eng._ 20, 85–93 (2012). Article  Google Scholar  * Ifft,


P.J., Lebedev, M.A. & Nicolelis, M.A.L. Cortical correlates of Fitts' law. _Front. Integr. Neurosci._ 5, 85 (2011). Article  Google Scholar  * Fitzsimmons, N.A., Lebedev, M.A.,


Peikon, I.D. & Nicolelis, M.A.L. Extracting kinematic parameters for monkey bipedal walking from cortical neuronal ensemble activity. _Front. Integr. Neurosci._ 3, 1–19 (2009). Article 


Google Scholar  * O'Doherty, J.E., Lebedev, M.A., Hanson, T.L., Fitzsimmons, N.A. & Nicolelis, M.A.L. A brain-machine interface instructed by direct intracortical microstimulation.


_Front. Integr. Neurosci._ 3, 20 (2009). Article  Google Scholar  * Lewicki, M.S. A review of methods for spike sorting: the detection and classification of neural action potentials.


_Network_ 9, R53–R78 (1998). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS Awards from the US National Institute of Mental Health (NIMH) DP1MH099903 and the US National


Institute of Neurological Disorders and Stroke (NINDS) R01NS073952 to M.A.L.N. supported this research. We thank L. Oliveira and T. Phillips for their gracious support during all


implantation surgeries and experimental logics. Additionally, many thanks go to S. Halkiotis for her continued help in the manuscript revision and submission process. We also thank T.


Vinholo for performing the extensive histology that is shown in this work and H. Powell for analyzing video data from the free roaming experiment. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS


* Department of Neurobiology, Duke University, Durham, North Carolina, USA David A Schwarz, Mikhail A Lebedev, Timothy L Hanson, Gary Lehew, Jim Meloy, Sankaranarayani Rajangam, Zheng Li, 


Arjun Ramakrishnan, Andrew Tate & Miguel A L Nicolelis * Center for Neuroengineering, Duke University, Durham, North Carolina, USA David A Schwarz, Mikhail A Lebedev, Timothy L Hanson, 


Gary Lehew, Jim Meloy, Sankaranarayani Rajangam, Vivek Subramanian, Peter J Ifft, Zheng Li, Arjun Ramakrishnan, Andrew Tate, Katie Z Zhuang & Miguel A L Nicolelis * Monterey Spine,


Monterey, California, USA Dragan F Dimitrov * Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA Vivek Subramanian, Peter J Ifft, Katie Z Zhuang & Miguel


A L Nicolelis * Department of Psychology and Neuroscience, Duke University, Durham, North Carolina, USA Miguel A L Nicolelis * Edmond and Lily Safra International Institute of Neuroscience


of Natal, Natal, Brazil Miguel A L Nicolelis Authors * David A Schwarz View author publications You can also search for this author inPubMed Google Scholar * Mikhail A Lebedev View author


publications You can also search for this author inPubMed Google Scholar * Timothy L Hanson View author publications You can also search for this author inPubMed Google Scholar * Dragan F


Dimitrov View author publications You can also search for this author inPubMed Google Scholar * Gary Lehew View author publications You can also search for this author inPubMed Google


Scholar * Jim Meloy View author publications You can also search for this author inPubMed Google Scholar * Sankaranarayani Rajangam View author publications You can also search for this


author inPubMed Google Scholar * Vivek Subramanian View author publications You can also search for this author inPubMed Google Scholar * Peter J Ifft View author publications You can also


search for this author inPubMed Google Scholar * Zheng Li View author publications You can also search for this author inPubMed Google Scholar * Arjun Ramakrishnan View author publications


You can also search for this author inPubMed Google Scholar * Andrew Tate View author publications You can also search for this author inPubMed Google Scholar * Katie Z Zhuang View author


publications You can also search for this author inPubMed Google Scholar * Miguel A L Nicolelis View author publications You can also search for this author inPubMed Google Scholar


CONTRIBUTIONS D.A.S., M.A.L. and M.A.L.N. designed experiments and wrote the paper. D.A.S., V.S., M.A.L. and M.A.L.N. analyzed data. D.A.S., M.A.L., S.R., A.R., P.J.I., A.T., T.L.H. and


K.Z.Z. performed the experiments. D.A.S., J.M. and G.L. designed and constructed animal headcaps and manufactured wireless units. G.L. designed and constructed the microwire recording cubes.


D.A.S. and T.L.H. wrote the wireless software. T.L.H. designed and constructed the wireless system. T.L.H. and Z.L. wrote the BMI software and contributed analysis code. D.F.D. designed and


performed the surgical procedures. CORRESPONDING AUTHOR Correspondence to Miguel A L Nicolelis. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests.


SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–13 and Supplementary Tables 1–4 (PDF 2673 kb) WIRELESS BMI 30 second clip of monkey C performing cursor


control with only brain activity, task overlay showing the cursor on the bottom right corner (MP4 3042 kb) BMI WHEELCHAIR CONTROL Video showing macaque controlling robotic cart end effector


with its cortical activity. (MP4 4466 kb) FREELY MOVING WIRELESS RECORDINGS Sample video showing freely moving macaque with an overlay of firing activity divided into left and right


hemisphere. Sample frames from video show behavior with firing activity overlay. Each square represents the firing activity of a single neuron, averaged over 3 30s bins (video framerate).


(MP4 2210 kb) NEURON WAVEFORM CHRONOLOGY Animation of mean waveforms for a single connector (left hemisphere M1) in monkey M. Transparent colored area represented standard deviation of


waveform. Date of recording is shown on top (note some images can correspond to the same date of recording). (MP4 5537 kb) NEURON WAVEFORM CHRONOLOGY Animation of mean waveforms for a single


connector (left hemisphere M1) in monkey N. Transparent colored area represented standard deviation of waveform. Date of recording is shown on top (note some images can correspond to the


same date of recording). (MP4 3679 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Schwarz, D., Lebedev, M., Hanson, T. _et al._ Chronic, wireless


recordings of large-scale brain activity in freely moving rhesus monkeys. _Nat Methods_ 11, 670–676 (2014). https://doi.org/10.1038/nmeth.2936 Download citation * Received: 16 May 2013 *


Accepted: 12 March 2014 * Published: 28 April 2014 * Issue Date: June 2014 * DOI: https://doi.org/10.1038/nmeth.2936 SHARE THIS ARTICLE Anyone you share the following link with will be able


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