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Principles of neural ensemble physiology underlying the operation of brain–machine interfaces

Abstract

Research on brain–machine interfaces has been ongoing for at least a decade. During this period, simultaneous recordings of the extracellular electrical activity of hundreds of individual neurons have been used for direct, real-time control of various artificial devices. Brain–machine interfaces have also added greatly to our knowledge of the fundamental physiological principles governing the operation of large neural ensembles. Further understanding of these principles is likely to have a key role in the future development of neuroprosthetics for restoring mobility in severely paralysed patients.

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Figure 1: Principles of a brain–machine interface.
Figure 2: Neuronal activity during a reaching task.
Figure 3: Discrimination of spatiotemporal microstimulation patterns by owl monkeys.
Figure 4: The concept of a brain–machine–brain (BMBI) interface with artificial sensory feedback.
Figure 5: Neuronal responses in rat somatosensory cortex to passively applied stimuli versus active discrimination of the same stimuli.

References

  1. Carmena, J. M. et al. Learning to control a brain–machine interface for reaching and grasping by primates. PLoS Biol. 1, e42 (2003).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  2. Chapin, J. K., Moxon, K. A., Markowitz, R. S. & Nicolelis, M. A. Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex. Nature Neurosci. 2, 664–670 (1999).

    CAS  PubMed  Article  Google Scholar 

  3. Donoghue, J. P. Connecting cortex to machines: recent advances in brain interfaces. Nature Neurosci. 5 (Suppl.), 1085–1088 (2002).

    CAS  PubMed  Article  Google Scholar 

  4. Fetz, E. E. Volitional control of neural activity: implications for brain–computer interfaces. J. Physiol. 579, 571–579 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. Kennedy, P. R. & Bakay, R. A. Restoration of neural output from a paralyzed patient by a direct brain connection. Neuroreport 9, 1707–1711 (1998).

    CAS  Article  PubMed  Google Scholar 

  6. Lebedev, M. A. & Nicolelis, M. A. Brain–machine interfaces: past, present and future. Trends Neurosci. 29, 536–546 (2006).

    CAS  PubMed  Article  Google Scholar 

  7. Musallam, S., Corneil, B. D., Greger, B., Scherberger, H. & Andersen, R. A. Cognitive control signals for neural prosthetics. Science 305, 258–262 (2004).

    CAS  PubMed  Article  Google Scholar 

  8. Nicolelis, M. A. Actions from thoughts. Nature 409, 403–407 (2001).

    CAS  Article  PubMed  Google Scholar 

  9. Nicolelis, M. A. Brain–machine interfaces to restore motor function and probe neural circuits. Nature Rev. Neurosci. 4, 417–422 (2003).

    CAS  Article  Google Scholar 

  10. Schwartz, A. B., Cui, X. T., Weber, D. J. & Moran, D. W. Brain-controlled interfaces: movement restoration with neural prosthetics. Neuron 52, 205–220 (2006).

    CAS  PubMed  Article  Google Scholar 

  11. Serruya, M. D., Hatsopoulos, N. G., Paninski, L., Fellows, M. R. & Donoghue, J. P. Instant neural control of a movement signal. Nature 416, 141–142 (2002).

    CAS  Article  PubMed  Google Scholar 

  12. Taylor, D. M., Tillery, S. I. & Schwartz, A. B. Direct cortical control of 3D neuroprosthetic devices. Science 296, 1829–1832 (2002).

    CAS  PubMed  Article  Google Scholar 

  13. Wessberg, J. et al. Real-time prediction of hand trajectory by ensembles of cortical neurons in primates. Nature 408, 361–365 (2000).

    CAS  Article  PubMed  Google Scholar 

  14. Chapin, J. K. Neural prosthetic devices for quadriplegia. Curr. Opin. Neurol. 13, 671–675 (2000).

    CAS  PubMed  Article  Google Scholar 

  15. Donoghue, J. P., Nurmikko, A., Black, M. & Hochberg, L. R. Assistive technology and robotic control using motor cortex ensemble-based neural interface systems in humans with tetraplegia. J. Physiol. 579, 603–611 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Friehs, G. M., Zerris, V. A., Ojakangas, C. L., Fellows, M. R. & Donoghue, J. P. Brain–machine and brain–computer interfaces. Stroke 35, 2702–2705 (2004).

    PubMed  Article  Google Scholar 

  17. Mussa-Ivaldi, F. A. & Miller, L. E. Brain–machine interfaces: computational demands and clinical needs meet basic neuroscience. Trends Neurosci. 26, 329–334 (2003).

    CAS  PubMed  Article  Google Scholar 

  18. Birbaumer, N. Breaking the silence: brain–computer interfaces (BCI) for communication and motor control. Psychophysiology 43, 517–532 (2006).

    Article  PubMed  Google Scholar 

  19. Birbaumer, N. & Cohen, L. G. Brain–computer interfaces: communication and restoration of movement in paralysis. J. Physiol. 579, 621–636 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Cohen, E. D. Prosthetic interfaces with the visual system: biological issues. J. Neural Eng. 4, R14–R31 (2007).

    PubMed  Article  Google Scholar 

  21. Dobkin, B. H. Brain–computer interface technology as a tool to augment plasticity and outcomes for neurological rehabilitation. J. Physiol. 579, 637–642 (2007).

    CAS  PubMed  Article  Google Scholar 

  22. Kubler, A. & Kotchoubey, B. Brain–computer interfaces in the continuum of consciousness. Curr. Opin. Neurol. 20, 643–649 (2007).

    PubMed  Article  Google Scholar 

  23. Kubler, A. & Neumann, N. Brain–computer interfaces — the key for the conscious brain locked into a paralyzed body. Prog. Brain Res. 150, 513–525 (2005).

    PubMed  Article  Google Scholar 

  24. Leuthardt, E. C., Schalk, G., Moran, D. & Ojemann, J. G. The emerging world of motor neuroprosthetics: a neurosurgical perspective. Neurosurgery 59, 1–14 (2006).

    PubMed  Article  Google Scholar 

  25. Lotte, F., Congedo, M., Lecuyer, A., Lamarche, F. & Arnaldi, B. A review of classification algorithms for EEG-based brain–computer interfaces. J. Neural Eng. 4, R1–R13 (2007).

    CAS  PubMed  Article  Google Scholar 

  26. Mason, S. G., Bashashati, A., Fatourechi, M., Navarro, K. F. & Birch, G. E. A comprehensive survey of brain interface technology designs. Ann. Biomed. Eng. 35, 137–169 (2007).

    CAS  PubMed  Article  Google Scholar 

  27. Pfurtscheller, G. & Neuper, C. Future prospects of ERD/ERS in the context of brain–computer interface (BCI) developments. Prog. Brain Res. 159, 433–437 (2006).

    PubMed  Article  Google Scholar 

  28. Wolpaw, J. R. Brain–computer interfaces as new brain output pathways. J. Physiol. 579, 613–619 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Birbaumer, N. et al. A spelling device for the paralysed. Nature 398, 297–298 (1999).

    CAS  Article  PubMed  Google Scholar 

  30. Karim, A. A. et al. Neural internet: web surfing with brain potentials for the completely paralyzed. Neurorehabil. Neural Repair 20, 508–515 (2006).

    PubMed  Article  Google Scholar 

  31. Kennedy, P. R., Kirby, M. T., Moore, M. M., King, B. & Mallory, A. Computer control using human intracortical local field potentials. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 339–344 (2004).

    PubMed  Article  Google Scholar 

  32. Nijboer, F. et al. A P300-based brain–computer interface for people with amyotrophic lateral sclerosis. Clin. Neurophysiol. 119, 1909–1916 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Nicolelis, M. A., Baccala, L. A., Lin, R. C. & Chapin, J. K. Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system. Science 268, 1353–1358 (1995).

    CAS  PubMed  Article  Google Scholar 

  34. Nicolelis, M. A., Lin, R. C., 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).

    CAS  PubMed  Article  Google Scholar 

  35. O'Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971).

    CAS  PubMed  Article  Google Scholar 

  36. Wilson, M. A. & McNaughton, B. L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).

    CAS  PubMed  Article  Google Scholar 

  37. Baker, S. N. et al. Multiple single unit recording in the cortex of monkeys using independently moveable microelectrodes. J. Neurosci. Methods 94, 5–17 (1999).

    CAS  PubMed  Article  Google Scholar 

  38. deCharms, R. C., Blake, D. T. & Merzenich, M. M. A multielectrode implant device for the cerebral cortex. J. Neurosci. Methods 93, 27–35 (1999).

    CAS  PubMed  Article  Google Scholar 

  39. Eliades, S. J. & Wang, X. Neural substrates of vocalization feedback monitoring in primate auditory cortex. Nature 453, 1102–1106 (2008).

    CAS  PubMed  Article  Google Scholar 

  40. Hatsopoulos, N., Joshi, J. & O'Leary, J. G. Decoding continuous and discrete motor behaviors using motor and premotor cortical ensembles. J. Neurophysiol. 92, 1165–1174 (2004).

    PubMed  Article  Google Scholar 

  41. Jackson, A. & Fetz, E. E. Compact movable microwire array for long-term chronic unit recording in cerebral cortex of primates. J. Neurophysiol. 98, 3109–3118 (2007).

    PubMed  Article  Google Scholar 

  42. 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).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. Nicolelis, M. A. et al. Chronic, multisite, multielectrode recordings in macaque monkeys. Proc. Natl Acad. Sci. USA 100, 11041–11046 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. Nicolelis, M. A. et al. Simultaneous encoding of tactile information by three primate cortical areas. Nature Neurosci. 1, 621–630 (1998).

    CAS  PubMed  Article  Google Scholar 

  45. Santhanam, G., Ryu, S. I., Yu, B. M., Afshar, A. & Shenoy, K. V. A high-performance brain–computer interface. Nature 442, 195–198 (2006).

    CAS  Article  PubMed  Google Scholar 

  46. Hochberg, L. R. et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–171 (2006).

    CAS  PubMed  Article  Google Scholar 

  47. Patil, P. G., Carmena, J. M., Nicolelis, M. A. & 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 (2004).

    PubMed  Article  Google Scholar 

  48. Truccolo, W., Friehs, G. M., Donoghue, J. P. & Hochberg, L. R. Primary motor cortex tuning to intended movement kinematics in humans with tetraplegia. J. Neurosci. 28, 1163–1178 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  49. Bizzi, E., Accornero, N., Chapple, W. & Hogan, N. Arm trajectory formation in monkeys. Exp. Brain Res. 46, 139–143 (1982).

    CAS  PubMed  Article  Google Scholar 

  50. Bizzi, E., Mussa-Ivaldi, F. A. & Giszter, S. Computations underlying the execution of movement: a biological perspective. Science 253, 287–291 (1991).

    CAS  PubMed  Article  Google Scholar 

  51. Cohen, Y. E. & Andersen, R. A. A common reference frame for movement plans in the posterior parietal cortex. Nature Rev. Neurosci. 3, 553–562 (2002).

    CAS  Google Scholar 

  52. Evarts, E. V. & Fromm, C. Information processing in the sensorimotor cortex during voluntary movement. Prog. Brain Res. 54, 143–155 (1980).

    CAS  PubMed  Article  Google Scholar 

  53. Georgopoulos, A. P. Spatial coding of visually guided arm movements in primate motor cortex. Can. J. Physiol. Pharmacol. 66, 518–526 (1988).

    CAS  PubMed  Article  Google Scholar 

  54. Georgopoulos, A. P., Schwartz, A. B. & Kettner, R. E. Neuronal population coding of movement direction. Science 233, 1416–1419 (1986).

    CAS  PubMed  Article  Google Scholar 

  55. Kakei, S., Hoffman, D. S. & Strick, P. L. Muscle and movement representations in the primary motor cortex. Science 285, 2136–2139 (1999).

    CAS  PubMed  Article  Google Scholar 

  56. Lebedev, M. A. & Wise, S. P. Insights into seeing and grasping: distinguishing the neural correlates of perception and action. Behav. Cogn. Neurosci. Rev. 1, 108–129 (2002).

    PubMed  Article  Google Scholar 

  57. Paz, R., Wise, S. P. & Vaadia, E. Viewing and doing: similar cortical mechanisms for perceptual and motor learning. Trends Neurosci. 27, 496–503 (2004).

    CAS  Article  PubMed  Google Scholar 

  58. Polit, A. & Bizzi, E. Processes controlling arm movements in monkeys. Science 201, 1235–1237 (1978).

    CAS  PubMed  Article  Google Scholar 

  59. Todorov, E. Optimality principles in sensorimotor control. Nature Neurosci. 7, 907–915 (2004).

    CAS  PubMed  Article  Google Scholar 

  60. Wise, S. P., di Pellegrino, G. & Boussaoud, D. The premotor cortex and nonstandard sensorimotor mapping. Can. J. Physiol. Pharmacol. 74, 469–482 (1996).

    CAS  PubMed  Google Scholar 

  61. Andersen, R. A., Musallam, S. & Pesaran, B. Selecting the signals for a brain–machine interface. Curr. Opin. Neurobiol. 14, 720–726 (2004).

    CAS  PubMed  Article  Google Scholar 

  62. Bashashati, A., Fatourechi, M., Ward, R. K. & Birch, G. E. A survey of signal processing algorithms in brain–computer interfaces based on electrical brain signals. J. Neural Eng. 4, R32–57 (2007).

    PubMed  Article  Google Scholar 

  63. Lilly, J. C. in Biological and Biochemical Bases of Behavior (eds Harlow, H. F. & Woolsey, C. N.) 83–100 (Univ. of Wisconsin Press, Madison, Wisconsin, 1958).

    Google Scholar 

  64. Lilly, J. C. Distribution of 'motor' functions in the cerebral cortex in the conscious, intact monkey. Science Abstr. 124, 937 (1956).

    Google Scholar 

  65. Gerstein, G. L. & Aertsen, A. M. Representation of cooperative firing activity among simultaneously recorded neurons. J. Neurophysiol. 54, 1513–1528 (1985).

    CAS  PubMed  Article  Google Scholar 

  66. Gerstein, G. L., Perkel, D. H. & Dayhoff, J. E. Cooperative firing activity in simultaneously recorded populations of neurons: detection and measurement. J. Neurosci. 5, 881–889 (1985).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  67. Gerstein, G. L., Perkel, D. H. & Subramanian, K. N. Identification of functionally related neural assemblies. Brain Res. 140, 43–62 (1978).

    CAS  PubMed  Article  Google Scholar 

  68. Kruger, J. & Bach, M. Simultaneous recording with 30 microelectrodes in monkey visual cortex. Exp. Brain Res. 41, 191–194 (1981).

    CAS  PubMed  Article  Google Scholar 

  69. McNaughton, B. L., Barnes, C. A. & O'Keefe, J. The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp. Brain Res. 52, 41–49 (1983).

    CAS  Article  PubMed  Google Scholar 

  70. Shin, H. C. & Chapin, J. K. Mapping the effects of motor cortex stimulation on single neurons in the dorsal column nuclei in the rat: direct responses and afferent modulation. Brain Res. Bull. 22, 245–252 (1989).

    CAS  PubMed  Article  Google Scholar 

  71. Barlow, H. B. Single units and sensation: a neuron doctrine for perceptual psychology? Perception 1, 371–394 (1972).

    CAS  Article  PubMed  Google Scholar 

  72. Hubel, D. H. & Wiesel, T. N. Early exploration of the visual cortex. Neuron 20, 401–412 (1998).

    CAS  Article  PubMed  Google Scholar 

  73. Averbeck, B. B. & Lee, D. Coding and transmission of information by neural ensembles. Trends Neurosci. 27, 225–230 (2004).

    CAS  PubMed  Article  Google Scholar 

  74. Covey, E. Neural population coding and auditory temporal pattern analysis. Physiol. Behav. 69, 211–220 (2000).

    CAS  PubMed  Article  Google Scholar 

  75. Doetsch, G. S. Patterns in the brain. Neuronal population coding in the somatosensory system. Physiol. Behav. 69, 187–201 (2000).

    CAS  PubMed  Article  Google Scholar 

  76. Sakurai, Y. Population coding by cell assemblies — what it really is in the brain. Neurosci. Res. 26, 1–16 (1996).

    CAS  PubMed  Article  Google Scholar 

  77. Young, T. On the theory of light and colours. Philos. Trans. R. Soc. Lond. B Biol. Sci. 92, 12–48 (1802).

    Google Scholar 

  78. Hebb, D. O. The Organization of Behavior: A Neuropsychological Theory (Wiley, New York, 1949).

    Google Scholar 

  79. Barlow, H. B. in The Cognitive Neurosciences (ed. Gazzaniga, M.) 415–435 (MIT Press, Cambridge, 1995).

    Google Scholar 

  80. Barlow, H. B. Pattern recognition and the responses of sensory neurons. Ann. NY Acad. Sci. 156, 872–881 (1969).

    CAS  PubMed  Article  Google Scholar 

  81. Cajal, R. Histology of the Nervous System of Man and Vertebrates (Oxford Univ. Press, New York, 1899).

    Google Scholar 

  82. Hubel, D. H. Eye, Brain and Vision (W. H. Freeman and Company, New York, 1988).

    Google Scholar 

  83. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. 160, 106–154 (1962).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  84. Breakspear, M. & Stam, C. J. Dynamics of a neural system with a multiscale architecture. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 1051–1074 (2005).

    PubMed  PubMed Central  Article  Google Scholar 

  85. Serences, J. T. & Yantis, S. Selective visual attention and perceptual coherence. Trends Cogn. Sci. 10, 38–45 (2006).

    Article  PubMed  Google Scholar 

  86. Simon, S. A., de Araujo, I. E., Gutierrez, R. & Nicolelis, M. A. The neural mechanisms of gustation: a distributed processing code. Nature Rev. Neurosci. 7, 890–901 (2006).

    CAS  Article  Google Scholar 

  87. Bichot, N. P., Thompson, K. G., Chenchal Rao, S. & Schall, J. D. Reliability of macaque frontal eye field neurons signaling saccade targets during visual search. J. Neurosci. 21, 713–725 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  88. Brecht, M., Schneider, M., Sakmann, B. & Margrie, T. W. Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex. Nature 427, 704–710 (2004).

    CAS  Article  PubMed  Google Scholar 

  89. Houweling, A. R. & Brecht, M. Behavioural report of single neuron stimulation in somatosensory cortex. Nature 451, 65–68 (2008).

    CAS  Article  PubMed  Google Scholar 

  90. Shadlen, M. N. & Newsome, W. T. Neural basis of a perceptual decision in the parietal cortex (area LIP) of the rhesus monkey. J. Neurophysiol. 86, 1916–1936 (2001).

    CAS  PubMed  Article  Google Scholar 

  91. Fetz, E. E. Operant conditioning of cortical unit activity. Science 163, 955–958 (1969).

    CAS  PubMed  Article  Google Scholar 

  92. Fetz, E. E. & Finocchio, D. V. Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns. Exp. Brain Res. 23, 217–240 (1975).

    CAS  PubMed  Article  Google Scholar 

  93. Fetz, E. E. & Finocchio, D. V. Operant conditioning of specific patterns of neural and muscular activity. Science 174, 431–435 (1971).

    CAS  PubMed  Article  Google Scholar 

  94. Moritz, C. T., Perlmutter, S. I. & Fetz, E. E. Direct control of paralysed muscles by cortical neurons. Nature 456, 639–642 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. Eliades, S. J. & Wang, X. Chronic multi-electrode neural recording in free-roaming monkeys. J. Neurosci. Methods 172, 201–214 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  96. Guillory, K. S. & Normann, R. A. A 100-channel system for real time detection and storage of extracellular spike waveforms. J. Neurosci. Methods 91, 21–29 (1999).

    CAS  PubMed  Article  Google Scholar 

  97. Mountcastle, V. B., Reitboeck, H. J., Poggio, G. F. & Steinmetz, M. A. Adaptation of the Reitboeck method of multiple microelectrode recording to the neocortex of the waking monkey. J. Neurosci. Methods 36, 77–84 (1991).

    CAS  PubMed  Article  Google Scholar 

  98. Musallam, S., Bak, M. J., Troyk, P. R. & Andersen, R. A. A floating metal microelectrode array for chronic implantation. J. Neurosci. Methods 160, 122–127 (2007).

    PubMed  Article  Google Scholar 

  99. Nicolelis, M. A., Ghazanfar, A. A., Faggin, B. M., Votaw, S. & Oliveira, L. M. Reconstructing the engram: simultaneous, multisite, many single neuron recordings. Neuron 18, 529–537 (1997).

    CAS  PubMed  Article  Google Scholar 

  100. Grinvald, A. Imaging input and output dynamics of neocortical networks in vivo: exciting times ahead. Proc. Natl Acad. Sci. USA 102, 14125–14126 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  101. Grinvald, A., Frostig, R. D., Siegel, R. M. & Bartfeld, E. High-resolution optical imaging of functional brain architecture in the awake monkey. Proc. Natl Acad. Sci. USA 88, 11559–11563 (1991).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  102. Lendvai, B., Stern, E. A., Chen, B. & Svoboda, K. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881 (2000).

    CAS  PubMed  Article  Google Scholar 

  103. Logothetis, N. K., Guggenberger, H., Peled, S. & Pauls, J. Functional imaging of the monkey brain. Nature Neurosci. 2, 555–562 (1999).

    CAS  PubMed  Article  Google Scholar 

  104. Nikolenko, V., Poskanzer, K. E. & Yuste, R. Two-photon photostimulation and imaging of neural circuits. Nature Methods 4, 943–950 (2007).

    CAS  PubMed  Article  Google Scholar 

  105. Ohki, K., Chung, S., Ch'ng, Y. H., Kara, P. & Reid, R. C. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433, 597–603 (2005).

    CAS  PubMed  Article  Google Scholar 

  106. Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006).

    CAS  PubMed  Article  Google Scholar 

  107. Rainer, G., Augath, M., Trinath, T. & Logothetis, N. K. Nonmonotonic noise tuning of BOLD fMRI signal to natural images in the visual cortex of the anesthetized monkey. Curr. Biol. 11, 846–854 (2001).

    CAS  PubMed  Article  Google Scholar 

  108. Siegel, R. M., Duann, J. R., Jung, T. P. & Sejnowski, T. Spatiotemporal dynamics of the functional architecture for gain fields in inferior parietal lobule of behaving monkey. Cereb. Cortex 17, 378–390 (2007).

    PubMed  Article  Google Scholar 

  109. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D. W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161–165 (1997).

    CAS  Article  PubMed  Google Scholar 

  110. Ts'o, D. Y., Frostig, R. D., Lieke, E. E. & Grinvald, A. Functional organization of primate visual cortex revealed by high resolution optical imaging. Science 249, 417–420 (1990).

    CAS  PubMed  Article  Google Scholar 

  111. Yuste, R. Fluorescence microscopy today. Nature Methods 2, 902–904 (2005).

    CAS  Article  PubMed  Google Scholar 

  112. Schmidt, E. M. Single neuron recording from motor cortex as a possible source of signals for control of external devices. Ann. Biomed. Eng. 8, 339–349 (1980).

    CAS  PubMed  Article  Google Scholar 

  113. Isaacs, R. E., Weber, D. J. & Schwartz, A. B. Work toward real-time control of a cortical neural prothesis. IEEE Trans. Rehabil. Eng. 8, 196–198 (2000).

    CAS  PubMed  Article  Google Scholar 

  114. Wolpaw, J. R. & McFarland, D. J. Control of a two-dimensional movement signal by a noninvasive brain-computer interface in humans. Proc. Natl Acad. Sci. USA 101, 17849–17854 (2004).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  115. Fitzsimmons, N. A., Drake, W., Hanson, T. L., Lebedev, M. A. & Nicolelis, M. A. Primate reaching cued by multichannel spatiotemporal cortical microstimulation. J. Neurosci. 27, 5593–5602 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  116. Lebedev, M. A., O'Doherty, J. E. & Nicolelis, M. A. Decoding of temporal intervals from cortical ensemble activity. J. Neurophysiol. 99, 166–186 (2008).

    PubMed  Article  Google Scholar 

  117. Santucci, D. M., Kralik, J. D., Lebedev, M. A. & Nicolelis, M. A. Frontal and parietal cortical ensembles predict single-trial muscle activity during reaching movements in primates. Eur. J. Neurosci. 22, 1529–1540 (2005).

    PubMed  Article  Google Scholar 

  118. Wessberg, J. & Nicolelis, M. A. Optimizing a linear algorithm for real-time robotic control using chronic cortical ensemble recordings in monkeys. J. Cogn. Neurosci. 16, 1022–1035 (2004).

    PubMed  Article  Google Scholar 

  119. Zacksenhouse, M. et al. Cortical modulations increase in early sessions with brain–machine interface. PLoS ONE 2, e619 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  120. Costa, R. M. et al. Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction. Neuron 52, 359–369 (2006).

    CAS  PubMed  Article  Google Scholar 

  121. Dzirasa, K. et al. Dopaminergic control of sleep-wake states. J. Neurosci. 26, 10577–10589 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  122. Lin, S. C., Gervasoni, D. & Nicolelis, M. A. Fast modulation of prefrontal cortex activity by basal forebrain noncholinergic neuronal ensembles. J. Neurophysiol. 96, 3209–3219 (2006).

    Article  PubMed  Google Scholar 

  123. Haykin, S. Adaptive Filter Theory (PrenticeHall, Upper Saddle River, New Jersey, 2002).

    Google Scholar 

  124. Fetz, E. E. Are movement parameters recognizably coded in activity of single neurons? Behav. Brain Sci. 15, 679–690 (1992).

    Google Scholar 

  125. Carmena, J. M., Lebedev, M. A., Henriquez, C. S. & Nicolelis, M. A. Stable ensemble performance with single-neuron variability during reaching movements in primates. J. Neurosci. 25, 10712–10716 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  126. Ghazanfar, A. A., Krupa, D. J. & Nicolelis, M. A. Role of cortical feedback in the receptive field structure and nonlinear response properties of somatosensory thalamic neurons. Exp. Brain Res. 141, 88–100 (2001).

    CAS  PubMed  Article  Google Scholar 

  127. Ghazanfar, A. A. & Nicolelis, M. A. Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex. Cereb. Cortex 9, 348–361 (1999).

    CAS  PubMed  Article  Google Scholar 

  128. Ghazanfar, A. A., Stambaugh, C. R. & Nicolelis, M. A. Encoding of tactile stimulus location by somatosensory thalamocortical ensembles. J. Neurosci. 20, 3761–3775 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  129. de Araujo, I. E. et al. Food reward in the absence of taste receptor signaling. Neuron 57, 930–941 (2008).

    CAS  PubMed  Article  Google Scholar 

  130. Soares, E. S. et al. Behavioral and neural responses to gustatory stimuli delivered non-contingently through intra-oral cannulas. Physiol. Behav. 92, 629–642 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  131. Glaser, E. M. & Ruchkin, D. S. Principles of Neurobiological Signal Analysis (Academic Press, New York, 1976).

    Google Scholar 

  132. Quian Quiroga, R. & Panzeri, S. Extracting information from neuronal populations: information theory and decoding approaches. Nature Rev. Neurosci. 10, 173–185 (2009).

    CAS  Article  Google Scholar 

  133. Faisal, A. A., Selen, L. P. & Wolpert, D. M. Noise in the nervous system. Nature Rev. Neurosci. 9, 292–303 (2008).

    CAS  Article  Google Scholar 

  134. Fontanini, A. & Katz, D. B. Behavioral states, network states, and sensory response variability. J. Neurophysiol. 100, 1160–1168 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  135. Getting, P. A. Emerging principles governing the operation of neural networks. Annu. Rev. Neurosci. 12, 185–204 (1989).

    CAS  PubMed  Article  Google Scholar 

  136. Nicolelis, M. A. Computing with thalamocortical ensembles during different behavioural states. J. Physiol. 566, 37–47 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. van Beers, R. J., Baraduc, P. & Wolpert, D. M. Role of uncertainty in sensorimotor control. Philos. Trans. R. Soc. Lond. B Biol. Sci. 357, 1137–1145 (2002).

    PubMed  PubMed Central  Article  Google Scholar 

  138. Abeles, M. Neural Circuits of the Cerebral Cortex (Cambridge Univ. Press, Cambridge, 1991).

    Book  Google Scholar 

  139. Chestek, C. A. et al. Single-neuron stability during repeated reaching in macaque premotor cortex. J. Neurosci. 27, 10742–10750 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  140. Brooks, V. B., Adrien, J. & Dykes, R. W. Task-related discharge of neurons in motor cortex and effects of denatate cooling. Brain Res. 40, 85–88 (1972).

    CAS  PubMed  Article  Google Scholar 

  141. Niki, H. & Watanabe, M. Prefrontal unit activity and delayed response: relation to cue location versus direction of response. Brain Res. 105, 79–88 (1976).

    CAS  PubMed  Article  Google Scholar 

  142. Sanchez, J. C. et al. Ascertaining the importance of neurons to develop better brain–machine interfaces. IEEE Trans. Biomed. Eng. 51, 943–953 (2004).

    PubMed  Article  Google Scholar 

  143. Ghazanfar, A. A. & Schroeder, C. E. Is neocortex essentially multisensory? Trends Cogn. Sci. 10, 278–285 (2006).

    PubMed  Article  Google Scholar 

  144. Graziano, M. S. & Gross, C. G. Spatial maps for the control of movement. Curr. Opin. Neurobiol. 8, 195–201 (1998).

    CAS  PubMed  Article  Google Scholar 

  145. Avillac, M., Deneve, S., Olivier, E., Pouget, A. & Duhamel, J. R. Reference frames for representing visual and tactile locations in parietal cortex. Nature Neurosci. 8, 941–949 (2005).

    CAS  PubMed  Article  Google Scholar 

  146. Benedek, G., Eordegh, G., Chadaide, Z. & Nagy, A. Distributed population coding of multisensory spatial information in the associative cortex. Eur. J. Neurosci. 20, 525–529 (2004).

    PubMed  Article  Google Scholar 

  147. Bridgeman, B. Multiplexing in single cells of the alert monkeys visual cortex during brightness discrimination. Neuropsychologia 20, 33–42 (1982).

    CAS  PubMed  Article  Google Scholar 

  148. Driver, J. & Noesselt, T. Multisensory interplay reveals crossmodal influences on 'sensory-specific' brain regions, neural responses, and judgments. Neuron 57, 11–23 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  149. Friedrich, R. W., Habermann, C. J. & Laurent, G. Multiplexing using synchrony in the zebrafish olfactory bulb. Nature Neurosci. 7, 862–871 (2004).

    CAS  PubMed  Article  Google Scholar 

  150. Lebedev, M. A., Messinger, A., Kralik, J. D. & Wise, S. P. Representation of attended versus remembered locations in prefrontal cortex. PLoS Biol. 2, e365 (2004).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  151. Stanford, T. R. & Stein, B. E. Superadditivity in multisensory integration: putting the computation in context. Neuroreport 18, 787–792 (2007).

    PubMed  Article  Google Scholar 

  152. Stein, B. E. & Stanford, T. R. Multisensory integration: current issues from the perspective of the single neuron. Nature Rev. Neurosci. 9, 255–266 (2008).

    CAS  Article  Google Scholar 

  153. Fitzsimmons, N. A., Lebedev, M. A., Peikon, I. D. & Nicolelis, M. A. Decoding of monkey bipedal walking from cortical neuronal ensembles. Front. Integr. Neurosci. 3, 3 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  154. Alexander, R. M. Bipedal animals, and their differences from humans. J. Anat. 204, 321–330 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  155. Dietz, V. Do human bipeds use quadrupedal coordination? Trends Neurosci. 25, 462–467 (2002).

    PubMed  Article  Google Scholar 

  156. Prilutsky, B. I., Sirota, M. G., Gregor, R. J. & Beloozerova, I. N. Quantification of motor cortex activity and full-body biomechanics during unconstrained locomotion. J. Neurophysiol. 94, 2959–2969 (2005).

    PubMed  Article  Google Scholar 

  157. Narayanan, N. S., Kimchi, E. Y. & Laubach, M. Redundancy and synergy of neuronal ensembles in motor cortex. J. Neurosci. 25, 4207–4216 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  158. Shadlen, M. N. & Newsome, W. T. The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J. Neurosci. 18, 3870–3896 (1998).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  159. Schwartz, A. B., Taylor, D. M. & Tillery, S. I. Extraction algorithms for cortical control of arm prosthetics. Curr. Opin. Neurobiol. 11, 701–707 (2001).

    CAS  PubMed  Article  Google Scholar 

  160. Velliste, M., Perel, S., Spalding, M. C., Whitford, A. S. & Schwartz, A. B. Cortical control of a prosthetic arm for self-feeding. Nature 453, 1098–1101 (2008).

    CAS  Article  PubMed  Google Scholar 

  161. Cohen, D. & Nicolelis, M. A. Reduction of single-neuron firing uncertainty by cortical ensembles during motor skill learning. J. Neurosci. 24, 3574–3582 (2004).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  162. Lashley, K. S. An examination of the “continuity theory” as applied to discrimination learning. J. Gen. Psychol. 26, 241–265 (1942).

    Article  Google Scholar 

  163. Lashley, K. S. The mechanism of vision: XV. Preliminary studies of the rat's capacity for detail vision. J. Gen. Psychol. 18, 123–193 (1938).

    Article  Google Scholar 

  164. Leonardo, A. Degenerate coding in neural systems. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 191, 995–1010 (2005).

    PubMed  Article  Google Scholar 

  165. Reeke, G. N. Jr & Edelman, G. M. Selective networks and recognition automata. Ann. NY Acad. Sci. 426, 181–201 (1984).

    PubMed  Article  Google Scholar 

  166. Tononi, G., Sporns, O. & Edelman, G. M. Measures of degeneracy and redundancy in biological networks. Proc. Natl Acad. Sci. USA 96, 3257–3262 (1999).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  167. Merzenich, M. M. et al. Topographic reorganization of somatosensory cortical areas 3b and 1 in adult monkeys following restricted deafferentation. Neuroscience 8, 33–55 (1983).

    CAS  PubMed  Article  Google Scholar 

  168. Merzenich, M. M. et al. Progression of change following median nerve section in the cortical representation of the hand in areas 3b and 1 in adult owl and squirrel monkeys. Neuroscience 10, 639–665 (1983).

    CAS  PubMed  Article  Google Scholar 

  169. Krupa, D. J., Wiest, M. C., Shuler, M. G., Laubach, M. & Nicolelis, M. A. Layer-specific somatosensory cortical activation during active tactile discrimination. Science 304, 1989–1992 (2004).

    CAS  PubMed  Article  Google Scholar 

  170. Chen, L. L. & Wise, S. P. Evolution of directional preferences in the supplementary eye field during acquisition of conditional oculomotor associations. J. Neurosci. 16, 3067–3081 (1996).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  171. Laubach, M., Wessberg, J. & Nicolelis, M. A. Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task. Nature 405, 567–571 (2000).

    CAS  PubMed  Article  Google Scholar 

  172. Li, C. S., Padoa-Schioppa, C. & Bizzi, E. Neuronal correlates of motor performance and motor learning in the primary motor cortex of monkeys adapting to an external force field. Neuron 30, 593–607 (2001).

    CAS  PubMed  Article  Google Scholar 

  173. Mitz, A. R., Godschalk, M. & Wise, S. P. Learning-dependent neuronal activity in the premotor cortex: activity during the acquisition of conditional motor associations. J. Neurosci. 11, 1855–1872 (1991).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  174. Padoa-Schioppa, C., Li, C. S. & Bizzi, E. Neuronal activity in the supplementary motor area of monkeys adapting to a new dynamic environment. J. Neurophysiol. 91, 449–473 (2004).

    PubMed  Article  Google Scholar 

  175. Padoa-Schioppa, C., Li, C. S. & Bizzi, E. Neuronal correlates of kinematics-to-dynamics transformation in the supplementary motor area. Neuron 36, 751–765 (2002).

    CAS  PubMed  Article  Google Scholar 

  176. Paz, R., Boraud, T., Natan, C., Bergman, H. & Vaadia, E. Preparatory activity in motor cortex reflects learning of local visuomotor skills. Nature Neurosci. 6, 882–890 (2003).

    CAS  PubMed  Article  Google Scholar 

  177. Paz, R. & Vaadia, E. Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex. PLoS Biol. 2, e45 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  178. Rokni, U., Richardson, A. G., Bizzi, E. & Seung, H. S. Motor learning with unstable neural representations. Neuron 54, 653–666 (2007).

    CAS  PubMed  Article  Google Scholar 

  179. Wise, S. P., Moody, S. L., Blomstrom, K. J. & Mitz, A. R. Changes in motor cortical activity during visuomotor adaptation. Exp. Brain Res. 121, 285–299 (1998).

    CAS  PubMed  Article  Google Scholar 

  180. de Lange, F. P., Roelofs, K. & Toni, I. Motor imagery: a window into the mechanisms and alterations of the motor system. Cortex 44, 494–506 (2008).

    PubMed  Article  Google Scholar 

  181. Decety, J. The neurophysiological basis of motor imagery. Behav. Brain Res. 77, 45–52 (1996).

    CAS  PubMed  Article  Google Scholar 

  182. Jeannerod, M. & Frak, V. Mental imaging of motor activity in humans. Curr. Opin. Neurobiol. 9, 735–739 (1999).

    CAS  PubMed  Article  Google Scholar 

  183. Neuper, C., Muller-Putz, G. R., Scherer, R. & Pfurtscheller, G. Motor imagery and EEG-based control of spelling devices and neuroprostheses. Prog. Brain Res. 159, 393–409 (2006).

    PubMed  Article  Google Scholar 

  184. Jackson, A., Mavoori, J. & Fetz, E. E. Long-term motor cortex plasticity induced by an electronic neural implant. Nature 444, 56–60 (2006).

    CAS  PubMed  Article  Google Scholar 

  185. Bach-y-Rita, P. & S., W. K. Sensory substitution and the human–machine interface. Trends Cogn. Sci. 7, 541–546 (2003).

    PubMed  Article  Google Scholar 

  186. Segond, H., Weiss, D. & Sampaio, E. Human spatial navigation via a visuo-tactile sensory substitution system. Perception 34, 1231–1249 (2005).

    PubMed  Article  Google Scholar 

  187. Eliades, S. J. & Wang, X. Dynamics of auditory-vocal interaction in monkey auditory cortex. Cereb. Cortex 15, 1510–1523 (2005).

    PubMed  Article  Google Scholar 

  188. Lin, S. C. & Nicolelis, M. A. Neuronal ensemble bursting in the basal forebrain encodes salience irrespective of valence. Neuron 59, 138–149 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  189. Pantoja, J. et al. Neuronal activity in the primary somatosensory thalamocortical loop is modulated by reward contingency during tactile discrimination. J. Neurosci. 27, 10608–10620 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  190. Pereira, A. et al. Processing of tactile information by the hippocampus. Proc. Natl Acad. Sci. USA 104, 18286–18291 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  191. Stapleton, J. R., Lavine, M. L., Nicolelis, M. A. & Simon, S. A. Ensembles of gustatory cortical neurons anticipate and discriminate between tastants in a single lick. Front. Neurosci. 1, 161–174 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  192. Kim, H. K. et al. Continuous shared control stabilizes reach and grasping with brain–machine interfaces. IEEE Trans. Biomed. Eng. 53, 1164–1173 (2005).

    Article  Google Scholar 

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We thank N. Fitzsimmons for his assistance with designing figures for this manuscript.

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Nicolelis, M., Lebedev, M. Principles of neural ensemble physiology underlying the operation of brain–machine interfaces. Nat Rev Neurosci 10, 530–540 (2009). https://doi.org/10.1038/nrn2653

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