Faculty Directory
Lee Miller

Professor of Physiology

Professor of Physical Medicine & Rehabilitation

Professor of Biomedical Engineering


Ward 5-315
Chicago, IL 60611

312-503-8677Email Lee Miller


Biomedical Engineering

Research Interests

Signal production and processing

The three fundamental goals of my research are the following:

  1. To understand the nature of the brain's own signals — the "language" in which movement commands are expressed by neurons in the central nervous system.
  2. To understand the mechanisms by which these signals are produced — the nature of the connections among networks of neurons, and the transformations that occur in the signals as they propagate throughout these networks.
  3. To develop applications of these basic principles that could be of therapeutic value to human patients. Much of this work is done in collaboration with students and faculty from the Biomedical Engineering Department and the Interdepartmental Neuroscience Program (NUIN).

In a practical sense, understanding how the brain encodes its movement commands comes down to the problem of deciphering the information contained in signals recorded from the brain. Neurons in motor areas of the cerebral cortex as well as in the brainstem, send their signals to the spinal cord, ultimately to control the activity of about 50 muscles of the arm and hand that are necessary for reaching, grasping and the manipulation of objects. Most of the experiments in my laboratory involve recordings made directly from the brains of animals during behavior. In these experiments, we are able to study the signals produced by individual neurons in the intricate circuits comprising real neural networks.

My research has shown that neurons in the motor cortex encode the activity of small groups of muscles that act synergistically to control movement. Different neurons control different groups of muscles, and together, the entire network produces coordinated movement. I have also studied two brainstem motor areas, the red nucleus, and the superior colliculus, which have similar organization, although each has a somewhat specialized function. Red nucleus controls predominantly groups of extensor muscles involved in hand function, while the certain parts of the colliculus control the shoulder muscles that help to direct reaching movements.

In the past, my lab has studied mainly the connections from these neurons to muscles. We are now beginning to look at the relations among neurons that give rise to their coordinated activity. This has become possible with the advent of chronically implanted arrays of electrodes that allow simultaneous recordings from 100 or more neurons. We are developing powerful computational tools to study the relations among these neurons, referred to as their "functional connectivity". While such tools can be developed (and are being studied) using simulated, artificial neural networks, comparison of such results with our data from actual neural networks is invaluable.

Our increased understanding of the signals in the brain, together with technological improvements in electronics and computers has given rise recently to a new field called "Brain Machine Interface". As the term implies, these are literally attempts to meld mind and machine. My laboratory is involved in several projects that use recordings from micro-electrodes implanted in the motor cortex as a source of control signals. Much work has been invested in the development of BMIs that are capable of controlling the position of a computer cursor or a robotic limb. However, because of my lab's interest in the control of muscles, we are instead working to develop a BMI that could restore control to the paralyzed muscles of a spinal cord injured patient. The approach is to record from the brain, predict the intended muscle activity, and bypass the injured spinal cord by directly activating the muscles through electrical stimulation. In addition to the potential of experiments like these to impact motor disorders in human patients, they also offer innovative new approaches to understanding the nature of the brain's command signals that control limb movement.

Selected Publications

Rebesco JM, Miller LE (2011) Enhanced detection threshold for in vivo cortical stimulation produced by Hebbian conditioning.Journal of Neural Engineering 8: 016011.

Rebesco JM, Miller LE (2010) Altering Function in Cortical Networks by Short-Latency, Paired Stimulation. Conf Proc, IEEE Eng Med Biol Soc.

Oby ER, Ethier C, Bauman M, Perreault EJ, Ko J, Miller LE (2010) Prediction of Muscle Activity from Cortical Signals to Restore Hand Grasp in Subjects with Spinal Cord Injury. In: O'Weiss KG (ed) Statistical Signal Processing for Neuroscience and Neurotechnology. Academic Press, Elsevier.

Ethier C, Oby ER, Bauman M, Miller LE (2010) Cortically controlled functional electrical stimulation: a neuroprosthesis for grasp function. Conf Proc, 10th Vienna International Workshop on FES and 15th IFESS Annual Conference 2010.

Slutzky MW, Jordan LR, Bauman MJ, Miller LE (2010) A new rodent behavioral paradigm for studying forelimb movement. JNS Methods 192: 228-232.

Rebesco JM, Stevenson IH, Koerding K, Solla SA, Miller LE (2010) Rewiring neural interactions by micro-stimulation.Frontiers in Systems Neuroscience 4: 39.

Slutzky MW, Jordan LR, Miller LE (2010) Optimal spacing of surface electrode arrays for brain machine interface applications.Journal of Neural Engineering 7: 26004.

Perreault EJ, Ethier C, Pohlmeyer EA, Oby ER, Miller LE (2009) A Brain-Machine Interface for Restoring Hand Function Following Paralysis. Asilomar Conference on Signals, Systems and Computers.

Brill N, Polasek K, Oby E, Ethier C, Miller L, Tyler D (2009) Nerve cuff stimulation and the effect of fascicular organization for hand grasp in nonhuman primates. Conf Proc IEEE Eng Med Biol Soc 1: 1557-1560.

Holdefer RN, Miller LE (2009) Dynamic Correspondence between Purkinje Neuronal Discharge and Forelimb Muscle Activation in the Macaque. Brain Res 1295: 67-75.

Fagg AH, Ojakangas GW, Miller LE, Hatsopoulos NG (2009) Kinetic trajectory decoding using motor cortical ensembles. IEEE Trans Neural Syst Rehabil Eng 17: 487-496.

Fagg AH, Hatsopoulos NG, London BM, Reimer J, Solla SA, Wang D, Miller LE (2009) Toward a Biomimetic, Bidirectional, Brain Machine Interface. in: 31th Annual International IEEE EMBS Conference, Minneapolis. embc 2009 v13

Pohlmeyer EA, Jordon LR, Kim P, and Miller LE. (2009) A fully implanted drug delivery system for peripheral nerve blocks in behaving animals. Journal of neuroscience method. 182: 165-171. JNS Methods v182p165

Miller LE, Gibson A (2009) The Red Nucleus. In: Squire L (ed) The New Encyclopedia of Neuroscience. Elsevier Ltd, Oxford. pp 55-62. Ency NS v8p55

Pohlmeyer EA, Oby ER, Perreault EJ, Solla SA, Kilgore KL, Kirsch RF, Miller LE (2009) Toward the Restoration of Hand Use to a Paralyzed Monkey: Brain-Controlled Functional Electrical Stimulation of Forearm Muscles. PLoS ONE 4: e5924. PLoSONE v4e5924

Stevenson IH, Rebesco JM, Hatsopoulos NG, Haga Z, Miller LE, Kording KP (2009) Bayesian inference of functional connectivity and network structure from spikes. IEEE Transactions on Neural Systems and Rehabilitation Engineering 17, 203-213. IEEE TNSRE v17p203

Stevenson IH, Rebesco JM, Miller LE, Kording KP (2008) Inferring functional connections between neurons. Curr Opin Neurobiol 18: 582-588. Curr Opin NeuroBiol v18p582

Morrow MM, Pohlmeyer EA, Miller LE (2008) Control of muscle synergies by cortical ensembles. In: Sternad D (ed) Progress in Motor Control - A Multidisciplinary Perspective. Springer, New York, pp 179-199. Adv Exp Med Biol v629p179

London BM, Jordan LR, Jackson CR, Miller LE (2008) Electrical stimulation of the proprioceptive cortex (area 3a) used to instruct a behaving monkey. IEEE Transactions on Neural Systems and Rehabilitation Engineering 16:32-36. IEEE TNSRE v16p32

Pohlmeyer EA, Solla SA, Perreault EJ, Miller LE (2007) Prediction of upper limb muscle activity from motor cortical discharge during reaching. Journal of Neural Engineering 4:369-379. JNE v4p369.pdf

Fagg AH, Hatsopoulos NG, de Lafuente V, Moxon KA, Nemati S, Rebesco JM, Romo R, Solla SA, Reimer J, Tkach D, Pohlmeyer EA, Miller LE (2007) Biomimetic brain machine interfaces for the control of movement. J Neurosci 27: 11842-11846.JNS v27p11842.pdf

Gdowski MJ, Miller LE, Bastianen CA, Nenonene EK, Houk JC (2007) Signaling patterns of globus pallidus internal segment neurons during forearm rotation. Brain Research 1155:56-69. Brain Res v1155p56.pdf

Pohlmeyer E.A., Perreault E.J., Slutzky M.W., Kilgore K.L., Kirsch R.F., Taylor D.M., Miller L.E. (2007) Real-time control of the hand by intracortically controlled functional neuromuscular stimulation. In: The 10th IEEE International Conference on Rehabilitation Robotics, The Netherlands ICORR 2007.pdf

Mussa-Ivaldi F.A., Miller L.E., Rymer W.Z., Weir R.F. (2007) Neural Engineering. In: Parasuraman R, Rizzo M (eds) Neuroergonomics: The Brain at Work. Oxford University Press, Oxford, pp 293-312

Westwick, D.T., Pohlmeyer, E.A., Solla, S.A., Miller, L.E., and Perreault, E.J. (2006) Identification of Multiple-Input Systems with Highly Coupled Inputs: Application to EMG Prediction from Multiple Intracortical Electrodes. Neural Comput 18, 329-355.Neural Comp v18p329.pdf

Morrow, M.M., Jordan, L.R., and Miller, L.E. (2006) A direct comparison of the task-dependent discharge of M1 in hand-space and muscle-space. J Neurophysiol. 97, 1786-1798. JNP v97p1786.pdf

Fishbach, A., Roy, S.A., Bastianen, C., Miller, L.E., and Houk, J.C. (2006) Deciding when and how to correct a movement: discrete submovements as a decision making process. Exp Brain Res. 177, 45-63. EBR v177p45.pdf

Holdefer, R.N., Houk, J.C., and Miller, L.E. (2005) Movement-related discharge in the cerebellar nuclei persists after local injections of GABA(A) antagonists. J Neurophysiol 93, 35-43. JNP v93p35.pdf

Fishbach, A., Roy, S.A., Bastianen, C., Miller, L.E., and Houk, J.C. (2005) Kinematic properties of on-line error corrections in the monkey. Exp Brain Res 164, 442-457. EBR v164p442.pdf

Miller, L.E. (2004) Limb movement: getting a handle on grasp. Curr Biol 14, R714-715. Curr Biol v14pR714.pdf

Novak, K.E., Miller, L.E., and Houk, J.C. (2003) Features of motor performance that drive adaptation in rapid hand movements. Exp Brain Res 148, 388-400. EBR v148p388.pdf

Mussa-Ivaldi, F.A., and Miller, L.E. (2003) Brain-machine interfaces: computational demands and clinical needs meet basic neuroscience. Trends Neurosci 26, 329-334. TINS v26p329.pdf

Morrow, M.M., and Miller, L.E. (2003) Prediction of muscle activity by populations of sequentially recorded primary motor cortex neurons. J Neurophysiol 89, 2279-2288. JNP v89p2279.pdf

Pohlmeyer, E.A., Miller, L.E., Mussa-Ivaldi, F.A., Perreault, E.J., and Solla, S.A. (2003) Prediction of EMG from Multiple Electrode Recordings in Primary Motor Cortex. In Annual mtg., IEEE Int. Conf. Eng. in Med. Biol. Soc.: Cancun

Miller, L.E., Holdefer, R.N., and Houk, J.C. (2002) The Role of the Cerebellum in Modulating Voluntary Limb Movement Commands. Archives Italiennes Biologie 140, 175-183

Novak, K.E., Miller, L.E., and Houk, J.C. (2002) The use of overlapping submovements in the control of rapid hand movements. Exp Brain Res 144, 351-364

Holdefer, R.N., and Miller, L.E. (2002) Primary motor cortical neurons encode functional muscle synergies. Exp Brain Res 146, 233-243

Gdowski, M.J., Miller, L.E., Parrish, T., Nenonene, E.K., and Houk, J.C. (2001) Context dependency in the globus pallidus internal segment during targeted arm movements. J Neurophysiol 85, 998-1004

Lunenburger, L.,2004 Kleiser, R., Stuphorn, V., Miller, L.E., and Hoffmann, K.P. (2001) A possible role of the superior colliculus in eye-hand coordination. Prog Brain Res 134, 109-125

Houk, J.C., and Miller, L.E. (2001) Cerebellum: Movement regulation and cognitive functions. In Encyclopedia of Life Sciences. (Macmillan)

Novak, K.E., Miller, L.E., and Houk, J.C. (2000) Kinematic properties of rapid hand movements in a knob turning task. Exp Brain Res 132, 419-433

Holdefer, R.N., Miller, L.E., Chen, L.L., and Houk, J.C. (2000) Functional connectivity between cerebellum and primary motor cortex in the awake monkey. J Neurophysiol 84, 585-590

Sarrafizadeh, R., Miller, L.E., and Houk, J.C. (1999) Red Nucleus. In Encyclopedia of Neuroscience, G. Adelman and B. Smith, eds. (Elsever Science), pp. 1794-1795

Stuphorn, V., Hoffmann, K.P., and Miller, L.E. (1999) Correlation of primate superior colliculus and reticular formation discharge with proximal limb muscle activity. Journal of Neurophysiology 81, 1978-1982

Miller, L.E., and Sinkjaer, T. (1998) Primate red nucleus discharge encodes the dynamics of limb muscle activity. J. Neurophysiol. 80, 59-70

Mason, C.R., Miller, L.E., Baker, J.F., and Houk, J.C. (1998) Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations. J Neurophysiol 79, 537-554

Nocher, J.D., Lee, J.S., and Miller, L.E. (1996) A magnetic field system using implanted sensors to track limb movements in the monkey. J. Neuroscience Methods 67, 203-210

Novak, K.E., Miller, L.E., and Houk, J.C. (1996) Biological mechanisms for optimal control. In Ninth annual Yale workshop on Adaptive and Learning Systems. pp. 201-206, Yale University: Center for Systems Science, Dunham Laboratory

Sinkjaer, T., Miller, L.E., Andersen, T., and Houk, J.C. (1995) Synaptic linkages between red nucleus cells and limb muscles during a multi-joint motor task. Experimental Brain Research 102, 546-550

Miller, L.E., and Houk, J.C. (1995) Motor co-ordinates in primate red nucleus: preferential relation to muscle activation versus kinematic parameters. J. Physiol. 488, 533-548

Theeuwen, M., Gielen, C.C., Miller, L.E., and Doorenbosch, C. (1994) The relation between the direction dependence of electromyographic amplitude and motor unit recruitment thresholds during isometric contractions. Exp Brain Res 98, 488-500

Theeuwen, M., Gielen, C.C., and Miller, L.E. (1994) The relative activation of muscles during isometric contractions and low-velocity movements against a load. Exp Brain Res 101, 493-505

Theeuwen, M., Miller, L.E., and Gielen, C.C.A.M. (1993)Are the orientations of head and arm related during pointing movements? Journal of Motor Behavior 25, 242-250

Miller, L.E., van Kan, P.L.E., Sinkjaer, T., Andersen, T., Harris, G.D., and Houk, J.C. (1993) Correlation of primate red nucleus discharge with muscle activity during free-form arm movements. J. Physiol. London 469, 213-243

Miller, L.E., Theeuwen, M., and Gielen, C.C.A.M. (1992) The control of arm pointing movements in three dimensions. Exp. Brain Res. 90, 415-426

Miller, L.E., Sinkjaer, T., Andersen, T., Laporte, D.J., and Houk, J.C. (1992) Correlation analysis of relations between red nucleus discharge and limb muscle activity during reaching movements in space. In Control of arm movement in space: Neurophys. and Comp. approaches, R. Caminiti, P.B. Johnson and Y. Burnod, eds. (Heidelberg: Springer-Verlag)

Miller, L.E., Gielen, C.C.A.M., Theeuwen, M., and Doorenbosch, C. (1992) The activation of mono- and biarticular muscles in multijoint movements. In Control of arm movement in space: Neurophys. and Comp. approaches, R. R. Caminiti, P.B. Johnson and Y. Burnod, eds. (Heidelberg: Springer-Verlag), pp. 1-16

Wu, C., Houk, J.C.Y.K., and Miller, L.E. (1990) Nonlinear damping of limb motion. In Multiple muscle systems, J.M. Winters S.L.-Y. Woo, ed. (Springer-Verlag New York)

Houk, J.C., Dessem, D.A., Miller, L.E., and Sybirska, E.H. (1987) Correlation and spectral analysis of relations between single unit discharge and muscle activities. J. Neurosci. Meth. 21, 201-224

Gielen, C.C., Houk, J.C., Marcus, S.L., and Miller, L.E. (1984) Viscoelastic properties of the wrist motor servo in man. Ann Biomed Eng 12, 599-620