Lee E. Miller

Lee E. Miller
Associate Professor PhD, Northwestern University
lm [at] northwestern [dot] edu	Ward 5-011	(312) 503-8677

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.

Go to: Miller Lab Web Site


*Figure Legend 1:* The micro-electrode array that we use to record signals from the brain is manufactured by Cyberkinetics, Inc. It is 4 mm across and contains 100 electrodes. The array is chronically implanted in the brain, and wired to a connector on the skull.

Selected Publications:

Pohlmeyer, E. A., S. A. Solla, et al. (in press). "Prediction of upper limb muscle activity from motor cortical discharge during reaching." Journal of Neural Engineering.

London, B. M., L. R. Jordan, et al. (in press). "Electrical stimulation of the proprioceptive cortex (area 3a) used to instruct a behaving monkey." IEEE Transactions on Neural Systems and Rehabilitation Engineering.

Fagg, A. H., N. G. Hatsopoulos, et al. (In press). "Biomimetic brain machine interfaces for the control of movement." Journal of Neuroscience.

Westwick, D. T., E. A. Pohlmeyer, et al. (2006). "Identification of Multiple-Input Systems with Highly Coupled Inputs: Application to EMG Prediction from Multiple Intracortical Electrodes." Neural Comput 18(2): 329-55.

Morrow, M. M., L. R. Jordan, et al. (2006). "A direct comparison of the task-dependent discharge of M1 in hand-space and muscle-space." J Neurophysiol.

Fishbach, A., S. A. Roy, et al. (2006). "Deciding when and how to correct a movement: discrete submovements as a decision making process." Exp Brain Res.

Holdefer, R. N., J. C. Houk, et al. (2005). "Movement-related discharge in the cerebellar nuclei persists after local injections of GABA(A) antagonists." J Neurophysiol 93(1): 35-43.

Fishbach, A., S. A. Roy, et al. (2005). "Kinematic properties of on-line error corrections in the monkey." Exp Brain Res 164(4): 442-57.

Miller, L. E. (2004). "Limb movement: getting a handle on grasp." Curr Biol 14(17): R714-5.
Novak, K. E., L. E. Miller, et al. (2003). "Features of motor performance that drive adaptation in rapid hand movements." Exp Brain Res 148: 388-400.

Mussa-Ivaldi, F. A. and L. E. Miller (2003). "Brain-machine interfaces: computational demands and clinical needs meet basic neuroscience." Trends Neurosci 26(6): 329-34.

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

Miller, L. E., R. N. Holdefer, et al. (2002). "The Role of the Cerebellum in Modulating Voluntary Limb Movement Commands." Archives Italiennes Biologie 140: 175-183.

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

Holdefer, R., 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.

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.

Stuphorn, V., Hoffmann, K.-P. and Miller, L.E. (1999) Correlation of primate superior colliculus discharge with activity of shoulder and arm musculature. J. Neurophysiol. 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. Neurosci. Meth. 67: 203-210.

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. (Lond) 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.