Journal of Rehabilitation Research and Development
Vol. 36 No. 2,
FROM BENCH TO BEDSIDE
by Tamara T. Sowell and Apostolos P. Georgopoulos, MD
The March 12, 1999 issue of Science (283:5408:1752-7) published an article on VA-sponsored research entitled "Motor Cortical Encoding of Serial Order in a Context - Recall Task," by Adam F. Carpenter, Apostolos P. Georgopoulos, and Guissepe Pellizzer, of the Department of Veterans Affairs Brain Sciences Center in Minneapolis Minnesota.
Dr. Georgopoulos and his colleagues were surprised to discover that the motor cortex is not just responsible for sending the message to make a movement but that it actually is involved in planning the movement. This discovery could identify new ways to treat brain disorders, such as in a stroke. He and his colleagues taught a serial order task to primates and rewarded them with snacks for making the right decisions. The monkeys learned that they would see spots of light appearing on a dark computer screen in a particular order, for example, the first at 12 o'clock, the second at 2 o'clock, the third at 9 and the fourth at 5. Provided with a handle controlling a pointer, the animals then were shown one of the light spots and were rewarded if they pointed at the spot on the screen where the next light in the sequence should appear.
As the animals performed these tasks, the researchers monitored activity of their brain cells and were surprised to find a very strong signal from motor cortex cells. This burst of nerve cell activity took place as the monkeys observed the signal and remembered the sequence, before they made any movement with the pointer. Georgopoulos stated, "The motor cortex clearly was involved in this process and not just the movement."
Dr. Georgopoulos and his colleagues have long believed that the motor cortex may be involved in functions that are far more complex than are currently known.
Tamara T. Sowell, Editor
Journal of Rehabilitation Research and Development, Department of Veterans Affairs Rehabilitation Research and Development Service
Apostolos P. Georgopoulos, MD
Brain Sciences Center, Department of Veterans Affairs Medical Center, Minneapolis, MN 55417; Center for Cognitive Sciences, Departments of Neuroscience and Psychology, and Departments of Neurology and Physiology, University of Minnesota, Minneapolis, MN 55455
Discovering the Unexpected: Encoding of Serial Order in the Motor Cortex
A fascinating aspect of brain research is that there is hardly a dull moment. The brain is such a complex organ that there are almost always unexpected findings to surprise you and brighten your day. By "unexpected," I mean a finding that doesn't really fit into the commonly held view of what an area is supposed to do. The value of this observation is that it forces a change on this conceptual framework. Conceptual frameworks of what a brain area is supposed to do are usually narrow: we love to pigeonhole functions into neatly arranged brain regions, and the old phrenologic picture is still in full force. Of course, to a good extent, this is a valid approach: visual cortex is for vision, auditory cortex for audition, and motor cortex for movement - so far so good. The problem arises when this approach becomes Procrustes's bed for the facts, that is, too restrictive: then a reevaluation is in order.
Over the past 15-odd years, my colleagues and I have been investigating the activity of cells in the motor cortex with respect to classical motor functions, such as the neural encoding of parameters of movement and force, but also with respect to functions that relate to the planning of the motor response. In the former studies, we discovered the directional tuning of motor cortical cells and clarified their on-line relations to the evolving movement; in the latter, we discovered a surprising involvement of the motor cortex in more subtle processes relating to the conditions and rules under which a movement is generated. Most of these conditions are spatial in nature; for example, reaching to memorized targets in space or moving at an angle from a stimulus direction. To these, we have now added the encoding of temporal, serial order, information in motor cortical cell activity. Specifically, we discovered that single cells in the motor cortex care about the sequence in which potential targets are presented. This finding was quite unexpected. How is it that a structure that is supposed to be nothing but an "upper motor neuron," just telling the muscles what to do, can be involved in such a higher order function as serial order?
The answer to this question lies not in what the solid data at hand are, but rather in how we think about the motor cortex. As we know from neuroanatomical tracing studies, the motor cortex is interconnected with a large number of cortical and subcortical areas; from this, it follows that cell activity can reflect potentially various aspects of these diverse inputs, depending on the demands of a specific task. It seems that the motor cortex is involved in practically every aspect of movement planning and/or decision-making. This forces us to broaden our conceptual scheme, as follows: the motor cortex, as are many other areas, is a member of partially overlapping networks that process information concerning the planning and implementation of an upcoming movement. Therefore, the results obtained in a particular study will depend on which networks are engaged by the particular task. For example, if the task is simply the pushing of a button, then motor cortical activity will be recorded that relates to the implementation of this movement. If, on the other hand, a movement to the third of seven targets is required, then motor cortical activity also will relate to the serial order of the stimuli in the sequence, reflecting the engagement of the "temporal order" network, and so on. There is nothing mysterious about the participation of the motor cortex in different networks subserving different functions; rather, the obstacle is our intellectual inertia to see things in novel ways.
How does all of this relate to rehabilitation? First, it opens our eyes to look for subtle deficits in motor planning that could be present, for example, in a stroke involving the motor cortex, and which could contribute to the more obvious motor deficits. Identifying and paying attention to such subtle alterations in spatial-motor processing of an upcoming movement may lead to novel ways for rehabilitation. Second, it enlarges our view of such a stroke, from an "upper motor neuron" type to a more general, multifactorial condition, which would be properly treated by multifactorial means. The choice and application of these means can be hinted at by the results of basic research but are future challenges in rehabilitation research. This way, basic brain research and rehabilitation strategies go hand-in-hand.
Apostolos P. Georgopoulos, M.D.
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