3011 Wahl Hall East
3901 Rainbow Boulevard
Kansas City, KS 66160-7401
Phone: (913) 588-5970
Fax: (913) 588-5677
pcheney@kumc.edu
Specific research interests include: 1) brain mechanisms underlying the control of voluntary movements, 2) recovery of motor function following brain injury, and 3) the pathophysiology of motor and cognitive deficits associated with neuro-AIDS.
Modern neurophysiological techniques are used to investigate the function of neurons in the cerebral cortex and brainstem. The electrical discharges of single neurons is recorded in awake monkeys trained to perform various movement tasks. Computerized analysis techniques are used to reveal the functional contribution of a neuron to movement. In a separate project, the mechanisms by which HIV/SIV infect and damage the brain are investigated using neurobehavioral, neurophysiological and neuroanatomical measures. SIV infection in monkeys is used as model of HIV infection in humans.
Brain control of movement and movement disorders
Recent work has focused on the use of spike triggered averaging of EMG activity to characterize the motoneuronal targets of single corticospinal and rubrospinal neurons. Our recent findings show that the majority of single corticospinal neurons involved in arm reach and grasp tasks influence muscles of both distal and proximal joints acting as a functional synergy during some phase of the reaching task (see Fig. 1).
Fig. 1. Spike triggered averages from 24 forelimb muscles generated from the spikes of a single corticospinal neuron recorded in relation to a reach and grasp task. The averages show clear postspike facilitation in muscles at both proximal and distal joints (elbow, wrist and digit). Theses muscles represent a functional synergy underlying a specific phase of the movement task.
In other work, stimulus triggered averaging of EMG activity has been used to map primary motor cortex with respect to 24 muscles of the forelimb. Collapsing maps for all distal muscles and all proximal muscles reveals one of the consistent features in the intra-areal representation of the forelimb in primary motor cortex (see Fig. 2).
Fig. 2. Representation of distal (blue) and proximal (red) muscles in primary motor cortex of the rhesus monkey constructed from output effects in stimulus triggered averages computed at 15 microamps during a reach and grasp task. Primary motor cortex is unfolded and represented in two dimensions. The purple area represents sites which evoked effects in combinations of proximal and distal muscles. These sites may be particularly important in mediating coactivation of distal and proximal muscles commonly observed during reach and grasp. From Park, Belhaj-Saif, Gordon and Cheney, J. Neuroscience 21: 2784-2792, 2001.
Neuro-AIDS
The broad objective of this project is to identify mechanisms by which the AIDS virus injures the brain and ways of preventing this injury. The use of animal models is an important approach to investigating many questions about disease mechanisms in humans. The best animal model of AIDS for research purposes is the rhesus macaque monkey. A naturally occurring virus called simian immunodeficiency virus (SIV) infects these monkeys and produces a disease that has many of the characteristics of HIV infection in humans but on a time scale of months rather than years. Using this model, we have identified behavioral and neurophysiological impairments and have correlated them with immunological, virological and neuropathological measures. Fig. 3 illustrates data from 6 monkeys performing a motor skill task. Data on the left in red is from 4 monkeys with rapidly progressing disease. Data on the right is from 2 monkeys with slowly progressing disease. The white bars indicate time of innoculation. Note that most of the monkeys with rapidly progressing disease show a very gradual decline in performance followed by a precipitous decline which occurs before the onset of overt clinical signs of disease (onset of clinical signs is marked by the green bars). Monkeys with slowly progressing disease either did not show declines on this task (or other tasks) or only showed declines after the onset of overt clinical signs. The results demonstrate that only monkeys with a rapidly progressing disease course show neurological impairments. Monkeys with a slowly progressing course have systemic disease but do not get neurological disease. Results from a multi-system evoked potential study confirm these findings. This model is now being used to investigate questions about the mechanisms by which the virus injures neurons and the effects of opiate drugs on disease severity and progression.
Fig. 3. Performance on a motor skill task for 2 monkeys with slowly progressing disease (right column) and 4 monkeys with rapidly progressing disease (left column). This task required the monkey to remove food pellets from a well in a rotating plexiglas disk. The speed at which the monkey was successful on 50% of the trials was quantified. Time as specific dates tested is plotted on the horizontal axis. (from Marcario et al., J. Medical Primatology 28: 105-117, 1999)
McKiernan, B.J., Marcario, J.K., Hill-Karrer, J. and Cheney, P.D. Correlations between the magnitude of Corticomotoneuronal cell postspike effects and the strength of cell-target muscle covariation. J. Neurophysiol. 83: 99-115, 2000
Belhaj-Saif, A. and Cheney, P.D. Plasticity in the distribution of red nucleus mediated poststimulus effects on forearm muscles associated with unilateral pyramidal tract lesions. J. Neurophysiol. 83: 3147-3153, 2000.
Park, M.C., Belhaj-Saif, A. and Cheney, P.D. Chronic recording of EMG activity from large numbers of forelimb muscles in awake macaque monkeys. J. Neurosci. Methods 15: 153-160, 2000.
Cheney, P.D., Park, M.C. Belhaj-Saïf, A. Hill-Karrer, J. McKiernan, B.J. and Marcario, J. K.Cortical motor areas an their properties: implications for neuroprosthetics. Prog. Brain Res. 128: 135-160, 2000
Park, M.C., Belhaj-Saif, A. and Cheney, P.D. Consistent features in the forelimb representation of primary motor cortex of rhesus macaques. J. Neurosci. 21: 2784-2792, 2001.
Cheney, P.D. Electrophysiological Methods for Mapping Brain Motor Circuits. In: Brain Mapping: The Methods, Second Edition, A. W. Toga and J. C. Mazziotta (Eds.), New York, NY: Academic Press, 2002.
Back row, left to right:
Gustaf Van Aker, Paul Cheney, Becca McPherson*, Ian Edwards
Front row, left to right:
Marie-Helene Boudrias**, Heather Hudson, Darcy Griffin, Mariam Riazi-Kermani
*As of August 1, 2007 Becca's New address will be: Biology Department, Seton Hall University, South Orange, New Jersey
**As of September 1, 2007 Marie-Helene's new address will be Department of Clinical Neurology, Oxford Univeristy, Oxford, England
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The University of Kansas Medical Center