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 stimulus triggered averaging of EMG activity to characterize the motoneuronal targets of corticospinal 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 .
Figure 1. Stimulus triggered averages from 24 forelimb muscles generated from the 15 µA stimuli applied to primary motor cortex (M1) in a rhesus monkey performing a reach-to-grasp task. The averages show clear poststimulus facilitation in muscles at both proximal (shoulder and elbow) and distal (wrist and digit) joints. Poststimulus suppression is also present in FCU and PL. Using this approach, the representation of individual muscles and muscle groups in M1 was mapped.
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 (Figure1). 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).
Figure 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.
SIV Infected Macaque
HIV Infected Humans
Figure 3. Profile of behavioral deficits in SIV infected rhesus macaques compared to HIV infected humans. From Cheney et al. J. Neurovirology, in press, 2008.
Using this model, we have identified behavioral and neurophysiological impairments and have correlated them with immunological, virological and neuropathological measures. Figure 3 summarizes the profile of behavioral deficits in SIV infected rhesus macaques with deficits in HIV infected humans. The macaque model of neuro-AIDS is now being used to investigate questions about the mechanisms by which the virus injures neurons and the influence of drugs of abuse, for example, opiates, on disease severity and progression.
Back row, left to right:
Gustaf Van Aker, Will Messamore, Paul Cheney, Ian Edwards
Front row, left to right:
Mariam Riazi-Kermani, Darcy Griffin, Heather Hudson, Hongyu Zhang
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
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.
Park, M.C., Belhaj-Saif, A. and Cheney, P.D. Distribution and properties of poststimulus effects in proximal and distal forelimb muscles from primary motor cortex in rhesus macaques. J. Neurophysiol. 92: 2968-2984, 2004.
Marcario, J.K., Manaye, K.F., SantaCruz, K.S., Mouton, P.R., Berman, N.E.J., and Cheney, P.D. Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus. J. Neurovirol. 10: 387-399, 2004.
Cheney, P.D., Belhaj-Saïf, A. and Boudrias, M.H. Principles of Corticospinal System Organization and Function. In: Handbook of Clinical Neurophysiology, Vol. 4, Clinical Neurophysiology of Motor Neuron Diseases, A. Eisen, Editor, New York, NY: Elsevier Science, pp. 59-96, 2004.
Boudrias, M.H, Belhaj-Saïf and Cheney, P.D. Output Properties of Supplementary Motor Area (SMA) in Rhesus Macaques. Cerebral Cortex 16: 632-638, 2006.
Marcario, J.K., Riazi, M., Adany, A., Kenjale, H., Fleming, H.K., Marquis, M., Nemon, O., Mayo, M., Yankee, T., Narayan, O., and Cheney, P.D. Effect of morphine on the neuropathogenesis of SIVmac infection in Indian rhesus macaques. J. Neuroimmune Pharmacology 3: 12-25, 2008.
Griffin, D.M., Hudson, H.M., Belhaj-Sa?f, A., McKiernan, B.J. and Cheney, P.D. Do Corticomotoneuronal Cells Predict Target Muscle EMG Activity? J. Neurophysiol. 99: 1169-1186, 2008.
Cheney, P.D., Riazi, M. and Marcario, J.K. Behavioral and Neurophysiological Hallmarks of SIV Infection in Macaque Monkeys. J. Neurovirol. 14: 301-308, 2008.
Riazi, M., Marcario, J.K., Samson, F.K., Kenjale, H., Adany, I., Staggs, V., Ledford, E., Marquis, J., Narayan, O., and Cheney, P.D. Rhesus macaque model of chronic opiate dependence and neuro-AIDS: longitudinal assessment of auditory brainstem responses and visual evoked potentials. J. Neuroimmune Pharmacology 4: 260-275, 2009.
Griffin, D.M., Hudson, H.M., Belhaj-Sa?f, A. and Cheney, P.D. Stability of output effects from motor cortex to forelimb muscles in primates. J. Neurosci., 29: 1915-1927, 2009.
Boudrias, M.H., Lee, S.P., Svojanovsky, S. and Cheney, P.D. Forelimb muscle representations and output properties of the motor areas in the mesial wall of rhesus macaques. Cerebral Cortex, in press
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