A computer model of rigidity and related motor dysfunction in Parkinson's disease

This work explores the involvement of spinal circuits in the generation of parkinsonian rigidity and related motor dysfunction. A computer model of spinal proprioceptive input processing, derived from previous work on spasticity modeling, was adapted to the simulation of parkinsonian rigidity. Model parameters were varied to generate simulations reproducing experimental data obtained using the pendulum test of the leg in 10 parkinsonian patients and 3 healthy subjects. Convenient reproductions of experimental traces in rigidity were obtained by the combination of a low reflex gain and a decrease in reflex threshold. These findings are consistent with studies reporting an increase of spinal interneuron excitability and proprioception deficits in Parkinson's disease (PD). Moreover, as the threshold parameter was much lowered, our model generated typical features of parkinsonian resting tremor, endorsing the hypothesis of a participation of a spinal oscillator in this disorder. Finally, tuning the reflex gain during simulations of rigidity resulted in the generation of active movement, opening some hypotheses on pathophysiology of motor dysfunction in PD, and notably, of akinesia. More generally, this work accredits the hypothesis of the involvement of an aperiodic, altered supra‐spinal motor drive in PD, resulting in spinal dysfunction, through specific descending motor pathways. This may lead to a search for new (spinal) pharmacological targets in PD. It emphasizes further the value of computer modeling in understanding motor control in health and disease. © 2003 Movement Disorder Society

[1]  A. Struppler Tremor and skeletal muscle tone. , 1993, Stereotactic and functional neurosurgery.

[2]  I Fukumoto Computer simulation of parkinsonian tremor. , 1986, Journal of biomedical engineering.

[3]  T Bajd,et al.  Testing and modelling of spasticity. , 1982, Journal of biomedical engineering.

[4]  R. Lee,et al.  Evidence for abnormal long-loop reflexes in rigid Parkinsonian patients , 1975, Brain Research.

[5]  Y. Agid,et al.  Overactivity of cervical premotor neurons in Parkinson’s disease , 1998, Journal of neurology, neurosurgery, and psychiatry.

[6]  Inman Vt,et al.  Comparison of electrical activity and duration of tension in the human rectus femoris muscle. , 1976 .

[7]  E. Pierrot-Deseilligny,et al.  Transmission of the cortical command for human voluntary movement through cervical propriospinal premotoneurons , 1996, Progress in Neurobiology.

[8]  M Hallett,et al.  Physiological mechanisms of rigidity in Parkinson's disease. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[9]  J W Langston,et al.  Quantification of dyskinesia in Parkinson's disease: Validation of a novel instrumental method , 1999, Movement disorders : official journal of the Movement Disorder Society.

[10]  M. Aminoff,et al.  Sensory perception in Parkinson disease. , 1997, Archives of neurology.

[11]  H J Ralston,et al.  Comparison of electrical activity and duration of tension in the human rectus femoris muscle. , 1976, Electromyography and clinical neurophysiology.

[12]  R B Stein,et al.  Estimating mechanical parameters of leg segments in individuals with and without physical disabilities. , 1996, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[13]  James A. Mortimer,et al.  Evidence for a quantitative association between EMG stretch responses and Parkinsonian rigidity , 1979, Brain Research.

[14]  F. Hlawatsch,et al.  Linear and quadratic time-frequency signal representations , 1992, IEEE Signal Processing Magazine.

[15]  O. Foerster Zur analyse und pathophysiologie der striären bewegungsstörungen , 1921 .

[16]  W. Clower Lesions as Therapy: Rigidity and Parkinsons Disease , 2001, Journal of the history of the neurosciences.

[17]  J C Rothwell,et al.  Physiology and Anatomy of Possible Oscillators in the Central Nervous System , 2008, Movement disorders : official journal of the Movement Disorder Society.

[18]  F. W. Cody,et al.  Proprioceptive control of wrist movements in Parkinson's disease. Reduced muscle vibration-induced errors. , 1997, Brain : a journal of neurology.

[19]  C. Marsden The mysterious motor function of the basal ganglia , 1982, Neurology.

[20]  P. Rack,et al.  The role of reflexes in the resting tremor of Parkinson's disease. , 1986, Brain : a journal of neurology.

[21]  N. Bathien,et al.  Reciprocal continuous inhibition in rigidity of Parkinsonism. , 1977, Journal of neurology, neurosurgery, and psychiatry.

[22]  Max B. Streifler,et al.  Parkinson's disease : anatomy, pathology and therapy , 1990 .

[23]  J. Burne,et al.  Reflex origin of Parkinsonian tremor , 1987, Experimental Neurology.

[24]  P. Delwaide,et al.  Short‐latency autogenic inhibition in patients with parkinsonian rigidity , 1991, Annals of neurology.

[25]  C. Marsden,et al.  Spinal rigidity following acute myelitis , 1997, Movement disorders : official journal of the Movement Disorder Society.

[26]  F. Walshe,et al.  OBSERVATIONS ON THE NATURE OF THE MUSCULAR RIGIDITY OF PARALYSIS AGITANS, AND ON ITS RELATIONSHIP TO TREMOR , 1924 .

[27]  G Carrault,et al.  A comprehensive model of spastic hypertonia derived from the pendulum test of the leg , 2001, Muscle & nerve.

[28]  P. Delwaide,et al.  Projections from basal ganglia to tegmentum: a subcortical route for explaining the pathophysiology of Parkinson’s disease signs? , 2000, Journal of Neurology.

[29]  B. Bergamasco,et al.  Early modification of stretch reflex in Parkinson's disease , 1993, Acta neurologica Scandinavica.

[30]  M. Shindo,et al.  Muscular weakness in Parkinson's disease. , 1990, Advances in neurology.

[31]  Marco Schieppati,et al.  Medium‐Latency Stretch Reflexes of Foot and Leg Muscles Analysed by Cooling the Lower Limb in Standing Humans , 1997, The Journal of physiology.

[32]  J C Rothwell,et al.  The behaviour of the long-latency stretch reflex in patients with Parkinson's disease , 1983, Journal of neurology, neurosurgery, and psychiatry.