**10. Acknowledgments**

The author would like to acknowledge support of the National Institutes of Health, Nebraska Tobacco Settlement Biomedical Research Development Fund, Health Future Foundation of Creighton University, and Faculty Development Fund of School of Pharmacy and Health Professions, Creighton University in Omaha Nebraska, USA.

### **11. References**


However, with the treatment of medication on advanced stage of this progressive disease, many patients experience motor complications, which is broadly classified as "wearing off reactions", "On-Off reactions", dyskinesia, confusion, sleepiness, hallucination, and low blood pressure when standing (Stacy, 2009). In patients who are severely affected or in those who fail to respond satisfactorily to pharmacological therapy, surgical treatments have reportedly been effective in reducing symptoms and improving function. These include pallidotomy, thalamotomy and subthalamotomy, and high frequency deep brain stimulation via electrodes implanted in the globus pallidus, thalamus (a "relay station" deep in brain), or subthalamic nucleus. Rigidity can be specifically improved by subthalamic

Evidence has indicated that no single mechanism can account for parkinsonian rigidity, which is influenced by a multitude of physiological phenomena and biomechanical features. Treatment of rigidity primarily involves an administration of dopaminergic medication. However, serious side effects usually occur after a few years' drug treatment. Therefore, rehabilitative programs are highly desirable for patients with Parkinson's disease. A better understanding of the comprehensive characteristics of parkinsonian rigidity is crucial for designing effective evidence-based exercise program and physical therapy intervention. An objective assessment of rigidity is essential for evaluating the efficacy of therapeutic interventions, especially in large clinical studies in which trials are conducted across

The author would like to acknowledge support of the National Institutes of Health, Nebraska Tobacco Settlement Biomedical Research Development Fund, Health Future Foundation of Creighton University, and Faculty Development Fund of School of Pharmacy

Alibiglou, L.; Rymer, WZ.; Harvey, RL. & Mirbagheri MM. (2008). The relation between

Andrews, CJ.; Burke, D. & Lance, JW. (1972). The response to muscle stretch and shortening

Angel, RW. (1983). Muscular contractions elicited by passive shortening. *Adv Neurol*, Vol.39,

Bantam Medical Dictionary (2000). 3rd edition, New York, USA: Bantam Books,

Berardelli, A. & Hallett, M. (1984). Shortening reaction of human tibialis anterior. *Neurology,*

Berardelli, A.; Sabra, AF. & Hallett, M. (1983). Physiological mechanisms of rigidity in Parkinson's disease. *J Neurol Neurosurg Psychiatry,* Vol.46, pp. 45-53.

Ashworth scores and neuromechanical measurements of spasticity following

and Health Professions, Creighton University in Omaha Nebraska, USA.

stroke. *J Neuroeng Rehabil*, Vol.5, pp. 18-31.

in Parkinsonian rigidity. *Brain,* Vol.95, pp. 795-812.

nucleus deep brain stimulation (Temperli et al., 2003).

**9. Conclusion** 

multiple centers.

**11. References** 

**10. Acknowledgments** 

pp. 555-563.

Incorporated.

Vol. 34, pp. 242-246.


Physiological and Biomechanical Analyses of Rigidity in Parkinson's Disease 503

Hallett, M. (2003). Parkinson revisited: pathophysiology of motor signs. *Adv Neurol*, Vol.91,

Holzbaur, KR.; Murray, WM. & Delp, SL. (2005) A model of the upper extremity for

Hong, M.; Perlmutter, J.S. & Earhart, G.M. (2007). Enhancement of rigidity in Parkinson's

Jahanshahi, M.; Jones, CR.; Zijlmans, J.; Katzenschlager, R.; Lee, L.; Quinn, N.; Frith, CD. &

Jankovic, J.; McDermott, M.; Carter, J.; Gauthier, S.; Goetz, C.; Golbe, L.; Huber, S.; Koller,

Kearney, RE.; Stein, RB. & Parameswaran, L. (1997). Identification of intrinsic and reflex

Kirollos, C.; Charlett, A.; O'Neill, CJ.; Kosik, R.; Mozol, K.; Purkiss, AG.; Bowes, SG.;

Lance, JW.; Burke, D. & Andrews, CJ. (1973). The reflex effects of muscle vibration. In: *New* 

Lang, A.E. & Lozano, A.M. (1998). Parkinson's disease. First of two parts. *N Engl J Med*,

Lee, HM.; Huang, YZ.; Chen, JJ. & Hwang, IS. (2002). Quantitative analysis of the velocity

Lee, RG. & Tatton, WG. (1975). Motor responses to sudden limb displacements in primates

Levin, J.; Krafczyk, S.; Valkovic, P.; Eggert, T.; Claassen, J. & Bötzel, K. (2009). Objective

Mak, MK.; Wong, EC. & Hui-Chan, CW. (2007). Quantitative measurement of trunk rigidity

Martinez-Martin, P. (1993). "Rating sales in Parkinson's disease," In: *Parkinson's Disease and* 

Marsden, CD. (1990). Neurophysiology. In: *Parkinson's disease*, G. Stern, (Ed.), 57-98, Johns

Matthews, PBC. (1959). The dependence of tension upon extension in the stretch reflex of the

soleus muscle of the decerebrate cat. *J Physiol*, Vol.147, pp.521-546

implications in parkinsonism. *Br J Clin Pharmaco*, Vol. 41, pp.557-64. Lance, JW. (1980). Pathophysiology of spasticity and clinical experience with baclofen, In:

3:44-462, ISBN 978-380-5514-09-5 Basel: Karger, Switzerland

*Neurosurg Psychiatry*, Vol.72, pp. 621–9.

stimulation. *Mov Disord*, Vol.24(1), pp. 57-63.

Hopkins University Press, Baltimore, MD, USA.

in Parkinsonian patients*. J Neurol*, Vol.254, pp. 202–209.

*J Neurol Sci*, Vol.2, pp. 285-293.

Wilkins, Baltimore, MD, USA.

disease with activation. *Mov Disord*, Vol. 22, pp. 1164-8.

motor timing in Parkinson's disease. *Brain*, Vol. 133, pp.727-745.

simulating musculoskeletal surgery and analyzing neuromuscular control. *Ann* 

Lees AJ. (2010). Dopaminergic modulation of striato-frontal connectivity during

W.; Olanow, C.; Shoulson, I. et al. (1990). Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.

contributions to human ankle stiffness dynamics. *IEEE Trans Biomed Eng*, Vol.44,

Nicholson, PW.; Hunt, WB.; Weller, C.; Dobbs, SM. & Dobbs, RJ. (1996). Objective measurement of activation of rigidity: diagnostic, pathogenetic and therapeutic

*Spasticity: disordered motor control,* R. G. Feldman, R. R. Young, W. P. Koella, (Ed). 185-203, ISBN – 978-081-5132-40-0, Year Book Medical Publishers, Chicago, Illinois,

*Developments in Electromyography and Clinical Neurophysiology*, J. E. Desmedt (Ed),

related pathophysiology of spasticity and rigidity in the elbow flexors. *J Neurol* 

with specific CNS lesions and in human patients with motor system disorders. *Can* 

measurement of muscle rigidity in Parkinsonian patients treated with subthalamic

*Movement Disorders*, 2nd ed, J. Jankovic, E. Tolosa, (Eds.), 281-292, Williams &

pp. 19-28.

*Biomed Eng*, Vol.33. pp. 829–840.

*Neurol*, Vol. 40, pp.1529-34.

pp. 493-504.

USA.

339:1044-53.


Dietrichson, P. (1971). Phasic ankle reflex in spasticity and Parkinsonian rigidity. The role of

Dietz, V. (1987). Changes of inherent muscle stiffness in Parkinson's disease. *J Neurol* 

Dietz, V.; Quintern, J. & Berger, W. (1981). Electrophysiological studies of gait in spasticity

Dorsey, E.R.; Constantinescu, R.; Thompson, JP.; Biglan, KM.; Holloway, RG.; Kieburtz, K.;

Elias, S.; Israel, Z. & Bergman, H. (2008). Physiology of Parkinson's disease. In: *Therapeutics* 

Fahn, S. & Elton, RL. (1987) Members of the UPDRS development committee. Unified

Fahn, S. (2003). Description of Parkinson's disease as a clinical syndrome. *Ann NY Acad Sci*,

Fahn, S. & Sulzer, D. (2004). Neurodegeneration and neuroprotection in Parkinson disease.

Feldman, AG. (1966). Functional tuning of the nervous system on control of movement or

Forester, O. (1921). Zur Analyse und Pathophysiologie der striaten Bewegungsstörungen. *Z* 

Fung, VS. & Thompson, PD. (2002). Rigidity and spasticity, In: *Parkinson's disease and* 

Fung, VS.; Burne, JA. & Morris, JG. (2000). Objective quantification of resting and activated

Galiana, L.; Fung, J. & Kearney, R. (2005). Identification of intrinsic and reflex ankle stiffness

Goetz, CG.; Tilley, BC.; Shaftman, SR.; Stebbins, GT.; Fahn, S.; Martinez-Martin, P.; Poewe,

Gordon, AM.; Huxley, AF. & Julian, FJ. (1966). The variation in isometric tension with sarcomere length in vertebrate muscle fibres. *J Physiol*, Vol. 184, pp. 170-192.

components in stroke patients. *Exp Brain Res*, Vol.165, pp. 422-434.

36, John Wiley & Sons Ltd., ISBN 978-0-470-06648-5, West Sussex, UK. Endo, T.; Okuno, R.; Yokoe, M.; Akazawa, K. & Sakoda, S. (2009). A novel method for

Healthcare, ISBN 978-088-1671-32-2, Florham, New Jersey, USA.

and rigidity. Evidence that altered mechanical properties of muscle contribute to

Marshall, FJ.; Ravina, BM.; Schifitto, G.; Siderowf, A. & Tanner, CM. (2007). Projected number of people with Parkinson disease in the most populous nations,

*of Parkinson's Disease and Other Movement Disorders,* M. Hallett, W. Poewe, (Ed). 25-

systematic analysis of rigidity in Parkinson's disease. *Mov Disord*, Vol.24, pp. 2218-

parkinson's disease rating scale, In: *Recent developments in Parkinson's disease,* S. Fahn, D. C. Marsden, P. Jenner, P. Teychenne, (Ed). 153-164, Macmillian

maintenance of a steadyposture. II. Controllable parameters of the muscle.

*Movement Disorders*, J. J. Jankovic, E. Tolosa (4th. Ed.), 473-482, Lippincott Williams

parkinsonian rigidity: a comparison of angular impulse and work scores. *Mov* 

W.; Sampaio, C.; Stern, MB.; Dodel, R.; Dubois, B.; Holloway, R.; Jankovic, J.; Kulisevsky, J; Lang, AE.; Lees, A.; Leurgans, S.; LeWitt, PA.; Nyenhuis, D.; Olanow, CW.; Rascol, O.; Schrag, A.; Teresi, JA.; van Hilten, JJ. & LaPelle, N. (2008). Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. *Mov* 

the fusimotor system. *Acta Neurol Scand*, Vol.47, pp. 22-51.

*Neurosurg Psychiatry*, Vol. 50, pp. 944.

hypertonia. *Brain*, Vol.104, pp. 431-449.

2224.

Vol.991, pp. 1-14.

*NeuroRx*, Vol. 1, pp.139-54.

*Disord*, Vol.15, pp. 48-55

*Disord*, Vol.23, pp. 2129-2170

*Biophysics*, Vol.11, pp. 565-578.

*Ges Neurol Psychiat*, Vol.73, pp. 1-169

& Wilkins, ISBN: 0-7817-7881-6, Philadelphia, USA.

2005 through 2030. *Neurol*, Vol. 68(5), pp.384-6.


Physiological and Biomechanical Analyses of Rigidity in Parkinson's Disease 505

Rack, PM. & Westbury, DR. (1969). The effects of length and stimulus rate on tension in the

Richards, M.; Marder, K.; Cote, L. & Mayeux, R. (1994). Interrater reliability of the Unified

Robichaud, JA.; Pfann, KD.; Comella, CL.; Brandabur, M. & Corcos DM. (2004). Greater

Rondot, P. & Metral, S. (1973). Analysis of the shortening reaction in man. In: *New* 

Rothwell, JC.; Obeso, JA.; Traub, MM. & Marsden, CD. (1983). The behaviour of the long-

Rushworth, G. (1960). Spasticity and rigidity: An experimental study and review. *J Neurol* 

Rymer, WZ. & Katz, RT. (1994). Mechanisms of spastic hypertonia. *Phys Med Rehabil: State of* 

Rymer, WZ.; Houk. JC. & Crago, PE. (1979). Mechanisms of the clasp-knife reflex studied in

Sepehri, B.; Esteki, A.; Ebrahimi-Takamjani, E.; Shahidi, GA.; Khamseh, F. & Moinodin, M.

Shapiro, MB.; Vaillancourt, DE.; Sturman, MM.; Metman, LV.; Bakay, RA. & Corcos, DM.

Sherrington, CS. (1909). On plastic tonus and proprioceptive reflexes. *Q J Exp Physiol* , Vol.2,

Sinkjaer, T. & Magnussen, I. (1994). Passive, intrinsic and reflex-mediated stiffness in the ankle extensors of hemiparetic patients. *Brain*, Vol.117, pp. 355–363. Sinkjaer, T.; Toft, E.; Larsen, K.; Andreassen, S. & Hansen, HJ. (1993). Non-reflex and reflex

Tanner, CM. & Ben-Shlomo, Y. (1999). Epidemiology of Parkinson's disease. *Adv Neurol*

Tanner, CM. & Goldman, SM. (1996). Epidemiology of Parkinson's disease. *Neurol Clin*,

Temperli, P.; Ghika, J.; Villemure, J.G.; Burkhard, P.R.; Bogousslavsky, J. & Vingerhoets, F.J.

Teräväinen, H.; Tsui, JKC.; Mak, E., & Calne, DB. (1989). Optimal indices for testing

Tunik, E.; Poizner, H.; Adamovich, SV.; Levin, MF. & Feldman, AG. (2004). Deficits in

Van Dillen, LR. & Roach, KE. (1988). Interrater reliability of a clinical scale of rigidity. *Phys* 

parkinsonian rigidity. *Can. J. Neurol Sci.*, Vol.16, pp. 180-183.

(2007). Quantification of rigidity in Parkinson's disease. *Ann Biomed Eng*, Vol.35(12),

(2007). Effects of STN DBS on rigidity in Parkinson's disease. *IEEE Trans Neural Syst* 

mediated ankle joint stiffness in in multiple sclerosis patients with spasticity.

(2003). How do parkinsonian signs return after discontinuation of subthalamic

adaptive upper limb control in response to trunk perturbations in Parkinson's

Parkinson's Disease Rating Scale motor examination. *Mov Disord*, Vol.9(1), pp. 89-

impairment of extension movements as compared to flexion movements in

*Developments in Electromyography and Clinical Neurophysiology*, J.E. Desmedt, (Ed),

latency stretch reflex in patients with Parkinson's disease. *J Neurol Neurosurg* 

isometric cat soleus muscle. *J Physiol*, Vol. 204, pp. 443-460.

Parkinson's disease. *Exp Brain Res*, Vol. 156, pp.240-254.

*Psychiatry*, Vol.46, pp. 35-44

pp. 2196-203.

pp. 109- 156.

Vol.80, pp.153-159.

Vol.14, pp.317-335.

*Neurosurg Psychiatry*, Vol.23, pp. 99-118

an animal model. *Exp Brain Res*, Vol.37, pp. 93-113.

*the Art Reviews*, Vol.8, pp. 441-454.

*Rehabil Eng*. Vol.15, pp. 173-181.

*Muscle Nerve*, Vol.16, pp. 69–76.

DBS? *Neurology*, Vol.60, pp. 78-81.

*Ther*, Vol.68(11), pp. 1679-81.

disease. *Exp Brain Res*, Vol.159, pp.23-32.

3:629-634, ISBN 978-380-5514-09-5, Basel: Karger, Switzerland

91.


Matthews, PBC. (1991). The human stretch reflex and the motor cortex. *Trends Neurosci*,

Meara, RJ. & Cody, FWJ. (1993). Stretch reflexes of individual parkinsonian patients studied

Mera, T.O.; Johnson, M.D.; Rothe, D.; Zhang, J.; Xu, W.; Ghosh, D.; Vitek, J. & Alberts, J.L.

Meinders, M.; Price, R.; Lehmann, JF. & Questad, KA (1996). The stretch reflex response in

Mirbagheri, MM.; Barbeau, H.; Ladouceur, M. & Kearney, RE. (2001). Intrinsic and reflex

Mirbagheri, MM.; Chen, D. & Rymer W.Z. (2010). Quantification of the effects of an alpha-2

Mirbagheri, M.M.; Tsao, C. & Rymer, W.Z. (2009). Natural history of neuromuscular

Mortimer, JA. & Webster, DD. (1979). Evidence for a quantitative association between EMG stretch responses and Parkinsonian rigidity. *Brain Res*., Vol.162, pp. 169-173. Obeso, JA.; Linazasoro, G.; Rothwell, JC.; Jahanshahi, M. & Brown, R. (1996). Assessing the effects of pallidotomy in Parkinson's disease. *The Lancet,* Vol. 347(9013), pp. 1490 Ondo, WG.; Jankovic, J.; Lai, EC.; Sankhla, C.; Khan, M.; Ben-Arie, L.; Schwartz, K.;

Park, B.K.; Kwon, Y.; Kim, J.W.; Lee, J.H.; Eom, G.M.; Koh, S.B.; Jun, J.H. & Hong, J. (2010).

Patrick, S.K.; Denington, A.A.; Gauthier, M.J.; Gillard, D.M. & Prochazka, A. (2001).

Pollock. LJ. & Davis, L. (1930). Muscle tone in Parkinsonian states. *Arch Neurol Psychiatry*,

Powell, D.; Hanson, N.; Threlkeld, AJ.; Fang, X. & Xia, R. (2011). Enhancement of

Powell, D.; Threlkeld, AJ.; Fang, X.; Muthumani, A. & Xia, R. Amplitude- and velocity-

Prochazka, A.; Bennett, DJ.; Stephens. MJ.; Patrick, SK.; Sears-Duru, R.; Roberts, T, &

Rabey, JM.; Bass, H.; Bonuccelli, U.; Brooks, D.; Klotz, P.; Korczyn, AD.; Kraus, P.; Martinez-

identification technique. *J Neuroeng Rehabil*, Vol.7, pp. 29-35.

pallidotomy. *Neurology,* Vol.50(1), pp. 266-70

rigidity. *IEEE T Neur Sys Reh*, Vol.99, ISSN: 1534-4320

during changes in clinical rigidity following medication. *Electroencephalogr Clin* 

(2009). Objective quantification of arm rigidity in MPTP-treated primates. *J Neurosci* 

the normal and spastic ankle: effect of ankle position. *Arch Phys Med Rehabil*, Vol.

stiffness in normal and spastic, spinal cord injured subjects. *Exp Brain Res*, Vol.141,

adrenergic agonist on reflex properties in spinal cord injury using a system

properties after stroke: a longitudinal study. *J Neurol Neurosurg Psychiatry,* Vol. 80,

Grossman, RG. & Krauss, JK. (1998). Assessment of motor function after stereotactic

Analysis of viscoelastic properties of wrist joint for quantification of Parkinsonian

Quantification of the UPDRS Rigidity Scale. *IEEE Trans Neural Syst Rehabil Eng.,*

parkinsonian rigidity with contralateral hand activation. *Clin Neurophysiol* Vol.122,

dependency of rigidity measured at the wrist in Parkinson's disease. *Clin* 

Jhamandas, JH. (1997). Measurement of rigidity in Parkinson's disease. *Mov Disord*,

Martin, P.; Morrish, P.; Van Sauten, W. & Van Hilten, B. (1997). Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials. *J Neuropharmacol*, Vol.20(4), pp. 322-37.

Vol.14, pp. 87-91

77(5), pp. 487-92.

pp. 446-459.

pp. 1212-1217.

Vol. 9, pp. 31-41.

pp. 1595-1601.

Vol.23, Pp. 303- 319

*Neurophysiol (in press)*.

Vol.12, pp. 24-32

*Neurophysiol*, Vol.89, pp. 261-268

*Methods*. Vol.177(1):20-29.


**23** 

*Brazil* 

**Mesothalamic Dopaminergic Activity:** 

Movement, sleep and cognition: three connected realms enriching to the human life. Three

A degenerative process in dopaminergic neurons from the substantia nigra (SN) midbrain nucleus is the basic origin underlying a set of symptoms developed in patients with Parkinson's Disease (PD) (Andrade & Ferraz, 2003). The devastating motor difficulties usually do not appear isolated. Indeed, PD consists of distinct kinds of manifestations involving motor and mental rigidity as well as sleep alterations (Dubois & Pillon, 1996; Rye

Even though impairments in other brain nuclei also contribute to the symptoms present in PD **(**Braak et al., 2000**)**, it is surprising how so distinct brain systems suffer influence of the degenerative alterations in the SN. This phenomenon may be regarded as a simple consequence of the connections between the SN and diverse brain areas. As a matter of fact, it also highlights that distinct behavioral aspects are achieved through the sharing of brain resources. Here, we examine - through a neurocomputational model - relationships between alterations in the mesothalamic dopaminergic activity (MDA) and sleep impairments in PD. With origins in the SN, the mesothalamic pathway (MP) reaches the thalamic complex, in particular the thalamic reticular nucleus (TRN). Investigations on such dopaminergic pathway, evidenced by Freeman and colleagues (Freeman et al., 2001), have been contributing to a more global comprehension of cognitive processes in the brain. Based on experimental results (Florán et al., 2004), the mathematical model proposed in (Madureira et al., 2010) indicates a way by which the mesothalamic dopamine inhibits neurons in the TRN. And computational simulations of this model suggest that alterations in the MDA lead to inattention symptoms as observed in PD and Attention Deficit Hyperactivity Disorder

Thalamic neurons are able to spike under tonic and burst states (Steriade et al., 1993; Llinás & Steriade, 2006). Whenever in the tonic state, these neurons respond linearly to input stimuli. By this way, they propagate information reliably from perceptual systems to the cerebral cortex, where a more refined processing takes place. This mode of activity is crucial to the thalamocortical filtering of perceptual stimuli that allows attention focusing

**1. Introduction** 

(ADHD).

harmed realms limiting parkinsonian patients.

(Madureira et al., 2007, 2010; Carvalho, 1994).

et al., 2000; De Cock et al., 2008; Arnulf & Leu-Semenescu, 2009).

**Implications in Sleep Alterations in** 

**Parkinson's Disease** 

*Laboratório Nacional de Computação Científica* 

Daniele Q. M. Madureira

