**4. Non-neural factor responsible for parkinsonian rigidity**

Evidence has indicated that in addition to neural-mediated abnormal muscle reflex responses, the non-neural component also contributes to parkinsonian rigidity (Dietz, 1987; Dietz et al., 1981; Watts et al., 1986). The non-neural component includes visco-elastic (i.e., mechanical) properties of muscle fiber and passive connective tissues. Dietz et al. (1981) examined ten patients with parkinsonian rigidity aiming to identify the physiological mechanism with respect to altered muscle activity to account for impaired gait pattern in Parkinson's disease. Compared to healthy control subjects, parkinsonian patients exhibited significantly stronger EMG activity in tibialis anterior during the swing phase of gait, while the strength and timing of EMG activity recorded from triceps surae were similar in two groups of participants. The authors stated that the increased muscle tone in parkinsonian rigidity cannot be explained by the electrical activity of the antagonist muscle groups of the limb, since there was no co-contraction of tibialis anterior and triceps surae muscles. It was concluded that the altered mechanical properties of muscle fibers were mainly responsible for the increased muscle tone in rigidity. This conclusion was also drawn by Watts et al. (1986) who examined elbow joint of patients with Parkinson's disease and normal controls by using a torque motor. Even in patients with relatively mild symptoms, the upper limb was stiffer than controls in the totally relaxed state with no EMG activity present. The study findings suggested that changes in the passive mechanical properties of the upper limb likely accounted for greater passive stiffness. Using the torque motor, natural progression of the disease can be quantified and followed.

Evidence indicates that neural and non-neural mechanisms operate in parallel, both contributing to parkinsonian rigidity. However, there is no simple and easy solution in differentiation and quantification of the neural and non-neural components because clinical measures of rigidity consist of the two parallel components. Using advanced technology and computational algorithm, a few sophisticated approaches have been developed to segregate the two responsible factors and quantify the individual component contributing to the overall joint stiffness (Kearney et al., 1997; Meinders et al., 1996; Sinkjaer et al., 1993; Sinkjaer & Magnussen, 1994; Zhang & Rymer, 1997). One approach, termed as parallel-cascaded system identification technique, was initially applied to separate the overall stiffness into neural reflex stiffness and non-neural mechanical stiffness at ankle joint in normal healthy adults (Kearney et al., 1997; Mirbagheri et al., 2000). Subsequently, the system identification approach has been applied to characterize the dynamic joint stiffness and to quantify the neural and non-neural contribution to the abnormal muscle tone in spasticity associated with upper motor neuron syndromes, such as stroke and spinal cord injury (Alibiglou et al., 2008; Galiana et al., 2005; Mirbagheri et al., 2001, 2009, 2010). The validity of this method has been demonstrated as well as its efficiency, accuracy and advantages by Mirbagheri et al. (2000) and Alibiglou et al. (2008).

More recently, we have applied the parallel-cascaded system identification technique to make a distinction between the neural and non-neural contributions to rigidity in patients with Parkinson's disease (Xia et al., 2010). Patients participated in the protocol under two medication states: initially under a temporary overnight withdrawal of dopaminergic medication and then after the resumption of medication. The results have shown that both neural and non-neural components contributed to parkinsonian rigidity, with the neural component being predominating over the non-neural to the overall rigidity. Medication therapy caused a reduction of torque resistance in the neural reflex torque, but did not

Evidence has indicated that in addition to neural-mediated abnormal muscle reflex responses, the non-neural component also contributes to parkinsonian rigidity (Dietz, 1987; Dietz et al., 1981; Watts et al., 1986). The non-neural component includes visco-elastic (i.e., mechanical) properties of muscle fiber and passive connective tissues. Dietz et al. (1981) examined ten patients with parkinsonian rigidity aiming to identify the physiological mechanism with respect to altered muscle activity to account for impaired gait pattern in Parkinson's disease. Compared to healthy control subjects, parkinsonian patients exhibited significantly stronger EMG activity in tibialis anterior during the swing phase of gait, while the strength and timing of EMG activity recorded from triceps surae were similar in two groups of participants. The authors stated that the increased muscle tone in parkinsonian rigidity cannot be explained by the electrical activity of the antagonist muscle groups of the limb, since there was no co-contraction of tibialis anterior and triceps surae muscles. It was concluded that the altered mechanical properties of muscle fibers were mainly responsible for the increased muscle tone in rigidity. This conclusion was also drawn by Watts et al. (1986) who examined elbow joint of patients with Parkinson's disease and normal controls by using a torque motor. Even in patients with relatively mild symptoms, the upper limb was stiffer than controls in the totally relaxed state with no EMG activity present. The study findings suggested that changes in the passive mechanical properties of the upper limb likely accounted for greater passive stiffness. Using the torque motor, natural progression of

Evidence indicates that neural and non-neural mechanisms operate in parallel, both contributing to parkinsonian rigidity. However, there is no simple and easy solution in differentiation and quantification of the neural and non-neural components because clinical measures of rigidity consist of the two parallel components. Using advanced technology and computational algorithm, a few sophisticated approaches have been developed to segregate the two responsible factors and quantify the individual component contributing to the overall joint stiffness (Kearney et al., 1997; Meinders et al., 1996; Sinkjaer et al., 1993; Sinkjaer & Magnussen, 1994; Zhang & Rymer, 1997). One approach, termed as parallel-cascaded system identification technique, was initially applied to separate the overall stiffness into neural reflex stiffness and non-neural mechanical stiffness at ankle joint in normal healthy adults (Kearney et al., 1997; Mirbagheri et al., 2000). Subsequently, the system identification approach has been applied to characterize the dynamic joint stiffness and to quantify the neural and non-neural contribution to the abnormal muscle tone in spasticity associated with upper motor neuron syndromes, such as stroke and spinal cord injury (Alibiglou et al., 2008; Galiana et al., 2005; Mirbagheri et al., 2001, 2009, 2010). The validity of this method has been demonstrated as well as its efficiency, accuracy and advantages by Mirbagheri et al.

More recently, we have applied the parallel-cascaded system identification technique to make a distinction between the neural and non-neural contributions to rigidity in patients with Parkinson's disease (Xia et al., 2010). Patients participated in the protocol under two medication states: initially under a temporary overnight withdrawal of dopaminergic medication and then after the resumption of medication. The results have shown that both neural and non-neural components contributed to parkinsonian rigidity, with the neural component being predominating over the non-neural to the overall rigidity. Medication therapy caused a reduction of torque resistance in the neural reflex torque, but did not

**4. Non-neural factor responsible for parkinsonian rigidity** 

the disease can be quantified and followed.

(2000) and Alibiglou et al. (2008).

decrease the non-neural mechanical torque. This observation appears to be attributed to the mechanism of anti-Parkinson medication therapy.
