Ruiping Xia

Progression of motor symptoms in Parkinson’s disease

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms — rigidity, bradykinesia and tremor — due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.

Analysis of interactive effect of stretch reflex and shortening reaction on rigidity in Parkinson’s disease ☆

OBJECTIVE To examine the correlation between rigidity and interaction of stretch reflex and shortening reaction during passive movements of the wrist and to compare this correlation with that between rigidity and stretch reflex alone. METHODS Twelve subjects with Parkinsons disease participated in the study in Off-medication and On-medication states. A servomotor imposed wrist flexion and extension within +/-30 degrees at velocities 50 and 280 degrees/s, while joint torque and EMG of the wrist flexors and extensors were recorded. Rigidity was quantified by integrating torque with joint angle, i.e., objective rigidity (OR) score, for extension and flexion, respectively. The interaction between EMG responses was estimated by calculating a ratio of normalized EMG in stretched to shortened muscles for both movements. RESULTS The OR scores were more strongly correlated with the EMG ratios than with EMG of the stretched muscles alone. The strongest and significant correlation was found between the OR score and EMG ratio during the extension at high velocity in the Off-medication (r=0.792, p=0.002). CONCLUSIONS Both stretch reflex and shortening reaction are important determinants of rigidity. SIGNIFICANCE Study findings provide new insight into mechanistic descriptions of rigidity and have implications for development and evaluation of interventions.

Rate of Information Transmission in Human Manual Control of an Unstable System

The complexity of human-machine interaction (HMI) is rapidly growing in modern industrial, medical, and military systems. Human operators are often challenged by control of high-order systems or unstable systems near the limits of controllability. However, there is no quantitative indication of human performance and cognitive workload in these difficult HMI tasks. Here, we characterize HMI as information flows measured in bits per second (b/s). We propose a control-theoretic framework to estimate the rate of information transmission in manual control. We demonstrate our method in an example of stabilizing an inverted pendulum, where we derive that, for a normal human operator, the information-transmission rate of manual control with one degree of freedom ranges between 3 and 4 b/s. This quantitative indication reveals the potential and limitation of human manual control and is instructive to the design of HMI interfaces that may maximally utilize human control commands.

Human strategies in balancing an inverted pendulum with time delay

The strategy of human manual control is investigated in balancing an inverted pendulum under time-delay constraints. Experiments show that as the task becomes more difficult due to the increase in time delay, the human operator adopts a more discrete-like strategy. Interpretation of the discrete-control mechanism is provided by relating the observed human responses with a human-performance model.

Parkinson’s Disease Is Associated with Greater Regularity of Repetitive Voluntary Movements

Bradykinesia is a cardinal symptom of Parkinsons disease (PD). Both aging and disease are shown to be associated with decreased adaptability to environmental stresses characterized by reduced complexity (or increased regularity) of biorhythms. The purpose of this study was to investigate the regularity of movement in individuals with PD, and the effect of dopaminergic medication. Nine subjects with PD and eight controls performed wrist flexion/extension movements at maximal velocity and range of motion. Subjects with PD were tested under two medication conditions. Approximate entropy (ApEn) was calculated to assess the regularity of the movement, with the smaller value associated with the greater regularity. Data revealed that subjects with PD had lower ApEn values than controls. Medication did not alter the ApEn values. These findings demonstrate that impaired voluntary movement in individuals with PD is associated with increased regularity of movement and this exaggerated regularity appears less sensitive to anti-PD medication.

Modulation of reflex responses in hand muscles during rhythmical finger tasks in a subject with writer’s cramp

The objective of this study was to examine phase- and task-dependent modulation of stretch reflexes during repetitive finger movements in writer’s cramp, and compare them with normal controls from our previous study. A subject with writer’s cramp conducted two rhythmic tasks, index finger abduction (RFA) and a pen-squeezing (RPS) task akin to handwriting. Stretch reflexes were evoked by mechanical perturbations at random phases of each task. Surface electromyograms (EMG) were recorded from two hand muscles, first dorsal interosseous (FDI) and flexor digitorum superficialis (FDS). The reflex response and background EMG activity of each muscle were modulated in a phase-dependent manner in both tasks. However, they varied largely in phase during the RFA task, but in approximately inverse phase-relationship during RPS. Reflex sensitivity, as represented by the slope of the linear regression between response and background, was much lower for both muscles in the ‘writing’ task (RPS) than in the RFA task with its positively correlated responses. These phase- and task-related modulation patterns differed dramatically from those observed in our control subjects, where reflex responses were modulated largely in phase with background activity and reflex sensitivity was much higher, particularly in FDI during RFA and FDS during RPS. The altered reflex modulation patterns in writer’s cramp may reflect deficiencies of integration of proprioceptive afferent inputs and reduced inhibition at cortical and spinal levels during writing performance. Results from this case study support clinically identified task-specific feature of focal hand dystonia.

System Identification and Modeling Approach to Characterizing Rigidity in Parkinson's Disease: Neural and Non-Neural Contributions

Rigidity (muscle stiffness) is one of the most disabling symptoms in Parkinsons disease (PD). It is clinically defined as an increased resistance to passive movement of a joint. There is a fundamental gap between mechanistic and applied approaches to understanding this symptom. The objective of the current study was to apply a system identification and modeling approach to differentiating the contributions of neural (enhanced muscle reflex) and non-neural (altered mechanical properties of muscle fibers) factors to rigidity. Six patients participated in the study. The wrist joint torque and muscle activities of the wrist muscles were measured during externally induced movements. Each subject was tested in the Off- and On- medication states. System identification and modeling approach was applied to separate the neural from the non-neural component with respect to the overall stiffness. Results show that both factors are responsible for rigidity in PD. Neural-related reflex component is the predominant factor in overall rigidity. Medication therapy decreased the level of reflex component to overall rigidity.

Deep brain stimulation enhances movement complexity during gait in individuals with Parkinson’s disease

Deep brain stimulation (DBS) is associated with substantial improvements in motor symptoms of PD. Emerging evidence has suggested that nonlinear measures of complexity may provide greater insight into the efficacy of anti-PD treatments. This study investigated sample entropy and complexity index values in individuals with PD when DBS was OFF compared to ON. Five individuals with PD using DBS performed a four-minute treadmill walking task while 3D kinematics were collected over two periods of 30 s. Participants were tested in the DBS-ON and DBS-OFF conditions. Sample entropy (SE) and complexity index (CI) values were calculated for ankle, knee and hip joint angles. Paired samples t-tests were used to compare mean SE and CI values between the DBS-OFF and DBS-ON conditions, respectively. No differences in SE or CI were observed between the DBS-ON and DBS-OFF conditions at the ankle. At the knee, the DBS-ON was associated with greater SE and CI values than the DBS-OFF condition. At the hip, DBS-ON was associated with greater SE and CI values than the DBS-OFF condition. DBS enhances complexity of movement at the hip and knee joints while complexity at the ankle joint is not significantly altered. Greater complexity of knee and hip joint motion may represent increased adaptability and a greater number of available strategies to complete the gait task.