Quantification of neural reflex and muscular intrinsic contributions to parkinsonian rigidity.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by rigidity, bradykinesia, resting tremor, and postural instability. Rigidity, defined as an increased resistance to passive movement of a joint, progresses faster than other motor signs in PD. Rigidity is attributable to both exaggerated neural reflex and altered muscle mechanical properties. However, little is known about the contributions of individual components to rigidity. Further, there is no evidence regarding the effects of dopaminergic medication on individual components. Objectives of this study were to quantify the contributions of neural reflexes and intrinsic muscle properties to rigidity and investigate the effects of medication on each contributing component. Joint torque and muscle activities of the wrist in 14 patients and 14 controls were measured during externally induced movements. Each subject with PD was tested in Off- and On-medication states. A system identification technique was applied to differentiate and quantify the neural reflex and intrinsic mechanical components. A mixed model of ANOVA was performed to compare the differences between the two components of rigidity for both groups, and to compare between the Off- and On-medication states for patients. The results showed that reflex and intrinsic components are comparable (p > 0.05), and both are enhanced in subjects with PD than in the controls (p < 0.05). Medication decreased the reflex component of rigidity (p < 0.01). It is concluded that both reflex and intrinsic factors are responsible for rigidity. Present findings are clinically significant as they may provide guidance in development of effective therapeutic interventions.

Differentiation between the contributions of shortening reaction and stretch-induced inhibition to rigidity in Parkinson's disease.

Parkinsonian rigidity is characterized by an increased resistance of a joint to externally imposed motion that remains uniform with changing joint angle. Two candidate mechanisms are proposed for the uniformity of rigidity, involving neural-mediated excitation of shortening muscles, i.e., shortening reaction (SR), or inhibition of stretched muscles, i.e., stretch-induced inhibition (SII). To date, no study has addressed the roles of these two phenomena in rigidity. The purpose of this study was to differentiate these two phenomena, and to quantify the potential contribution of each to wrist joint moment in 17 patients with parkinsonian rigidity, in both Off- and On-medication states. Joint position, torque, and EMGs of selected muscles were collected during externally imposed flexion and extension motions. Moments of shortened and stretched muscles were estimated using a biomechanical model. Slopes of the estimated torque-angle curve were calculated for shortened and stretched muscles, separately. A mixed model ANOVA was performed to compare the contribution between the two mechanisms. During flexion, slopes were significantly (P = 0.003) smaller for SR than for SII, whereas during extension, slopes for SII were significantly (P = 0.003) smaller. Results showed that both SR and SII contributed to rigidity. Which mechanism predominates appeared to be associated with the direction of movement. The findings provide new insights into the biomechanical underpinnings of this common symptom in Parkinson's disease.

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.

Normalizing EMG to Background Muscle Activation Masks Medication-Induced Reductions in Reflex Amplitudes in Parkinsonian Rigidity.

OBJECTIVES: Exaggerated reflex responses to passive stretch and shortening contribute to parkinsonian rigidity. Studies have reported medication-induced reductions in rigidity in the absence of attenuated reflex magnitudes. The purpose of this study was to determine if normalization procedures mask medication-induced reductions in reflex responses in Parkinson's disease. METHODS: Twelve participants with PD performed passive wrist flexion and extension movements after a 12-hour withdrawal from dopaminergic medication and 60 minutes after medication was administered. EMG was recorded from wrist flexors and extensors. Raw EMG signals were conditioned and normalized to mean background EMG amplitudes collected 100 ms prior to the onset of passive movement by division and by subtraction. RESULTS: Raw EMG amplitudes were significantly reduced. No medication-related reductions were observed during passive flexion or extension when EMG amplitudes were normalized by division. When EMG amplitudes were normalized by subtraction, significant reductions were observed following administration of dopaminergic medication during flexion and extension. Dopaminergic medication was associated with significant reductions in rigidity work scores and significant increases in moment-angle slope plots. CONCLUSIONS: These findings demonstrate that EMG normalization techniques may hinder data interpretation in studies of altered reflex responses in individuals with Parkinson's disease following the administration of dopaminergic medication.

A Comparison of the Effects of Continuous versus Discontinuous Movement Patterns on Parkinsonian Rigidity and Reflex Responses to Passive Stretch and Shortening.

OBJECTIVE: Quantify the effect of a continuous compared to discontinuous movement trajectory on parkinsonian rigidity and reflex responses to passive stretch and shortening. METHODS: Eighteen participants with Parkinson's disease (PD) performed passive wrist flexion and extension movements through a 90° range of motion at 50 °/sec using continuous (CONT) and discontinuous (DISC) movement trajectories. Participants were tested in both the OFF-MED and ON-MED states. Rigidity was quantified by rigidity work score and slopes of the moment-angle plots during both flexion and extension. Reflex response was quantified by mean EMG amplitudes of forearm musculature. RESULTS: No differences were observed between CONT and DISC for rigidity (p = 0.18) or moment-angle plot slopes (Flexion: p = 0.97; Extension: p = 0.89). However, medication was associated with reductions in rigidity (p = 0.02) and increases in moment-angle plot slopes (Flexion: p = 0.03; Extension: p = 0.02). The CONT compared to DISC trajectory was associated with greater EMG amplitudes in the shortened muscles (p = 0.04) and smaller EMG ratios (p < 0.05) during flexion, and greater EMG amplitudes in the lengthened muscles (p = 0.02) during extension. Dopaminergic medication reduced EMG amplitudes in stretched muscles during extension (p < 0.05). CONCLUSIONS: The nature of the movement trajectory (continuous vs. discontinuous) used during clinical assessment does not alter the presentation of rigidity in PD. Rigidity is reduced with the administration of dopaminergic medication, independent of movement trajectory. SIGNIFICANCE: These data suggest that the presentation of rigidity used in the determination of diagnosis, treatment and prognosis in PD will not be affected by the continuous nature of the movement trajectory used during clinical assessment.

Promoting Community Health and Eliminating Health Disparities Through Community-Based Participatory Research.

In physical therapy, there is increasing focus on the need at the community level to promote health, eliminate disparities in health status, and ameliorate risk factors among underserved minorities. Community-based participatory research (CBPR) is the most promising paradigm for pursuing these goals. Community-based participatory research stresses equitable partnering of the community and investigators in light of local social, structural, and cultural elements. Throughout the research process, the CBPR model emphasizes coalition and team building that joins partners with diverse skills/expertise, knowledge, and sensitivities. This article presents core concepts and principles of CBPR and the rationale for its application in the management of health issues at the community level. Community-based participatory research is now commonly used to address public health issues. A literature review identified limited reports of its use in physical therapy research and services. A published study is used to illustrate features of CBPR for physical therapy. The purpose of this article is to promote an understanding of how physical therapists could use CBPR as a promising way to advance the profession's goals of community health and elimination of health care disparities, and social responsibility. Funding opportunities for the support of CBPR are noted.

Parkinson's disease is associated with greater regularity of repetitive voluntary movements.

Bradykinesia is a cardinal symptom of Parkinson's 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.

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.

Amplitude- and velocity-dependency of rigidity measured at the wrist in Parkinson's disease.

OBJECTIVE: Quantify the effects of increased amplitude and rate of muscle stretch on parkinsonian rigidity. METHODS: Eighteen subjects with Parkinson's disease participated in this study. Subjects' tested hand was passively displaced through 60° and 90° ranges of wrist flexion and extension at velocities of 50°/s and 280°/s in both treated and untreated conditions. Joint angular position, resistance torque, and surface electromyography (EMG) of the wrist flexors and extensors were recorded. Rigidity was quantified by normalized work scores and normalized angular impulses for flexion and extension, separately. Reflex responses of stretched and shortened muscles were quantified by mean EMG and EMG ratio. A series of ANOVAs was performed to determine the effect of amplitude, velocity and medication on selected variables. RESULTS: Both work scores and angular impulses revealed that the larger displacement amplitude and the higher velocity were associated with significantly greater rigidity, increased EMG ratio and mean EMG of stretched muscles. Dopaminergic medication was not associated with a reduction in rigidity. CONCLUSIONS: Parkinsonian rigidity is modulated by the amplitude and rate of muscle stretch. SIGNIFICANCE: These findings shed light on the biomechanical underpinnings and physiological characteristics of rigidity and may inform clinical rigidity assessment in Parkinson's disease.

Enhancement of parkinsonian rigidity with contralateral hand activation.

OBJECTIVE: Quantify the enhancement of parkinsonian rigidity associated with a contralateral activation maneuver. METHODS: Twelve subjects with PD and eight controls participated in the study protocol. Subjects' tested hand was displaced by a servo-motor throughout wrist flexion and extension motions of 60° without and with a concurrent gripping activation in the contralateral hand, referred to as Passive and Active conditions, respectively. Subjects with PD were tested in both OFF-MED and ON-MED states. Rigidity was quantified by integrating torque with position during both flexion and extension (torque resistance). ANOVA was performed to assess the effect of contralateral activation on rigidity. RESULTS: PD patients had significantly (0.038) enhanced torque resistance in OFF-MED compared to healthy controls and ON-MED. In the Active condition, differences in torque resistance were magnified (p=0.002). Medication substantially reduced differences in torque resistance between controls and PD patients in the Passive and Active conditions. CONCLUSIONS: A contralateral activation maneuver substantially increases rigidity in patients with PD, specifically the OFF-MED state. Rigidity is reduced with the application of dopaminergic medication, even with the presence of a contralateral activation maneuver. SIGNIFICANCE: These data support the use of a contralateral activation maneuver as a tool in the diagnosis of PD.

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.

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 Parkinson's 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.

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.

Phase-dependent and task-dependent modulation of stretch reflexes during rhythmical hand tasks in humans.

Phase-dependent and task-dependent modulation of reflexes has been extensively demonstrated in leg muscles during locomotory activity. In contrast, the modulation of reflex responses of hand muscles during rhythmic movement is poorly documented. The objective of this study was to determine whether comparable reflex modulation occurs in muscles controlling finger motions during rhythmic, fine-motor tasks akin to handwriting. Twelve healthy subjects performed two rhythmic tasks while reflexes were evoked by mechanical perturbations applied at various phases of each task. Electromyograms (EMGs) were recorded from four hand muscles, and reflexes were averaged during each task relative to the movement phase. Stretch reflexes in all four muscles were found to be modulated in amplitude with respect to the phase of the rhythmic tasks, and also to vary distinctly with the tasks being conducted. The extent and pattern of reflex modulation differed between muscles in the same task, and between tasks for the same muscle. Muscles with a primary role in each task showed a higher correlation between reflex response and background EMG than other muscles. The results suggest that the modulation patterns observed may reflect optimal strategies of central-peripheral interactions in controlling the performance of fine-motor tasks. As with comparable studies on locomotion, the phase-dependency of the stretch reflexes implies a dynamically fluctuating role of proprioceptive feedback in the control of the hand muscles. The clear task-dependency is also consistent with a dynamic interaction of sensory feedback and central programming, presumably adapted to facilitate the successful performance of the different fine-motor tasks.

Oculomanual Coordination in Tracking of Pseudorandom Target Motion Stimuli.

Oculomanual coordination was investigated in 9 healthy subjects during tracking of pseudorandom motion stimuli. Each subject was required to track visual stimuli under eye-hand (EH) and eye-alone (EA) conditions. Subjects were exposed to 3 types of mixed sinusoidal stimulus with varying frequency or amplitude of the highest frequency component, or various degrees of irregularity. Progressive degradation in tracking performance was nonlinearly induced by an increase in either (a) the highest frequency component or (b) its amplitude, but not by stimulus irregularity. No significant difference was found in eye velocity gain and phase under the EH and EA conditions. Eye and hand responses were found to be highly correlated in gain and phase when compared across frequencies and motion stimuli. The results suggest that frequency and amplitude are dominant factors controlling the breakdown of oculomanual performance in response to pseudorandom stimuli. Frequency responses of smooth pursuit eye movements are not affected by the hand motion in pursuit of unpredictable stimuli. Eye and hand motor systems appear to share common nonlinear drive mechanisms when pursuing pseudorandom target motion stimuli.

The role of shortening reaction in mediating rigidity in Parkinson's disease.

Rigidity in Parkinson's disease (PD) is defined as an increased resistance to passive movement of a joint. The plastic-type rigidity is uniform and constant throughout the entire range of motion, whereas the cogwheel-type rigidity is accompanied by tremor. Rigidity in PD has been understudied. Thus, its pathophysiological basis remains unclear. The purpose of the study is to examine neuromuscular/biomechanical properties of PD rigidity and to provide its physiological characteristics. We hypothesize that PD rigidity presents as a flattened trace of joint torque vs. angular position (torque-angle relation) of the wrist, because the forces generated by lengthening muscles are offset by activation of the antagonist, i.e. show "shortening reaction" (SR). Experiments were conducted on six PD subjects medication OFF and ON. PD severity was assessed based on the unified Parkinson's disease rating scale. Each subject sat on a chair and was instructed to relax, with the wrist coupled to the device. The servomotor applied constant velocity displacement to create wrist flexion/extension. Electromyographic (EMG) responses were monitored from wrist muscles, along with position, velocity and torque. EMG magnitudes were computed over the movement period. Slopes were derived from the torque-angle trace. Results showed that SRs were routinely recorded OFF medication, but substantially reduced ON medication. Due to the interaction of SR, torque-angle relation was flatter OFF medication and became steeper ON medication. Correlation analyses showed that a strong correlation (R=0.65) existed between SR and torque-angle slope OFF medication, exclusively. We suggest that SR may play an important role in mediating the mechanical features of PD rigidity.