Robert G. Lee

Parkinson's disease and exposure to agricultural work and pesticide chemicals

This population-based case-control study of 130 Calgary residents with neurologist-confirmed idiopathic Parkinsons disease (PD) and 260 randomly selected age- and sex-matched community controls attempted to determine whether agricultural work or the occupational use of pesticide chemicals is associated with an increased risk for PD. We obtained by personal interviews lifetime occupational histories, including chemical exposure data, and analyzed the data using conditional logistic regression for matched sets. In the univariate analysis, a history of field crop farming, grain farming, herbicide use, or insecticide use resulted in a significantly increased crude estimate of the PD risk, and the data suggested a dose-response relation between the PD risk and the cumulative lifetime exposure to field crop farming and to grain farming. However, in the multivariate analysis, which controlled for potential confounding or interaction between the exposure variables, previous occupational herbicide use was consistently the only significant predictor of PD risk. These results support the hypothesis that the occupational use of herbicides is associated with an increased risk for PD.

Parkinson's disease A test of the multifactorial etiologic hypothesis

We studied the relative etiologic importance upon the development of Parkinsons disease (PD) of occupational exposure to herbicides and other compounds, ionizing radiation exposure, family history of PD and essential tremor, smoking, and history of various viral and other medical conditions. We identified patients (n = 130) with neurologist-confirmed idiopathic PD through contacts with Calgary general hospitals, long-term care facilities, neurologists, the Movement Disorder Clinic, and the Parkinsons Society of Southern Alberta, and selected two matched (by sex and age ± 2.5 years) community controls for each case by random digit dialing. We obtained lifetime work, chemical, radiation, medical, and smoking exposure histories and family histories of PD and essential tremor by personal interviews, and analyzed the data using conditional logistic regression for matched sets. After controlling for potential confounding and interaction between the exposure variables, using multivariate statistical methods, having a family history of PD was the strongest predictor of PD risk, followed by head trauma and then occupational herbicide use. Cases and controls did not differ in their previous exposures to smoking or ionizing radiation; family history of essential tremor; work-related contact with aluminum, carbon monoxide, cyanide, manganese, mercury, or mineral oils; or history of arteriosclerosis, chicken pox, encephalitis, hypertension, hypotension, measles, mumps, rubella, or Spanish flu. These results support the hypothesis of a multifactorial etiology for PD, probably involving genetic, environmental, trauma, and possibly other factors.

Quantitative analysis of human movement synergies: constructive pattern analysis for gait.

To record three-dimensional coordinates of the joints from normal human subjects during locomotion, we used a digital motion analysis system (ELITE). Recordings were obtained under several different conditions, which included normal walking and stepping over obstacles. Principal component analysis was used to analyze coordinate data after conversion of the data to segmental angles. This technique gave a stable summary of the redundancy in gait kinematic data in the form of reduced variables (principal components). By modeling the shapes of the phase plots of reduced variables (distortion analysis) and using a limited number of model parameters, good resolution was obtained between subtly different conditions. Hence, it was possible to accurately resolve small distributed changes in gait patterns within subjects. These methods seem particularly suited to longitudinal studies in which relevant movement features are not known a priori. Assumptions and neurophysiological applications are discussed.

Parkinson's disease and exposure to rural environmental factors : a population based case-control study

To determine whether a history of exposure to rural environmental factors leads to an increased likelihood of developing idiopathic Parkinsons disease, we conducted a case-control study of 130 cases and 260 randomly selected community controls (matched with the cases by sex and age +/- 2.5 years at a ratio of 2 controls: 1 case) in the city of Calgary. The data were collected by personal interviews and were analyzed using conditional logistic regression for matched sets. The ages of the cases ranged from 36.5 to 90.7 years (mean = 68.5 +/- 11.3 years). The mean age at diagnosis was 61.1 +/- 12.4 years. The mean duration of disease was 7.8 +/- 0.6 years. Eleven (9.1%) cases were diagnosed before age 40. In this sample from the Province of Alberta, Canada, no significant increase in risk for Parkinsons disease was associated with a history of rural living, farm living, or well water drinking in early childhood or at any time during the first 45 years of life.

Control strategies in directing the hand to moving targets

SummaryWe have evaluated the use of visual information about the movement of a target in two tasks tracking and interceptions — involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components — the time taken for target motion to be detected, and a fixed processing time — provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses.

Impaired “natural reciprocal inhibition” in patients with spasticity due to incomplete spinal cord injury

Experiments were performed to compare the ability of normal subjects and patients with spinal spasticity to suppress antagonist H reflexes during isometric ankle contractions. Soleus H reflex suppression was examined during tonic pretibial muscle contractions in which the torque levels were constant and during dynamic pretibial muscle contractions in which the torque followed a predetermined ramp. As well, subjects were instructed to alternately contract ankle plantarflexors and dorsiflexors at various frequencies to examine patterns of EMG activity during rhythmically alternating isometric contractions in antagonist muscles. Patients with incomplete spinal cord injury demonstrated reduced ability to suppress soleus H reflexes during pretibial muscle contraction. At slow speeds of alternating contraction, spinal cord injured patients retained the ability to perform alternating isometric pretibial/soleus muscle contractions. The patients demonstrated abnormal coactivation in soleus muscle during faster alternating isometric ankle muscle contractions. Furthermore, the patients who demonstrated the greatest impairment in natural reciprocal inhibition, also displayed the largest amount of coactivation. In general, the results would suggest that impairment of natural reciprocal inhibition is correlated with an increase in the amount of antagonist muscle coactivation seen during alternating isometric muscle contractions.

Multi-Joint Reaching Movements and Eye-Hand Tracking in Cerebellar Incoordination: Investigation of a Patient with Complete Loss of Purkinje Cells

Performance on an eye-hand tracking task and a multi-joint reaching movement to a visual target was studied in a patient with stable cerebellar ataxia and in control subjects. The patient subsequently died and a full neuropathological examination was performed. The neuropathological findings were similar to those seen in patients with paraneoplastic cerebellar degeneration, but no tumor was found at autopsy eight years after onset of the patients cerebellar syndrome. A severe cerebellar cortical degeneration with complete Purkinje cell loss was demonstrated, whereas cerebellar nuclei and brainstem structures showed no neuronal loss. Tracking performance by the patient was characterized by abnormally large numbers of high velocity movements and hand direction reversals, and by excessive lagging of the hand behind the target in time. In the multi-joint reaching movement, the patient showed a delay in movement onset at the elbow joint compared to movement onset at the shoulder joint. The velocity profile of the movement at the shoulder joint was abnormal. The duration of the acceleration phase was poorly correlated with both peak angular velocity and the duration of the deceleration phase. One of the most striking findings was the inability of the patient to consistently produce the same movement direction from trial to trial while reaching to the same target. Our data suggests that the cerebellar cortex is involved in multiple aspects of motor control including visuomotor integration mechanisms.

Adaptive modification of oculomotor pursuit influences manual tracking responses

We have addressed the question of whether adaptively modifying the oculomotor response to a visual pursuit stimulus has an influence on a related manual tracking response. Subjects used their unseen right hand to track targets moving at constant velocities while visually fixating a stationary LED. Manual tracking performance was compared before and after a 20 min period during which smooth pursuit eye movements alone were adaptively enhanced by adding 50% of the instantaneous eye position signal to target position. Compared with the preadaptation trials, hand gain was markedly increased during the postadaptation period. These results imply that the adaptation occurred at a level common to both motor systems, probably in CNS structures concerned with visual motion processing.

Pathophysiology of Rigidity and Akinesia in Parkinson’s Disease

Although rigidity and akinesia are two of the cardinal features of Parkinsons disease, their exact pathophysiology remains uncertain. Mechanisms which may contribute to rigidity include accentuation of the long-latency component of the stretch reflex and enhanced fusimotor drive causing increased sensitivity of muscle spindles. Current evidence concerning the role of these factors in rigidity is reviewed. The relationship between akinesia, prolonged reaction times, and delay in initiation of internally generated movements in parkinsonian patients is discussed.

Modification of motor output to compensate for unanticipated load conditions during rapid voluntary movements.

Mechanisms responsible for load compensation during fast voluntary movements were investigated in 20 normal subjects trained to carry out rapid wrist flexions against a standard load. When an unanticipated increase in load occurred, there was a compensatory increase in agonist EMG and decrease in antagonist EMG. Unanticipated decreases in load produced reciprocal changes with a decrease in agonist EMG and an increase in antagonist EMG. The latency of these EMG changes was quite short and compatible with a spinal reflex mechanism rather than a long loop response. The results suggest that mechanisms exist at the spinal level to allow rapid modification of motor programs when unanticipated load conditions are encountered on initiation of movement.