Analysis of Rapid Alternating Movements in Cree Subjects Exposed to Methylmercury and in Subjects with Neurological Deficits

doi:10.1006/enrs.1998.3885

Environmental Research

Volume 80, Issue 1, January 1999, Pages 64-79

https://doi.org/10.1006/enrs.1998.3885 Get rights and content

Abstract

To quantify rapid alternating movements (RAMs) we used a simple prototype developed in our laboratory that requires the subject to rotate two hand-held foam spheres connected to optical encoders via flexible rods. Ninety-six participants, including 30 control subjects, 36 Cree subjects exposed to methylmercury, 21 subjects with Parkinson's disease, 6 subjects with cerebellar deficits, and 3 subjects with essential tremor, were involved in the study (though data for 5 were later removed). Twelve characteristics were developed and calculated from the raw data. Conditions examined included two hands at natural cadence (NC2), right and left hands separately at fast cadence (FCl), and both hands at fast cadence (FC2). Two ratios (FC2/NC2) and (FC2/FC1) combining these conditions were also examined. Test–retest reliability was >0.80 for most characteristics but was <0.70 for some characteristics, especially in the conditions executed at normal cadence. Correlations between characteristics and numbers of outliers with respect to the control group distribution were used to reduce the set of characteristics from 12 to 7 (i.e., duration, range, maximum slope, similarity in shape, smoothness, sharpness, and coherence). ANOVAs on the three largest groups generated significant results for most characteristics in the three conditions and the two ratios for Cree subjects and subjects with Parkinson's disease. ANOVAs on 3 age-matched groups (n=6) suggest that methylmercury affects the performance of the Cree subjects with the higher exposure, especially in terms of smoothness, sharpness, and coherence. These preliminary results suggest that this test is sufficiently specific and sensitive to characterize the performance of different groups of subjects. Ratios tend to improve discrimination for Cree subjects in a few characteristics but not for patients with Parkinson's disease.

References (9)

G.E. McKeown-Eyssen et al.
Validity and reproducibility of a screening examination for neurological abnormality in persons exposed to methylmercury
J. Clin. Epidemiol.
(1990)
M. Okada et al.
A method for quantification of alternate pronation and supination of forearms
Comput. Biomed. Res.
(1983)
A. Beuter et al.
Diadocho-kinesimetry: A study of patients with Parkinson's disease and manganese exposed workers
Neurotoxicology
(1994)
U. Halsband et al.
The role of premotor cortex and the supplementary motor area in the temporal control of movement in man
Brain
(1993)

There are more references available in the full text version of this article.

Cited by (42)

Aging, motor function, and sensitivity to calcium channel blockers: An investigation using chronic methylmercury exposure
2016, Behavioural Brain Research
Citation Excerpt :
Chronic adult-onset exposure to the global pollutant methylmercury (MeHg) has been linked to nervous system damage, “glove and stocking” sensory disturbances, weakness, cerebellar ataxia, and visual and auditory dysfunction in human populations [1–4]. Lower exposure produces mild sensorimotor dysfunction [5–7] and tremor [8–10]. Accordingly, sensorimotor dysfunction is a primary behavioral marker of protracted adult-onset MeHg exposure.
Methylmercury (MeHg) neurotoxicity is thought to be mediated, in part, by dysregulation of calcium (Ca²⁺) homeostasis, a mechanism that may also slowly and progressively degrade neuronal function during normal aging. Longitudinal studies of MeHg exposure provide a powerful approach to studying neural and behavioral mechanisms by which both MeHg toxicity and aging affect motor function. Wheel-running and rotarod performance were assessed in two age groups of BALB/c mice chronically exposed to 0 or 1.2 mg/kg/day MeHg and 0 or 20 mg/kg/day nimodipine, a 1,4-dihyrdopyridine L-type calcium channel blocker (CCB), for approximately 8.5 months. Adults began exposure on postnatal day (PND) 72 and retired breeders on PND 296. A log-survivor bout analysis partitioned wheel-running into bouts that identified motor (within-bout rates) and motivational (bout-initiation rates) influences. Retired breeders ran farther, because of a higher bout-initiation rates, but performed more poorly on the rotarod than younger adults, a difference unaffected by nimodipine. MeHg produced relatively age-independent deficits in wheel-running and rotarod performance, whereas nimodipine afforded greater protection to adult mice than to retired breeders. Rotarod performance and within-bout response rate were more sensitive to and more reliable predictors of MeHg toxicity than bout-initiation rate, which was least affected by MeHg exposure. Thus the motivation to run was unimpaired as the ability to do so declined. While chronic MeHg exposure produced functionally similar behavior deficits between age groups, the age-dependent neuroprotection by nimodipine supports the notion that underlying neurobiological systems mediated by Ca²⁺ signaling, are differentially affected in older adults.
Are quantitative and clinical measures of bradykinesia related in advanced Parkinson's disease?
2013, Journal of Neuroscience Methods
Citation Excerpt :
Others have also used timed motor tasks to measure movement properties (Duval et al., 2001; Ghassemi et al., 2006). Specifically, quantitative analysis of rapid alternating movements (RAM) is one motor task that was used by our group (Duval et al., 2001; Ghassemi et al., 2006) and others (Okada, 1983; Beuter et al., 1999; Vaillancourt et al., 2004) to assess bradykinesia in PD and other disorders. Interestingly, the possible relationship between quantitatively assessed variables of RAM and a clinical assessment of bradykinesia was never performed.
Bradykinesia is usually assessed using clinical rating scales. In some circumstances, a laboratory assessment of bradykinesia using tools of higher resolution is required. One task often used for the evaluation of bradykinesia is a rapid alternating movement (RAM) of the hand. However, the relationship between clinical scores of bradykinesia and the properties of a RAM task assessed quantitatively has yet to be determined.
Identify which of the commonly used properties of a RAM task are related to a clinical score of bradykinesia and assess the strength of this relationship.
Nineteen patients with idiopathic Parkinson's disease were tested ON and OFF medication. They performed three trials of the RAM task and were assessed clinically using the Unified Parkinson's disease rating scale in each condition and with each hand.
A statistically significant correlation was observed between the clinical score of bradykinesia and two of the properties of the RAM task; namely mean and maximal velocity.
These results indicate that a RAM task does provide a measure of bradykinesia but it is only moderately correlated to a clinical rating of this motor symptom.
We propose that the results from the RAM task represent a measure of “core bradykinesia” while a clinical evaluation represents a composite score of bradykinesia, movement amplitude and motor coordination.
Dietary selenium protects against selected signs of aging and methylmercury exposure
2010, NeuroToxicology
Acute or short-term exposure to high doses of methylmercury (MeHg) causes a well-characterized syndrome that includes sensory and motor deficits. The environmental threat from MeHg, however, comes from chronic, low-level exposure, the consequences of which are poorly understood. Selenium (Se), an essential nutrient, both increases deposition of mercury (Hg) in neurons and mitigates some of MeHg's neurotoxicity in the short term, but it is unclear whether this deposition produces long-term adverse consequences. To investigate these issues, adult Long–Evans rats were fed a diet containing 0.06 or 0.6 ppm of Se as sodium selenite. After 100 days on these diets, the subjects began consuming 0.0, 0.5, 5.0, or 15 ppm of Hg as methylmercuric chloride in their drinking water for 16 months. Somatosensory sensitivity, grip strength, hindlimb cross (clasping reflex), flexion, and voluntary wheel-running in overnight sessions were among the measures examined. MeHg caused a dose- and time-dependent impairment in all measures. No effects appeared in rats consuming 0 or 0.5 ppm of Hg. Somatosensory function, grip strength, and flexion were among the earliest signs of exposure. Selenium significantly delayed or blunted MeHg's effects. Selenium also increased running in unexposed animals as they aged, a novel finding that may have important clinical implications. Nerve pathology studies revealed axonal atrophy or mild degeneration in peripheral nerve fibers, which is consistent with abnormal sensorimotor function in chronic MeHg neurotoxicity. Lidocaine challenge reproduced the somatosensory deficits but not hindlimb cross or flexion. Together, these results quantify the neurotoxicity of long-term MeHg exposure, support the safety and efficacy of Se in ameliorating MeHg's neurotoxicity, and demonstrate the potential benefits of Se during aging.
Quantitative assessment of neuromotor function in workers with current low exposure to mercury vapor
2008, NeuroToxicology
Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg⁰). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg⁰, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 μg/g (range 1.3–25) creatinine (μg/gC), while that in referents was 0.7 μg/gC (range 0.2–4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years × μg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye–hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg⁰ on neuromotor function at the exposure levels studied.
Bradykinesia is not a "systematic" feature of adult-onset Huntington's disease; implications for basal ganglia pathophysiology
2008, Brain Research
Citation Excerpt :
After 10 s the participants were asked to return to the rest state for the remaining 20 s. Three trials were recorded in each condition with periods of rest in between trials. RAM tasks have been validated by us (Duval et al., 2001, 2006a,b; Ghassemi et al., 2006) and others (Okada and Okada, 1983; Beuter et al., 1999; Fimbel et al., 2005) to measure slowness of movement in different populations, and represent the ability of subjects to generate high velocity and to maintain it for several seconds. It is a natural movement that has little to no learning curve associated to it.
Our goal was to determine whether bradykinesia is present in choreic adult-onset Huntington's disease (HD) patients, and determine the impact of chorea on their voluntary movements. We recorded whole-body involuntary movements (WBIM) and voluntary motor acts simultaneously, using a magnetic tracker system, in 15 choreic HD patients and 15 healthy age- and gender-matched control subjects. Participants were asked to perform two distinct tasks; a manual-tracking (MT) task yielding a measure of chorea intrusion during accurate movements, and a rapid alternating movement (RAM) task, yielding measures of bradykinesia. Results show that patients with HD presented with deviations from the target that hindered their ability to match the target velocity during the MT task. Furthermore, error in performance was correlated with the amplitude of whole-body chorea (Rho = 0.67), illustrating the deleterious effect of chorea during accurate movements. However, patients with choreic HD presented with significantly higher RAM range and velocity than matched controls, therefore ruling out the idea that bradykinesia is a systematic feature of HD even when chorea is predominant. The present results imply that patients may have benefited from an intact direct pathway (“select ON” pathway in the focused attention model of basal ganglia function) that allowed them to supersede any dysfunctions associated with the progressive alteration of the “control function“ (striatal–globus pallidus–subthalamic) pathway responsible for generating the chorea. Finally, the present results suggest that patients with adult-onset HD having chorea would greatly benefit from improved treatments aiming at reducing their involuntary movements while maintaining proper motor function.
Bradykinesia in patients with essential tremor
2006, Brain Research
We compared the level of bradykinesia during rapid alternating movements (RAM) in patients with essential tremor (ET) with that of patients with Parkinson's disease (PD) having either the “tremor dominant” or “akinetic-rigid” form of PD, and 10 healthy controls. We found an increase of pronation–supination cycle duration in the PD and ET group, suggestive of bradykinesia. RAM range was, however, similar between groups. The akinetic-rigid group showed a distinct increase in RAM amplitude fluctuation, suggesting that rigidity modified the characteristics of the observed bradykinesia. In conclusion, slow movements should then be considered as part of the ET symptomatology.

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^☆: The study received approval from the ethics committee of the University of Québec at Montréal and was conducted in agreement with the procedures proposed. Accordingly, all subjects gave informed consent.

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Regular ArticleAnalysis of Rapid Alternating Movements in Cree Subjects Exposed to Methylmercury and in Subjects with Neurological Deficits☆

Abstract

J. Clin. Epidemiol.

Comput. Biomed. Res.

Diadocho-kinesimetry: A study of patients with Parkinson's disease and manganese exposed workers

Neurotoxicology

The role of premotor cortex and the supplementary motor area in the temporal control of movement in man

Brain

Regular Article
Analysis of Rapid Alternating Movements in Cree Subjects Exposed to Methylmercury and in Subjects with Neurological Deficits☆