Aging, frailty and complex networks.

When people age their mortality rate increases exponentially, following Gompertz's law. Even so, individuals do not die from old age. Instead, they accumulate age-related illnesses and conditions and so become increasingly vulnerable to death from various external and internal stressors. As a measure of such vulnerability, frailty can be quantified using the frailty index (FI). Larger values of the FI are strongly associated with mortality and other adverse health outcomes. This association, and the insensitivity of the FI to the particular health variables that are included in its construction, makes it a powerful, convenient, and increasingly popular integrative health measure. Still, little is known about why the FI works so well. Our group has recently developed a theoretical network model of health deficits to better understand how changes in health are captured by the FI. In our model, health-related variables are represented by the nodes of a complex network. The network has a scale-free shape or "topology": a few nodes have many connections with other nodes, whereas most nodes have few connections. These nodes can be in two states, either damaged or undamaged. Transitions between damaged and non-damaged states are governed by the stochastic environment of individual nodes. Changes in the degree of damage of connected nodes change the local environment and make further damage more likely. Our model shows how age-dependent acceleration of the FI and of mortality emerges, even without specifying an age-damage relationship or any other time-dependent parameter. We have also used our model to assess how informative individual deficits are with respect to mortality. We find that the information is larger for nodes that are well connected than for nodes that are not. The model supports the idea that aging occurs as an emergent phenomenon, and not as a result of age-specific programming. Instead, aging reflects how damage propagates through a complex network of interconnected elements.

A Frailty Index Based On Deficit Accumulation Quantifies Mortality Risk in Humans and in Mice.

Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index. Here we show the results of extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 [1.04-1.05] in humans; 1.15 [1.12-1.18] in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.

Prevalence of and factors associated with frailty and disability in older adults from China, Ghana, India, Mexico, Russia and South Africa.

BACKGROUND: The severe burden imposed by frailty and disability in old age is a major challenge for healthcare systems in low- and middle-income countries alike. The current study aimed to provide estimates of the prevalence of frailty and disability in older adult populations and to examine their relationship with socioeconomic factors in six countries. METHODS: Focusing on adults aged 50+ years, a frailty index was constructed as the proportion of deficits in 40 variables, and disability was assessed using the World Health Organization Disability Assessment Schedule (WHODAS 2.0), as part of the Study on global AGEing and adult health (SAGE) Wave 1 in China, Ghana, India, Mexico, Russia and South Africa. RESULTS: This study included a total of 34,123 respondents. China had the lowest percentages of older adults with frailty (13.1%) and with disability (69.6%), whereas India had the highest percentages (55.5% and 93.3%, respectively). Both frailty and disability increased with age for all countries, and were more frequent in women, although the sex gap varied across countries. Lower levels of both frailty and disability were observed at higher levels of education and wealth. Both education and income were protective factors for frailty and disability in China, India and Russia, whereas only income was protective in Mexico, and only education in South Africa. CONCLUSIONS: Age-related frailty and disability are increasing concerns for older adult populations in low- and middle-income countries. The results indicate that lower levels of frailty and disability can be achieved for older people, and the study highlights the need for targeted preventive approaches and support programs.

Frailty in relation to the risk of falls, fractures, and mortality in older Chinese adults: results from the Beijing Longitudinal Study of Aging.

OBJECTIVES: Falls are well known to be associated with adverse health outcomes, especially when complicated by fracture. Falls are more common in people who are frail and readily related to several items in the frailty phenotype. Less is known about the relationship between falls and frailty defined as deficit accumulation. Our objective was to investigate the relationship between falls, fractures, and frailty based on deficit accumulation. DESIGN: Representative cohort study, with 8 year follow-up. SETTING: The Beijing Longitudinal Study of Aging (BLSA). PARTICIPANTS: 3,257 Chinese people aged 55+ years at baseline. MEASUREMENTS: A frailty index (FI) was constructed using 33 health deficits, but excluding falls and fractures. The rates of falls, fractures and death as a function of age and the FI were analyzed. Multivariable models evaluated the relationships between frailty and the risk of recurrent falls, fractures, and mortality adjusting for age, sex, and education. Self or informant reported fall and fracture data were verified against participants' health records. RESULTS: Of 3,257 participants at baseline (1992), 360 people (11.1%) reported a history of falls, and 238 (7.3%) reported fractures. By eight years, 1,155 people had died (35.3%). The FI was associated with an increased risk of recurrent falls (OR=1.54; 95% confidence interval (CI)=1.34-1.76), fractures (OR=1.07; 95% CI=0.94-1.22), and death (OR=1.50, 95% CI=1.41-1.60). The FI showed a significant effect on mortality in a multivariate Cox regression model (Hazard Rate=1.29, 95% CI=1.25-1.33). When adjusted for the FI, neither falls nor fractures were associated with mortality. CONCLUSION: Falls and fractures were common in older Chinese adults, and associated with frailty. Only frailty was independently associated with death.

Trajectories of changes over twelve years in the health status of Canadians from late middle age.

Aging in a given individual can be characterized by the number of deficits (symptoms, signs, laboratory abnormalities, disabilities) that they accumulate. The number of accumulated deficits, more than their nature, well characterizes health status in individuals - the proportion of deficits present in an individual to deficits considered is known as a frailty index. While on average deficits accumulate with age, individual trajectories in the number of deficits is highly dynamic. Transitions in the number of deficits over a fixed time interval can be represented by the Poisson law, with the Poisson mean dependent on the deficit numbers at baseline. Here we present an extension of the model to make possible predictions for any given time period. Using data from the Canadian National Population Health Survey of people aged 55 and over (n=4330), followed during 7cycles being the baseline and 6cycles of follow-up every 2years, we found that the transition in the number of deficits during any time period can be approximated using a time dependent Poisson distribution with the Poisson mean tending to decelerate over time, according to square-root-of-time kinetics characteristic for stochastic processes (e.g. diffusion, Brownian motion ) while the probability of death shows a pattern of time acceleration with a high degree of precision, "explaining" over 98% of variance. The model predicts a variety of changes in health status including the possibility of health improvement indicating the repair/remodeling abilities of the organism. The model is valuable for estimating how changes in health can influence mortality across the life course from late middle age.

How Might Deficit Accumulation Give Rise to Frailty?

Frailty is a multiply determined vulnerability state. People who are frail are at risk of many adverse health outcomes, including death. For any individual, this risk can only be expressed probabilistically. Even very fit people can suddenly die or become catastrophically disabled, but their risk of both is much lower than a very frail person, who might nevertheless suddenly succumb without worsening health. Frailty occurs with ageing, a stochastic, dynamic process of deficit accumulation. Deficits occur ubiquitously at subcellular levels, ultimately affecting tissues, organs and integrated organ action, especially under stress. Some people are disposed to accumulate deficits at higher rates, but on average, deficit accumulation varies across the life course and likely is mutable. In this way, the clinical definition of frailty is distinct from the statistical definition, which sees frailty as a fixed factor for an individual. Recent, early animal work links subcellular deficits to whole body frailty. In humans, clinically detectable health deficits combine to increase the risk of adverse health outcomes. The rate of deficit accumulation occurs with remarkable regularity around the world, as does a limit to frailty. Of note, when 20+ deficits are counted, these characteristics are indifferent to which deficits are considered. The expression of risk in relation to deficit accumulation varies systematically. For example, at any given level of deficit accumulation, men are more susceptible to adverse health outcomes than are women. Likewise, in China, the lethality of deficit accumulation appears to be higher than in Western countries. In consequence, it may be necessary to better distinguish between frailty and physiological reserve; the latter may apply chiefly in relation to microscopic deficits. The expression of frailty risk in relation to deficit accumulation depends on the environment, including both the physical and social circumstances in which people find themselves.

Transitions in cognitive status in relation to frailty in older adults: a comparison of three frailty measures.

OBJECTIVES: Cognitive decline is related to frailty. Frailty can be operationalized in different ways, which have an unknown impact on the estimation of risk. Here, we compared 3 frailty measures in relation to cognitive changes and mortality in the Canadian Study of Health and Aging (CSHA). DESIGN: Prospective population-based study, with 5 year follow up. PARTICIPANTS/SETTING: 2,305 subjects aged 70+ years. METHODS: For each participant, cognitive status was measured by the errors in the Modified Mini-Mental State Examination (3MS) score. Three frailty measures were used: a Frailty Index based on the Comprehensive Geriatric Assessment (FI-CGA) evaluated from 47 potential deficits, a Clinical Frailty Score and the Fried frailty phenotype. Multivariate Poisson regression and multivariate logistic regression were used to examine the association between baseline cognitive errors and frailty and death, respectively, while controlling for possible confounders (age, sex, education, and baseline cognitive status). RESULTS: Changes in cognitive status were strongly associated with baseline cognition and frailty, however defined. In multivariate models adjusted for age, sex and education, each frailty measure was associated with cognitive decline and with mortality. The frailest people (from the highest FI-CGA tertile) rarely showed cognitive improvement or stabilization (1.5%, 95% CI=0.002%-2.8%) compared with non-frail people (from the lowest tertile of the FI-CGA), of whom 27.8% (95% CI=24.5%-31.1%) did not deteriorate. CONCLUSIONS: Frail elderly people have an increased risk of cognitive decline. All frailty measures allowed quantification of individual vulnerability and predict both cognitive changes and mortality.

Aging, frailty and age-related diseases.

The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.

Comparison of two frailty measures in the Conselice Study of Brain Ageing.

OBJECTIVES: Uncertainty about the definition of frailty is reflected by the development of many ways to identify frail people. We aimed to compare the validity of two frailty measures in participants of the Conselice Study of Brain Aging. DESIGN: Prospective population-based study with 4 year follow up. PARTICIPANTS/SETTING: 1,016 subjects aged 65 and over in a rural Italian population. METHODS: For each participant, a Frailty Index (FI) and a Conselice Study of Brain Aging Score (CSBAS) were determined. The FI was created from 43 deficits according to a standardized methodology; 7 variables derived from a previously validated Easy Prognostic Score comprised the CSBAS. RESULTS: The FI had characteristic properties described in other population samples, with a gamma distribution, a 99% limit of about 0.64 and higher values in women than men. CSBAS and FI were strongly correlated with each other (r = 0.72) and both correlated with age (r = 0.32, r = 0.27, respectively). Each was independently predictive of death in a multivariate model, with greater specificity and sensitivity than age alone. CONCLUSIONS: Frailty can be measured by different tools and facilitates a more direct quantification of individual vulnerability than chronological age alone. Though the Frailty Index and the Conselice Study of Brain Aging Score are underpinned by different rationales, clinical utility will continue to motivate their development.

Effect of smoking on the accumulation of deficits, frailty and survival in older adults: a secondary analysis from the Canadian Study of Health and Aging.

OBJECTIVES: Smoking has adverse effects on a variety of organ systems but little is known about the relationship between smoking and frailty. We aimed to investigate differences in health status between smoking and non smoking older adults. DESIGN AND SETTING: The Canadian Study of Health and Aging, a nationally representative cohort study. PARTICIPANTS: Nine thousand and eight community-dwelling men and women age 65 years and over at baseline. MEASUREMENTS: Smoking status was determined using a Self-Assessed Risk Factor Questionnaire. Comparisons were made between never smokers, light smokers and heavy smokers with heavy smokers defined as those who smoked >or= 1 pack per day for 20 years or more. A frailty index (FI) generated from 40 self-reported health deficits was also modified to exclude 5 variables that could be directly attributed to smoking (e.g. cough). Decedent information was collected over 10 years. RESULTS: Average FI values increased exponentially with age. For both men and women, heavy smokers were the most frail, light smokers had intermediate frailty status and never smokers were fittest. Modification of the FI did not impact these differences. Heavy smokers had significantly worse mortality than non smokers and higher rates of death in smokers persisted in the oldest old. 120 month survival curves, grouped for age, sex and smoking status showed that male smokers > 75 years had the highest mortality rates. CONCLUSIONS: Smoking causes poorer health status at older ages which can be captured by the frailty index. Higher rates of death in smokers persist in the oldest old, with no emergence of "survivors" with fitness or longevity advantages.

Gait and posture impairment, parkinsonism and cognitive decline in older people.

Our objective was to examine the frequency of gait and posture impairment and parkinsonism in 3 waves of the Canadians Study of Health and Aging (CSHA) and to determine their relationship to the development of cognitive impairment-not dementia (CIND) and dementia. A secondary analysis of a Canadian population-based cohort study was performed. People 65 years of age and older without cognitive impairment or dementia underwent examination for the presence of gait or posture impairment (GPI) or parkinsonism (based on the presence of 2/3 signs among resting tremor, rigidity or bradykinesia), both defined by a clinical examination. Risk for development of cognitive impairment or dementia was examined at 5 and 10 year follow up in pre-specified logistic regression models adjusted for age, sex, education and in separate models, frailty. The frequency of GPI ranged from 25 to 30% in cognitively unimpaired to 46-53% in CIND and demented subjects. Parkinsonism was more common with increasing cognitive impairment at each wave of the CSHA. Both GPI and parkinsonism predicted cognitive decline. Frailty reduced, but did not eliminate the impact of these motor measures and was itself a significant predictor of cognitive decline. In conclusion, motor impairment and frailty are common in older people and are associated with an increased risk of cognitive decline and dementia. GPI is common in CIND, while GPI and parkinsonism are both common in dementia.

A vascular risk factor index in relation to mortality and incident dementia.

To develop a method for quantifying risks of death and dementia in relation to vascular risk factors the Gothenburg H-70 1901-02 birth cohort was studied (n=380, was followed over 20 years, with 103 incident dementia cases). Separate vascular risk factor indices were calculated using 23 vascular risk factors to predict: (i) dementia-free-survival, and (ii) incident dementia derived from post hoc optimal separation of affected and unaffected cases. Classification of adverse outcomes (dementia/non-dementia; alive/dead) was assessed using receiver-operator characteristic (ROC) curves, and the area under the curve (AUC). Each index showed high separation between affected and unaffected cases. For dementia/non-dementia, the AUC was 0.74+/-0.02 for 10 year and 0.67+/-0.02 for 20 year; for death/survival, the AUC was 0.75+/-0.02 for 10 years and 0.79+/-0.03 for 20 years. Of note, few items were important in both indexes, and most showed reciprocal effects (e.g. decreased the risk of death but increased the risk of dementia). Our results suggest that vascular risk factor indexes can give robust estimates of dementia and life span prognoses in elderly people, but death and dementia have different risk profiles. This may be because of death being a competing risk for incident late-onset dementia.

Interjoint coordination dynamics during reaching in stroke.

A technique is described that characterizes the dynamics of the interjoint coordination of arm reaching movements in healthy subjects (n=10) and in patients who had sustained a left-sided cerebrovascular accident (n=18). All participants were right-handed. Data from the affected right arm of patients with stroke were compared with those from the right arm of healthy subjects. Seated subjects made 25 pointing movements in a single session. Movements were made from an initial target located ipsilaterally to the right arm beside the body, to a final target located in front of the subject in the contralateral arm workspace. Kinematic data from the finger, wrist, elbow, both shoulders and sternum were recorded in three dimensions at 200 Hz with an optical tracking system. Analysis of interjoint coordination was based on the patterns of temporal delay between rotations at two adjacent joints (shoulder and elbow). The data were reduced to a single graph (Temporal Coordination or TC index) integrating the essential temporal characteristics of joint movement (the angular displacements, velocities and timing). TC segments, duration and amplitude, were analysed. The analysis was sensitive to the differences in interjoint coordination between healthy subjects and patients with arm motor deficits. In patients, the temporal coordination between elbow and shoulder movements was disrupted from the middle to the end of the reach. More specifically, in mid-reach, all patients had difficulty coordinating elbow flexion with shoulder horizontal adduction. In addition, patients with severe arm hemiparesis had difficulty changing elbow movement direction from flexion to extension and in coordinating this change with shoulder movement. At the end of the reach, patients with severe hemiparesis had deficits in the execution of elbow extension while all patients had impaired coordination of elbow extension and shoulder horizontal adduction. In addition, active ranges of joint motions were significantly decreased in the stroke compared to the healthy subjects. Finally, TC analysis revealed significant relationships between specific aspects of disrupted interjoint coordination and the level of motor impairment, suggesting that it may be a useful tool in the identification of specific movement coordination deficits in neurological impaired populations that can be targeted in treatment for arm motor recovery.

Accumulation of deficits as a proxy measure of aging.

This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individual's life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

Superposition of independent units of coordination during pointing movements involving the trunk with and without visual feedback.

Previous studies addressing the problem of the control of multiple degrees of freedom have examined the influence of trunk movement on pointing movements within the arm's reach. Such movements may be controlled by two functionally independent units of coordination (synergies): one involving only arm joints and producing the hand trajectory to the target (the transport synergy), and the other coordinating trunk and arm movements leaving the hand trajectory unchanged (the compensatory synergy). The question of whether or not this functional subdivision depends on visual feedback was addressed in the present study. We also tested whether or not the motor effects of different synergies are summated as independent components, a control strategy called "superposition." Finally, we investigated whether or not the relationship between different degrees of freedom within each synergy could be considered linear resulting in proportional changes in different joint angles. Seated subjects produced fast, uncorrected arm movements to an ipsi- or a contralateral target in the direction of +/-45 degrees to the sagittal midline of the trunk. Targets could be reached using the arm alone (control trials) or by combining the arm motion with a forward or backward trunk motion produced by hip flexion or extension (test trials), with and without visual feedback. The shape of the hand trajectory, its direction and tangential velocity, movement precision, joint angles and the sequence of the trunk and hand recruitment and de-recruitment were measured. In both visual conditions, the direction of the hand trajectory observed in control trials was generally preserved in test trials. In terms of sequencing, even in the absence of vision, the trunk movement was initiated before the onset of and outlasted the hand shift, indicating that the potential influence of the trunk on the hand movement was compensated by rotations in the elbow and shoulder joint. The analysis of other variables also implied that the effects of trunk recruitment on the hand trajectory were minor compared to those which could be observed if these effects were not compensated by appropriate changes in the arm joint angles. It was concluded that an arm-trunk compensatory synergy is present in pointing movements regardless of visual feedback. Principal component analysis showed that the relationship between elbow, shoulder and hip joint angles in individual arm and combined arm-trunk movements cannot be considered linear, implying that this relationship is adjusted according to the changing arm geometry. The changes in each arm joint angle (elbow, shoulder) elicited by a forward trunk bending in one block of trials were compared with those elicited by a backward bending in another block, whereas the hand moved to the same target in both blocks. These changes were opposite but of similar magnitude. As a result, for each moment of movement, the mean joint angle obtained by averaging across two directions of trunk motion was practically identical to that in control trials in which the trunk was motionless. It is concluded that the transport and arm-trunk compensatory synergies are combined as independent units, according to the principle of superposition. This principle may simplify the control of the coordination of a redundant number of degrees of freedom.

Dynamics of cognitive aging: distinguishing functional age and disease from chronologic age in a population.

This paper introduces a methodological approach to the dynamics of cognitively normal (i.e., successful) aging compared with aging accompanied by different types of cognitive impairment and dementia. Using secondary analysis of a national representative database (Canadian Study of Health and Aging, 1991-1992), the authors show that the occurrence of an adverse event (symptom, sign, or disease), or the accumulation of a number of events, may be modeled as a logistic function of chronologic age in a population. In the cognitively normal, a linear relation between the logarithm of the odds of events and chronologic age was present for the majority of symptoms and signs. This regression represents the accumulation of each sign in a cognitively successful, aging population. The authors then estimated which ages for this cognitively unimpaired group correspond to the odds of the occurrence of symptoms found for a cognitively impaired population at any given chronologic age. This may be regarded as functional age, based upon the accumulation of a particular functional deficit in the impaired population, analogous to the concept of frailty. The dynamics of aging are a complex process of accumulation of deficits (morbidity), whereby decline from some previously healthy level of synergistically associated symptoms and signs results in distinct patterns of disease and staging. The modeling of these dynamics takes us a step further toward the definition and refinement of disease and normal aging.

The rate of decline in function in Alzheimer's disease and other dementias.

BACKGROUND: Functional impairment over time is a necessary condition for the diagnosis of dementia. Increasingly, it is recognized that rates of decline may not follow a linear progression. This variability may indicate that dementia in Alzheimer's disease represents disease rather than inevitable aging. In order to investigate decline in function in dementia, we developed a model of the rate of decline in functions in Alzheimer's disease and in other dementias in comparison with normal aging. METHODS: Secondary analysis of a cross-sectional, representative sample of Canadians aged 65 and older (N = 2,914) was performed. We calculated a measure identified as an impairment index, defined as the probability of the occurrences of an impairment or disability in a structured clinical examination. RESULTS: The rate of functional decline varies for different diagnostic groups and increases with severity of the disease. The distribution for the rate of decline in dementia is distinct from that in aging without cognitive impairment. In those without cognitive impairment, the distribution is exponential. Elderly persons with dementia of any type showed a log-normal distribution. CONCLUSIONS: The difference in the distributions between aging with and without dementia likely reflects fundamental differences in the processes of decline in functions in the two groups. This suggests that the declines seen in persons with dementia are distinct from normal aging. It also has implications for the testing of antidementia medications, in that modeling treatment effects based on an assumption of linear decline is likely to be flawed.

1998 ISEK Congress Keynote Lecture: Multi-muscle control in human movements. International Society of Electrophysiology and Kinesiology.

It has been suggested that the coordination of the activity of multiple muscles results from the comparison of the actual configuration of the body with a referent configuration specified by the nervous system so that the recruitment and gradation of the activity of each skeletal muscle depend on the difference between these two configurations. Active movements may be produced by the modification of the referent configuration. The hypothesis predicts the existence of a global minimum in electromyographic (EMG) activity of multiple muscles during movements involving reversals in direction. This prediction was tested in five subjects by analysing movements resembling the act of reaching for an object placed beyond one's reach from a sitting position. In such movements, initially sitting subjects raise their body to a semi-standing position and then return to sitting. Consistent with the hypothesis is the observation of a global minimum in the surface EMG activity of 16 muscles of the arm, trunk and leg at a specific phase of the movement. When the minimum occurred, EMG activity of each muscle did not exceed 2-7% of its maximal activity during the movement. As predicted, global EMG minima occurred at the phase corresponding to the reversal in movement direction, that is, during the transition from raising to lowering of the body. The global EMG minimum may represent the point at which temporal matching occurs between the actual and the referent body configurations. This study implies a specific link between motor behavior and the geometric shape of the body modified by the brain according to the desired action.