Slowing of Movements in Healthy Aging as a Rational Economic Response to an Elevated Effort Landscape.

Why do we move slower as we grow older? The reward circuits of the brain, which tend to invigorate movements, decline with aging, raising the possibility that reduced vigor is due to the diminishing value that our brain assigns to movements. However, as we grow older, it also becomes more effortful to make movements. Is age-related slowing principally a consequence of increased effort costs from the muscles, or reduced valuation of reward by the brain? Here, we first quantified the cost of reaching via metabolic energy expenditure in human participants (male and female), and found that older adults consumed more energy than the young at a given speed. Thus, movements are objectively more costly for older adults. Next, we observed that when reward increased, older adults, like the young, responded by initiating their movements earlier. Yet, unlike the young, they were unwilling to increase their movement speed. Was their reluctance to reach quicker for rewards due to the increased effort costs, or because they ascribed less value to the movement? Motivated by a mathematical model, we next made the young experience a component of aging by making their movements more effortful. Now the young responded to reward by reacting faster but chose not to increase their movement speed. This suggests that slower movements in older adults are partly driven by an adaptive response to an elevated effort landscape. Moving slower may be a rational economic response the brain is making to mitigate the elevated effort costs that accompany aging.

Effects of reward and effort history on decision making and movement vigor during foraging.

During foraging, animals explore a site and harvest reward and then abandon that site and travel to the next opportunity. One aspect of this behavior involves decision making, and the other involves movement control. These two aspects of behavior may be linked via an underlying desire to maximize a single normative utility: the sum of all rewards acquired, minus all efforts expended, divided by time. According to this theory, the history of rewards, and not just its immediate availability, should dictate how long one should stay and harvest reward and how vigorously one should travel to the next opportunity. We tested this theory in a series of experiments in which humans used their hand to harvest tokens at a reward patch and then used their arm to reach toward another patch. After a history of high rewards, the subjects not only shortened their harvest duration but also moved more vigorously toward the next reward opportunity. In contrast, after a history of high effort they lengthened their harvest duration but reduced their movement vigor, reaching more slowly to the next reward site. Thus, a history of high reward or low effort biased decisions by promoting early abandonment of the reward site and biased movements by promoting vigor.NEW & NOTEWORTHY Much of life is spent foraging. Whereas previous work has focused on the decision regarding time spent harvesting from a reward patch, here we test the idea that both decision making and movement control are tuned to optimize the net rate of reward in an environment. Our results show that movement patterns reflect not just immediate expectations but also past experiences in the environment, providing fundamental insight into the factors governing volitional control of arm movements.

Common Mechanisms of Learning in Motor and Cognitive Systems.

Rapid progress in our understanding of the brain's learning mechanisms has been accomplished over the past decade, particularly with conceptual advances, including representing behavior as a dynamical system, large-scale neural population recordings, and new methods of analysis of neuronal populations. However, motor and cognitive systems have been traditionally studied with different methods and paradigms. Recently, some common principles, evident in both behavior and neural activity, that underlie these different types of learning have become to emerge. Here we review results from motor and cognitive learning, relying on different techniques and studying different systems to understand the mechanisms of learning. Movement is intertwined with cognitive operations, and its dynamics reflect cognitive variables. Training, in either motor or cognitive tasks, involves recruitment of previously unresponsive neurons and reorganization of neural activity in a low dimensional manifold. Mapping of new variables in neural activity can be very rapid, instantiating flexible learning of new tasks. Communication between areas is just as critical a part of learning as are patterns of activity within an area emerging with learning. Common principles across systems provide a map for future research.

Effort cost of reaching prompts vigor reduction in older adults.

As people age, they move slower. Is age-related reduction in vigor a reflection of a reduced valuation of reward by the brain, or a consequence of increased effort costs by the muscles? Here, we quantified cost of movements objectively via the metabolic energy that young and old participants consumed during reaching and found that in order reach at a given speed, older adults expended more energy than the young. We next quantified how reward modulated movements in the same populations and found that like the young, older adults responded to increased reward by initiating their movements earlier. Yet, their movements were less sensitive to increased reward, resulting in little or no modulation of reach speed. Lastly, we quantified the effect of increased effort on how reward modulated movements in young adults. Like the effects of aging, when faced with increased effort the young adults responded to reward primarily by reacting faster, with little change in movement speed. Therefore, reaching required greater energetic expenditure in the elderly, suggesting that the slower movements and reactions exhibited in aging are partly driven by an adaptive response to an elevation in the energetic landscape of effort. That is, moving slower appears to be a rational economic consequence of aging. Significance statement: Healthy aging coincides with a reduction in speed, or vigor, of walking, reaching, and eye movements. Here we focused on disentangling two opposing sources of aging-related movement slowing: reduced reward sensitivity due to loss of dopaminergic tone, or increased energy expenditure movements related to mitochondrial or muscular inefficiencies. Through a series of three experiments and construction of a computational model, here we demonstrate that transient changes in reaction time and movement speed together offer a quantifiable metric to differentiate between reward- and effort-based alterations in movement vigor. Further, we suggest that objective increases in the metabolic cost of moving, not reductions in reward valuation, are driving much of the movement slowing occurring alongside healthy aging.

Metabolic costs of walking and arm reaching in persons with mild multiple sclerosis.

Movement slowness is a common and disruptive symptom of multiple sclerosis (MS). A potential cause is that individuals with MS slow down to conserve energy as a behavioral adjustment to heightened metabolic costs of movement. To investigate this prospect, we measured the metabolic costs of both walking and seated arm reaching at five speeds in persons with mild MS (pwMS; n = 13; 46.0 ± 7.7 yr) and sex- and age-matched controls (HCs; n = 13; 45.8 ± 7.8 yr). Notably, the cohort of pwMS was highly mobile and no individuals required a cane or aid when walking. We found that the net metabolic power of walking was approximately 20% higher for pwMS across all speeds (P = 0.0185). In contrast, we found no differences in the gross power of reaching between pwMS and HCs (P = 0.492). Collectively, our results suggest that abnormal slowness of movement in MS-particularly reaching-is not the consequence of heightened effort costs and that other sensorimotor mechanisms are playing a considerable role in slowing.NEW & NOTEWORTHY Individuals with multiple sclerosis (MS) often move more slowly than those without the disease. A possible cause is that movements in MS are more energetically expensive and slowing is an adaptation to conserve metabolic resources. Here, we find that while walking is more costly for persons with MS, arm-reaching movements are not. These results bring into question the driving force of movement slowness in MS and implicate other motor-related networks contributing to slowing.

Learning vs. minding: How subjective costs can mask motor learning.

When learning new movements some people make larger kinematic errors than others, interpreted as a reduction in motor-learning ability. Consider a learning task where error-cancelling strategies incur higher effort costs, specifically where subjects reach to targets in a force field. Concluding that those with greater error have learned less has a critical assumption: everyone uses the same error-canceling strategy. Alternatively, it could be that those with greater error may be choosing to sacrifice error reduction in favor of a lower effort movement. Here, we test this hypothesis in a dataset that includes both younger and older adults, where older adults exhibited greater kinematic errors. Utilizing the framework of optimal control theory, we infer subjective costs (i.e., strategies) and internal model accuracy (i.e., proportion of the novel dynamics learned) by fitting a model to each population's trajectory data. Our results demonstrate trajectories are defined by a combination of the amount learned and strategic differences represented by relative cost weights. Based on the model fits, younger adults could have learned between 65-90% of the novel dynamics. Critically, older adults could have learned between 60-85%. Each model fit produces trajectories that match the experimentally observed data, where a lower proportion learned in the model is compensated for by increasing costs on kinematic errors relative to effort. This suggests older and younger adults could be learning to the same extent, but older adults have a higher relative cost on effort compared to younger adults. These results call into question the proposition that older adults learn less than younger adults and provide a potential explanation for the equivocal findings in the literature. Importantly, our findings suggest that the metrics commonly used to probe motor learning paint an incomplete picture, and that to accurately quantify the learning process the subjective costs of movements should be considered.

Saccade vigor reflects the rise of decision variables during deliberation.

During deliberation, as we quietly consider our options, the neural activities representing the decision variables that reflect the goodness of each option rise in various regions of the cerebral cortex.1,2,3,4,5,6,7 If the options are depicted visually, we make saccades, focusing gaze on each option. Do the kinematics of these saccades reflect the state of the decision variables? To test this idea, we engaged human participants in a decision-making task in which they considered two effortful options that required walking across various distances and inclines. As they deliberated, they made saccades between the symbolic representations of their options. These deliberation period saccades had no bearing on the effort they would later expend, yet saccade velocities increased gradually and differentially: the rate of rise was faster for saccades toward the option that they later indicated as their choice. Indeed, the rate of rise encoded the difference in the subjective value of the two options. Importantly, the participants did not reveal their choice at the conclusion of deliberation, but rather waited during a delay period, and finally expressed their choice by making another saccade. Remarkably, vigor for this saccade dropped to baseline and no longer encoded subjective value. Thus, saccade vigor appeared to provide a real-time window to the otherwise hidden process of option evaluation during deliberation.

Movement control, decision-making, and the building of Roman roads to link them.

In science, as in life, one can only hope to both inform others, and be informed by them. The commentaries associated with our book Vigor have highlighted the many ways in which the theory that we proposed can be improved. For example, there are a myriad of factors that need to be considered in a fully encompassing objective function. The neural mechanisms underlying the links between movement and decision-making have yet to be unraveled. The implications of a two-way interaction between movement and decisions at both the individual and social levels remain to be understood. The commentaries outline future questions, and encouragingly highlight the diversity of science communities that may be linked via the concept of vigor.

Whole body adaptation to novel dynamics does not transfer between effectors.

How does the brain coordinate concurrent adaptation of arm movements and standing posture? From previous studies, the postural control system can use information about previously adapted arm movement dynamics to plan appropriate postural control; however, it is unclear whether postural control can be adapted and controlled independently of arm control. The present study addresses that question. Subjects practiced planar reaching movements while standing and grasping the handle of a robotic arm, which generated a force field to create novel perturbations. Subjects were divided into two groups, for which perturbations were introduced in either an abrupt or a gradual manner. All subjects adapted to the perturbations while reaching with their dominant (right) arm and then switched to reaching with their nondominant (left) arm. Previous studies of seated reaching movements showed that abrupt perturbation introduction led to transfer of learning between arms, but gradual introduction did not. Interestingly, in this study neither group showed evidence of transferring adapted control of arm or posture between arms. These results suggest primarily that adapted postural control cannot be transferred independently of arm control in this task paradigm. In other words, whole body postural movement planning related to a concurrent arm task is dependent on information about arm dynamics. Finally, we found that subjects were able to adapt to the gradual perturbation while experiencing very small errors, suggesting that both error size and consistency play a role in driving motor adaptation.NEW & NOTEWORTHY This study examined adaptation of arm and postural control to novel dynamics while standing and reaching and subsequent transfer between reaching arms. Neither arm nor postural control was transferred between arms, suggesting that postural planning is highly dependent on the concurrent arm movement.

Using metabolic energy to quantify the subjective value of physical effort.

Economists have known for centuries that to understand an individual's decisions, we must consider not only the objective value of the goal at stake, but its subjective value as well. However, achieving that goal ultimately requires expenditure of effort. Surprisingly, despite the ubiquitous role of effort in decision-making and movement, we currently do not understand how effort is subjectively valued in daily movements. Part of the difficulty arises from the lack of an objective measure of effort. Here, we use a physiological approach to address this knowledge gap. We quantified objective effort costs by measuring metabolic cost via expired gas analysis as participants performed a reaching task against increasing resistance. We then used neuroeconomic methods to quantify each individual's subjective valuation of effort. Rather than the diminishing sensitivity observed in reward valuation, effort was valued objectively, on average. This is significantly less than the near-quadratic sensitivity to effort observed previously in force-based motor tasks. Moreover, there was significant inter-individual variability with many participants undervaluing or overvaluing effort. These findings demonstrate that in contrast with monetary decisions in which subjective value exhibits diminishing marginal returns, effort costs are valued more objectively in low-effort reaching movements common in daily life.

Walking: How visual exploration informs step choice.

We rely on gaze to guide subsequent steps during walking, more so when the terrain ahead is more uncertain. New research shows that the increased visual exploration during walking as the terrain becomes more uncertain reflects our preference for accuracy over effort in step choice.

Précis of Vigor: Neuroeconomics of Movement Control.

Why do we run toward people we love, but only walk toward others? Why do people in New York seem to walk faster than other cities? Why do our eyes linger longer on things we value more? There is a link between how the brain assigns value to things, and how it controls our movements. This link is an ancient one, developed through shared neural circuits that on one hand teach us how to value things, and on the other hand control the vigor with which we move. As a result, when there is damage to systems that signal reward, like dopamine and serotonin, that damage not only affects our mood and patterns of decision-making, but how we move. In this book, we first ask why, in principle, evolution should have developed a shared system of control between valuation and vigor. We then focus on the neural basis of vigor, synthesizing results from experiments that have measured activity in various brain structures and neuromodulators, during tasks in which animals decide how patiently they should wait for reward, and how vigorously they should move to acquire it. Thus, the way we move unmasks one of our well-guarded secrets: how much we value the thing we are moving toward.

Ultrasonographic and biochemical assessments as early prediction of polycystic ovarian syndrome in obese women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as a common cause of hormonal disturbance and obesity. The diagnosis of PCOS was done by different methods including clinical signs as anovulation, hyperandrogenism, biochemical markers and ultrasounographic investigation. This study investigated comparative outcomes of ultrasonographic and biochemical markers for early prediction of PCOS in obese women. SUBJECTS AND METHODS: Seventy-five patients were clinically diagnosed with obese, PCOS and obese with PCOS and twenty-five normal age matched subjects were enrolled as control. Abdominal and transvaginal ultrasonographic for assessment of ovarian properties. In addition, BMI, serum free testosterone, dehydroepiandrosterone (DHEA), insulin, glycosylated hemoglobin (HbA1c) and LDL-c levels were evaluated. RESULT: In obese patients with PCOs (20%) ovaries revealed normal appearance in morphology while the rest (80%) showed PCOs in the form of cysts of 2-8 mm in diameter peripherally arranged around stroma. A significant elevation of free testosterone, DHEA and insulin in obese with or without PCOS compared with obese group (p<0.001). A positive correlation with hormonal abnormalities of increased HA1c, LDL-c, free testosterone, DHEA and insulin compared with obese only. CONCLUSION: According to our study findings, ovarian morphology combined with biochemical markers is more reliable for early prediction and diagnosis of PCOS for interpretation and management.

Saccade vigor and the subjective economic value of visual stimuli.

Decisions are made based on the subjective value that the brain assigns to options. However, subjective value is a mathematical construct that cannot be measured directly, but rather is inferred from choices. Recent results have demonstrated that reaction time, amplitude, and velocity of movements are modulated by reward, raising the possibility that there is a link between how the brain evaluates an option and how it controls movements toward that option. Here, we asked people to choose among risky options represented by abstract stimuli, some associated with gain (points in a game), and others with loss. From their choices we estimated the subjective value that they assigned to each stimulus. In probe trials, a single stimulus appeared at center, instructing subjects to make a saccade to a peripheral target. We found that the reaction time, peak velocity, and amplitude of the peripherally directed saccade varied roughly linearly with the subjective value that the participant had assigned to the central stimulus: reaction time was shorter, velocity was higher, and amplitude was larger for stimuli that the participant valued more. Naturally, participants differed in how much they valued a given stimulus. Remarkably, those who valued a stimulus more, as evidenced by their choices in decision trials, tended to move with shorter reaction time and greater velocity in response to that stimulus in probe trials. Overall, the reaction time of the saccade in response to a stimulus partly predicted the subjective value that the brain assigned to that stimulus.NEW & NOTEWORTHY Behavioral economics relies on subjective evaluation, an abstract quantity that cannot be measured directly but must be inferred by fitting decision models to the choice patterns. Here, we present a new approach to estimate subjective value: with nothing to fit, we show that it is possible to estimate subjective value based on movement kinematics, providing a modest ability to predict a participant's preferences without prior measurement of their choice patterns.

Role of muscle coactivation in adaptation of standing posture during arm reaching.

The ability to maintain stable, upright standing in the face of perturbations is a critical component of daily life. A common strategy for resisting perturbations and maintaining stability is muscle coactivation. Although arm muscle coactivation is often used during adaptation of seated reaching movements, little is known about postural muscle activation during concurrent adaptation of arm and standing posture to novel perturbations. In this study we investigate whether coactivation strategies are employed during adaptation of standing postural control, and how these strategies are prioritized for adaptation of standing posture and arm reaching, in two different postural stability conditions. Healthy adults practiced planar reaching movements while grasping the handle of a robotic arm and standing on a force plate; the robotic arm generated a velocity-dependent force field that created novel perturbations in the forward (more stable) or backward (less stable) direction. Surprisingly, the degree of arm and postural adaptation was not influenced by stability, with similar adaptation observed between conditions in the control of both arm movement and standing posture. We found that an early coactivation strategy can be used in postural adaptation, similar to what is observed in adaptation of arm reaching movements. However, the emergence of a coactivation strategy was dependent on perturbation direction. Despite similar adaptation in both directions, postural coactivation was largely specific to forward perturbations. Backward perturbations led to less coactivation and less modulation of postural muscle activity. These findings provide insight into how postural stability can affect prioritization of postural control objectives and movement adaptation strategies.NEW & NOTEWORTHY Muscle coactivation is a key strategy for modulating movement stability; this is centrally important in the control of standing posture. Our study investigates the little-known role of coactivation in adaptation of whole body standing postural control. We demonstrate that an early coactivation strategy can be used in postural adaptation, but muscle activation strategies may differ depending on postural stability conditions.

Asymmetric valuation of gains and losses in effort-based decision making.

Our decisions are often swayed by a desire to avoid losses over a desire to acquire gains. While loss aversion has been confirmed for decisions about money or commodities, it is unclear how individuals generally value gains relative to losses in effort-based decisions. For example, do individuals avoid greater work more than they seek out less work? We examined this question in the context of physical effort, using an arm-reaching task in which decreased effort was framed as a gain and increased effort was framed as a loss. Subjects performed reaching movements against different levels of resistance that increased or decreased the effort demands of the reaches. They then chose to accept or reject various lotteries, each with a possibility of performing less effortful reaches and a possibility of performing more effortful reaches, compared to the certain outcome of performing reaches against a fixed reference level of effort. Subjects avoided higher effort conditions more than they sought lower effort conditions, demonstrating asymmetric valuation of gains and losses. Using prospect theory, we explored various model formulations to determine subject-specific valuation of effort in these mixed gambles. A nonlinear model of effort valuation demonstrating increasing sensitivity to absolute effort best described the effort lottery choices. In contrast to the loss-aversion observed in financial decisions, there was no evidence of loss aversion in effort-based decisions. Rather, we observed moderate relief-seeking behavior. This model confirms that gains and losses are valued asymmetrically. This is due to the combined effects of increasing sensitivity to absolute effort and moderate relief-seeking, leading to a net effect of greater avoidance of higher effort. Asymmetric valuation was magnified on a later day of testing. In contrast, subjects were loss-averse in a comparable financial task. We suggest that consideration of nonlinear effort valuation can inform future studies of sensorimotor control and exercise motivation.

Movement Vigor as a Reflection of Subjective Economic Utility.

To understand subjective evaluation of an option, various disciplines have quantified the interaction between reward and effort during decision making, producing an estimate of economic utility, namely the subjective 'goodness' of an option. However, variables that affect utility of an option also influence the vigor of movements toward that option. For example, expectation of reward increases speed of saccadic eye movements, whereas expectation of effort decreases this speed. These results imply that vigor may serve as a new, real-time metric with which to quantify subjective utility, and that the control of movements may be an implicit reflection of the brain's economic evaluation of the expected outcome.

Poor estimates of motor variability are associated with longer grooved pegboard times for middle-aged and older adults.

Goal-directed movements that involve greater motor variability are performed with an increased risk that the intended goal will not be achieved. The ability to estimate motor variability during such actions varies across individuals and influences how people decide to move about their environment. The purpose of our study was to identify the decision-making strategies used by middle-aged and older adults when performing two goal-directed motor tasks and to determine if these strategies were associated with the time to complete the grooved pegboard test. Twenty-one middle-aged (48 ± 6 yr; range 40-59 yr, 15 women) and 20 older adults (73 ± 4 yr; range 65-79 yr, 8 women) performed two targeted tasks, each with two normalized target options. Decision-making characteristics were not associated with time to complete the test of manual dexterity when the analysis included all participants, but slower pegboard times were associated with measures of greater movement variability during the target-directed actions. When the data were clustered on the basis of pegboard time rather than age, relatively longer times for the faster group were associated with greater motor variability during the prescribed tasks, whereas longer times for the slower group were associated with increased risk-seeking behavior (α) and greater variability in the targeted actions. NEW & NOTEWORTHY This study was the first to examine the association between decision-making choices and an NIH Toolbox test of manual dexterity (grooved pegboard test) performed by middle-aged and older adults. Significant associations were observed between decision-making choices and time to complete the test when the analyses were based on pegboard times rather than chronological age. This result indicates that decision-making choices of middle-aged and older adults, independent of age, were associated with time to complete a test of manual dexterity.

Control of movement vigor and decision making during foraging.

During foraging, animals decide how long to stay at a patch and harvest reward, and then, they move with certain vigor to another location. How does the brain decide when to leave, and how does it determine the speed of the ensuing movement? Here, we considered the possibility that both the decision-making and the motor control problems aimed to maximize a single normative utility: the sum of all rewards acquired minus all efforts expended divided by total time. This optimization could be achieved if the brain compared a local measure of utility with its history. To test the theory, we examined behavior of people as they gazed at images: they chose how long to look at the image (harvesting information) and then moved their eyes to another image, controlling saccade speed. We varied reward via image content and effort via image eccentricity, and then, we measured how these changes affected decision making (gaze duration) and motor control (saccade speed). After a history of low rewards, people increased gaze duration and decreased saccade speed. In anticipation of future effort, they lowered saccade speed and increased gaze duration. After a history of high effort, they elevated their saccade speed and increased gaze duration. Therefore, the theory presented a principled way with which the brain may control two aspects of behavior: movement speed and harvest duration. Our experiments confirmed many (but not all) of the predictions, suggesting that harvest duration and movement speed, fundamental aspects of behavior during foraging, may be governed by a shared principle of control.