Terra incognita of the uncontrolled manifold (UCM).

The review addresses the central concept of the uncontrolled manifold (UCM) hypothesis, which has become a major framework for analysis of performance-stabilizing motor synergies. The major goals are to summarize the status quo in the field and to ask new questions stimulating new studies. We focus on a few main questions: What is the UCM? What are the likely neural origins of the UCM? How is the UCM reflected in movement patterns? Are properties of the UCM similar in all directions? We contrast experience-based features of movements seen very soon after the movement initiation vs. those based on on-line sensory feedback signals. Further, we address a number of poorly explored issues such as the differences in characteristic times of processes within the UCM and orthogonal to the UCM space, the interplay between movement stability and optimality, the origin of preferred sharing patterns of performance variables across abundant sets of elements and of their inter-trial variability, problems with the UCM-based analysis in different spaces, and likely neurophysiological mechanisms contributing to the UCM formation. In particular, we focus on the UCM in spaces of hypothetical neural control variables, which we associate with the reciprocal and coactivation commands to the effectors. Analysis of performance-stabilizing synergies within the UCM framework in abundant spaces of kinetic, kinematic and electromyographic variables at the selected level of analysis may be practically useful. However, mapping findings in such studies onto neural control mechanisms has been challenging.

Two classes of action-stabilizing synergies reflecting spinal and supraspinal circuitry.

We explored force-stabilizing synergies during accurate four-finger constant force production tasks in spaces of finger modes (commands to fingers computed to account for the finger interdependence) and of motor unit (MU) firing frequencies. The main specific hypothesis was that the multifinger synergies would disappear during unintentional force drifts without visual feedback on the force magnitude, whereas MU-based synergies would be robust to such drifts. Healthy participants performed four-finger accurate cyclical force production trials followed by trials of constant force production. Individual MUs were identified in the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). Principal component analysis was applied to motor unit frequencies to identify robust MU groups (MU-modes) with parallel scaling of the firing frequencies in FDS, in EDC, and the combined MUs of FDS + EDC. The framework of the uncontrolled manifold hypothesis was used to quantify force-stabilizing synergies when visual feedback on the force magnitude was available and 15 s after turning the visual feedback off. Removing visual feedback led to a force drift toward lower magnitudes, accompanied by the disappearance of multifinger synergies. In contrast, MU-mode synergies were minimally affected by removing visual feedback off and continued to be robust for the FDS and for the EDC, while being absent for the (FDS + EDC) analysis. We interpret the findings within the theory of hierarchical control of action with spatial referent coordinates. The qualitatively different behavior of the multifinger and MU-mode-based synergies likely reflects the difference in the involved neural circuitry, supraspinal for the former and spinal for the latter.NEW & NOTEWORTHY Two types of synergies, in the space of commands to individual fingers and in the space of motor unit groups, show qualitatively different behaviors during accurate multifinger force-production tasks. After removing visual feedback, finger force synergies disappear, whereas motor unit-based synergies persist. These results point at different neural circuitry involved in these two basic classes of synergies: supraspinal for multieffector synergies, and spinal for motor unit-based synergies.

Two aspects of feed-forward control of action stability: effects of action speed and unexpected events.

We explored two types of anticipatory synergy adjustments (ASA) during accurate four-finger total force production task. The first type is a change in the index of force-stabilizing synergy during a steady state when a person is expecting a signal to produce a quick force change, which is seen even when the signal does not come (steady-state ASA). The other type is the drop in in the synergy index prior to a planned force change starting at a known time (transient ASA). The subjects performed a task of steady force production at 10% of maximal voluntary contraction (MVC) followed by a ramp to 20% MVC over 1 s, 3 s, and as a step function (0 s). In another task, in 50% of the trials during the steady-state phase, an unexpected signal could come requiring a quick force pulse to 20% MVC (0-surprise). Inter-trial variance in the finger force space was used to quantify the index of force-stabilizing synergy within the uncontrolled manifold hypothesis. We observed significantly lower synergy index values during the steady state in the 0-ramp trials compared to the 1-ramp and 3-ramp trials. There was also larger transient ASA during the 0-ramp trials. In the 0-surprise condition, the synergy index was significantly higher compared to the 0-ramp condition whereas the transient ASA was significantly larger. The finding of transient ASA scaling is of importance for clinical studies, which commonly involve populations with slower actions, which can by itself be associated with smaller ASAs. The participants varied the sharing pattern of total force across the fingers more in the task with "surprises". This was coupled to more attention to precision of performance, i.e., inter-trial deviations from the target as reflected in smaller variance affecting total force, possibly reflecting higher concentration on the task, which the participants perceived as more challenging compared to a similar task without surprise targets.

Force matching: motor effects that are not reported by the actor.

We explored unintentional drifts of finger forces during force production and matching task. Based on earlier studies, we predicted that force matching with the other hand would reduce or stop the force drift in instructed fingers while uninstructed (enslaved) fingers remain unaffected. Twelve young, healthy, right-handed participants performed two types of tasks with both hands (task hand and match hand). The task hand produced constant force at 20% of MVC level with the Index and Ring fingers pressing in parallel on strain gauge force sensors. The Middle finger force wasn't instructed, and its enslaved force was recorded. Visual feedback on the total force by the instructed fingers was either present throughout the trial or only during the first 5 s (no-feedback condition). The other hand matched the perceived force level of the task hand starting at either 4, 8, or 15 s from the trial initiation. No feedback was ever provided for the match hand force. After the visual feedback was removed, the task hand showed a consistent drift to lower magnitudes of total force. Contrary to our prediction, over all conditions, force matching caused a brief acceleration of force drift in the task hand, which then reached a plateau. There was no effect of matching on drifts in enslaved finger force. We interpret the force drifts within the theory of control with spatial referent coordinates as consequences of drifts in the command (referent coordinate) to the antagonist muscles. This command is not adequately incorporated into force perception.

The control and perception of antagonist muscle action.

The review covers a range of topics related to the role of the antagonist muscles in agonist-antagonist pairs within the theory of the neural control of movements with spatial referent coordinates, the principle of abundance, and the uncontrolled manifold hypothesis. It starts with the mechanical role of the antagonist in stopping movements and providing necessary levels of effector mechanical characteristics for fast movements. Further, it discusses the role of antagonist muscle activation bursts during voluntary movements, force production, and postural tasks. Recent studies show that agonist and antagonist motor units are united into common groups related to two basic commands, reciprocal and coactivation. A number of phenomena are considered including intra-muscle synergies stabilizing net force production, unintentional force drifts during isometric force production, effects of voluntary muscle coactivation on force production and perception, and perceptual errors caused by various factors including lack of visual feedback and muscle vibration. Taken together, the findings suggest inherent instability of neural commands (time functions of the stretch reflex threshold) to antagonist muscles requiring visual information for accurate performance. They also suggest that neural commands to antagonist muscles are not readily incorporated into kinesthetic perception leading to illusions and errors in matching tasks.

Unintentional drifts in performance during one-hand and two-hand finger force production.

We explored the phenomena of force drifts and unintentional finger force production (enslaving), and their dependence on visual feedback. Predictions have been drawn based on the theory of control with spatial referent coordinates for condition with feedback on instructed (master) finger force, enslaved finger force, and total force for one-hand and two-hand tasks. Subjects produced force under the different feedback conditions without their knowledge. No feedback condition was also used for the one-hand tasks. Overall, feedback of master finger force led to an increase in the enslaved force, feedback on the slave finger force led to a drop in the master force, feedback on the total force led to balanced drifts in the master force down and enslaved force up, and under the no-feedback condition, master and total force drifted down with large variability in the enslaved force drifts. The patterns were the same in both hands in the two-hand tasks when feedback was provided on the forces of one hand only (without subject's knowledge). The index of enslaving always drifted toward higher values. We interpret the findings as reflecting three main factors: drifts in the referent coordinates toward actual finger coordinates, spread of cortical excitation over representations of the fingers, and robust sharing of referent coordinates between the two hands in bimanual tasks. The large consistent drifts in enslaving toward higher values have to be considered in studies of multi-finger synergies.

Unintentional force drifts in the lower extremities.

We explored the phenomenon of unintentional force drift seen in the absence of visual feedback during knee extension contractions in isometric conditions. Based on the importance of knee extensors for the anti-gravity function, we hypothesized that such force drifts would be slower and smaller compared to those reported for the upper extremities. We also explored possible effects of foot dominance and gender on the force drifts. Young healthy persons produced isometric knee extension contractions to different levels, ranging from 15 to 25% of maximal voluntary contraction force, with the help of visual feedback, and then, the visual feedback was turned off. Force change over the time interval without visual feedback was quantified. In the absence of visual feedback, force drifted to smaller magnitudes. The drift magnitude expressed in percent of the initial force magnitude was smaller for smaller initial force levels, ranging between 8 and 15% of the initial force for the initial force magnitude of 15% and 25% of maximal voluntary contraction force. The time exponent of the force drift was independent of the initial force magnitude and was, on average, 6.45 s. There were no significant effects of foot dominance or gender, although the male subjects tended to show stronger scaling of the drift magnitude with the initial force level compared to the female subjects. The results show that unintentional force drift is a common phenomenon across limbs and muscle groups. This conclusion fits the theory of control with spatial referent coordinates and the general tendency of all natural systems to drift to states with lower potential energy.

Postural adjustments to self-triggered perturbations under conditions of changes in body orientation.

We studied anticipatory and compensatory postural adjustments (APAs and CPAs) associated with self-triggered postural perturbations in conditions with changes in the initial body orientation. In particular, we were testing hypotheses on adjustments in the reciprocal and coactivation commands, role of proximal vs. distal muscles, and correlations between changes in indices of APAs and CPAs. Healthy young participants stood on a board with full support or reduced support area and held a standard load in the extended arms. They released the load in a self-paced manned with a standard small-amplitude arm movement. Electromyograms of 12 muscles were recorded and used to compute reciprocal and coactivation indices between three muscle pairs on both sides of the body. The subject's body was oriented toward one of three targets: straight ahead, 60° to the left, and 60° to the right. Body orientation has stronger effects on proximal muscle pairs compared to distal muscles. It led to more consistent changes in the reciprocal command compared to the coactivation command. Indices of APAs and CPAs showed positive correlations across conditions. We conclude that the earlier suggested hierarchical relations between the reciprocal and coactivation command could be task-specific. Predominance of negative or positive correlations between APA and CPA indices could also be task-specific.

Motor unit-based synergies in a non-compartmentalized muscle.

The concept of synergies has been used to address the grouping of motor elements contributing to a task with the covariation of these elements reflecting task stability. This concept has recently been extended to groups of motor units with parallel scaling of the firing frequencies with possible contributions of intermittent recruitment (MU-modes) in compartmentalized flexor and extensor muscles of the forearm stabilizing force magnitude in finger pressing tasks. Here, we directly test for the presence and behavior of MU-modes in the tibialis anterior, a non-compartmentalized muscle. Ten participants performed an isometric cyclical dorsiflexion force production task at 1 Hz between 20 and 40% of maximal voluntary contraction and electromyographic (EMG) data were collected from two high-density wireless sensors placed on the skin over the right tibialis anterior. EMG data were decomposed into individual motor unit frequencies and resolved into sets of MU-modes. Inter-cycle analysis of MU-mode magnitudes within the framework of the uncontrolled manifold (UCM) hypothesis was used to quantify force-stabilizing synergies. Two or three MU-modes were identified in all participants and trials accounting, on average, for 69% of variance and were robust to cross-validation measurements. Strong dorsiflexion force-stabilizing synergies in the space of MU-modes were present in all participants and for both electrode locations as reflected in variance within the UCM (median 954, IQR 511-1924) exceeding variance orthogonal to the UCM (median 5.82, IQR 2.9-17.4) by two orders of magnitude. In contrast, MU-mode-stabilizing synergies in the space of motor unit frequencies were not present. This study offers strong evidence for the existence of synergic control mechanisms at the level of motor units independent of muscle compartmentalization, likely organized within spinal cord circuitry.

The legacy of Gerald L. Gottlieb in human movement neuroscience.

In this paper, we review the legacy of Gerald (Gerry) Gottlieb in various fields related to the neural control of human movement. His studies on the myotatic (stretch) reflex and postmyotatic responses to ankle joint perturbations paved the way for current explorations of long-loop reflexes and their role in the control of movement. The dual-strategy hypothesis introduced order into a large body of literature on the triphasic muscle activation patterns seen over a variety of voluntary movements in healthy persons. The dual-strategy hypothesis continues to be important for understanding the performance of subjects with disordered motor control. The principle of linear synergy (covariance of joint torques) was an attempt to solve one of the notorious problems of motor redundancy, which remains an important topic in the field. Gerry's attitude toward the equilibrium-point hypothesis varied between rejection and using it to explore patterns of hypothetical control variables and movement variability. The discovery of reciprocal excitation in healthy neonates fostered other studies of changes in spinal cord physiology as motor skills develop. In addition, studies of people with spasticity and the effects of treatment with intrathecal baclofen were crucial in demonstrating the possibility of unmasking voluntary movements after suppression of the hyperreflexia of spasticity. Gerry Gottlieb contributed a significant body of knowledge that formed a solid foundation from which to study a variety of neurological diseases and their treatments, and a more comprehensive and parsimonious foundation to describe the neural control of human movement.

Unintentional force drifts across the human fingers: implications for the neural control of finger tasks.

We explored the unintentional force drift across the four fingers of the dominant hand during accurate force production in isometric conditions caused by turning the visual feedback on force off. Our hypotheses were that the Index finger would show smallest drifts and best ability to eliminate the drifts with knowledge of performance in previous trials. Young healthy subjects produced force at 20% of the maximal force level by one finger at a time. There was no significant difference among the fingers in the root mean square error of force during performance with visual feedback. Turning visual feedback off caused force drift to lower magnitudes. The magnitude of force drift was the largest during tasks performed by the Index finger. After each block of twelve trials, the subjects were given feedback on the drift magnitude in that block and used it to correct performance in future trials. There was a total of six blocks. The magnitude of drift correction between consecutive blocks correlated with the magnitude of drift in the earlier block only after the second and fourth blocks. The Index finger failed to improve its performance more than other fingers and demonstrated significant residual drifts to lower force magnitudes in the sixth block of trials. These findings falsified both our hypotheses. Taken together with earlier studies showing advantage of the Index finger across a variety of tasks that require quick and accurate changes in performance, our results suggest that effector specialization along the stability-agility continuum is not limited to the phenomenon of cortical arm/hand dominance but can also be seen across fingers of a hand controlled by the same hemisphere, possibly reflecting the differences in the finger role in prehensile tasks.

Reciprocal and coactivation commands at the level of individual motor units in an extrinsic finger flexor-extensor muscle pair.

We explored the synergic organization of motor units in extrinsic finger muscles, flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC). Healthy subjects produced accurate cyclical force by pressing with the middle phalanges of one of the three fingers (Index, Middle, and Ring) and all three together. Two wireless sensor arrays were used to record and identify motor unit action potentials in FDS and EDC. Stable motor unit groups were identified within each muscle and across both muscles. Analysis of motor units combined over the two muscles showed one of the first two motor unit groups with consistently opposite signs of the loading factors for the FDS and EDC motor units, and the other group with consistently same signs of the loading factors for the two muscles. We interpret the two motor unit groups as reflections of the reciprocal and co-activation commands within the theory of control with spatial referent coordinates. Force changes within the cycle were primarily associated with the modulation of the co-activation motor unit group. Analysis of inter-cycle variance within the spaces of motor unit groups defined for FDS and EDC separately showed force-stabilizing synergies across both single-finger and three-finger tasks. In contrast, analysis within the motor unit groups defined across both muscles failed to show force-stabilizing synergies. We interpret these results as a reflection of the trade-off across levels within a hierarchical control system.

Synergic control of a single muscle: The example of flexor digitorum superficialis.

KEY POINTS: We used the idea of synergic control and the framework of the uncontrolled manifold hypothesis to explore the synergic control of a single muscle. Individual motor units in flexor digitorum superficialis formed two-three groups (MU-modes) with parallel changes in firing frequency, robust over force-up and force-down segments. There were strong force-stabilizing synergies in the MU-mode space during accurate cyclical force production. The results show, for the first time, that the idea of synergic control is applicable to individual muscles. The results suggest that segmental spinal mechanisms, such as recurrent inhibition and stretch reflex, probably play a major role in the synergic control of action. ABSTRACT: In the present study, for the first time, we have used the idea of synergic control and the framework of the uncontrolled manifold (UCM) hypothesis to test two hypotheses: (i) individual motor units are organized into stable groups (MU-modes) with parallel scaling of firing rates with changes in the muscle force, and (ii) the gains of MU-mode involvement co-vary to stabilize the desired force magnitude. Young healthy subjects performed accurate cyclical force tracing tasks at 1 Hz by pressing with intermediate phalanges; only one finger was instructed to produce force at a time. Surface electromyographic signal from flexor digitorum superficialis was recorded and used to identify individual motor units and their firing frequencies. Principal component analysis with rotation and factor extraction was used to identify MU-modes, which showed similar compositions over the force-up and force-down task segments. Inter-cycle variance analysis in the MU-mode space confirmed the existence of strong synergies stabilizing finger force. There were no synergies stabilizing MU-mode magnitude in the space of individual motor units. This is the first application of the UCM framework to the neural control of a single muscle. It extends the applicability of this approach to analysis of individual muscles. We discuss the importance of the findings for the idea of hierarchical control and the notion of muscle compartments. The results suggest that segmental spinal mechanisms, such as recurrent inhibition and stretch reflex, probably play a major role in the synergic control of action.

Efference copy in kinesthetic perception: a copy of what is it?

A number of notions in the fields of motor control and kinesthetic perception have been used without clear definitions. In this review, we consider definitions for efference copy, percept, and sense of effort based on recent studies within the physical approach, which assumes that the neural control of movement is based on principles of parametric control and involves defining time-varying profiles of spatial referent coordinates for the effectors. The apparent redundancy in both motor and perceptual processes is reconsidered based on the principle of abundance. Abundance of efferent and afferent signals is viewed as the means of stabilizing both salient action characteristics and salient percepts formalized as stable manifolds in high-dimensional spaces of relevant elemental variables. This theoretical scheme has led recently to a number of novel predictions and findings. These include, in particular, lower accuracy in perception of variables produced by elements involved in a multielement task compared with the same elements in single-element tasks, dissociation between motor and perceptual effects of muscle coactivation, force illusions induced by muscle vibration, and errors in perception of unintentional drifts in performance. Taken together, these results suggest that participation of efferent signals in perception frequently involves distorted copies of actual neural commands, particularly those to antagonist muscles. Sense of effort is associated with such distorted efferent signals. Distortions in efference copy happen spontaneously and can also be caused by changes in sensory signals, e.g., those produced by muscle vibration.

One more time about motor (and non-motor) synergies.

We revisit the concept of synergy based on the recently translated classical book by Nikolai Bernstein (On the construction of movements, Medgiz, Moscow 1947; Latash, Bernstein's Construction of Movements, Routledge, Abingdon 2020b) and progress in understanding the physics and neurophysiology of biological action. Two aspects of synergies are described: organizing elements into stable groups (modes) and ensuring dynamical stability of salient performance variables. The ability of the central nervous system to attenuate synergies in preparation for a quick action-anticipatory synergy adjustments-is emphasized. Recent studies have demonstrated synergies at the level of hypothetical control variables associated with spatial referent coordinates for effectors. Overall, the concept of synergies fits naturally the hierarchical scheme of control with referent coordinates with an important role played by back-coupling loops within the central nervous system and from peripheral sensory endings. Further, we review studies showing non-trivial changes in synergies with development, aging, fatigue, practice, and a variety of neurological disorders. Two aspects of impaired synergic control-impaired stability and impaired agility-are introduced. The recent generalization of the concept of synergies for non-motor domains, including perception, is discussed. We end the review with a list of unresolved and troubling issues.

Synergies at the level of motor units in single-finger and multi-finger tasks.

We explored the organization of motor units recorded in the flexor digitorum superficialis into stable groups (MU-modes) and force-stabilizing synergies in spaces of MU-modes. Young, healthy participants performed one-finger and three-finger accurate cyclical force production tasks. Two wireless sensor arrays (Trigno Galileo, Delsys, Inc.) were placed over the proximal and distal portions of the muscle for surface recording and identification of motor unit action potentials. Principal component analysis with Varimax rotation and factor extraction was used to identify MU-modes. The framework of the uncontrolled manifold hypothesis was used to analyze inter-cycle variance in the space of MU-modes and compute the index of force-stabilizing synergy. Multiple linear regression between the first MU-mode in the three-finger task and the first MU-modes in the three single-finger tasks showed no differences between the data recorded by the two electrodes suggesting that MU-modes were unlikely to be synonymous with muscle compartments. Multi-MU-mode synergies stabilizing task force were documented across all tasks. In contrast, there were no force-stabilizing synergies in the three-finger task analyzed in the space of individual finger forces. Our results confirm the synergic organization of motor units in single-finger tasks and, for the first time, expand this result to multi-finger tasks. We offer an interpretation of the findings within the theoretical scheme of control with spatial referent coordinates expanded to the analysis of individual motor units. The results confirm trade-offs between synergies at different hierarchical levels and expand this notion to intra-muscle synergies.

Perturbation-induced fast drifts in finger enslaving.

We explored changes in finger forces and in an index of unintentional finger force production (enslaving) under a variety of visual feedback conditions and positional finger perturbations. In particular, we tested a hypothesis that enslaving would show a consistent increase with time at characteristic times of about 1-2 s. Young healthy subjects performed accurate force production tasks under visual feedback on the total force of the instructed fingers (index and ring) or enslaved fingers (middle and little). Finger feedback was covertly alternated between master and enslaved fingers in a random fashion. The feedback could be presented over the first 5 s of the trial only or over the whole trial duration (21 s). After 5 s, the fingers were lifted by 1 cm, and after 15 s, the fingers were lowered to the initial position. The force of the instructed fingers drifted toward lower magnitudes in all conditions except the one with continuous feedback on that force. The force of enslaved fingers showed variable behavior across conditions. In all conditions, the index of enslaving showed a consistent increase with the time constant varying between 1 and 3 s. We interpret the results as pointing at the spread of excitation to enslaved fingers (possibly, in the cortical M1 areas). The relatively fast changes in enslaving under positional finger perturbations suggest that quick changes of the input into M1 from pre-M1 areas can accelerate the hypothesized spread of cortical excitation.

On the origin of finger enslaving: control with referent coordinates and effects of visual feedback.

When a person tries to press with a finger, other fingers of the hand produce force unintentionally. We explored this phenomenon of enslaving during unintentional force drifts in the course of continuous force production by pairs of fingers of a hand. Healthy subjects performed accurate force production tasks by finger pairs Index-Middle, Middle-Ring, and Ring-Little with continuous visual feedback on the combined force of the instructed (master) fingers or of the noninstructed (enslaved) fingers. The feedback scale was adjusted to ensure that the subjects did not know the difference between these two, randomly presented, conditions. Across all finger pairs, enslaved force showed a drift upward under feedback on the master finger force, and master force showed a drift downward under feedback on the enslaved finger force. The subjects were unaware of the force drifts, which could reach over 50% of the initial force magnitude over 15 s. Across all conditions, the index of enslaving increased by ∼50% over the trial duration. The initial moment of force magnitude in pronation-supination was not a consistent predictor of the force drift magnitude. These results falsify the hypothesis that the counter-directional force drifts reflected drifts in the moment of force. They suggest that during continuous force production, enslaving increases with time, possibly due to the spread of excitation over cortical finger representations or other mechanisms, such as increased synchronization of firing of α-motoneurons innervating different compartments of extrinsic flexors. These changes in enslaving, interpreted at the level of control with referent coordinates for the fingers, can contribute to a variety of phenomena, including unintentional force drifts.NEW & NOTEWORTHY We report a consistent slow increase in finger enslaving (force production by noninstructed fingers) when visual feedback was presented on the force produced by either two instructed fingers or two noninstructed fingers of the hand. In contrast, force drifts could be in opposite directions depending on the visual feedback. We interpret enslaving and its drifts at the level of control with referent coordinates for the involved muscles, possibly reflecting spread of cortical excitation.

What do people match when they try to match force? Analysis at the level of hypothetical control variables.

We used the theory of control with spatial referent coordinates (RC) to explore how young, healthy persons modify finger pressing force and match forces between the two hands. Three specific hypotheses were tested related to patterns of RC and apparent stiffness (defined as the slope of force-coordinate relation) used in the presence of visual feedback on the force and in its absence. The subjects used the right hand to produce accurate force under visual feedback; further the force could be increased or decreased, intentionally or unintentionally (induced by controlled lifting or lowering of the fingertips). The left hand was used to match force without visual feedback before and after the force change; the match hand consistently underestimated the actual force change in the task hand. The "inverse piano" device was used to compute RC and apparent stiffness. We found very high coefficients of determination for the inter-trial hyperbolic regressions between RC and apparent stiffness in the presence of visual feedback; the coefficients of determination dropped significantly without visual feedback. There were consistent preferred sharing patterns in the space of RC and apparent stiffness between the task and match hands across subjects. In contrast, there was much less consistency between the task and match hands in the magnitudes of RC and apparent stiffness observed in individual trials. Compared to the task hand, the match hand showed consistently lower magnitudes of apparent stiffness and, correspondingly, larger absolute magnitudes of RC. Involuntary force changes produced by lifting and lowering the force sensors led to significantly lower force changes compared to what could be expected based on the computed values of apparent stiffness and sensor movement amplitude. The results confirm the importance of visual feedback for stabilization of force in the space of hypothetical control variables. They suggest the existence of personal traits reflected in preferred ranges of RC and apparent stiffness across the two hands. They also show that subjects react to external perturbations, even when instructed "not to interfere": Such perturbations cause unintentional and unperceived drifts in both RC and apparent stiffness.

Synergic control of action in levodopa-naïve Parkinson's disease patients: II. Multi-muscle synergies stabilizing vertical posture.

Postural instability is a major disabling feature in Parkinson's disease (PD). We quantified the organization of leg and trunk muscles into synergies stabilizing the center of pressure (COP) coordinate within the uncontrolled manifold hypothesis in levodopa-naïve patients with PD and age-matched control subjects. The main hypothesis was that changes in the synergic control of posture are present early in the PD process even before levodopa exposure. Eleven levodopa-naïve patients with PD and 11 healthy controls performed whole-body cyclical voluntary sway tasks and a self-initiated load-release task during standing on a force plate. Surface electromyographic activity in 13 muscles on the right side of the body was analyzed to identify muscle groups with parallel scaling of activation levels (M-modes). Data were collected both before ("off-drug") and approximately 60 min after the first dose of 25/100 carbidopa/levodopa ("on-drug"). COP-stabilizing synergies were quantified for the load-release task. Levodopa-naïve patients with PD showed no COP-stabilizing synergy "off-drug", whereas controls showed posture-stabilizing multi-M-mode synergy. "On-drug", patients with PD demonstrated a significant increase in the synergy index. There were no significant drug effects on the M-mode composition, anticipatory postural adjustments, indices of motor equivalence, or indices of COP variability. The results suggest that levodopa-naïve patients with PD already show impaired posture-stabilizing multi-muscle synergies that may be used as promising behavioral biomarkers for emerging postural disorders in PD. Moreover, levodopa modified synergy metrics differently in these levodopa-naïve patients compared to a previous study of patients on chronic antiparkinsonian medications (Falaki et al. in J Electromyogr Kinesiol 33:20-26, 2017a), suggesting different neurocircuitry involvement.