Three Levels of Neural Control Contributing to Performance-stabilizing Synergies in Multi-finger Tasks.

We tested a hypothesis on force-stabilizing synergies during four-finger accurate force production at three levels: (1) The level of the reciprocal and coactivation commands, estimated as the referent coordinate and apparent stiffness of all four fingers combined; (2) The level of individual finger forces; and (3) The level of firing of individual motor units (MU). Young, healthy participants performed accurate four-finger force production at a comfortable, non-fatiguing level under visual feedback on the total force magnitude. Mechanical reflections of the reciprocal and coactivation commands were estimated using small, smooth finger perturbations applied by the "inverse piano" device. Firing frequencies of motor units in the flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) were estimated using surface recording. Principal component analysis was used to identify robust MU groups (MU-modes) with parallel changes in the firing frequency. The framework of the uncontrolled manifold hypothesis was used to compute synergy indices in the spaces of referent coordinate and apparent stiffness, finger forces, and MU-mode magnitudes. Force-stabilizing synergies were seen at all three levels. They were present in the MU-mode spaces defined for MUs in FDS, in EDC, and pooled over both muscles. No effects of hand dominance were seen. The synergy indices defined at different levels of analysis showed no correlations across the participants. The findings are interpreted within the theory of control with spatial referent coordinates for the effectors. We conclude that force stabilization gets contributions from three levels of neural control, likely associated with cortical, subcortical, and spinal circuitry.

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 Role of Imitation, Primitives, and Spatial Referent Coordinates in Motor Control: Implications for Writing and Reading.

We review a body of literature related to the drawing and recognition of geometrical two-dimensional linear drawings including letters. Handwritten letters are viewed not as two-dimensional geometrical objects but as one-dimensional trajectories of the tip of the implement. Handwritten letters are viewed as composed of a small set of kinematic primitives. Recognition of objects is mediated by processes of their creation (actual or imagined)-the imitation principle, a particular example of action-perception coupling. The concept of spatial directional field guiding the trajectories is introduced and linked to neuronal population vectors. Further, we link the kinematic description to the theory of control with spatial referent coordinates. This framework allows interpreting a number of experimental observations and clinical cases of agnosia. It also allows formulating predictions for new experimental studies of writing.

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.

Effects of fatigue on intramuscle force-stabilizing synergies.

We applied the recently introduced concept of intramuscle synergies in spaces of motor units (MUs) to quantify indexes of such synergies in the tibialis anterior during ankle dorsiflexion force production tasks and their changes with fatigue. We hypothesized that MUs would be organized into robust groups (MU modes), which would covary across trials to stabilize force magnitude, and the indexes of such synergies would drop under fatigue. Healthy, young subjects (n = 15; 8 females) produced cyclical, isometric dorsiflexion forces while surface electromyography was used to identify action potentials of individual MUs. Principal component analysis was used to define MU modes. The framework of the uncontrolled manifold (UCM) was used to analyze intercycle variance and compute the synergy index, ΔVZ. Cyclical force production tasks were repeated after a nonfatiguing exercise (control) and a fatiguing exercise. Across subjects, fatigue led, on average, to a 43% drop in maximal force and fewer identified MUs per subject (29.6 ± 2.1 vs. 32.4 ± 2.1). The first two MU modes accounted for 81.2 ± 0.08% of variance across conditions. Force-stabilizing synergies were present across all conditions and were diminished after fatiguing exercise (1.49 ± 0.40) but not control exercise (1.76 ± 0.75). Decreased stability after fatigue was caused by an increase in the amount of variance orthogonal to the UCM. These findings contrast with earlier studies of multieffector synergies demonstrating increased synergy index under fatigue. We interpret the results as reflections of a drop in the gain of spinal reflex loops under fatigue. The findings corroborate an earlier hypothesis on the spinal nature of intramuscle synergies.NEW & NOTEWORTHY Across multielement force production tasks, fatigue of an element leads to increased indexes of force stability (synergy indexes). Here, however, we show that groups of motor units in the tibialis anterior show decreased indexes of force-stabilizing synergies after fatiguing exercise. These findings align intramuscle synergies with spinal mechanisms, in contrast to the supraspinal control of multimuscle synergies.

Multi-muscle synergies in preparation for gait initiation in Parkinson's disease.

OBJECTIVE: We investigated changes in indices of muscle synergies prior to gait initiation and the effects of gaze shift in patients with Parkinson's disease (PD). A long-term objective of the study is to develop a method for quantitative assessment of gait-initiation problems in PD. METHODS: PD patients without clinical signs of postural instability and two control groups (age-matched and young) performed a gait initiation task in a self-paced manner, with and without a quick prior gaze shift produced by turning the head. Muscle groups with parallel scaling of activation levels (muscle modes) were identified as factors in the muscle activation space. Synergy index stabilizing center of pressure trajectory in the anterior-posterior and medio-lateral directions (indices of stability) was quantified in the muscle mode space. A drop in the synergy index in preparation to gait initiation (anticipatory synergy adjustment, ASA) was quantified. RESULTS: Compared to the control groups, PD patients showed significantly smaller synergy indices and ASA for both directions of the center of pressure shift. Both PD and age-matched controls, but not younger controls, showed detrimental effects of the prior gaze shift on the ASA indices. CONCLUSIONS: PD patients without clinically significant posture or gait disorders show impaired stability of the center of pressure and its diminished adjustment during gait initiation. SIGNIFICANCE: The indices of stability and ASA may be useful to monitor pre-clinical gait disorders, and lower ASA may be relevant to emergence of freezing of gait in PD.

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.

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.

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.

Optimality, Stability, and Agility of Human Movement: New Optimality Criterion and Trade-Offs.

This review of movement stability, optimality, and agility is based on the theory of motor control with changes in spatial referent coordinates for the effectors, the principle of abundance, and the uncontrolled manifold hypothesis. A new optimality principle is suggested based on the concept of optimal sharing corresponding to a vector in the space of elemental variables locally orthogonal to the uncontrolled manifold. Motion along this direction is associated with minimal components along the relatively unstable directions within the uncontrolled manifold leading to a minimal motor equivalent motion. For well-practiced actions, this task-specific criterion is followed in spaces of referent coordinates. Consequences of the suggested framework include trade-offs among stability, optimality, and agility, unintentional changes in performance, hand dominance, finger specialization, individual traits in performance, and movement disorders in neurological patients.

Intramuscle Synergies: Their Place in the Neural Control Hierarchy.

We accept a definition of synergy introduced by Nikolai Bernstein and develop it for various actions, from those involving the whole body to those involving a single muscle. Furthermore, we use two major theoretical developments in the field of motor control-the idea of hierarchical control with spatial referent coordinates and the uncontrolled manifold hypothesis-to discuss recent studies of synergies within spaces of individual motor units (MUs) recorded within a single muscle. During the accurate finger force production tasks, MUs within hand extrinsic muscles form robust groups, with parallel scaling of the firing frequencies. The loading factors at individual MUs within each of the two main groups link them to the reciprocal and coactivation commands. Furthermore, groups are recruited in a task-specific way with gains that covary to stabilize muscle force. Such force-stabilizing synergies are seen in MUs recorded in the agonist and antagonist muscles but not in the spaces of MUs combined over the two muscles. These observations reflect inherent trade-offs between synergies at different levels of a control hierarchy. MU-based synergies do not show effects of hand dominance, whereas such effects are seen in multifinger synergies. Involuntary, reflex-based, force changes are stabilized by intramuscle synergies but not by multifinger synergies. These observations suggest that multifinger (multimuscle synergies) are based primarily on supraspinal circuitry, whereas intramuscle synergies reflect spinal circuitry. Studies of intra- and multimuscle synergies promise a powerful tool for exploring changes in spinal and supraspinal circuitry across patient populations.

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.

Intra-muscle Synergies Stabilizing Reflex-mediated Force Changes.

We used the framework of the uncontrolled manifold hypothesis to explore force-stabilizing synergies and motor equivalence in the spaces of individual motor unit (MU) firing frequencies. Healthy subjects performed steady force production tasks by pressing with one finger or three fingers of a hand. Surface EMG was used to identify individual MU action potentials. MUs formed stable groups (MU-modes) with parallel scaling of the firing frequency in both flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC) that allowed identifying them with the reciprocal and coactivation commands. Smooth lifting of the fingers by an "inverse piano" device led to an unintentional, reflex-based force increase. There was significantly larger motion in the space of MU-modes that kept the force unchanged (motor equivalent) compared to motion that changed force (non-motor equivalent). The force change was stabilized by co-varying contributions of the MU-modes defined separately for FDS and EDC. In contrast, analysis of the three-finger task in the space of individual finger forces showed no synergies stabilizing total force change. Effects of hand dominance were seen on multi-finger synergies but not intra-muscle synergies. We conclude that spinal mechanisms, such as recurrent inhibition and reflex loops from proprioceptors, contribute significantly to intra-muscle synergies, while multi-finger synergies reflect supra-spinal processes. These results provide methods to explore the contributions of spinal vs supraspinal circuitry to changed motor synergies in populations with a variety of neurological disorders.

Synergic control in asymptomatic welders during multi-finger force exertion and load releasing while standing.

Motor synergies, i.e., neural mechanisms that organize multiple motor elements to ensure stability of actions, are affected by several neurological condition. Asymptomatic welders showed impaired synergy controlling the stability of multi-finger action compared to non-welders and this impairment was associated with microstructural damage in the globus pallidus. We further explored the effect of welding-related metal exposure on multi-finger synergy and extended our investigation to posture-stabilizing synergy during a standing task. Occupational, MRI, and performance-stabilizing synergies during multi-finger accurate force production and load releasing while standing were obtained from 29 welders and 19 age- and sex-matched controls. R2* and R1 relaxation rate values were used to estimate brain iron and manganese content, respectively, and diffusion tensor imaging was used to reflect brain microstructural integrity. Associations of brain MRI (caudate, putamen, globus pallidus, and red nucleus), and motor synergy were explored by group status. The results revealed that welders had higher R2* values in the caudate (p = 0.03), putamen (p = 0.01), and red nucleus (p = 0.08, trend) than controls. No group effect was revealed on multi-finger synergy index during steady-state phase of action (ΔVZss). Compared to controls, welders exhibited lower ΔVZss (-0.106 ± 0.084 vs. 0.160 ± 0.092, p = 0.04) and variance that did not affect the performance variable (VUCM, 0.022 ± 0.003 vs. 0.038 ± 0.007, p = 0.03) in the load releasing, postural task. The postural synergy index, ΔVZss, was associated negatively with higher R2* in the red nucleus in welders (r = -0.44, p = 0.03), but not in controls. These results suggest that the synergy index in the load releasing during a standing task may reflect welding-related neurotoxicity in workers with chronic metals exposure. This finding may have important clinical and occupational health implications.

Synergies Stabilizing Vertical Posture in Spaces of Control Variables.

In this study, we address the question: Can the central nervous system stabilize vertical posture in the abundant space of neural commands? We assume that the control of vertical posture is associated with setting spatial referent coordinates (RC) for the involved muscle groups, which translates into two basic commands, reciprocal and co-activation. We explored whether the two commands co-varied across trials to stabilize the initial postural state. Young, healthy participants stood quietly against an external horizontal load and were exposed to smooth unloading episodes. Linear regression between horizontal force and center of mass coordinate during the unloading phase was computed to define the intercept (RC) and slope (apparent stiffness, k). Hyperbolic regression between the intercept and slope across unloading episodes and randomization analysis both demonstrated high indexes of co-variation stabilizing horizontal force in the initial state. Higher co-variation indexes were associated with lower average k values across the participants suggesting destabilizing effects of muscle coactivation. Analysis of deviations in the {RC; k} space keeping the posture unchanged (motor equivalent) between two states separated by a voluntary quick body sway showed significantly larger motor equivalent deviations compared to non-motor equivalent ones. This is the first study demonstrating posture-stabilizing synergies in the space of neural control variables using various computational methods. It promises direct applications to studies of postural disorders and rehabilitation.

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.

Recent Advances in the Neural Control of Movements: Lessons for Functional Recovery.

We review the current views on the control and coordination of movements following the traditions set by Nikolai Bernstein. In particular, we focus on the theory of neural control of effectors - from motor units to individual muscles, to joints, limbs, and to the whole body - with spatial referent coordinates organized into a hierarchy with multiple few-to-many mappings. Further, we discuss synergies ensuring stability of natural human movements within the uncontrolled manifold hypothesis. Synergies are organized within the neural control hierarchy based on the principle of motor abundance. Movement disorders are discussed as consequences of an inability to use the whole range of changes in referent coordinates (as in spasticity) and an inability to ensure controlled stability of salient variables as reflected in indices of multi-element synergies and their adjustments in preparation to actions (as in brain disorders, including Parkinson's disease, multiple-system atrophy, and stroke). At the end of the review, we discuss possible implications of this theoretical approach to peripheral disorders and their rehabilitations using, as an example, osteoarthritis. In particular, "joint stiffening" is viewed as a maladaptive strategy, which can compromise stability of salient variables during walking.

Effects of hand muscle function and dominance on intra-muscle synergies.

The goal of the study was to explore the effects of hand dominance and muscle function (prime mover vs. supporting muscle) on recently discovered intra-muscle synergies as potential windows into their neural origin. Healthy right-handed subjects performed accurate cyclical force production tasks while pressing with the middle phalanges and distal phalanges of the fingers of the dominant and non-dominant hand. Surface electromyography was used to identify individual motor unit action potentials in two muscles, flexor digitorum superficialis (FDS) and extensor digitorum communis (EDC). Stable motor unit groups (MU-modes) were defined in each muscle and in both muscles together. The composition of the MU-modes allowed linking them to the reciprocal and co-activation command. Force-stabilizing synergies were quantified in each hand and during force production at both sites using the framework of the uncontrolled manifold hypothesis. Force-stabilizing synergies were seen in the spaces of MU-modes from FDS and EDC separately, but not of MU-modes defined for both muscles together. Synergy indices were similar for both hands and both sites of force application. In contrast, force-stabilizing synergies in the space of finger forces were present in the non-dominant hand and absent in the dominant hand. The data suggest existence of distributed mechanisms of synergic control. Finger force synergies are likely to reflect functioning of subcortical loops involving the basal ganglia and cerebellum, while MU-mode synergies are likely to reflect spinal circuitry. Studies of both force-based and motor-unit-based synergies may be clinically valuable for distinguishing effects of spinal and supraspinal disorders.