Ali Falaki

Impaired synergic control of posture in Parkinson's patients without postural instability

BACKGROUND Postural instability is one of most disabling motor symptoms in Parkinsons disease. Indices of multi-muscle synergies are new measurements of movement and postural stability. OBJECTIVES Multi-muscle synergies stabilizing vertical posture were studied in Parkinsons disease patients without clinical symptoms of postural instability (Hoehn-Yahr ≤ II) and age-matched controls. We tested the hypothesis that both synergy indices during quiet standing and synergy adjustments to self-triggered postural perturbations would be reduced in patients. METHODS Eleven Parkinsons disease patients and 11 controls performed whole-body tasks while standing. Surface electromyography was used to quantify synergy indices stabilizing center of pressure shifts in the anterior-posterior direction during a load-release task. RESULTS Parkinsons disease patients showed a significantly lower percentage of variance in the muscle activation space accounted for by the first four principal components, significantly reduced synergy indices during steady state, and significantly reduced anticipatory synergy adjustments (a drop in the synergy index prior to the self-triggered unloading). CONCLUSIONS The study demonstrates for the first time that impaired synergic control in Parkinsons disease can be quantified in postural tasks, even in patients without clinical manifestations of postural instability. Synergy measurements may provide a biomarker sensitive for early problems with postural stability in Parkinsons disease.

Anticipatory postural adjustments and anticipatory synergy adjustments: preparing to a postural perturbation with predictable and unpredictable direction

We explored two aspects of feed-forward postural control, anticipatory postural adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self-triggered unloading with known and unknown direction of the perturbation. In particular, we tested two main hypotheses predicting contrasting changes in APAs and ASAs. The first hypothesis predicted no major changes in ASAs. The second hypothesis predicted delayed APAs with predominance of co-contraction patterns when perturbation direction was unknown. Healthy subjects stood on the force plate and held a bar with two loads acting in the forward and backward directions. They pressed a trigger that released one of the loads causing a postural perturbation. In different series, the direction of the perturbation was either known (the same load released in all trials) or unknown (the subjects did not know which of the two loads would be released). Surface electromyograms were recorded and used to quantify APAs, synergies stabilizing center of pressure coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs were seen in all conditions. APAs were delayed, and predominance of co-contraction patterns was seen under the conditions with unpredictable direction of perturbation. In contrast, no significant changes in synergies and ASAs were seen. Overall, these results show that feed-forward control of vertical posture has two distinct components, reflected in APAs and ASAs, which show qualitatively different adjustments with changes in predictability of the direction of perturbation. These results are interpreted within the recently proposed hierarchical scheme of the synergic control of motor tasks. The observations underscore the complexity of the feed-forward postural control, which involves separate changes in salient performance variables (such as coordinate of the center of pressure) and in their stability properties.

Dopaminergic modulation of multi-muscle synergies in postural tasks performed by patients with Parkinson’s disease

BACKGROUND Postural instability is one of most disabling motor symptoms in Parkinsons disease. Indices of multi-muscle synergies are new measurements of postural stability. OBJECTIVES We explored the effects of dopamine-replacement drugs on multi-muscle synergies stabilizing center of pressure coordinate and their adjustments prior to a self-triggered perturbation in patients with Parkinsons disease. We hypothesized that both synergy indices and synergy adjustments would be improved on dopaminergic drugs. METHODS Patients at Hoehn-Yahr stages II and III performed whole-body tasks both off- and on-drugs while standing. Muscle modes were identified as factors in the muscle activation space. Synergy indices stabilizing center of pressure in the anterior-posterior direction were quantified in the muscle mode space during a load-release task. RESULTS Dopamine-replacement drugs led to more consistent organization of muscles in stable groups (muscle modes). On-drugs patients showed larger indices of synergies and anticipatory synergy adjustments. In contrast, no medication effects were seen on anticipatory postural adjustments or other performance indices. CONCLUSIONS Dopamine-replacement drugs lead to significant changes in characteristics of multi-muscle synergies in Parkinsons disease. Studies of synergies may provide a biomarker sensitive to problems with postural stability and agility and to efficacy of dopamine-replacement therapy.

Motor equivalence and structure of variance: multi-muscle postural synergies in Parkinson’s disease

We explored posture-stabilizing multi-muscle synergies with two methods of analysis of multi-element, abundant systems: (1) Analysis of inter-cycle variance; and (2) Analysis of motor equivalence, both quantified within the framework of the uncontrolled manifold (UCM) hypothesis. Data collected in two earlier studies of patients with Parkinson’s disease (PD) were re-analyzed. One study compared synergies in the space of muscle modes (muscle groups with parallel scaling of activation) during tasks performed by early-stage PD patients and controls. The other study explored the effects of dopaminergic medication on multi-muscle-mode synergies. Inter-cycle variance and absolute magnitude of the center of pressure displacement across consecutive cycles were quantified during voluntary whole-body sway within the UCM and orthogonal to the UCM space. The patients showed smaller indices of variance within the UCM and motor equivalence compared to controls. The indices were also smaller in the off-drug compared to on-drug condition. There were strong across-subject correlations between the inter-cycle variance within/orthogonal to the UCM and motor equivalent/non-motor equivalent displacements. This study has shown that, at least for cyclical tasks, analysis of variance and analysis of motor equivalence lead to metrics of stability that correlate with each other and show similar effects of disease and medication. These results show, for the first time, intimate links between indices of variance and motor equivalence. They suggest that analysis of motor equivalence, which requires only a handful of trials, could be used broadly in the field of motor disorders to analyze problems with action stability.

TASK-SPECIFIC STABILITY IN MUSCLE ACTIVATION SPACE DURING UNINTENTIONAL MOVEMENTS

We used robot-generated perturbations applied during position-holding tasks to explore stability of induced unintentional movements in a multidimensional space of muscle activations. Healthy subjects held the handle of a robot against a constant bias force and were instructed not to interfere with hand movements produced by changes in the external force. Transient force changes were applied leading to handle displacement away from the initial position and then back toward the initial position. Intertrial variance in the space of muscle modes (eigenvectors in the muscle activations space) was quantified within two subspaces, corresponding to unchanged handle coordinate and to changes in the handle coordinate. Most variance was confined to the former subspace in each of the three phases of movement, the initial steady state, the intermediate position, and the final steady state. The same result was found when the changes in muscle activation were analyzed between the initial and final steady states. Changes in the dwell time between the perturbation force application and removal led to different final hand locations undershooting the initial position. The magnitude of the undershot scaled with the dwell time, while the structure of variance in the muscle activation space did not depend on the dwell time. We conclude that stability of the hand coordinate is ensured during both intentional and unintentional actions via similar mechanisms. Relative equifinality in the external space after transient perturbations may be associated with varying states in the redundant space of muscle activations. The results fit a hierarchical scheme for the control of voluntary movements with referent configurations and redundant mapping between the levels of the hierarchy.

Synergies and Motor Equivalence in Voluntary Sway Tasks: The Effects of Visual and Mechanical Constraints

ABSTRACT The authors used two analyses developed within the framework of the uncontrolled manifold hypothesis to quantify multimuscle synergies during voluntary body sway: analysis of intertrial variance and analysis of motor equivalence with respect to the center of pressure (COP) trajectory. Participants performed voluntary sway tasks in the anteroposterior direction at 0.33 and 0.66 Hz. Muscle groups were identified in the space of muscle activations and used as elemental variables in the synergy analyses. Changing mechanical and vision feedback–based constraints led to significant changes in indices of sway performance such as COP deviations in the uninstructed, mediolateral direction and indices of spontaneous postural sway. In contrast, there were no significant effects on synergy indices. These findings show that the neural control of performance and of its stability may involve different control variables and neurophysiological structures. There were strong correlations between the indices of motor equivalence and those computed using the intercycle variance analysis. This result is potentially important for studies of patients with movement disorders who may be unable to perform multiple trials (cycles) at any given task, making analysis of motor equivalence of single trials a viable alternative to explore changes in stability of actions.

Unintentional movements induced by sequential transient perturbations in a multi-joint positional task

We explored the phenomenon of unintentional movements of a multi-joint effector produced by multiple transient changes in the external force. The subjects performed a position-holding task against a constant bias force produced by a robot and were instructed not to intervene voluntarily with arm movements produced by changes in the robot force. The robot produced a smooth force increase leading to hand movement from the trunk, followed by a dwell time. Then, the force dropped to its initial value leading to hand movement toward the initial position but with an undershot. Such perturbation episodes were repeated four times in a row. The accumulated perturbation and undershoot distances kept increasing without saturation within the sequence of four perturbation episode. The limb apparent stiffness before dwell time increased over sequential perturbations while apparent stiffness after dwell time decreased. We interpret the results as consequences of a drift of the hand referent coordinate (RC) caused by a hypothesized RC-back-coupling mechanism and a coupled drift of the apparent stiffness. The results show that RC-back-coupling continues to lead to unintentional movements over repeated perturbations and is accompanied by a relatively slow re-setting process.

Systemic effects of deep brain stimulation on synergic control in Parkinson's disease

OBJECTIVE We explored effects of deep brain stimulation (DBS) in patients with Parkinsons disease (PD) on the synergic control of fingers in a multi-finger force production task and of muscles in a task involving vertical posture. METHODS The finger task involved the four fingers of a hand producing accurate total force followed by a targeted quick force pulse. The postural task involved releasing a load from extended arms. The analysis of synergies was performed within the framework of the uncontrolled manifold hypothesis. RESULTS DBS led to no significant changes in indices of stability during steady-state phases. In contrast, DBS improved indices of agility, quantified as anticipatory synergy adjustments that reduced stability of salient performance variables in preparation to their quick change. There were moderate-to-strong correlations between indices of both stability and agility measured in the multi-finger force production and multi-muscle whole-body action. CONCLUSIONS Our results point at systemic changes in synergic control in PD. They show that DBS is effective in improving only one components of synergic control related to agility in performance being relatively ineffective for the stability component. SIGNIFICANCE The results show systemic brain mechanisms of synergies and suggest differential effects of DBS on indices of stability and agility.