Mark L. Latash - US grants

There are three distinct parts in the project. First, we are going to test the experimental basis of the equilibrium-point hypothesis and to compare some of the predictions of the hypothesis with experimental observations. In particular, the reproducibility of performance of subjects during different single-joint motor tasks requiring "not to intervene voluntarily" will be studied, the performance under instructions "not to intervene" and "to intervene" will be compared, electromyograms during perturbed single-joint movements will be theoretically predicted and compared with experimental observations. The second part of the project will be based on a new method, recently designed in our laboratory, which enables reconstruction of joint compliant characteristics and central control variable changes ("virtual trajectories") during single-joint movements. The method will be used for analysis of discrete single-joint movements and oscillatory movements against different loads. Reconstructed patterns of control variables will be compared with those predicted from the equilibrium-point hypothesis. Two hypotheses will be tested: 1). Joint stiffness changes are directed towards minimizing the difference between movement frequency and limb natural frequency; and 2) At the limb natural frequency, the virtual trajectory will have minimal peak-to-peak changes while the electromyograms of the major muscle groups will change monotonically with frequency. During the third part of the project, we plan to study virtual trajectories of multi-joint movements. In particular, we will be interested in compliant properties of the working point and individual joints and in compensation of errors created in one of the joints by corrections in other joints. The major hypothesis to be, tested is: The control variable for multi-joint movements is three-dimensional compliance of the working point. Experiments will be performed in which the subjects will learn a standard movement against a constant external load. Then, they will be required to reproduce the learned motor program while changes in the external load will occur in some of the trials. The subjects will be instructed "to reproduce the same time pattern of motor command while ignoring possible external load changes". Kinematic and dynamic parameters of the movements will be recorded. Electromyograms of major muscle groups will be recorded as well.

DESCRIPTION (Adapted from the Applicant's Abstract): The primary thrust of this project is to advance our understanding of the notion of synergy as the basic mechanism for overcoming the notorious redundancy of the neuro-muscular system for production of voluntary movements. They use the framework of the equilibrium-point hypothesis, to generalize it for multi-joint movements, and to suggest an explicit relation among control variables to individual joints as the basis for a simple synergy. This definition leads to a number of refutable specific hypotheses that are going to be addressed. Previous work analyzed kinematics and EMG patterns of the synergy. To make the next step, they plan to use the results of earlier studies which involved a method for the reconstruction of the hypothetical control patterns during single-joint movements and suggest a model predicting the EMG patterns based on the control signals and actual joint kinematics. They plan to reconstruct the hypothetical control patterns for each joint in a variety of conditions using a second-order joint model and inverse dynamics. Reconstructed patterns will then be used for calculations of EMG patterns which will be compared to experimental observations. They plan to apply these methods to unidirectional voluntary movements in a variety of experimental conditions and under different instructions, to motor tasks requiring application of isometric force, to motor tasks involving unexpectedly changed loading conditions, and to whole-arm movements involving all three major joints.

DESCRIPTION (provided by applicant): Our recent studies have shown that the well-documented drop in muscle force and an increase in its variability with age are accompanied by more subtle changes in the control of the hand/fingers. In particular, advanced age is associated with an impaired ability to produce both high magnitudes and accurate time profiles of moments of digit forces on a hand-held object. Recent research has also shown that the control of rotational actions is associated with specialized multi-digit synergies. Based on these findings, we have formulated six hypotheses related to age-related changes in multi-digit synergies involved in rotational actions. Three experiments with elderly and young participants will study multi-digit synergies using tasks representing typical situations of everyday usage of the hand: "Prismatic grasp" (drinking from a glass), "lever grasp" (opening a door handle), and "lid grasp" (turning a jar lid). We will analyze the variability in the performance of these tasks and also quantify multi-digit synergies involved in the gripping/pressing and rotational task components. Three experiments will study adjustments in multi-digit synergies prior to a voluntary rotation of a hand-held object, prior to a self-triggered load/torque perturbation, and in response to an unexpected perturbation. The final experiment will study effects of eight weeks of strength training on the performance of two multi-digit tasks and quantify changes in multi-digit synergies involved in the gripping and rotational task components. We will also quantify retention of the effects of training 6 months post-training. Two types of exercise will be used, one of which will specifically target intrinsic hand muscles, which have shown a greater age-related drop in force in our earlier studies. Outcome indices of experiments will be compared to performance in four clinical functional tests. The proposed studies will be unique in quantifying age-related impairments of multi-digit synergies that stabilize hand rotational actions and their relations to hand function. The last study will potentially have implications for optimization of hand exercise for elderly.

DESCRIPTION (provided by applicant): During the previous period of support, we have introduced, explored, and developed an approach to motor synergies based on the principle of abundance and using the computational tools of the uncontrolled manifold hypothesis. Now we suggest focusing on three major goals. First, we plan to analyze interaction of synergies at different levels of a control hierarchy. Second, we will explore the purposes and benefits of using synergic control to move closer to application of these ideas to everyday movements and disordered movements. Third, we will explore differences between the synergies involved in two basic classes of actions, discrete and cyclic. The planned experiments will address the following main questions: What is the purpose of synergies? How do synergies at different levels of a control hierarchy interact with each other? Are there qualitative differences in the synergic mechanisms during cyclic and discrete actions? We will perform eight experiments using several of the novel experimental devices constructed in our group, such as the "inverse piano", the "collapsing cup", and the "handle with spring-loaded sensors". Each experiment will test 2-4 specific hypotheses. The long-term goal of this research is to develop a coherent theoretical view on and advance the current understanding of how natural multieffector human movements are controlled and coordinated. Developing such a view would have a profound impact on the practice of preventing and treating motor disorders. These studies will also contribute to developing a toolbox to study motor synergies during both unimpaired and disordered movements. PUBLIC HEALTH RELEVANCE: The overarching goal of the proposed research is to advance the current understanding of the organization, purposes, and benefits of synergic control of movements. We plan to move closer to application of these ideas to everyday motor tasks and disordered movements. At the same time, we are developing a toolbox to study motor synergies;such a toolbox may be applied to both unimpaired and disordered movements.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is part of research intended to understand how finger coordination and hand function change with age. By performing this research, the investigators hope to improve present understanding of changes in motor coordination in the elderly and make recommendations for rehabilitation approaches to improve hand function.

DESCRIPTION (provided by applicant): The goal of the proposal is to explore the strategies used by the central nervous system when manipulating hand- held objects. Recently we developed a new mathematical method of inverse optimization - the 'Analytic Inverse Optimization' (ANIO) method -that allows for reconstructing unknown cost functions (CF) from experimental recordings (Terekhov et al. 2010). The first line of research will deal with the further development of the method and its application to human prehension. Experiment 1-A will explore whether all performers use CFs of the same class. Experiment 1-B will test whether the ANIO method yields estimates of the CFs that are reproducible over protracted periods of time. Experiment 1-C will explore the dependence of the CF class of functions on the number of fingers involved in the task. Experiment 1-D will address interaction between the optimization and variability in multi-finger prehension. The second line of research is based on previous results obtained in our lab and is intended to test the following hypotheses: Experiment 2-A will test the additivity hypothesis: suppose that the digit forces are affected by factors A, B, C, etc. The hypothesis assumes that the effects of the neural commands associated with the above factors are additive. In statistical terms it means that the effects of the factors are significant while their interactions are not. Experiment 2B extends the additivity hypothesis to the complex dynamic tasks. We expect to find that the pattern of grasping force changes as a sum of the effects of two commands associated with the movements along and normal to grasp direction, respectively. Experiment 2C will deal with testing a template control hypothesis according to which for every given combination of the object geometry and local friction the performers select a digit force pattern ('template') and then scale the digit forces with the load force. Experiment 2- D will consist of two parts in which effects of one finger fatigue or fatigue of all fingers will be explored. The goal is to test whether the fatigued finger exerts the same %% of its current maximal force as it did prior to fatigue. Essentially, the experiment will explore the 'robustness' of prehension control, using local fatigue as a perturbation tool. Under 'robustness' we understand ability to perform a task when performance potential of one of the contributing elements is diminished.

ABSTRACT Parkinson's disease (PD) is a common neurological disorder caused by progressive loss of dopamine- producing neurons in the substantia nigra. One of the main problems in treating PD is the lack of early biomarkers that would provide crucial information for making practical decisions on treatment and prevention plans for individual patients. Our main goal is to demonstrate that indices of stability of motor actions (indices of synergies) can and should be used as theory-based, quantitative, and objective biomarkers of PD. Our recent studies using the framework of the uncontrolled manifold (UCM) hypothesis to quantify synergies have shown that PD patients demonstrate impaired synergies (low stability of action) and impaired ability to adjust synergies in preparation to action (delayed and reduced anticipatory synergy adjustments, ASAs). In a few patients at stage-I (Hoehn-Yahr) of PD, changes in synergies and ASAs were seen during actions involving body parts without clinical signs of the disease. These results suggest that studying synergies may yields objective biomarkers that are able to detect and quantify impaired motor function in PD and may be sensitive to pre-motor-symptom stages of the disease. We plan to collect pilot data to support this hypothesis by studying a group of drug-naïve patients at stage-I (Hoehn-Yahr) of PD. Testing drug-naïve patients will allow disambiguating effects of PD from possible effects of long-term exposure to drugs on the non-symptomatic extremities. We also plan to determine the effects of dopamine replacement therapy on these indices. Our main specific hypotheses are: (1) Drug- naïve patients with PD stage-I will show reduced synergy indices and shorter, delayed ASAs as compared to healthy controls in both symptomatic and non-symptomatic hands/arms; and (2) These indices will be sensitive to dopamine-replacement drugs. Two specific aims will test the main hypotheses. Aim 1: To demonstrate and quantify changes in synergic control in symptomatic and asymptomatic extremities of newly diagnosed, drug-naïve HY stage-I PD patients. We will quantify indices of multi-finger synergies stabilizing total force and multi-joint synergies stabilizing hand trajectory in both upper extremities. We expect the synergy indices to be reduced similarly on both sides compared to controls. We also predict delayed and reduced ASAs in PD. Aim 2: To demonstrate and quantify the effectiveness of dopamine-replacement therapy in improving synergic control in PD patients. Studies described under Aim-1 will be repeated one hour after taking carbidopa/levodopa 25/100 regular, gold standard for dopaminergic replacement. We plan to show positive effects of the drug on the synergy indices across If successful, these results will help us to optimize design of a longer prospective study that would test the prognostic value of changed multi-finger and multi-joint synergies by following prospectively a large group of early-stage PD patients over several years to explore how synergy indices predict the occurrence of clinical symptoms such as emergence of symptoms on the less-affected body side, postural instability, and freezing of gait. tasks. We view the impaired synergies in the upper extremities as early reflections of a general disruption of the mechanisms of synergic control, which later leads to effects in other body parts including those involved in postural and locomotion tasks.