George E. Stelmach, Ph.D. - US grants

While it is generally acknowledged that the speed of most motor actions substantially decrease with advanced age, the predominance of the research on aging has primarily addressed cognitive processes, and for the most part, neglected fundamental motor operations. This research, while examining some cognitive-motor processes, breaks with tradition and systematically examines motor parameterization processes in the older adult. By functionally breaking down motor programming, execution and reprogramming operations across a series of experiments, it will be determined whether there are deficits in these processes. Ten experiments are proposed which will examine specific motor processes in three age groups (20-25, 40-45, 65-70 yrs); each experiment singles out one process for careful scrutiny by isolating a functional aspect of the parameterization process. These experiments, when taken collectively, will determine if age alters these motor processes and provide an in-depth profile of the parameterization process never seen before. The obtained data will be useful in both theoretical and clinical settings: the former by isolating and describing the extent of the various motor deficits examined and the latter by pointing to where restoration and maintenance methods should be directed.

The proposed research addresses several crucial aspects of Parkinsonian motor behavior by breaking down motor programming processes into identifiable functional operations. By systematically varying the functional aspects of voluntary movement preparation more will be understood about the information processing deficits that result from structure disturbances and set the stage for more detailed accounts of the motor physiology involved. The research is directed toward identifying, isolating, and documenting which motor processes contribute to akinetic and bradykinetic disorders through established behavior methods commonly employed in the study of motor control of normals. Five experiments are proposed which probe the following movement organization processes: Response Determination, Response Specification, Preprogramming and Reprogramming, and Bimanual Control. We are confident that both the scientist and the clinician will be served by the data: the former by having information on the locus of the disorders and the latter by being presented with interpretations from which more objective rehabilitory procedures can enolve.

The frequency of falls in the elderly increase in each life decade such that by the time one reaches the age of eighty, the probability of a damaging fall is about one in three. While there is evidence of a general slowing of sensory-motor processes (sensory input, response and execution) with age, the relative contribution of these processes to the increased frequency of falls in the elderly is not clear. Part I of this research specifically examines one aspect of sensory input related to falls, proprioception, to document its change with age. Further, postural sway and proprioceptive function in the lower extremities will be examined, and the relationship between them established. Subsequently, subjects with high composite postural sway scores and poor proprioceptive function will be given proprioceptive training to document the benefits of such practice and determine if postural stability is improved. Part II of the proposed research will establish whether the high incidence of falls in the elderly arises from deficits confined to the postural control system, or from a more fundamental impairment of voluntary movement in which the interplay between destabilizing voluntary actions and their accompanying postural adjustments break down. These studies will document how two distinct processes fundamental to postural control and implicated in falls change with age: proprioception and postural response organization during voluntary movement.

The research proposed will extend our initial work by studying the adequacy of motor preparation as well as by examining the processes that contribute to bradykinesia in Parkinson's disease patients. This research will allow precise description and identification of motor impairment by employing converging levels of analysis: reaction time, movement time, electromyographic and kinematics. Section I considers whether Parkinsonians adequately prepare movement by asking: whether Parkinsonians can control the amount of time they spend preparing movements, whether vision is used appropriately for movement amplitude preparation, and whether normal preparatory adjustments are made in the gain of long-latency reflexes (M1, M2, M3). Section II evaluates whether the context in which a movement is performed affects the organization and control of multi-joint hand movement. Section III addresses several related issues. Do Parkinsonians coordinate movement parts in a sequence, do they take longer to prepare responses within a sequence to identical responses prepared and executed on their own, and are responses in sequence timed as accurately as identical responses prepared and executed on their own? Upon completion of these series of experiments we should be able to determine whether akinesia and bradykinesia are primarily associated with inadequacies in preparatory processes, basic execution processes, and/or a combination of both. We are optimistic that both the basic scientist and the clinician will be well served by our data: the former by having information on the locus of the motor impairments and the latter by being presented with interpretations from which more objective assessment and rehabilitation procedures can evolve.

It is generally recognized in biomedical science that the physiological processes that underlie normal and abnormal motor control require understanding a set of mechanisms associated with neurochemical, bioelectric and biomechanic variables. New technologies are currently available that make it possible to record 3-dimensional kinematic movement data that was not easily obtained a few years ago. The purpose of this proposal is to upgrade our capabilities for NIH funded research by acquiring a 3- dimensional (Vicon) recording system. This recording system will compliment our existing electrophysologic, biomechanic and kinematic measures. A series of experiments are proposed which exploit new 3- dimensional movement recording opportunities within the framework of existing research grants. In particular we propose to use the Vicon system to enhance our research methodologies to assess the development of normal motor control processes, to describe motor dysfunctions in the elderly, Parkinson's disease and cerebellar patients, and to document motor recovery patterns in the acute brain injured. Further, experiments are proposed which use the 3- D system to examine the effects of respiratory muscle action and ventilatory regulation during exercise. The 3-D recording system will allow precise description and identification of motor physiology not currently possible in our laboratories by permitting the use of converging levels of analysis: electromyographic, movement dynamics, and kinematics. These data analyses will improve our ability to generate specific and testable hypotheses, permitting us to gain important new insights into the functional organization of the human motor system. we are optimistic that both the basic scientist and the clinican will be served by our data: the former by having information on the locus of the motor impairment and the latter by being presented with interpretations from which intervention procedures evolve.

This project builds upon our previous research that has been directed toward identifying the origins of micrographia, a handwriting impairment associated with Parkinson's disease, characterized by the progressive diminution of letter size. In this application finger, wrist, and arm movements in handwriting and drawing tasks are investigated by measuring the movements of the pen tip on an electronic display. To get more insight into the involved mechanisms, we use a neural network model of movement production based on anatomical, neurophysiological, pharmacological, and clinical studies. We propose 10 experiments that examine four main hypotheses originating from our recent research that can potentially explain aspects of micrographia. (1) PD patients have problems in coordinating multiple joint movements. This postulates that writing size is reduced when the arm, shoulder and wrist are used, compared to single joint movements. This leads us to predict that PD patients when executing complex movements simplify the coordination by producing a sequence of single joint movements. (2) PD patients have a reduced range of isochronic writing. This predicts that PD patients reduce size when they attempt to produce large movement amplitudes. Furthermore, due to the large inertial forces in arm movements, PD patients are predicted to exhibit a greater speed-size tradeoff for arm compared to fingers and wrist movements. (3) PD patients have increased joint stiffness. This predicts that PD patients will have force saturation problems due to inappropriate muscle activation when making small paced movements or fast normal sized movements with predetermined size. (4) PD patients have reduced sensory feedback. Reduced feedback is predicted to create movement outcome uncertainty which is compensated for by smaller movement sizes. This prediction will be verified by amplifying or degrading feedback. The present series of experiments constitute a comprehensive examination of the origins of reduced movement amplitude in PD.

DESCRIPTION (adapted from investigator's abstract): As individuals age, their movement control performance generally deteriorates; in particular, their movements get slower and more variable. We have shown that in an aiming task much of the slowing can be attributed to how the elderly subjects structure their movements. In comparison to younger subjects, they typically execute aiming movements that contain a shorter movement. We have also established that even with extended practice, the elderly do not change the relationship between these sub-movements which suggests that these modifications to the movement structure reflect fundamental changes in the motor system. In this application through a series of experiments, we seek to understand why the elderly alter the structure of their movements. Four major hypotheses are examined that probe potential causes of this modification: increase muscle cocontraction, increased force variability, reduced visuo-proprioceptive calibration, and reduced coordination control. In each experiment a methodology is employed that divides aiming movements into primary and secondary sub-movements and investigates their relationship to predictions made from the four hypotheses. This experimental sequence is the first to comprehensively examine primary and secondary sub-movements in the elderly.

9987619
Ji-Ping He - Arizona State University
IGERT: Neural and Musculoskeletal Adaptation in Forms and Function

This Integrative Graduate Education and Research Training (IGERT) award supports the establishment of a multidisciplinary graduate training program of education and research on neural and musculoskeletal adaptation in form and function. This theme is examined with integrated approaches from bioengineering, neurophysiology, physical anthropology, exercise sciences, computer and system sciences. The goal of the program is to introduce students with diverse biological and engineering backgrounds to the challenges of deciphering complex phenomena in integrative and computational neuroscience, motor diorders and rehabilitation. The program will foster interdisciplinary education and training in research efforts toward meeting these challenges. Graduate training will expand upon two related areas in which participating faculty have developed research and teaching collaborations: (1) mechanisms underlying neural control of movements, emphasizing hand function and locomotion, and (2) evolutionary morphology of the human hand and bipedality. Three interdisciplinary courses built around core research laboratories (Biomechanics/Anatomy, Neurophysiology/Neuroengineering, and Computation/Visualization) will anchor the program. Research training will be enhanced by access to medical imaging resources and by basic and applied research projects in collaboration with leading medical institutions, biomedical enterprises and evolutionary research resources at the Institute of Human Origins. The program addresses the multidisciplinary needs of graduate education, creates a rich environment for generation of innovative ideas for leading edge research in neuroengineering, evolutionary morphology, motor control, stereo modeling and visualization.

IGERT is an NSF-wide program intended to meet the challenges of educating Ph.D. scientists and engineers with the multidisciplinary backgrounds and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to catalyze a cultural change in graduate education by establishing new, innovative models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries. In the third year of the program, awards are being made to nineteen institutions for programs that collectively span all areas of science and engineering supported by NSF. The intellectual foci of this specific award reside in the Directorates for Engineering; Biological Sciences; Social, Behavioral, and Economic Sciences; Computer and Information Science and Engineering; and Education and Human Resources.

While advances in Parkinson's disease have been established in recent years, the pathogenesis of the disease is still not well understood. The primary goal of this project is to quantify how complex multijoint movement is impaired in Parkinsonian patients, thereby providing a better understanding of how motor control principles are compromised. Our working hypothesis concerning PD patients is that much of their difficulty with complex movements arises from their inability to coordinate body segments. We use a trunk-assisted prehension task and analyze trunk, arm, and aperture synchronization when speed, accuracy, sequencing of segments, and visual feedback constraints are imposed. We will analyze body segment synchronization, relative timing, spatial invariance, and synergies. Collectively, the results from these experiments will allow us to better understand how PD affects movement coordination patterns during the performance of complex actions. Comparisons of 'off' vs. 'on' states in Parkinson's disease patients may help determine if coordination impairments share a common levodopa basis. The experiments proposed are systematic, novel and use proven methodology. The proposed research should advance understanding of the fundamental principles that guide the coordination of multijoint movements in normal subjects. It will also increase understanding of the ways in which Parkinson's disease patients are restricted in the use of these principles. The results from four experiments should be useful to both the basic neuroscientist and clinical science communities, reducing the gap between fundamental knowledge of neural mechanisms and therapeutic intervention.

DESCRIPTION: (provided by applicant) One of the most debilitating aspects of Parkinson?s disease is the inability to initiate and execute movements as intended. The fundamental hypothesis behind the proposed research is that basal ganglia impairments, as reflected in Parkinson?s disease, causes a disruption in motor programming processes. It is postulated that there is increased noise in the basal ganglia that produce abnormal timing, patterning, and synchronization of discharges into the motor cortical areas. These irregularities in turn reduce motor programming capabilities that are reflected as alterations in the microstructure of a goal-oriented movement. We have documented that Parkinson?s patients produce movements that exhibit shortened primary submovement components, which then requires secondary, corrective movements. Seven experiments are proposed which examine whether the altered substructure of movements observed in PD is related to muscle activation patterns, force-force variability relationships, and/or a reduced capability to incorporate proprioceptive information at different stages of movement planning and execution. The results of these experiments will be evaluated in combination to allow us to determine which of these potential causes has the greatest impact on primary submovement distance. The data obtained will be useful in the basic science realm as well as the clinical setting; the former by isolating the various motor deficits associated with PD, which may allow for inferences to be made regarding structure-function relationships. In terms of clinical relevance these results will assist in identifying where practitioner interventions or outcome measures should be targeted.

[unreadable] DESCRIPTION (provided by applicant): Evidence indicates that Parkinson's Disease (PD) patients are particularly impaired in the performance of complex movements that require coordination of several joints. Studying these impairments is of considerable practical importance, because movements performed in everyday life (reaching, grasping, pointing, lifting, etc) are essentially multi-joint and the lack of coordination is one of the most debilitating aspects of the disease. Many studies have hypothesized that impairments in multi-joint movements arise from difficulties patients have in controlling several joints simultaneously. Data obtained in our lab suggest that the reason for multi-joint movement distortions in PD is different. We argue that PD patients have difficulties in the regulation of interactive torques. These torques may be considered as the effect of constraints imposed by peripheral biomechanics on control of the limbs. Healthy older adults overcome these constraints at normal movement speeds. Our data suggest that PD patients are unable to deal with the biomechanical constraints during movements of moderate and even low speeds. The purpose of the present proposal is (1) to demonstrate that the inability to properly regulate interactive torques is the major cause of multi-joint movement disruptions in PD, (2) to establish how interactive torques affect control at individual joints in multi-joint movements of the patients, and (3) to examine plausible reasons for the inability of patients to coordinate muscle torques necessary to modulate interactive torques at the joints. Our experiments utilize various arm movements, which manipulate joint coordination patterns stressing different roles of interactive torques in the control of joint movements. The data obtained in our experiments will provide important scientific and clinical contributions into knowledge of basal ganglia dysfunctions.