Karl M. Newell, Ph.D. - US grants

The focus of this proposal is to obtain an understanding of the motor control characteristics of the stereotypic movement disorders of the developmentally disabled, and in particular, those movements associated with tardive dyskinesia. Current characterizations of stereotypic behaviors rely largely on the natural observation of the observer and speculation about the appropriate categorization of movement disorders. It is proposed that a formal kinematic analysis of the movement disorders with subjects under neuroleptic medication and withdrawn from neuroleptic medication conditions and different task constraints will: (1) provide a description of the stereotypic movements that is consonant with movement parameters seen to reflect organizational coordination and control properties of the central nervous system; (2) allow comparison to matched 'normal' subjects on fundamental rhythmic and vocational activities and, while attempting to mimick the performance of stereotypic activities; (3) allow an examination of the effect of psychotropic drugs on the motor control characteristics of movement disorders; (4) provide a formal test of the observer checklist approach to characterizing stereotypic movements. The findings from the proposed experiments should provide a screening test than, for example DIS-Co, to assess tardive dyskinesia in various populations of mentally retarded people.

DESCRIPTION: (Adapted from investigator's abstract) Tardive dyskinesia is the syndrome of abnormal movements that arises from prolonged intake of neuroleptic medication. These abnormal movements can severely detract from performance in a wide range of motor skills, including vocational and self-help activities. A significant proportion of the abnormal movements associated with developmentally disabled individuals are reflections of tardive dyskinesia. It is not clear how these movement abnormalities differ from non-medication induced abnormal movements, such as institutionalized stereotypes of the developmentally disabled. The focus of this proposal is to continue to examine the motor control characteristics of the abnormal and stereotypic movement disorders of the developmentally disabled, and in particular, those abnormal movements associated with tardive dyskinesia. A formal movement analysis of the movement disorders of developmentally disabled subjects under neuroleptic medication and on addition and withdrawal from neuroleptic medication protocols will be conducted under a range of different postural and movement task conditions. This movement analysis will: (1) provide a description of the stereotypic movements that reflects organizational coordination and control properties of the central nervous system; (2) allow comparison to matched normal and other developmentally disabled groups that have not been on medical regimes; (3) allow an examination of the effects of neuroleptic medication on the motor control properties of movement disorders; (4) provide a formal test of the observer "rating scale" method currently used to characterize the abnormal movements of tardive dyskinesia; and (5) evaluate the posture and movement tests as a more sensitive screening device for tardive dyskinesia than the traditional techniques of clinical observation and motor performance rating scales.

abnormal involuntary movement; schizophrenia; antipsychotic agents; mental retardation; drug adverse effect; drug screening /evaluation; age difference; tremor; mental health epidemiology; chronic disease /disorder; drug administration rate /duration; rest; tardive dyskinesia; posture; gender difference; clinical research; human subject; automated medical record system;

The learning of movement skills is characterized by persistent change in behavior over time. There are many indices of change in motor behavior and many time scales (rates of change and time periods) over which the change in behavior occurs. A central proposition of this research is that time scales are fundamental in the description and prediction of the change in behavior that we infer as learning. The research stems from a theoretical framework based upon the concepts and tools of nonlinear dynamical systems; this framework was devised to account for both the persistent (relatively long-term, such as days, weeks, months) and transitory (relatively short-term, such as trial to trial) changes traditionally shown for the learning of motor skills. The last 100 years of research on the learning of motor skills has shown that a number of different functions of change are revealed in learning curves, such as an exponential, power law, S-shaped, logistic, sudden "discontinuous". Typically, different theories of learning make different assumptions about the time scales of change that are inherent in the mathematical equations used to fit learning data. Moreover, theories of learning tend to focus on one function of learning rather accommodate the complete set of learning functions. This research will test the proposition that a small set of principles from nonlinear dynamics can produce all of the standard functions of change observed in motor learning. A series of experiments conducted within a dynamical systems framework will examine, in a range of motor tasks, the time scales of change in motor learning. This research will provide a first test of the notion that a unified and parsimonious dynamical account of time scales of change can derive the established set of short- and long-term learning functions in motor learning. The promise of this theoretical and experimental approach to the time scales of motor learning is that it will lead us beyond traditional descriptions of learning toward a predictive science of human motor learning, that links theoretically to neural net approaches to human cognition and artificial system learning.

DESCRIPTION (provided by investigator): The introduction of the novel "atypical" antipsychotic medications (e.g., olanzapine, risperidone) has led to this class of medication becoming the most frequently used medication treatment for behavioral and psychiatric disorders associated with developmental disabilities. The atypical antipsychotics are purported to have both a lower risk of antipsychotic-induced side effects (e.g., dyskinesia) and selective beneficial effects for stereotypy and self-injury in persons with developmental disabilities. There have been few adequate tests to date of these assumptions in persons with developmental disabilities. In our previous work with typical antipsychotic medications, we validated a battery of instrumental tests for measuring antipsychotic- induced effects on motor control, and we characterized the dynamic nature of antipsychotic-induced effects on both aberrant behaviors and abnormal movements as a function of the addition, maintenance, and withdrawal of typical antipsychotic agents. In the proposed study, we will examine in persons with mental retardation the variety of potential antipsychotic-induced effects associated with atypical antipsychotic treatment (dsperidone and olanzapine) using behavioral observations, movement kinematic analyses, motor control tests and adaptive performance tasks. In the proposed study we will conduct an acute double-blind comparison of the atypical antipsychotics risperidone and olanzapine to each other and to placebo. A longterm follow up will also be conducted of the effects of the atypical antipsychotic treatment over a 1-year period in subjects who are clinical responders to acute treatment with either olanzapine or risperidone. The following questions will be addressed: (1) Does treatment with atypical antipsychotic medication significantly reduce the occurrence of stereotyped behaviors and abnormal movements? (2) How does atypical antipsychotic medication affect the movement dynamic properties of stereotyped behaviors and abnormal movements? (3) How does atypical antipsychotic medication affect the performance of adaptive, goaloriented actions? And (4) Are there differences between the short and long term effects of atypical antipsychotics on aberrant behavior, abnormal movements, and goal-oriented motor task performance?

DESCRIPTION (provided by applicant): This proposal seeks to conduct preliminary experiments on a new perspective to aging and the complexity of visual-motor output. The plan is to conduct a program of cross-sectional experiments on hand digit isometric force control tasks with healthy adults of different age groups (20-29, 60- 69, 70-79, and 80-89 year olds). The experiments are set-up to test the contrasting hypotheses that: (1) aging is reflected by a loss of complexity in behavior and physiology; and (2) that the aging complexity relation is a problem of adaptation that limits change in the coordination of the active degrees of freedom of the system. In this latter view, aging leads to a difficulty in adapting behavior to the task demands whether it is increasing or decreasing the complexity of behavior or the number of active degrees of freedom (individual components) that are regulated in movement. The motor tasks will include the manipulation of visual information (through intermittency and frequency filtering parameter changes) to test the proposition that visual-motor processing is a major source of the complexity/motor performance age-related deficit. The analysis will examine the noise and complexity structure of the visual-motor output using a range of techniques from nonlinear dynamics, both on an age group and individual difference basis. The integrative analyses across experiments will test whether the deterministic and stochastic structure of age-related individual performance variability is general or specific to particular task constraints. The proposed research will provide a theoretical, methodological and empirical basis for future experiments and modeling from this perspective with healthy aging, and-related disease states, including Parkinson's disease.

How do we learn to throw a ball or play an instrument, or perform any other skilled motor task? Our everyday experience tells us that practice is the key, with the anticipation that there will be ups and downs on the road to skilled performance. But researchers in the movement sciences see specific patterns in the time course of acquiring a motor skill, patterns that reveal the nature of motor learning.

For decades those patterns have been interpreted as revealing a power law of learning that holds across all time scales, from gradual improvements that occur over days to rapid improvements that occur in a matter of minutes or even seconds. Recent advances however have shown the picture to be more complex that previously thought. With funding from the National Science Foundation, Dr. Newell will investigate those complexities in the time scales of motor learning from a dynamic systems perspective. On his approach, learning is formalized as the evolution of an attractor landscape, where elevation corresponds to distance from the current state of learning to the goal state. The critical hypothesis is that learning curves are governed by attractor landscape dynamics, which are punctuated by bifurcations of the attractor organization. Bifurcations provide a scientific understanding of the everyday experience in which the work of practice pays off in sudden moment, as when a child suddenly gets it when learning to ride a bicycle. The research promises to build a foundation for dynamic systems theories of learning, not only for motor skills but for learning of all kinds in biological and cognitive systems