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Research on the Phenomenology of childhood motor disorders
-Kinematics and 3D Motion Capture
-Measuring the Speed of Motor Learning
-Mechanisms of Dystonic Hypertonia
-Pocket-Size Surface EMG Analysis Device
Kinematics and 3D Motion Capture
We use three-dimensional motion-capture technology to record reaching movements and muscle electrical activity in children with several different movement disorders. We have analyzed the movements using principal-components analysis (PCA) in order to extract fundamental elements that can be used to describe the movements. We have shown that children with secondary dystonia have increased variability of reaching. In further experiments we have shown that this variability contributes to a degradation of the relation between speed and accuracy that will impair a child’s ability to use a keyboard or assistive communication device.
In order to perform quantitative measurements and analyses of arm movements in children with hyperkinetic disorders, we use a magnetic motion-capture system that can read the three-dimensional position of the major joints of the upper extremity. Dr. Sanger has developed special-purpose software to analyze these data and to combine them with surface EMG and video. The software includes real-time three-dimensional reconstruction of the position of the major bones of the arm. This reconstruction can be used for feedback to children and potentially for the retraining of complex movements. Using this system, we have shown that arm movements in the hyperkinetic form of dystonia cannot be described by a consistent set of abnormal movements, but instead are described by a relatively normal reaching trajectory with superimposed random noise. Detailed investigation of the variability in arm movements using Principal Components Analysis suggests that dystonia includes a type of noise that cannot be described as an accentuation of normal movement variability, but instead may arise from a different and possibly pathological source. This is important because work by others has shown that chorea and ataxia may have more repeatable movements, and can therefore be distinguished from dystonia. Furthermore, recognition of the random nature of dystonic movements is important to develop new treatment methods.
Measuring the Speed of Motor Learning
Estimation of learning rate is critically important for any rational approach to designing an individualized retraining plan to improve motor performance in children. Currently, there are no results that quantify motor learning rate in children with motor disorders, and there is no technique to quantify learning rate in an individual child. We are developing two different methods for measuring learning. The first is based on the “force-field adaptation” paradigm. In this widely-studied paradigm, subjects must learn to compensate for forces generated by a robot that displace their hand during movement. This paradigm has never been applied to children with dystonia, and the laboratory has developed customized software and experimental designs that allow it, for the first time, to apply to this group of subjects. New experiments are being designed to use a “warping” of a virtual reality environment to investigate the ability of children with dystonia to learn a novel visual-motor mapping.
The second method for measuring learning is based on a completely new technique. Subjects must contract a single muscle to track a moving target, but the relation between the muscle and the target is constantly changing. The fastest speed at which this relation can change and yet the child can still “keep up” describes the child’s fastest ability to learn the task. By using the feedback error learning model and stability analysis, we can extract numerical estimates of the learning rate for each child. Ongoing experiments will validate the ability of this method to estimate differences in learning rate between subjects with different motor disorders.
Mechanisms of Dystonic Hypertonia
It is a commonly-held belief that increased stiffness (tone) in dystonia is due to co-contraction of opposing muscles. In contrast to this belief, we have shown that in children with hypertonic dystonia, co-contraction is only rarely present during movement and often is less than what is seen in control subjects. Furthermore, we have shown that for most children, hypertonia is due to reflex activation of muscles opposing passive movement, so that an attempt by the examiner to move a child’s joint is met with rapid activation of the muscle opposing the examiner’s attempts.
Over 50 years of research show that activation of motor cortex (either by voluntary attempts to hold posture, electrical stimulation, toxins, or seizures) leads to postures that are actively maintained by stretch reflexes. Therefore it is possible that dystonia results from any injury that leads to uncontrolled activation of motor cortex. If so, this would resolve the conundrum that results from the recent observation that dystonia can occur with disorders of multiple brain areas, including basal ganglia, sensory cortex, and cerebellum, since any source of involuntary activation of motor cortex could potentially result in hypertonic dystonia. This is a very exciting conjecture, since it places the origins of hypertonic dystonia upstream from motor cortex and provides an easily measurable marker of dystonia. This research represent a major shift in the understanding of hypertonia, and it has led to several new lines of work in the laboratory.
One line of work is to confirm the cortical localization of this phenomenon. We have developed the ability to do real-time cortico-muscular coherence measures that will be used to assess cortical involvement in dystonic reflex activation. Based on those results, we plan to perform experiments using transcranial magnetic stimulation to disrupt the transcortical reflex loop and modify the response to stretch. Combination of these two measures (and perhaps others, including changes in H-reflex recovery and blood-flow changes seen in motor cortex on fMRI) will be helpful to confirm a cortical origin of the dystonic reflexes. Modification of the cortical reflex loop using magnetic stimulation may provide the basis for a potential new treatment for hypertonic dystonia in children.
In order to determine whether reflex activation of muscle affects voluntary movement, we have developed a special-purpose robotic arm that can safely apply perturbations to the elbow of children during arm movement. These experiments will be able to quantify reflexes during movement and the role of these reflexes in reducing speed or accuracy of movement.
A pilot trial on a small number of children and young adults with dystonia has shown that reflex muscle activation in dystonia is sometimes determined by joint position, sometimes by joint velocity, and sometimes by a combination. This suggests that individual patients may be subclassified by the response to position and velocity perturbations. It is possible that different etiologies of dystonia lead to different subtypes, and we plan to study a larger group of patients in order to evaluate this possibility and determine whether the classification affects treatment efficacy.
In collaboration with Yanmin Yang, we are developing the ability to perform equivalent EMG and reflex measurements in transgenic mouse pups with mutations in the BPAG1 gene. These mice have degeneration of sensory systems and a severe progressive generalized dystonia that may provide a model for the involvement of sensory deficits in human dystonia.
Pocket-Size Surface EMG Analysis Device
In collaboration with clinicians at five institutions in the US, we are testing a portable surface EMG device designed by Dr. Sanger that can be used in the clinic to evaluate for the presence of spasticity and dystonia and that can be used to determine subtypes of dystonia. We have completed initial reliability and validity testing and a paper has been submitted for publication. If the device proves to be useful in larger trials (and at least two of the other centers are now very enthusiastic about using the device for clinical evaluation), this could provide a major new tool for the clinical evaluation of movement disorders in children and adults.