IX. Neurological and Vascular Disorders

A. General

[208] FIRING PATTERNS OF UPPER AND LOWER MOTONEURONS AND THEIR TRANSLATION FACTOR

Joseph F. Jabre, MD; Byron T. Salzsieder, SM; David B. Albert, SM
Boston VA Medical Center, Boston, MA 02130

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
Department of Neurology, Boston VA Medical Center, Boston, MA 02130

PURPOSE--Two characteristics shape the response of a motoneuron to a descending input: one is probabilistic, ascribed to its own physical and electrophysiological properties; the other is deterministic, ascribed to the descending impulses on it. In this work, we set out to study the probabilistic response of the motoneuron to derive a "translation factor" that determines the firing rate response of a given motoneuron to the descending drive. A better understanding of this response should give us insight to the adaptive mechanisms of the nervous system in strokes and other disorders of the corticospinal tract.

METHODOLOGY--Contractions in the first dorsal interosseous muscle were studied in four male subjects. The Precision Decomposition Technique was applied to the EMG signal to derive information about the firing rates of a family of motor units. After the individual firing rates for each motor unit were calculated, we calculated the average firing rate of the active motor units. The residual firing rates for the individual motor units not accounted for by the common drive were then calculated as the deviations from the mean (i.e., as the differences between the actual firing rates of each motor unit and the average firing rate). As the value of the mean is affected by the number of motor units in the study, it is primarily the distribution of the residual values which was of interest. To relate these properties, inherent to the motoneuron itself, to the motor unit size, we collected the macro potential of the active motor units via a special cannula recording that was trigger averaged on the firing rate of individual motor units. The macro potential, it has been shown, gives an estimate of the number and size of the muscle fibers in a motor unit.

PRELIMINARY RESULTS--Histograms were made of the actual, and the residual, firing rates, of one particular motor unit within the steady state period of the force. While both sets of steady-state data are roughly gaussian in shape, the residual firing rates fit the normal curve more closely than the actual firing rates. When a histogram was created of the average firing rate, a gaussian pattern was observed again. A translation factor between the average firing rate and the firing rate of each individual motor unit was then calculated as follows: first, the ratio was calculated, at each discrete point in time, between the average firing rate for all motor units and the firing rate of an individual motor unit; the translation factor was then taken to be the average of these ratios. The translation factor had an inverse correlation with the macro size of each unit confirming the intimate relationship between the electrophysiological characteristics of the motor unit as measured by the translation factor and its size as measured by the macro potential.

[209] THE ELECTROTWITCH: A DYNAMIC CONCEPT IN FORCE GENERATION BY THE MOTOR UNIT

Joseph F. Jabre, MD; Byron T. Salzsieder, SM; David B. Albert, SM
Boston VA Medical Center, Boston, MA 02130

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
Department of Neurology, Boston VA Medical Center, Boston, MA 02310

PURPOSE--In this project, we set out to demonstrate the relationship between the motor unit firing rates and the force they generate to determine the role played by the various electromechanical properties of the motor unit. In addition, we investigated the electromechanical lag between individual motor units in a contraction and their corresponding force to better understand the role played by motor units of different types in the generation of force. This should lead to a better understanding of the compensatory mechanisms utilized by the nervous system in diseases of muscle and nerves.

METHODOLOGY--A series of human-subject experiments at the NeuroMuscular Research Center yielded data on the firing trains of motor neurons in the first dorsal interosseous muscle and concurrent data on the force applied by the index finger of the subject on a force plate. The instantaneous firing rates of the motor units were calculated, and the resulting sequences were analyzed both individually and in comparison with the force data. Force graphs were then obtained and compared to a weighted sum of the motor unit firing rates. The weights used being the areas of the macro signals for each motor unit. Electromechanical lags were computed numerically by performing cross-correlations between the firing rate of each motor unit and the overall force, altering the time-offset between the two variables. The actual value of the electromechanical lag is taken to be that offset at which the correlation is greatest.

PRELIMINARY RESULTS--Since force generation is a function of the electrophysiological properties of a motor unit and the dynamic changes which result from its firing rates, a factor is derived to take into account the size and firing rate of the motor unit. We propose to use the product of the firing rate of the motor unit by its macro area to give an estimate of the force it generates. We refer to this factor as the electrical twitch of a motor unit or its "electrotwitch." Analysis of the firing rates versus the force data show that major features in the weighted sum of the firing rates are highly correlated with similar major features in the force. As for the electromechanical lag, it varied between 90 and 140 ms in our sample, with the smaller units having the shortest electromechanical lag and the larger units the longest. This is in keeping with studies which show that smaller motor units respond more quickly to a given change in the central drive than do larger motor units.

[210] EFFECTS OF AGING ON MOTOR UNIT FIRING BEHAVIOR: HAND DOMINANCE EFFECT

Zeynep Erim, PhD; Alexander Adam, BS; Carlo J. De Luca, PhD
NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: adam@bunmrg.bu.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B829-RA)

PURPOSE--Daily preferential use of a muscle has been associated with higher fatigue resistance and possibly increased percentage of slow-twitch fibers in muscles of the dominant hand. The present study was aimed at revealing any differences in the control properties of contralateral muscle pairs in individuals who show a clear preference for one hand.

METHODOLOGY--The first dorsal interosseous muscle in both hands of three right-handed and four left-handed male subjects was tested at a force level of 30 percent of maximal voluntary contraction.

PRELIMINARY RESULTS--The recruitment thresholds and the firing rates of motor units in the dominant hand were lower when compared to motor units in the nondominant hand. Contralateral differences were less pronounced in the left-handed subjects, possibly due to the certain level of ambidexterity among this group. A greater delay between common fluctuations of mean firing rates and the force were observed in the dominant hand. No difference was seen in the maximal voluntary contraction strength between the dominant and nondominant sides. The measured lower firing rates, lower recruitment thresholds, and greater firing rate-to-force lead times in the dominant hand are consistent with the notion of an increased percentage of slow-twitch fibers in the preferentially used muscle. Since slow-twitch fibers exhibit twitch fusion at lower contractile rates, motor units in the dominant muscle are able to generate force at lower firing rates than their counterparts in the nondominant hand.

RECENT PUBLICATIONS FROM THIS RESEARCH

[211] EFFECTS OF AGING ON MOTOR UNIT FIRING BEHAVIOR

Zeynep Erim, PhD; M. Faisal Beg, BS
NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: mirza@acs.bu.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B829-RA)

PURPOSE--A number of changes occur in the neuromuscular system with the natural aging process. There is a marked reduction in strength, agility, precision in muscle control, as well as an increased tendency to fatigue sooner. There have been a number of age-related studies on the morphological characteristics of the motor unit. However, little is known about the alterations that take place in the control strategies the central nervous system employs to produce force. It is hypothesized that along with the changes in motor unit properties with age, there is also an alteration in the activation pattern and firing behavior of motor units, possibly to accommodate the changes in the morphological properties. The results of this study will provide insight into these age-related changes and lay the groundwork for improving the quality of life for the elderly.

METHODOLOGY--The first dorsal interosseous muscle was chosen to be studied in both male and female subjects belonging to four age groups: 20-35, 35-50, 50-65, and older than 65. Contractions were performed at 20, 50, and 80 percent of the maximal voluntary contraction level of the subject. Electromyographic signals detected via needle and surface electrodes were recorded along with the force generated by the muscle.

PRELIMINARY RESULTS--Presently, we have tested six subjects in the age group 20-35 years, four in group 35-50, one in the 50-65 group, and three older than 65 years of age. The decomposition of the collected data into the firing activity of individual motor units was achieved using Precision Decomposition. Further testing of subjects and decomposition and data analysis are in progress.

[212] EFFECTS OF AGING ON MOTOR UNIT FIRING BEHAVIOR: RANK-ORDERED REGULATION OF MOTOR UNITS

Zeynep Erim, PhD; Carlo J. De Luca, PhD; Kiyoshi Mineo, PhD
NeuroMuscular Research Center, Boston University, Boston, MA 02215; Keio Medical School, Tokyo 160 Japan; email: erim@bu.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B829-RA)

PURPOSE--Henneman's monumental contributions to the field of motor unit control led to his well-known size principle indicating the correlation between the size of the motor unit and its recruitment order. The present study was undertaken to complement this work by investigating whether a parallel correlation existed between the recruitment rank, or threshold, of the motor unit and the firing rate at which it operated once recruited. A thorough understanding of the control of motor units in normal force generation is hoped to form the groundwork for developing tools to diagnose and treat individuals with impaired motor function.

METHODOLOGY--Myoelectric signals were detected from the tibialis anterior muscle while subjects generated isometric forces that linearly increased up to the maximal voluntary level. The firing behavior of motor units was studied as a function of the corresponding force output. The use of specialized data acquisition and processing techniques enabled the investigation of a wide range of motor units, in contrast to previous studies which had been limited to only the low-threshold motor units, due to the increased difficulty of reliable identification of motor unit activities at higher force levels.

PRELIMINARY RESULTS--The analysis of data revealed that the recruitment threshold of the motor unit was closely correlated to its other operational parameters, such as mean firing rate, initial firing rate, and response to the requirement to increase the force output. The observation of rank-ordered motor unit properties supports the theory of common drive, which states that motor units of a motoneuron pool are controlled not by individual control signals but by a common command signal. The rank-dependent distribution of motor unit properties would make it possible for motor units to generate different responses, suited to their individual physical properties, to a common input.

RECENT PUBLICATIONS FROM THIS RESEARCH

[213] EXERCISE TESTING AND TRAINING OF MULTIPLE SCLEROSIS PATIENTS

Janet A. Ponichtera-Mulcare, PhD; Thomas Mathews, MD; Kathleen O. Glaus, PhD, PsyD; Paul Webb, MD; D. Drew Pringle, Ed.D., Satyendra C. Gupta, MD
Dayton VA Medical Center, Dayton, OH 45428; School of Professional Psychology, Wright State University, Dayton, OH, 45435; email: jmulcare@desire.wright.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B747-2RA)

PURPOSE--The purpose of this 3-year study is to 1) further document metabolic and cardiopulmonary responses to leg and arm/leg exercise in order to standardize training norms for MS patients; 2) examine physiologic adaptations to both continuous and discontinuous exercise training protocols and at a greater than moderate level of intensity and duration; 3) evaluate the efficacy of a cooling garment to reduce thermal stress and its adverse affect upon exercise performance; and 4) determine the effects of these interventions upon independent and assisted ambulation, psychological status, and general health parameters. The stress-testing protocols will be used to obtain baseline measurements of physical capabilities/limitations, as well as to indicate changes in fitness as a result of exercise training.

METHODOLOGY--All 30 subjects with MS (15 ambulatory, 15 nonambulatory) will perform several pretraining tests to measure baseline body composition, joint range of motion, ambulation, psychological status, maximal aerobic power, and aerobic endurance. Gait characteristics will be studied using both kinematics and force plate measurements. Psychological status (i.e., affect, mood, and cognition) will be measured pre- and post-training using appropriate, validated tests for each (e.g., BDI, MDI, NIS, Trails A & B, FSS, Q-LES-Q, Wechsler Memory Scale-Revised, Aphasia Screening Test, Neuropsych Interview).

PROGRESS--We have recruited 18 individuals with MS. All 18 have received a preliminary neurological examination and finished body composition testing, resting ECG, medical history, maximal aerobic power, aerobic endurance, and psychological status; and 17 have completed gait analysis. At this point in time, 4 people have had to drop out and 1 has not started the exercise portion of the study due to health problems; therefore, 13 individuals are participating in the exercise portion of the study. Three individuals have completed 6 months of exercise (3 months with the cooling garment and 3 months without it) and have also completed their post testing, which includes the same tests conducted as before training with exception of resting ECG. The other 10 individuals have all completed at least 3 months of training and have finished their mid-point testing. Mid-point testing consists of maximal and endurance aerobic testing and psychological status. Efforts are being made to recruit more individuals for this study in order to have another group of individuals ready to train when the present group is finished. Six water flow and volume control devices are being used to keep water temperature and flow volume precise. All units are paired with an exercise bicycle for the training session. All six body cooling suits have been finished and tested several times to insure proper working condition. Many revisions have been made, and they are functioning as intended. The computer program necessary to run the maximal aerobic tests has been functioning properly, and over 100 maximal or endurance aerobic tests have been conducted. As for the psychological testing, all of the necessary testing forms have been received and psychological testing has been conducted as necessary.

FUTURE PLANS/IMPLICATIONS--Further research should evaluate other modes of exercise for testing and training, more aggressive protocols, and the efficacy of commercially available body cooling devices upon acute and chronic physiological, psychological, and functional outcomes following aerobic exercise training.

[214] SYNCHRONIZATION AND COMMON DRIVE OF MOTOR UNITS

Carson C. Chow, PhD; Carlo J. De Luca, PhD; James J. Collins, PhD
NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: ccc@acs.bu.edu

Sponsor: Boston University, Boston, MA 02215

PURPOSE--The synchronization of motor units is an experimentally robust phenomenon. However, it seems to have no apparent physiological purpose. It is the contention of this study that the observed synchronization is an epiphenomenon of common drive which has been previously proposed to explain the correlation of firing rates between different motor units.

METHODOLOGY--A simple common drive model was used to examine synchronization. The model consisted of integrate-and-fire neuronal oscillators driven by a common drive, which was composed of a DC signal and a correlated noise source. Each oscillator also received independent white noise. Synchronization was then analyzed in the model using methods similar to those utilized previously for the experimental data. The statistical tendencies of synchronization of the model were calculated analytically and with numerical simulations. These were then compared to the experimental data.

PRELIMINARY RESULTS--The common drive model predicts the behavior of synchronization in the data quite well. The model predicts that the probability of finding synchronization increases with the length of the spike train. The model also predicts that the number of observed consecutive synchronization events should occur with an exponential distribution. Both of these results have been confirmed experimentally.

[215] EVALUATION OF CARPAL TUNNEL SYNDROME

Gina Rajterowski, BS; Zeynep Erim, PhD; Markus Khouri, BS; Carlo J. De Luca, PhD
NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: erim@bu.edu

Sponsor: Boston University, Boston, MA 02215

PURPOSE--The number of cumulative trauma disorder cases reported by the U.S. Bureau of Labor Statistics in 1993 represented a 63 percent increase from the figures in 1990. Carpal tunnel syndrome (CTS), resulting from the compression of the median nerve at the carpal tunnel, is the most common type of cumulative trauma disorder. In spite of its prevalence in the modern work environment, the clinical tests currently used to assess the syndrome are subjective and often inconclusive. The purpose of this project was to design an objective, quantitative, and noninvasive method to evaluate a patient's involvement with CTS.

METHODOLOGY--An arm and hand restraint device was built that enables surface electromyographic and force measurements from the thenar and hypothenar muscle groups. This device allows the combined output force to be displayed on-line to the subject for visual feedback. The subject was asked to trace a trajectory displayed on a computer screen by controlling the strength of a pinching motion to be performed with the thumb and fifth digit. Specific instructions regarding how much force to exert with each finger were not provided to the subject. Five CTS and five nonimpaired subjects (controls) were tested using this experimental protocol. Force and surface electromyographic (EMG) signals from the thenar and hypothenar muscle groups were recorded.

PRELIMINARY RESULTS--Preliminary analysis of experimental data revealed different trends in patients and controls as expected. Regression analysis performed on force and EMG signals yielded several parameters that had statistically different means in the two populations. These parameters could ultimately be used to classify a subject in the nonimpaired or CTS groups, and to devise an index to provide a scaled measure of severity of damage.

[216] EFFECT OF MICROCLIMATE COOLING ON PHYSICAL FUNCTION IN MULTIPLE SCLEROSIS (MS)

George H. Kraft, MD; Alan D. Alquist, MD
University of Washington MS Clinical Center, Seattle, WA 98195-6490; email: ghkraft@u.washington.edu; flag@u.washington.edu

Sponsor: Multiple Sclerosis Association of America, Oaklyn, NJ 08107

PURPOSE--As clinicians actively engage in the care of a large number of MS patients, we consistently note that heat-sensitive patients (HSMS) are more adversely affected in certain activities than others; specifically, those activities requiring repeated effort. Typical acute physiologic, motor and self-perceived stress among HSMS patients include: worsening of existing neurologic signs and symptoms, the development of new signs and symptoms, and lassitude.

  This study focused on active cooling-induced effects upon motor function as measured by changes in: skeletal muscle strength, systemic endurance, and dynamic and standing balance.

METHODOLOGY--For inclusion in this study as HSMS, subjects met the following criteria: all had definite MS, were females aged 18-55, had a rating on the Kurtzke Expanded Disability Status Scale (EDSS) of 4.0-5.5, inclusive, a self-perception of heat sensitivity that impairs activities of daily living (ADL), and positive responses on the Thermal Sensitivity Inventory (TSI). All were medically stable with no change in signs, symptoms, or medications for chronic conditions including MS, and less than 20 percent over ideal body weight.

  We employed a one-group, two-treatment, repeated-measures, within-subjects design. The treatment (temperature) condition was randomly ordered and had two levels: sham body cooling (SC; 26.5 °C) and active body cooling (AC; 7 °C) and the order factor had two levels. Twenty-two HSMS subjects (4.0< EDSS on the Kurtzke Expanded Disability Status Scale <5.5) were recruited, 19 began experimentation; 18 subjects could perform the evaluations and 17 completed the experiment series. The data were analyzed employing a repeated measures analysis of variance method. The randomization sequence was used as a blocking factor.

  Subjects were fitted with a Mark I Medical Cooling Garment (Life Enhancement Technology, Mountain View, CA). The garment was fitted snugly to the torso and head to effect conductive cooling of each patient. The HSMS wore the garment for 60 min while resting comfortably in a chair. Body core temperature, heart rate, and brachial blood pressure were monitored every 5 min. The coolant temperature is regulated by, and pumped from, a temperature control unit. The coolant flow rate, pressure, and garment inlet and outlet temperatures were monitored continuously thoughout all experiments.

PROGRESS--Data collection and anaylsis are complete.

RESULTS--There was significant before and after evaluation by treatment condition interactions in several measurement domains: strength (quadriceps), F[1,15]4.53 (F=3.07, p<0.05), endurance task (leg cycling), F[1,15]8.84 (F=6.77, p<0.01), dynamic balance task (tandem gait), F[1,15]6.71 (F=3.07, p<0.05), single leg standing balance, F[1,15]7.48 (F=6.77, p<0.01), and ambulation velocity, F[1,15]3.18 (F=3.07, p<0.05). There were no pure order effects, however, an order by temperature by pre-post interaction in tandem gait, F[1,15]6.48 (F=3.07, p<0.05) and ambulation velocity, F[1,15]5.61 (F=3.07, p<0.05).

IMPLICATIONS--We conclude that active body cooling (7 °C) in a controlled microclimate cooling device will effectively increase motor function as measured by strength, coordination and endurance to effect repetitive activities.

FUTURE PLANS--We shall study similar performance outcomes when active liquid cooling is used chronically (long-term) among heat-labile MS patients.

[217] CENTRAL NERVOUS SYSTEM CONTROL RULES FOR VOLUNTARY MOVEMENT

Gerald L. Gottlieb, PhD
NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: glg@bu.edu

Sponsor: National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892

PURPOSE--To understand how the brain controls the limbs to perform purposeful movement, we need to know what kinds of commands are sent to the muscles and what variables are used to plan and construct them. For example, does the control system plan a movement's path and velocity through space and then from this computes the forces necessary to produce it? Does the system plan a path and rely on neurophysiological feedback mechanisms to generate the desired forces? Or, does it plan forces that from past experience it expects will produce a satisfactory movement, and then monitor the outcome to see if it was correct?

  The work of the Motor Control Lab focuses on this third alternative and performs experiments to test its hypotheses and implications. We predict that not only will a better understanding of brain function emerge from this research, but that it will lead to new insights and a better way of evaluating patients with motor deficits.

METHODOLOGY--Subjects were asked to make simple pointing movements, either in a special apparatus that limits motion to a single joint (the elbow or wrist) or unconstrained movement of the whole limb. The motion was measured by our apparatus and the concurrent electrical activity of the muscles (electromyography) was recorded from the skin with surface electrodes.

PRELIMINARY RESULTS--We have developed a model for how the muscle activation patterns are planned, based upon features of the planned movements such as its distance and speed, and the dynamic properties of the load. These are nonlinear rules because of constraints imposed by muscle contractile properties. Muscle forces are produced and from these, movement characteristics are emergent. Reflexes play a supportive and adaptive but subordinate role in this process. Movement skill emerges from practice in which individuals learn the proper muscle activation patterns by trial and error.

RECENT PUBLICATIONS FROM THIS RESEARCH
  • "Adequate Control Theory" for human single-joint elbow flexion on two tasks. Gottlieb GL, Chi-Hung C, Corcos DM. Ann Biomed Eng 1995:23:388-98.
  • Relations between joint torque, motion and EMG patterns at the human elbow. Gottlieb GL, Chi-Hung C, Corcos DM. Exp Brain Res 1995:103:164-7.

    [218] A THEORY OF SPATIOTEMPORAL CHAOS

    Carson C. Chow, PhD; Terence Hwa, PhD
    NeuroMuscular Research Center, Boston University, Boston, MA 02215; Department of Physics, University of San Diego, La Jolla, CA; email: ccc@acs.bu.edu

    Sponsor: National Science Foundation, Arlington, VA 22230

    PURPOSE--The majority of the theoretical results in the study of chaotic dynamics has been confined to low dimensional systems. However, many systems, including those found in biology, are spatially extended with many degrees of freedom. Here a theory to understand a specific type of spatiotemporal chaos (STC) is proposed. This theory could impact the understanding of other models related to neurophysiology.

    METHODOLOGY--The Kuramoto-Sivashinsky (KS) equation describing propagating chemical fronts was analyzed. Due to its simplicity it is often considered a paradigm of STC. The STC in the KS equation is manifested as the chaotic dynamics of coherent structures. The equation was analyzed using novel averaging and perturbation techniques in conjunction with numerical simulations. An understanding of the dynamics in the large system limit and in a statistical sense was desired.

    PRELIMINARY RESULTS--The deterministic KS equation exhibits STC that has specific statistical behavior and scaling that can be measured numerically. These were shown to be equivalent to those of a stochastically driven nonlinear diffusion equation. The latter was tenable to theoretical analysis by known techniques of statistical field theory. This result gives hope that other multiple degree of freedom systems, such as the collective dynamics of many coupled neurons, can be understood analytically.

    [219] APERIODIC STOCHASTIC RESONANCE IN MODEL NEURONS

    James J. Collins, PhD; Carson C. Chow, PhD; Thomas T. Imhoff, MS
    NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: collins@bunmrg.bu.edu

    Sponsor: National Science Foundation, Arlington, VA 22230

    PURPOSE--Stochastic resonance (SR) is a phenomenon wherein the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular level of noise. SR has been examined theoretically and experimentally in a wide variety of systems, including sensory neurons. All of this work, however, has been limited to the treatment of systems with periodic inputs. This focus has served to limit the applicability of SR to practical situations, given that real-world external signals are often not periodic. The objective of this study was to develop a theory and method for characterizing SR-type behavior in model neurons with aperiodic inputs. For this general type of behavior, we coined the term aperiodic stochastic resonance (ASR).

    METHODOLOGY--We developed two measures, the power norm and normalized power norm, for characterizing ASR. These measures enable one to quantify the two noise-induced effects associated with SR, such as signal amplification and optimal stimulus-response coherence. We conducted a series of computer experiments with the FitzHugh-Nagumo (FHN) neuronal model. We studied its dynamics under the influence of a subthreshold aperiodic signal plus noise. We also developed an analytical theory to account for the obtained dynamics of the FHN model.

    PRELIMINARY RESULTS--We found that the results from the FHN model exhibited characteristic signatures of SR-type behavior: as the input noise intensity was increased, the stimulus-response coherence rapidly increased to a clear peak and then slowly decreased. We also found that our analytical theory matched the numerical results. This work clearly shows that SR-type behavior is not limited to systems with periodic inputs. Thus, in general, noise can serve to enhance the response of a nonlinear system to a weak input signal, regardless of whether the signal is periodic or aperiodic.

    RECENT PUBLICATIONS FROM THIS RESEARCH

    [220] STOCHASTIC RESONANCE WITHOUT TUNING

    James J. Collins, PhD; Carson C. Chow, PhD; Thomas T. Imhoff, MS
    NeuroMuscular Research Center, Boston University, Boston, MA 02215; email: collins@bunmrg.bu.edu

    Sponsor: National Science Foundation, Arlington, VA 22230

    PURPOSE--Stochastic resonance (SR) is a phenomenon wherein the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular level of noise. SR has been proposed as a means for improving signal detection in a wide variety of systems, including sensory neurons. However, for SR to be utilized in a single-unit system (e.g., a sensory neuron), the intensity of the system's input noise must be dynamically modulated as a function of the changing nature of the signal to be detected. The objective of this study was to show that a fixed level of input noise can optimally enhance the ability of a summing network of excitable units to detect a range of subthreshold (weak) signals, which can be periodic or aperiodic.

    METHODOLOGY--We considered a summing network made of identical excitable units, which were taken to be FitzHugh-Nagumo (FHN) model neurons. Each unit was subjected to a common input signal and its own independent noise source. We assumed that information was transmitted by each unit via temporal changes in its firing rate. The network operated by summing the mean firing rate (MFR) signal from each unit to obtain a resultant MFR signal for the entire system. We conducted a series of computer experiments with this model.

    PRELIMINARY RESULTS--We found that the stimulus-response coherence for the system was enhanced as the size of the network was increased. We also showed that a fixed level of independent noise on each unit of a relatively large summing network could optimally enhance the network's ability to detect a range of subthreshold signals. Importantly, we also found that the presence of such noise did not significantly affect the network's ability to detect suprathreshold signals. These findings suggest that constant levels of internal or external noise on each neuron in a sensory system could optimally enhance the overall response of the system to a range of subthreshold signals, even for conditions wherein the individual responses of the neurons are not optimized.

    RECENT PUBLICATIONS FROM THIS RESEARCH

    [221] A NOVEL MECHATRONIC DEVICE FOR ASSESSMENT OF BALANCE SKILLS AND DEFICIENCIES

    Lars Oddsson, DrMedSci; Carlo J. De Luca, PhD; Mats Hansson, PhD; Alf Thorstensson, PhD
    NeuroMuscular Research Center, Boston University, Boston, MA 02215; Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institute, Lidingovagen 1, Stockholm, Sweden; email: loddsson@acs.bu.edu

    Sponsor: The Whitaker Foundation, 1700 N. Moore St., Suite 2200, Rosslyn, VA 22209

    PURPOSE--Subjects losing balance during standing display different preprogrammed behaviors to recover equilibrium, depending on the severity of the balance perturbation and the experience and condition of the subject. This project is focused on increasing our understanding about strategies used by the central nervous system to maintain equilibrium in situations when upright standing balance is challenged.

    METHODOLOGY--Subjects standing on a computer controlled moveable balance platform (BALDER) were exposed to balance perturbations at the feet in eight different directions. Whole body 3D kinematic information was recorded together with ground reaction forces. Electromyographic (EMG) activity was recorded bilaterally from muscles controlling movements of the arms, trunk and legs.

    PRELIMINARY RESULTS--Results to date appear to confirm previous findings in the literature and further expand on the concept of the utilization of strategies for the maintenance of balance following a perturbation. EMG activity of muscles controlling movements of the arms appeared within 100 ms after the perturbation. The ensuing arm movements displayed directional specificity with respect to the perturbation suggesting that they were a part of the postural program triggered by the postural perturbation.

    B. Swallowing Disorders

    [222] EFFECTS OF AGE ON OROPHARYNGEAL SWALLOWING

    JoAnne Robbins, PhD; Jennifer Wood, MS; Ross Levine, MD; Gail Dengel, MS; Kimberly A. Chignell, MS; Todd Kennell, MD
    William S. Middleton Memorial Veterans Hospital, Department of Medicine, 2500 Overlook Terrace, Madison, WI 53705; email: jrobbin2@facstaff.wisc.edu

    Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
    (Project #E727-2RA)

    PURPOSE--The long-term objective of this project is to increase understanding of the effects of aging on swallowing physiology in an effort to advance the diagnosis and treatment of swallowing disorders in age-related disease. Swallowing profiles will be compared in normal adults and unilateral stroke patients from 45 to 95 years of age. One hypothesis is that lingual pressure predicts hyolaryngeal and upper esophageal (UES) kinematic parameters, bolus transit measures, and dietary choices.

    METHODOLOGY--Recent efforts have focused on development of new instrumentation which allows for concurrent recording of video and physiologic data (multiple lingual pressures and submental EMG). Subjects perform two kinds of tasks, isometrics and barium swallows, with a thin strip of pressure-sensitive air-filled bulbs attached to the midsaggital line of the hard palate. The three pressure bulbs measure tongue strength simultaneously at anterior, mid-, and posterior palate. Pressure from each bulb is transduced and recorded on the Kay Elemetrics Workstation and linked with video data in order to facilitate understanding of amplitude by time relationships as they impact bolus transfer during swallowing. Two electrodes placed submentally record EMG in a time-linked fashion.

    PROGRESS--Pilot testing with new instrumentation has been completed on six nonimpaired young subjects (mean age 31) and six nonimpaired old subjects (mean age 78) in the bulb-in and bulb-out conditions to determine how the presence of the pressure bulbs affects swallowing. Principle components analysis of the submental EMG recordings indicated no significant systematic differences in the bulb-in and bulb-out conditions. The absence of a "bulb condition effect" indicates that swallowing physiology with the intraoral pressure measuring instrument in place is similar to normal swallowing, and we may therefore proceed with the new instrument as an integral part of our methodology. Significant differences in the EMG signal were found, however, for bolus viscosity (liquid/semisolid) and age. Older subjects tended to have reduced EMG amplitude and a smaller range of phase shifts relative to their young counterparts.

      While instrument development was underway, we used the Iowa Oral Performance Instrument (IOPI), a single air-filled pressure-sensitive bulb, to obtain maximum lingual pressures during isometric and saliva swallows in 15 nonimpaired old subjects (mean age 75) and 25 stroke patients (mean age 69). Performance on the isometric task did not distinguish normal from stroke groups nor did it differentiate stroke subjects from each other by site of lesion. However, the patients showed a trend toward reduced swallowing pressures at the blade position (p=0.07). Also, patients who generated lower isometric pressures tended to have slower oral transit duration on videofluoroscopy.

    IMPLICATIONS--Our preliminary findings suggest that task demands of a coordinated movement like swallowing may differentiate stroke patients from normal age-matched individuals, while isometric tasks do not. This notion has important diagnostic and treatment implications. That is, these data suggest that resistance exercises, specifically lingual strength-building exercises, may be useful for dysphagia prevention with aging while therapy goals focused on improving swallowing coordination may be more useful for a stroke patient.

    FUTURE PLANS--With development and pilot testing of intraoral pressure sensitive instrumentation completed, recruitment of normal and stroke subjects into the finalized protocol has begun. Analysis of multiple lingual pressures and EMG data is currently being facilitated by development of software. Isometric and swallowing pressure tasks in combination with videofluoroscopic data may reveal a diagnostic approach for determining the presence and type of neuropathology underlying dysphagia. Additionally, this research may contribute to improved rehabilitation strategies for stroke patients and facilitate development of a dysphagia prevention program for relatively healthy geriatric individuals.

    RECENT PUBLICATIONS FROM THIS RESEARCH

    C. Vascular Disorders

    [223] LUMBAR SYMPATHECTOMY IN THE PREVENTION OF MAJOR AMPUTATION OF THE EXTREMITY: A PILOT STUDY

    Bok Y. Lee, MD; Lee E. Ostrander, PhD
    Surgical Service, VA Medical Center, Castle Point, NY 12511; BME Department, Rensselaer Polytechnic Institute, Troy, New York 12180; email: ostral@rpi.edu

    Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
    (Pilot Project #A93-695PA)

    PURPOSE--The purpose of this study is to determine the role of lumbar sympathectomy in diabetic and nondiabetic patients with peripheral vascular disease, ischemic gangrene of the lower extremity, and impending limb loss, with or without bypass, and to investigate the content of substance P in the ventral root sympathetic ganglia and chain and peripheral tissue per and post-lumbar sympathectomy tissue biopsies at the ulcer site. We seek to determine whether diabetic patients with peripheral vascular disease have a lower sympathetic response to lumbar sympathectomy than those with peripheral vascular disease only.

    METHODOLOGY--Ten patients with peripheral arterial occlusive disease (presenting with ischemic gangrene of the foot or toes) and ten diabetic patients with peripheral arterial disease (presenting with gangrene or ulcers and impending limb loss) undergoing lumbar sympathectomy will be stratified in four equal groups. Biopsy of the affected area will be performed before and after the procedure for measurement of substance P content. Noninvasive vascular tests will be performed preoperatively and on postoperative days 1 and 4a; and at 3.6, and 12 months.

      The sympathectomy ganglia will be examined for substance P using immunohistolchemical assay, and the results will be compared among groups. Improvement of the subcutaneous and muscle blood flow as well as oxygen tension will be evaluated with TcPO2 laser Doppler and thermistor thermometry. A positive result will be considered improvement in healing of the chronic ulcers, prevention of a major amputation, or reduction of level of amputation.

    RESULTS--Of the 20 patients required for the study, 2 nondiabetics and 7 diabetics are currently enrolled. To date, two patients have had a 9-month follow-up. Some interesting observations made so far related to the quantitative measurements of substance P. Elevated levels of substance P were detected in diabetic foot ulcers compared to nondiabetics. In addition, statistically significant results in substance P have been seen in diabetic ulcers after sympathectomy, associated with healing of treated ulcers.

    [224] A PROSPECTIVE STUDY OF RISK FACTORS FOR DIABETIC FOOT ULCER

    Edward J. Boyko, MD; Douglas G. Smith, MD; Jessie H. Ahroni, ARNP, MN
    Seattle VA Medical Center (111M), Seattle, WA 98108; Department of Medicine University of Washington, Seattle, WA 98195; email: eboyko@u.washington.edu; dgsmith@u.washington.edu; ahroni.jessie@seattle.va.gov

    Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
    (Project #A318-4RA)

    PURPOSE--We are conducting prospective research designed to identify risk factors for foot ulceration associated with diabetes. We are examining the independent contributions of foot deformity, macrovascular and microvascular disease, peripheral neuropathy and behavioral factors on the risk of developing a full thickness diabetic foot ulcer.

    METHODOLOGY--Eligible subjects are enrolled in a general internal medicine clinic, and meet the criteria for diabetes mellitus by physician diagnosis or treatment with hypoglycemic medication or insulin. Participants attend a Diabetic Foot Clinic where we assess the presence of suspected risk factors grouped into four categories: circulation, neuropathy, foot deformity, and self-care behaviors. Circulation factors include lower extremity Doppler blood pressures, toe blood pressures, transcutaneous oximetry (TcPO2) at five lower extremity sites, laser Doppler flowmetry at the dorsal foot, arterial pulse palpation, venous filling time, and capillary refill time. Neuropathy measures in the lower extremities include monofilament testing, bioesthesiometry, deep tendon reflexes, measures of intrinsic muscle atrophy, and cardiovascular reflexes that reflect autonomic neuropathy. Foot deformity measures include clinical examinations, posture and gait assessments, joint ankle measurements, and Harris mat testing for abnormal pressure points. Behavioral factors assessed include type of footwear, diabetes history and control, foot self-care practices, and visual acuity.

      To assess development of the outcome of interest, all subjects receive yearly repeat examinations and a quarterly mailed questionnaire asking them to report the occurrence of ulcer. We compare rates of outcome occurrence (incidence) by exposures of interest to determine which particular factors are related to risk of diabetic foot ulcer.

    PROGRESS--To date we have enrolled 835 diabetic subjects from the Seattle VAMC general internal medicine outpatient clinic.

    PRELIMINARY RESULTS--As of January 1996, we observed 110, 6.1 per 100 person years (PY), foot ulcers occurring over a cumulative 1,812 PY. Using stepwise Cox regression analysis, the following factors were independently and significantly (<0.05) related to foot ulcer risk: insensitivity to the 5.07 monofilament, relative risk (RR)=3.0, 95 percent confidence interval (CI) 1.6-5.4; diminished vibratory sensation RR=2.1, 95 percent CI 1.2-3.5, orthostatic blood pressure drop of 30 mmHg RR=2.0, 95 percent CI 1.2-3.2; history of amputation RR=2.6, 95 percent CI 1.4-4.7; hallux rigidus RR 1.8, 95 percent CI 1.1-2.8; poor vision <20/40 bilaterally RR 1.7, 95 percent CI 1.1-2.7; and 30 mmHg TcPO2 decrease on the dorsal foot RR=1.7, 95 percent CI 1.1-2.5.

      We prospectively categorized 759 subjects for their risk of developing diabetic lower extremity complications by two standard risk stratification schemes. We found that one provided no information on the risk of foot complications and subjects categorized as high risk by the other had a risk of these complications only slightly higher than their average pretest risk. Multivariate logistic regression analysis identified five clinical factors predictive of diabetic foot ulceration and five clinical factors predictive of amputation. When all five factors are present the probability of a foot ulcer is 68 percent and the probability of an amputation is 84 percent.

    FUTURE PLANS/IMPLICATIONS--The etiology of diabetic foot ulcer is complex, and includes sensory and autonomic neuropathy, forefoot rigidity, low skin oxygenation, poor vision, and past history of amputation.

    RECENT PUBLICATIONS FROM THIS RESEARCH

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