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Biomedical subjects

A W Wiegner

Publications and source records attributed to A W Wiegner.

At least 19 recordsLinked to original sources
PubMed2005

Quantitative analysis of the "warm-up" phenomenon in myotonic dystrophy type 1.

To quantitate improvement in hand-grip myotonia and muscle strength (i.e., the "warm-up" phenomenon) in myotonic dystrophy type 1 (DM1), six successive, standardized maximum voluntary isometric contractions (MVICs) were recorded on 2 separate days using a computerized isometric hand-grip myometer in 25 genetically confirmed DM1 patients and in 17 normal controls. An automated computer program placed cursors along the declining (relaxation) phase of the MVICs at 90%, 50%, and 5% of peak force (PF) and calculated relaxation times (RTs) between these points. Mean 90% to 5% RT (a measure of myotonia) rapidly declined from 2.5 s in MVIC 1 to 0.8 s in MVIC 6 (warm-up = 1.7 s) in DM1; in controls, it remained 0.4 s for all six MVICs (warm-up = 0). In DM1, 70% of warm-up occurred between MVIC 1 and 2, almost exclusively in the terminal 50% to 5% phase of muscle relaxation. Day 1 warm-up was highly correlated with the severity of myotonia, and with day 2 warm-up. Improvement in myotonia was not accompanied by either transient paresis or improvement in PF. We conclude that, with this testing paradigm: warm-up of myotonia in DM1 can be reliably measured; is proportional to severity of myotonia; occurs rapidly, being most prominent between the first and second grips; mainly results from shortening of the terminal phase of muscle relaxation; and is not accompanied by significant warm-up in force output.

Adult↗
PubMed2004

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1.

OBJECTIVE: To quantitate hand muscle myotonia and to assess the relationship between CTG repeat length and myotonia in myotonic dystrophy type 1 (DM1). METHODS: First dorsal interosseous twitch and tetanic contractions evoked by single and 10-Hz ulnar nerve stimulation were recorded with a force transducer in 15 patients with genetically confirmed DM1 and 15 control subjects. An automated computer program analyzed three single and three tetanic recordings per subject on 2 successive days by placing cursors along the declining (relaxation) phase of the force recordings at 90, 50, and 5% of peak force (PF) and calculating relaxation times (RT) between these points. RESULTS: Tetanic and twitch RT was longer and PF lower in patients than subjects. RT (90 to 5%) was above the normal mean + 2.5 SD in 13 tetanic (87%) and 11 (73%) twitch patient recordings. In DM1, prolongation of RT was due mainly to delay in the terminal (50 to 5%), rather than the initial (90 to 50%) phase of relaxation, and was much greater in tetanic than single-twitch recordings. Mean test-retest variability was 19% for tetanic RT and 16% for tetanic PF. In DM1, both tetanic and twitch RT were positively correlated with leukocyte CTG repeat length. CONCLUSIONS: In DM1, myotonia of intrinsic hand muscles can be quantitated reliably by automated analysis of tetanic and twitch RT, targeting, in particular, the terminal phase of muscle relaxation after tetanic stimulation. Severity of hand muscle myotonia depends on CTG repeat length consistent with a "triplet repeat dosage" effect on chloride channel mRNA splicing and function.

Adult↗
PubMed1996

Force pattern of hypoxic myocardium applied to oxygenated muscle preparations: comparison with effects of regional ischemia on the contraction of non-ischemic myocardium.

OBJECTIVE: To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. METHODS: Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. RESULTS: Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. CONCLUSION: The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.

Animals↗
PubMed1996

Accuracy of motor responses in subjects with and without control of antagonist muscle.

1. The aim of this study was to investigate the role of the antagonist muscle in determining the accuracy of fast, single-joint motor responses to a target. We recently found that C5/C6 tetraplegic subjects, who lacked voluntary control of their triceps muscle, were less accurate than control subjects in producing fast flexion movements to a target. 2. Two hypotheses are proposed to account for these larger errors: 1) the ability of tetraplegic subjects to compensate for errors arising early in the motor response is impaired because of the lack of antagonist muscle activation; or 2) tetraplegic subjects lack antagonist (braking) force, so they must use much smaller accelerative forces when they move, in order to avoid overshooting their target. Because studies have shown that low levels of force are produced with less relative accuracy than larger forces, this relative inaccuracy of force generation by the motor control system at low force levels is responsible for the inaccuracy of tetraplegics' movements. To test these two hypotheses, we compared the variability of "fast and accurate as possible" force pulses in four control subjects and four C5/C6 tetraplegic subjects to targets at 15, 30, and 45% of maximum voluntary contraction. Multiple regression analyses were performed to look for patterns of agonist or antagonist muscle activation consistent with compensatory adjustments for early trajectory errors in both groups of subjects. 3. Force rise time was significantly prolonged in tetraplegic subjects, although there was some overlap between groups. At similar levels of effort, there were no significant differences in constant and variable errors of control and tetraplegic subjects. We also found no consistent statistical evidence for the presence of compensatory electromyographic activity in either group of subjects. Subjects who lacked the ability to make corrections involving the triceps muscle performed as well as subjects with normal triceps strength. This suggests that a corrective mechanism involving the triceps must have a weak role, if any, in these experiments. 4. Together with our observation that lower force targets are indeed associated with larger relative variable errors, in both control and tetraplegic subjects, the above results lead us to conclude that the second hypothesis listed above is more likely correct. The antagonist muscle clearly enables the production of briefer force pulses. In addition, the antagonist indirectly contributes to the accuracy of isotonic movements because antagonist braking allows larger agonist forces to be used. These larger agonist forces are less variable, and produce more accurate movements, than the smaller forces used by tetraplegic subjects.

Adult↗
PubMed1993

Variation in firing order of human soleus motoneurons during voluntary and reflex activation.

The activation of motoneurons in a muscle pool is said to proceed as an ordered array in response to both dorsal root stimulation and voluntary activation, with small motoneurons being recruited before larger ones. We have examined 19 voluntarily recruited soleus motor units in 5 normal subjects and found that in 18 cases, the lowest threshold motor unit recruited by slowly increasing 'tonic' voluntary activity was different from the lowest threshold unit recruited by electrical stimulation of the tibial nerve in the popliteal fossa (phasic Hoffman reflex). The initially recruited voluntary units were, however, part of the pool influenced by the stimulated afferents because, during tonic activation, the timing of their discharge could be shown to be altered by electrical stimulation at a lower intensity than that required for H recruitment at rest. These findings suggest that the pool of soleus motoneurons responding to the voluntary command "tonically plantar flex your ankle" differs somewhat, in order of activation, from the pool responding to phasic stimulation of the largest diameter fibers in the tibial nerve, perhaps because of inhomogeneities in the distribution of descending or segmental inputs to the soleus motoneuron pool. Whether this partitioning is functional or a reflection of minor, random variations in synaptic density remains to be determined.

Action Potentials↗
PubMed1993

Discharge properties of single motor units in patients with spinal cord injuries.

To study neurophysiological correlates of spastic paresis, we analyzed the discharge pattern of single motor units (SMUs) during sustained voluntary contraction from muscles weakened by spinal cord injury (SCI) and from muscles of near normal strength just at or above the level of injury. The average firing rate of SMUs was reduced in patients' biceps brachii and tibialis anterior muscles compared with controls, but not in the triceps brachii. Floating serial correlation coefficients obtained from successive interdischarge intervals were significantly more positive in patients than in controls in all three muscles. One statistical measure of regularity of discharge, akin to a coefficient of variation, was best able to differentiate patient and control SMUs. Increased discharge variability in muscles just above the level of injury suggested that subtle effects of traumatic SCIs were more extended than was clinically apparent. Although consistent statistical differences could be measured, these changes were not specific to SCI, nor were all SMUs equally affected.

Humans↗
PubMed1993

Portable system for quantifying motor abnormalities in Parkinson's disease.

In order to quantify motor disabilities in Parkinson's disease (PD), we designed a compact, portable, neurophysiological system based upon a personal computer to measure tremor, bradykinesia, and muscle tone. Tremor was detected by solid state accelerometers and translated into a digital signal. The system displayed the root mean square displacements and frequency distribution of the tremor in the horizontal and vertical planes, along with a reconstructed graphic image of the displacement. Bradykinesia was measured using a panel that detects release and depression of switches in response to auditory and visual signals; the system calculated subjects' reaction times and movement times in milliseconds. Tone at the elbow was measured by strapping the upper extremity to a lightweight low-friction cradle and then passively moving the cradle with an instrumented handle. Signals representing torque and arm angle were processed by the computer and displayed in real time on the screen with stiffness as a mean slope in Nm/degree. In clinical tests, quantitative measures of tremor, movement time and rigidity were significantly abnormal in PD patients compared to control subjects. We conclude that this system is a convenient and accurate method to quantitate important aspects of the parkinsonian syndrome, and may be applied to quantitate other movement disorders.

Adult↗
PubMed1992

Effects of weak antagonist on fast elbow flexion movements in man.

By using a mathematical model and experiments involving electrical simulation of antagonistic muscles, we have formed the hypothesis (Wierzbicka et al. 1986) that in one-joint movements the antagonist muscle not only provides braking torque but also controls movement time. To get additional experimental support for this hypothesis, we studied elbow flexion movements performed by patients with spinal cord injury at the C5-6 level who had relatively normal strength in their biceps muscle and little or no voluntary control of the triceps. Seven quadriplegic patients and six control subjects performed elbow flexion movements of 10 degrees, 20 degrees, and 30 degrees "as fast and accurately as possible". Despite the lack of antagonist, patients used the same "pulse height" strategy as control subjects to scale their responses with movement amplitude. However, patients' movement time was on average twice that of control subjects, and durations of both accelerative and decelerative phases of movement were increased. Movement speed and acceleration were reduced to 20-50% of the corresponding values of control subjects. Patients tended to overshoot the target to a larger extent than control subjects, particularly 10 degrees targets, with nearly twice the error. We performed the same experiments using an external torque motor to assist the weak triceps. When a constant extensor torque of 2.5 or 5 Nm was provided by the motor, patients were able to move faster, and movement accuracy improved to within the normal range. These results provide direct evidence that the lack of an antagonist has an important effect on completion time and accuracy of fast goal-directed movements.

Adult↗
PubMed1992

Kinematic models and human elbow flexion movements: quantitative analysis.

The smoothness with which movements are customarily performed has led Hogan (1984) to formulate a model for trajectory planning by the central nervous system in which the goal is to maximize smoothness, one measure of which is the integrated mean squared magnitude of jerk (jerk cost). We tested the applicability of this minimum-jerk model to one-joint goal directed movements performed by human subjects at different speeds and amplitudes, by comparing kinematic parameters and the jerk cost predicted by the mathematical model with values calculated from experimental data. We also tested a higher order, minimum-snap kinematic model. Normal subjects performed elbow flexions of 5 to 50 degrees "as rapidly and accurately as possible" and also at slower speeds. The boundary conditions of both models were adjusted to account for the failure of subjects to produce movements which reached equilibrium precisely at the target (so that acceleration and velocity reached zero together). Typically, fast movements (less than 300 ms duration) were fairly symmetric in that the durations and amplitudes of acceleration and deceleration were approximately equal; slower movements (greater than 300 ms) were asymmetric with strong, brief acceleration peaks and broad, slow deceleration peaks. In fast movements, the calculated jerk cost was consistently higher than predicted by the minimum-jerk model; a good fit to all kinematic parameters was provided by the minimum-snap model (a seventh-order polynomial). Neither model consistently predicted the trajectories of slower movements. We conclude that muscle/limb dynamics can account for the success of the minimum-snap model with fast movements, and that there is no evidence of planning for maximal smoothness in slower movements.

Brain↗
PubMed1991

Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy.

Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.

Acetylcholinesterase↗
PubMed1991

Abnormal most-rapid isometric contractions in patients with Parkinson's disease.

Fast isometric elbow flexor muscle contractions of specified amplitude in six normal subjects were compared with those of 11 patients with Parkinson's disease. Despite treatment, all patients exhibited deficits in this motor task. Three patients were able to produce rapid force pulses with normal contraction times, but the variability of their force responses was increased in comparison with the highly stereotyped responses produced by normal subjects. The other eight patients had prolonged contraction times and segmentation of the force profiles. The integrated area of the first agonist EMG burst and the rate of development of force (dF/dt) were less at any target level than what was needed to produce a fast response. The area of the EMG burst, however, did increase with target amplitude, and the relative increase of dF/dt, with target amplitude, was normal. It is concluded that the motor program subserving fast muscle contraction is preserved in Parkinson's disease, but its execution is characterised by improper scaling of motor output.

Adult↗
PubMed1990

Effects of muscle thixotropy on afferent activity in the hindlimb of the rat.

The increase with time of the stiffness of resting muscle and its effect on afferent nerve activity arising within the muscle were investigated in the leg of the anaesthetized rat. Nerve activity was recorded from the branch of the tibial nerve innervating the gastrocnemius muscle. A sinusoidal torque from a motor coaxial with the ankle produced small (less than 0.25 deg) oscillations of the resting foot that were interrupted by several cycles of a much larger amplitude displacement. After the perturbation, the same small torque caused larger (greater than 0.40 deg) oscillations, demonstrating a reduction in the resting or short-range stiffness of muscles acting at the joint. Turning off the torque for 30 s allowed the stiffness to return to its enhanced level. Afferent nerve activity in response to the small torque was greater following the perturbation, reflecting the larger oscillations. We conclude that thixotropic stiffening of muscles at rest reduces postural displacements produced by small torques as well as the quantity of afferent signals converging on the central nervous system from these events.

Afferent Pathways↗
PubMed1988

Motor unit synchronization in physiologic, enhanced physiologic, and voluntary tremor in man.

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.

Electromyography↗
PubMed1988

Papillary muscle structure-function relations in the aging spontaneously hypertensive rat.

Isolated left ventricle papillary muscle mechanics and structure were studied in male spontaneously hypertensive (SHR) rats and two control groups of animals, the normotensive Wistar (NR) and the Wistar-Kyoto rat (WKY). Active tension and its first derivative (dT/dtmax) normalized for muscle cross-sectional area were increased in preparations from the SHR at all ages studied relative to control groups (P less than 0.01). However, when these parameters were normalized for myofibrillar cross-sectional area determined from electronmicroscopic point counting data, differences between groups were no longer significant. Force-velocity relations provided no evidence for a depression of shortening velocity at any load in the SHR at any age relative to the two control groups. The duration of mechanical activity, as determined by time-to-peak isometric tension and analysis of muscle force-velocity-time relations, was prolonged only in the 18 month old SHR (P less than 0.01). Thus, while changes in isolated muscle performance occur at a time when hemodynamic impairment is reported in the intact animal (male 18 month SHR), no evidence for depression of isolated muscle function is seen in the SHR at 6, 12 or 18 months of age.

Age Factors↗
PubMed1987

A method for assessing significance of peaks in cross-correlation histograms.

Cross-correlation histograms have been widely used to analyze the interdependence of two simultaneously observed trains of neuronal spikes or muscle motor unit discharges. Here, a formula is presented for calculating a synchronization index from such a histogram to reliably detect subtle correlations such as short-term synchronization, even in the case of relatively sparse data, as well as allowing comparison of the degree of synchronization of grouped or correlated motor unit discharges. The index takes into account the number of counts in the histogram, number of bins, and width of the histogram peak. A table of critical values of the index, at several levels of statistical significance, is included.

Animals↗
PubMed1987

Mechanism of thixotropic behavior at relaxed joints in the rat.

When a relaxed joint is subjected to a small sinusoidal torque, the amplitude of the steady-state displacement response is increased up to severalfold by a transient larger perturbation. The original state, in which the relaxed joint is unexpectedly stiff, is restored by several seconds of inactivity. This thixotropic phenomenon has previously been observed in a variety of human joints. We have now investigated the mechanism of thixotropic behavior at relaxed joints in rats anesthetized with pentobarbital sodium, by using a series of preparations including the intact ankle joint, a blood-perfused soleus muscle preparation, an isolated soleus muscle, and ankle joint isolated by severing all muscular attachments. Thixotropic behavior was observed in all intact, isolated muscle, and isolated joint preparations. The contribution of the joint to thixotropic behavior was comparable to, and at times exceeded, the contribution of muscle. We also analyzed the short-range stiffness properties of relaxed, blood-perfused soleus muscles and found them to be similar to thixotropy with respect to range of action (0.2-0.3% of muscle length), elastic modulus (approximately 4 kg/cm2), and time course for redevelopment (time constant = 2.5 s at 34 degrees C). Thus thixotropic behavior at a relaxed joint may be attributed both to the joint structures and to short-range stiffness of muscles acting at the joint.

Animals↗