Karl Theodor Kalveram

The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

SummaryDegeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinsons disease. The neurotoxin MPTP (1-methyl-4phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinsons disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinsons disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as l-glutamate could be involved in neurodegenerative disorders including Parkinsons disease. We report in this study that the competitive NMDA antagonist CPP (3-((±)-2-carboxypiperazin-4yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinsons disease.

The duration component of the stress effect in stuttering

UNLABELLED The purpose of the present study was to investigate whether there is a relationship between stuttering on stressed syllables and the duration of these syllables. Sixteen adults who stutter read a text consisting of 226 syllables. The relative stress of each syllable was rated, and syllables were categorized into long- and short-stressed syllables, unstressed syllables and intermediate syllables lying in-between. In order to isolate effects caused by within-word position from those caused by linguistic stress, syllables in initial and in subsequent positions were analyzed separately. In both word position categories stressed syllables were stuttered more often than unstressed syllables. Stuttering frequency of intermediate syllables seems to be in-between stressed and unstressed syllables, just as their stress level is rated in-between. Results regarding the duration of stressed syllables do not allow final conclusions. EDUCATIONAL OBJECTIVES The reader will learn about and be able to describe (1) language factors related with stuttering events, (2) the stress effect in adults who stutter, and (3) methods to control for its confounding variables.

MONITORING RADIO PROGRAMS AND TIME OF DAY AFFECT SIMULATED CAR-DRIVING PERFORMANCE '

Whether radio monitoring, task difficulty, and time of day affect driving performance was examined in a computer-controlled, simulated driving task. Driving performance was defined as the absolute deviation of the car position from road midline as displayed on the computer monitor. We found for 12 men and 8 women (i) an expected, marked deterioration of performance with increasing task difficulty, (ii) a deterioration of performance in the morning, and (iii) a deterioration of performance when subjects concurrently listened to radio programs except for the easy task conducted in the morning. The latter is supposed to be caused by a reactive increase of effort, which is induced by the concurrent radio monitoring and stimulated through a perceived impairment of attention.

Fluency, fundamental frequency, and speech rate under frequency-shifted auditory feedback in stuttering and nonstuttering persons

Abstract Ten stuttering and ten nonstuttering persons produced spontaneous speech, while their auditory feedback provided by headphones was shifted in frequency by +1/2 octave and −1/2 octave. In persons who stutter the downward shift condition led to a significant fluency enhancement of 25% measured by the percentage of discontinuous speech time (PDST, corresponds to loss of time due to disfluencies). Although in the upward shift condition fluency measured by PDST was enhanced by 21%, the significance level was not reached. In nonstuttering persons, a difference in global fundamental frequency between the nonaltered auditory feedback condition and the upward shift condition in the opposite direction of the frequency shift indicates a slight compensating response. This change in global fundamental frequency corresponds to 36 cents (100 cents equals one semitone). Persons who stutter did not show such a change as a group. However, some stuttering individuals showed a change in global fundamental frequency up to two semitones, but change in global fundamental frequency does not correlate with fluency enhancement measured by PDST. The downward and the upward frequency shift do not affect global fluent speech rate, neither in stuttering nor in nonstuttering persons. It is concluded that fluency enhancement by frequency-shifted auditory is not based on global changes in speech production. Educational objectives : The reader will learn about and be able to describe (1) frequency-shifted auditory feedback (2) and its effects on fluency and fundamental frequency of (3) speakers who do and do not stutter.

Facial EMG responses to auditory stimuli.

Three studies were performed to investigate the effects of auditory stimuli (pure tones and environmental noise) of different intensities on surface EMG activity recorded over five facial muscle regions (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi, M. zygomaticus major, M. depressor anguli oris). The results show that with presentation of tones and noises of high intensity (> 85 dB) strong facial EMG reactions over muscles of the upper face (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi) were evoked. Among environmental noises of different valence but the same intensity, babys crying evoked EMG reactions over facial muscles in the mouth region, possibly indicating that the subjects demonstrated expressions of dislike during this particular stimulation. It is also discussed whether facial EMG reactions to auditory stimulation of different intensities could be connected to changes in muscle tone of the middle ear muscles. The contraction of these muscles modulates sensitivity to auditory stimulation. Thus, facial EMG activity of the muscles of the upper face could serve as an indicator of sensitivity to external auditory stimuli. However, the evaluation of pleasant and unpleasant emotional reactions in response to auditory stimulation seems to be impossible.

Predictive control of muscle responses to arm perturbations in cerebellar patients

OBJECTIVES To examine changes in predictive control of early antagonist responses to limb perturbations in patients with defined lesions of the cerebellum. METHODS Eight cerebellar patients and eight sex and age matched control subjects participated. Subjects held a handle that was rotated around the elbow joint. They were instructed to hold the forearm at 90° flexion against a mechanical perturbation. Extensor torque (5 Nm) was applied for 140 ms (pulse), or for 1400 ms (step) through an external motor. Motor responses were tested under two different conditions of anticipatory information. In the expected condition, subjects anticipated and received a pulse. Under the unexpected condition, subjects expected steps, but received unexpected pulses. Biceps and triceps EMG as well as angular kinematics were compared between expected and unexpected pulse perturbations to quantify possible effects of prediction. RESULTS In all healthy subjects, the degree of overshoot in the return flexion movement was significantly less in expected pulse perturbations compared with unexpected trials. The degree of amplitude reduction was significantly smaller in the patient group than in the control group (22.8% v 40.0%). During the expected trials, latency of peak triceps activity was on average 20% shorter in the control group, but 4% larger in the cerebellar patients. CONCLUSIONS In the expected condition, controls achieved a significant reduction in angular amplitude by generating triceps activity earlier, whereas the ability to use prediction for adjusting early antagonist responses after limb perturbation was impaired in cerebellar patients.

Integration of intrinsic muscle properties, feed-forward and feedback signals for generating and stabilizing hopping

It was hypothesized that a tight integration of feed-forward and feedback-driven muscle activation with the characteristic intrinsic muscle properties is a key feature of locomotion in challenging environments. In this simulation study it was investigated whether a combination of feed-forward and feedback signals improves hopping stability compared with those simulations with one individual type of activation. In a reduced one-dimensional hopping model with a Hill-type muscle (one contractile element, neither serial nor parallel elastic elements), the level of detail of the muscles force–length–velocity relation and the type of activation generation (feed-forward, feedback and combination of both) were varied to test their influence on periodic hopping. The stability of the hopping patterns was evaluated by return map analysis. It was found that the combination of feed-forward and proprioceptive feedback improved hopping stability. Furthermore, the nonlinear Hill-type representation of intrinsic muscle properties led to a faster reduction of perturbations than a linear approximation, independent of the type of activation. The results emphasize the ability of organisms to exploit the stabilizing properties of intrinsic muscle characteristics.

Energy management that generates terrain following versus apex-preserving hopping in man and machine

While hopping, 12 subjects experienced a sudden step down of 5 or 10 cm. Results revealed that the hopping style was “terrain following”. It means that the subjects pursued to keep the distance between maximum hopping height (apex) and ground profile constant. The spring-loaded inverse pendulum (SLIP) model, however, which is currently considered as template for stable legged locomotion would predict apex-preserving hopping, by which the absolute maximal hopping height is kept constant regardless of changes of the ground level. To get more insight into the physics of hopping, we outlined two concepts of energy management: “constant energy supply”, by which in each bounce—regardless of perturbations—the same amount of mechanical energy is injected, and “lost energy supply”, by which the mechanical energy that is going to be dissipated in the current cycle is assessed and replenished. When tested by simulations and on a robot testbed capable of hopping, constant energy supply generated stable and robust terrain following hopping, whereas lost energy supply led to something like apex-preserving hopping, which, however, lacks stability as well as robustness. Comparing simulated and machine hopping with human hopping suggests that constant energy supply has a good chance to be used by humans to generate hopping.

Inverse biomimetics: How robots can help to verify concepts concerning sensorimotor control of human arm and leg movements

Simulation test, hardware test and behavioral comparison test are proposed to experimentally verify whether a technical control concept for limb movements is logically precise, physically sound, and biologically relevant. Thereby, robot test-beds may play an integral part by mimicking functional limb movements. The procedure is exemplarily demonstrated for human aiming movements with the forearm: when comparing competitive control concepts, these movements are described best by a spring-like operating muscular-skeletal device which is assisted by feedforward control through an inverse internal model of the limb--without regress to a forward model of the limb. In a perspective on hopping, the concept of exploitive control is addressed, and its comparison to concepts derived from classical control theory advised.

Motivation effects in a dichotic listening task as evident from functional magnetic resonance imaging in human subjects

The present study addresses the effect of motivation on cerebral activity using functional magnetic resonance imaging. Five healthy volunteers performed a dichotic listening task in two sets of three trials during which high or low levels of achievement motivation were introduced. They were told that the first set would be used for calculation of intellectual capacity (high achievement motivation) and the second set for scanner calibration (neutral motivation). In three volunteers, high compared with neutral motivation produced activation in the right prefrontal cortex and the dorsal cingulate. We conclude that motivational effects may lead to significant activations and should be controlled in future cognitive imaging studies. We present preliminary evidence that right prefrontal and dorsal cingulate regions might be involved in motivational processes.