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M Wiesendanger

Publications and source records attributed to M Wiesendanger.

At least 19 recordsLinked to original sources
PubMed1992

Feedforward postural stabilization in a distal bimanual unloading task.

The aim of the present study was to investigate postural adjustments and positional stability in a bimanual unloading task, involving essentially the index finger, in order to test whether proactive adjustments are also observed in distal body segments. A second goal of the study was to evaluate the concept of a central command that would be responsible for coupling movement and posture. The positional disturbance of the right load-bearing index finger of healthy human subjects was studied under two types of manipulations: passive, i.e., imposed, unloading and active unloading, by the subject's left index finger. It was found that, in such a distal task, positional stabilization of the load-bearing finger was much better (by a factor of 6) in the active situation than the passive situation. This improvement was greater than previously reported for a proximal task. An electromyogram (EMG) analysis of the mostly implicated dorsal interosseous muscles revealed a typical unloading reflex in the passive situation (reactive mode) and a suppression of EMG before unloading onset in the active situation (proactive mode). Averaged records showed an almost perfect synchronization between the EMG suppression in the load-bearing interosseous muscle and the onset of the EMG burst of the unloading index finger. A trial-by-trial analysis, however, revealed a considerable scatter in intervals of the two EMG events, with a tendency of the activity burst in the left finger to occur slightly before the suppression of EMG in the load-bearing muscle. No positive correlation was found between the precision of synchronization (intervals near zero time) and the accuracy of performance, i.e., positional stability of the unloaded finger. Although the trial-by-trial variability was large, it is suggested that at least some of this variability is caused by a nonsteady state of motoneuronal excitability. In view of the low-pass property of the muscle, the observed variability in synchronization may be sufficiently precise to maintain the hypothesis of a central temporal coupling of the events in the two hands through a common command. However, the lack of a correlation between the degree of synchronization and the performance in stability argues rather in favor of separate commands to the two hands that select the parameters in the spatial domain. Finally, an intermanual EMG or torque analysis is proposed that might be useful in assessing the accuracy in goal achievement, i.e., the maintenance of a stable finger position in spite of the "internal" perturbation.

Electromyography↗
PubMed1992

Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation.

The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons.

Animals↗
PubMed1991

Corticomotoneuronal connections in the rat: evidence from double-labeling of motoneurons and corticospinal axon arborizations.

In order to investigate the possibility of direct corticomotoneuronal (CM) connections in the rat, an anterograde-retrograde double-labeling method was developed. Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde tracing of corticospinal axons was combined with retrograde labeling of spinal motoneurons either by a conjugate of choleragen subunit B with horseradish peroxidase (CB-HRP) or by wheat germ agglutinin (WGA). The location of PHA-L injection unilaterally in the forelimb area of sensorimotor cortex and the CB-HRP or WGA injections in corresponding contralateral wrist or digit extensors or flexors were determined and matched on the basis of movement responses elicited by intracortical microstimulation. Light microscopic observation showed, in addition to the main contralateral dorsal corticospinal tract (CST), the presence of four other CST minor components in the contralateral lateral, ipsilateral ventral, and ipsilateral dorsal funiculi of the cervical spinal white matter and at the base of contralateral dorsal horn of the gray matter, respectively. PHA-L-labeled CST axonal arbors were observed from Rexed's lamina I through lamina X of contralateral spinal gray matter, most extensively in laminae VI and VII; some CST axons reached the zone of motoneuronal somata in lamina IX and a few of them also entered the lateral and occasionally the ventral funiculi, ramifying in the white matter. Between the zones of PHA-L-labeled CST axonal arbors on the one hand and CB-HRP/WGA labeled spinal motoneuronal somata with their extensive dendritic trees on the other, there was a large overlap, covering partly both the gray and the white matter. PHA-L-labeled axonal boutons (en passant or terminaux) were seen to contact the dendrites or even the somata of motoneurons in the gray matter, according to light-microscopic criteria for identification of synaptic contacts. Axodendritic CM contacts were occasionally observed in the lateral funiculus of the white matter as well. In general, only a single contact was observed between an individual PHA-L-labeled CST axon and a given retrogradely labeled motoneuron. In contrast to the common notion that direct CM connections are a specialty of primates, the present morphological data support the presence of direct CM connections also in some other mammals, such as the rat.

Afferent Pathways↗
PubMed1991

Patterns of corticothalamic terminations following injection of Phaseolus vulgaris leucoagglutinin (PHA-L) in the sensorimotor cortex of the rat.

The morphology and spatial distribution of terminals emitted by corticothalamic axons originating from the rat motor cortex (as defined by intracortical microstimulations) were studied using Phaseolus vulgaris leucoagglutinin (PHA-L) as an anterograde tracer. After PHA-L injection in the face, forelimb or hindlimb motor cortical areas, small and densely packed boutons (about 1 micron in diameter), en passant and terminaux, were seen in the ventrolateral nucleus of the thalamus and, more sparsely, in the reticular nucleus, the nucleus ventrobasalis and the posterior nucleus of the thalamus. A separate projection with giant boutons (5-10 microns in diameter), en passant and terminaux, terminated in the posterior nucleus of the thalamus exclusively. Giant boutons originated from corticothalamic axons distinct from those providing small boutons. The corticothalamic projection originating from the motor cortex has basic organizational properties comparable to previous data obtained in the auditory and somatosensory corticothalamic projection systems.

Afferent Pathways↗
PubMed1991

Tizanidine-induced depression of polysynaptic cutaneous reflexes in nonanesthetized monkeys is mediated by an alpha 2-adrenergic mechanism.

Previous studies in anesthetized or reduced preparations of nonprimate animals revealed that the alpha 2-adrenergic agonist tizanidine, clinically used as an antispastic drug, effectively reduces polysynaptic flexor reflexes. To further clarify the invoked adrenergic mechanism for physiological motor functions, and in view of the clinical relevance of tizanidine, the effect of this substance was reinvestigated in awake, nonanesthetized monkeys. Systemic applications of tizanidine dose-dependently reduced the magnitude of the electromyographic response of the flexor reflex that was induced by nonnoxious stimulation of cutaneous afferents. Whereas the effects on the flexor response were consistent, the changes of the background electromyogram were much more variable, often not paralleling those of the reflex. The reflex depression produced by tizanidine could be prevented by pretreatment with the alpha 2-antagonist yohimbine. It is concluded that the action of tizanidine on spinal reflexes, and therefore probably also on hyperactive reflexes of spastic patients, is mediated via the alpha 2-adrenergic properties of the drug. On the basis of the present results, taken together with previous observations that tizanidine transiently inactivates neurons of the nucleus locus coeruleus, it is proposed that the reflex depression may be caused by a removal of a descending noradrenergic facilitation exerted on spinal reflex transmission. This interpretation leaves open further possible actions of tizanidine exerted directly on spinal interneurons.

Adrenergic alpha-Antagonists↗
PubMed1991

Trajectory of redirected corticospinal axons after unilateral lesion of the sensorimotor cortex in neonatal rat; a phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study.

The corticospinal neurons of the rat project almost exclusively to the contralateral spinal cord. Retrograde and anterograde tracing experiments showed that only about 2-4% of the corticospinal neurons of the sensorimotor cortex project to the ipsilateral spinal cord in the normal rat. The large majority of corticospinal axons (more than 90%) travel at spinal level at the base of the contralateral dorsal funiculus; in addition a few axons run in the contralateral lateral funiculus and at the base of the dorsal horn. The undecussated axons run in the ipsilateral dorsal (about 1-2%) and ventral (about 1-2%) funiculi. The rearrangement of the corticospinal projections was studied with various tracing methods in rats subjected to unilateral lesion of the sensorimotor cortex at Postnatal Day 2 to 4. Spinal injections of the tracer WGA-HRP that were restricted to the side opposite to the cortical lesion showed a significant increase of retrogradely labeled corticospinal neurons in the intact cortex as compared to the proportion of ipsilateral projections in control experiments. This was consistent with an increased density of anterogradely labeled corticospinal terminals in the spinal cord ipsilateral to an injection of WGA-HRP in the motor cortex opposite to neonatal lesion, in comparison to normal rats. The trajectory of these "aberrant" ipsilateral corticospinal projections resulting from the neonatal lesion of the opposite sensorimotor cortex was analyzed by means of the anterograde tracer phaseolus vulgaris-leucoagglutinin (PHA-L), injected in the motor cortex. These data indicated that decussated corticospinal axons recross at spinal levels, close to their terminal zone, where they appear to ramify and terminate in the spinal gray including the motoneurons. Such recrossing axons thus represent one new possible mechanism, among other previously reported ones, contributing to the increase of ipsilateral corticospinal projections in rats subjected to neonatal cortical lesion.

Animals↗
PubMed1991

Comparison of neural activity in the supplementary motor area and in the primary motor cortex in monkeys.

Neuronal activity recorded from the primary motor cortex (MI) and from the supplementary motor area (SMA) was compared in two monkeys trained to perform conditioned arm movements. A handle had to be held in a central waiting position until a visual go and cueing signal indicated to the monkey to move the handle either to a medial or to a lateral target zone (choice reaction time paradigm). Unit and representative electromyographic data were analyzed in relation either to the go signal or to movement onset. In 240 penetrations, 431 SMA neurons and 353 MI neurons were found with activity related to the task. The majority of neurons (303 in MI, 290 in SMA) displayed activity changes after the go signal and before movement onset. Of these "short-lead neurons", 71% in MI and 41% in SMA were clearly related to movement execution. The distribution of lead times in MI and SMA neurons was completely overlapping without any statistical difference among subgroups. The remaining neurons were as well related to the go signal as to movement onset, or were better related to the visual go signal. The response latencies to this signal were not statistically different in SMA and MI neurons. Activity changes during the waiting period was observed more frequently in SMA (47%) than in MI (32%); modulations restricted to the waiting period occurred in 14% of SMA neurons, but were exceptional in MI neurons (3%). It is concluded from these experiments that a surprisingly large proportion of SMA neurons have "MI-like" properties, in that they are temporally recruited together with MI neurons, with similar patterns of discharges during the task. This then suggests that the two interconnected areas operate in parallel. A population of SMA neurons is involved in some processing that is not as predominantly expressed in MI. This activity could relate to sensory, timing, or other higher-order aspects of response preparation, and/or motor functions such as postural stabilization.

Animals↗
PubMed1990

Concomitant depression of locus coeruleus neurons and of flexor reflexes by an alpha 2-adrenergic agonist in rats: a possible mechanism for an alpha 2-mediated muscle relaxation.

The alpha 2-agonist tizanidine, clinically used as an antispastic drug, also strongly reduces polysynaptic flexor reflexes. The hypothesis was tested that the noradrenergic coerulespinal system exerts a tonic facilitation on spinal reflexes and that the depressant effects of tizanidine may be explained by an alpha 2-mediated autoinhibition of the tonic activity of locus coeruleus neurons, resulting in a disfacilitation of the spinal reflexes. The following results support this working hypothesis: (1) systemic injections of tizanidine markedly decreased the spontaneous activity of locus coeruleus neurons, but not of non-locus coeruleus neurons. The alpha 2-antagonist yohimbine reversed this effect. (2) The time course of diminished locus coeruleus activity paralleled that of depressed flexor reflexes. (3) Flexor reflexes were also markedly depressed by the alpha 1-adrenergic antagonist prazosin, administered alone, which is in line with the proposition that the noradrenergic system exerts a tonic facilitation on spinal neurons by way of alpha 1-adrenergic receptor activation. (4) Flexor reflexes were facilitated by conditioning microstimulation of locus coeruleus neurons, and this effect was reversed by prazosin. (5) Flexor reflexes significantly diminished in size following placement of an irreversible lesion in the ipsilateral locus coeruleus. Although these results strongly support the above hypothesis regarding a descending modulatory function of the descending locus coeruleus system on spinal reflexes, possible additional mechanisms, perhaps also involving the ascending projection of the locus coeruleus to supraspinal motor structures, remain to be elucidated.

Adrenergic alpha-Agonists↗
PubMed1987

Transient responses to load perturbations of the forearm in a monkey with a chronic lesion in the internal capsule.

Small electrolytic lesions were produced in the internal capsule of a monkey. The changes in muscle tone were quantified by studying the EMG responses of elbow muscles and the mechanical responses of the forearm to pseudo-random torque perturbations applied to the elbow joint. Immediately following the lesion, the EMG responses of both biceps and triceps muscles were depressed. Subsequently, biceps responses recovered and became eventually greater than in the control. Triceps responses, instead, remained low throughout the follow-up period (3 months). The mechanical behavior of the forearm was characterized in terms of the dynamic relationship between the applied torque perturbations and the resulting changes in elbow angle. After the lesion, the damping of the elbow responses decreased relative to the control. Possible mechanisms for the observed changes in the EMG and mechanical behavior are discussed.

Animals↗
PubMed1978

Spinal projection to the dorsolateral nucleus of the caudal basilar pons in the cat.

In the cat, a spinal projection to a restricted area of the basilar pontine grey has been revealed with use of anterograde degeneration technique (Fink-Heimer). The area was ipsilateral to the spinal lesion, restricted to the far caudal limit of the pons, and included the dorsal and the dorsolateral subdivisions of the pontine nuclei (PN). Comparisons following high cervical, midthoracic and upper lumbar spinal lesions did not reveal any somatotopic organization. Only a few spinopontine fibers had origins below segmental level L4. Lesions of various quadrants of the cord indicated that the spinopontine fibers ascended through the dorsolateral funiculus, and not through either the dorsal or the ventral funiculi. Comparison with the degeneration effects of cerebral cortical lesions showed that the spinal projection to the PN overlapped to some extent with the projection from the first sensorimotor and second somatosensory cortices. In the rat no comparable spinopontine projection was found. It is suggested that the spinopontine pathway might forward information to the cerebellum from visceral sensory receptors or perhaps from pools of spinal interneurons.

Animals↗
PubMed1976

Input from trigeminal cutaneous afferents to neurones of the inferior olive in rats.

Extracellular recordings were obtained from inferior olivary neurones of the rat. The responses of fifty neurones evoked by electrical stimulation of a branch of the trigeminal nerve were recorded. Maxillary nerve stimulation was most effective. The response was characterized by an early discharge (single spike and wave, typically with latencies between 16 and 30 msec) and a weak late discharge which followed a period of inhibition of about 100 msec. Half of the neurones responded to one branch of the trigeminal nerve only whereas the other neurons displayed a varying degree of convergence, including sometimes a convergence from limb nerves. Forty-nine olivary neurones were tested for cutaneous receptive fields. Ten out of these had small receptive fields (less than 20% of the contralateral face) and a low threshold to mechanical stimuli. Twenty neurones which had larger receptive fields responded also to low-threshold or to medium-threshold (i.e. non-nociceptive) mechanical stimuli. None of the neurones displayed receptive fields more extensive than half of the contralateral face and some of the larger fields had a small, low-threshold focus. Olivary neurones responding to electrical stimulation of trigeminal nerves or mechanical stimulation of the face were located in the medial segment of the olivary complex (dorsal accessory and principal olive). A few cells only were located in the lateral segment. It is concluded that neurones of the inferior olive receive a substantial input from trigeminal afferents and are capable of transmitting precise somatotopical information to the cerebellum.

Afferent Pathways↗
PubMed1975

Why transcortical reflexes?

Experiments in humans and in monkeys have indicated that load perturbations, occurring during voluntary movements and postural activity, may be automatically compensated for. Overall muscle stiffness opposing load changes is determined by the visco-elastic properties of the muscle, by segmental reflex actions and finally by long-loop reflexes. Under certain circumstances, for instance when the subject or the experimental monkey is "prepared" to counteract perturbations which are unpredictable in time, the long-loop "reflexes" appear to be responsible for most of the corrective muscle tension. Experiments in anaesthetized monkeys revealed that signals from stretch afferents reach neurons of the motor cortex, possibly via a relay in the cortical area 3a. The latencies of these responses to well controlled muscle stretches were in the same range as motor cortical cell discharges recorded in alert monkeys subjected to load perturbations. Furthermore, these responses of cells in the motor cortex also had the appropriate timing to indicate a causal relationship with the long-latency electromyographic responses to load changes referred to above. These experimental results therefore strongly support the hypothesis, first proposed by Phillips (1969), of a transcortical servo-loop adjusting motor cortical output according to the load conditions in which movements are performed. The major advantage of transcortical regulations as opposed to segmental regulations, seems to be a powerful gain control acting at the cortical level; it was repeatedly shown that the long-loop reflexes are strongly modifiable and under voluntary control. It is suggested that an adaptive gain control at the cortical level is a prerequisite to preserve the complex capabilities of the motor cortex as the chief "executive" for skilled, preprogrammed movements. A loss of this adaptive gain control may be, at least partly, the cause of motor disorders such as rigidity in Parkinsonian patients, as reported by Tatton and Lee (1975). It is suggested that further investigations of the control of transcortical reflexes may aid in the understanding of the pathophysiology of motor disabilities.

Animals↗