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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↗
PubMed1989

What is the role of the supplementary motor area in movement initiation?

The hierarchical position of the supplementary motor area (SMA) relative to the primary motor cortex is discussed on the basis of neurological observations and of animal experiments. In the last 10 years evidence has accumulated, especially from studies on the human brain, that the supplementary motor area is a hierarchically superior structure involved in the processes of movement initiation. Single unit studies in subhuman primates also revealed neuronal populations related to aspects of movement preparation rather than to the movement per se. However, we report that a surprisingly large subpopulation of SMA neurones has features classically found in the primary motor cortex (MI). These MI-like neurones precede movement onset by a relatively short interval. The occurrence of such "short-lead neurones" was somewhat higher in MI, but the histograms of lead-times were completely overlapping in the two areas. Taken together with the fact that the SMA is microexcitable and is part of the origin of the pyramidal tract, these findings suggest that the SMA functions also in parallel with MI as concluded by Woolsey and coworkers (1952). Finally, the SMA and MI are reciprocally interconnected, a situation which is not unlike that of the cortical visual areas.

Animals↗
PubMed1988

Sensory inputs to the agranular motor fields: a comparison between precentral, supplementary-motor and premotor areas in the monkey.

Kinesthetic responses of neurones in the motor cortex, including the primary motor (MI), the supplementary motor (SMA) and the postarcuate premotor (PMC) areas, were investigated in the awake, chronically prepared monkey. In all three subareas, neurones were recorded which responded to passive elbow flexions and extensions induced by a torque motor. In the SMA, such cells were restricted to its posterior portion where intracortical microstimulation produced limb and trunk movements. The majority of SMA cells responds to both displacement directions, a quarter to either flexion or extension. Although the total proportion of SMA neurones responding to arm displacements was low (15%), it was noted that in 'correct' somatotopic penetrations, the responsiveness could be prominent. The latency distribution of the kinesthetic responses was similar to that of MI neurones with slightly less response latencies shorter than 20 ms in the SMA. With manually applied stimuli, SMA neurones responded mostly to joint rotations, but not to light cutaneous stimuli. Only two SMA neurones with somatosensory responses were identified as descending projection neurones, and some neurones were found to be modulated also during active grasping. In the PMC, a higher proportion of neurones (27%) reacted to the standardized arm displacements, the majority again responding to both directions. The latency distribution of the kinesthetic responses was similar to that of SMA neurones. In contrast to SMA neurones, many PMC neurones responded to light cutaneous stimuli. It was found that some of the 'somatosensory' PMC neurones were sometimes driven also by moving visual and, rarely, by auditory stimuli. Although there are obvious differences in the nature and possibly also in the amount of sensory inputs to the three motor cortical areas, the present results indicate that all three subareas receive somatosensory feedback and that they might therefore all be implicated in the generation of sensory-driven motor output.

Afferent Pathways↗
PubMed1987

Topography of the corticofugal projection to the lateral reticular nucleus in the monkey.

The cortical projection to the lateral reticular nucleus (LRN) was explored in monkeys prepared for autoradiography and horseradish peroxidase (HRP) histochemistry. An unambiguous projection was revealed only in cases with injections of the precentral forelimb and hindlimb areas. The forelimb area projection occupied centromedial segments, the hindlimb area projection occupied ventrolateral segments of the LRN with very little overlap. Some sparse labeling was also seen with injections of the supplementary motor area (SMA), but only when the lectin-bound tracer HRP was injected and not when autoradiography was used. Retrogradely labeled cortical cells occupied a larger cortical area in one case with injection of free HRP into the LRN. Since the additional expanse of cortex, however, was not examined in anterograde cases, and since the injected marker substance had diffused to neighboring structures, the significance of the labeled cells outside the precentral motor cortex is questionable. There was no evidence for a projection from the precentral face area with either anterograde tracing method. The corticoreticular projection was bilateral and only slightly more marked contralateral to the injection. The labeling was largely confined to the magnocellular division with minor amounts in the parvicellular division (especially in the hindlimb cases). The subtrigeminal portion was spared in all cases. It is concluded that the LRN constitutes another somatotopically organized precerebellar nucleus relaying signals from the motor cortex to the cerebellum. Compared with the corticopontocerebellar pathway in monkeys, however, the LRN is only a minor component of the corticocerebellar transmission system.

Animals↗
PubMed1987

Cortical and peripheral effects on single neurons of the lateral reticular nucleus in the monkey.

The aim of this study was to extend the anatomical study of the corticoreticular organization in the monkey by means of microelectrophysiological techniques. Considering the relatively modest projection (see companion paper, Wiesendanger and Wiesendanger, '87), it was surprising to see that over 70% of the investigated LRN neurons were influenced from at least one cortical stimulation site. Many neurons responded, however, with long latencies suggesting an indirect transmission line. In line with the anatomical tracing study, most short-latency responses were obtained from the motor cortex. Postcentral cortex and the SMA were, in general, less effective sites for evoking responses in the LRN. LRN neurons with similar cortical inputs tended to be clustered together suggesting that the corticoreticular projection is discretely organized with an "intermingled somatotopy". The majority of the 87 tested LRN neurons were not reactive to any peripheral stimulus (33%) or responded only to nociceptive peripheral stimulation (31%). Very large receptive fields were seen in 8% of the units. However, a significant proportion of LRN neurons (10%) had restricted receptive fields and reacted to gentle cutaneous stimuli, and others (17%) responded to discrete passive rotations of one or more joints. There was often a somatotopical correspondence between the peripheral and the cortical inputs. It is concluded that the LRN in monkeys is under the influence of the motor cortex, which, however, may be exerted to a major extent via indirect pathways. The electrophysiological data suggest a discrete rather than a diffuse relationship with the LRN.

Animals↗
PubMed1987

Input and output organization of the supplementary motor area.

Recent work on the supplementary motor area (SMA) in Macaca fascicularis led to the conclusion that this area is involved mainly in the preparation of self-paced movements. Results are presented indicating that the posterior portion of the SMA is also directly involved in movement execution and that it receives various sensory inputs. The main results are as follows: (1) The SMA has direct access to the spinal cord by way of corticospinal neurons, but the density of these neurons is lower than in the primary motor cortex (MI). (2) Intracortical microstimulation effects can be elicited in the SMA. Facilitatory effects on ongoing EMG activity can even be produced by single micropulses (8/s). The shortest latencies are compatible with an oligosynaptic or monosynaptic transmission. (3) SMA neurons respond (as do MI neurons) to external perturbations. (4) Anatomical tracing studies revealed that basal ganglia outflow to the SMA via the thalamus is important; our results suggest that dentate outflow contributes as well. (5) Many cells of the SMA may covary with conditioned movements in the same way as MI neurons do. It is argued that it is difficult to compare the lead-time of MI and SMA neurons since 'early' discharges may be coupled with anticipatory postural events.

Animals↗
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↗
PubMed1987

The adrenergic agonist tizanidine has differential effects on flexor reflexes of intact and spinalized rat.

Tizanidine with its predominant alpha 2-adrenergic properties is a potent myorelaxant drug used clinically in spastic patients. The aim of this study is to analyse further the mechanisms by which this substance exerts its influence on spinal reflexes. It was found that tizanidine dose-dependently diminished flexor reflexes in intact chloralose-anaesthetized rats, and also, but slightly less, in unanaesthetized decerebrate rats. In spinalized rats (1-5 days postoperatively), flexor reflexes were, however, enhanced by tizanidine, especially by the higher doses. Pretreatment with the alpha 2-blocker yohimbine antagonized the depressant action of tizanidine in intact rats whereas the alpha 1-blocker prazosin antagonized the facilitatory action of tizanidine in the spinalized rats. The reflex depression might be explained by a removal of a tonic facilitation of spinal neurons by the descending noradrenergic fibres, because tizanidine is likely to reduce, like clonidine, the spontaneous activity of locus coeruleus neurons by presynaptic autoinhibition. In spinalized preparations, a net facilitatory alpha 1-mediated action may be revealed by the higher doses of tizanidine that would be unopposed by the alpha 2-mediated disfacilitation.

Adrenergic alpha-Agonists↗
PubMed1986

The supplementary motor area modulates perturbation-evoked discharges of neurones in the precentral motor cortex.

The hypothesis was tested that the supplementary motor cortex (SMA) may influence the responsiveness of area 4 neurones to kinesthetic stimuli. In the awake monkey, responses to arm displacements were recorded with and without conditioning intracortical stimulation of the SMA. In 14 of 26 tested area 4 neurones, there was an increase of the response latency and/or a decrease of the response magnitude when the peripheral stimulus was conditioned by SMA stimulation. Field potentials evoked by the displacements were reduced in 3 out of 7 recordings. These findings suggest that the SMA exerts subtle inhibitory effects on the motor cortex or its inputs.

Animals↗