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Biomedical subjects

M Wiesendanger

Publications and source records attributed to M Wiesendanger.

At least 73 records · Page 4Linked to original sources

Further investigations of the efferent linkage of the supplementary motor area (SMA) with the spinal cord in the monkey.

Intracortical microstimulation of the supplementary motor area (SMA) was studied in awake monkeys. With short trains of micropulses, contralateral muscle twitches mainly in shoulder and proximal arm muscles were elicited. There was an indication of a rostro-caudal representation of distal to proximal forelimb, trunk, and proximal to distal hindlimb muscles. However, an intermingling of efferent zones was much more prominent as compared to the precentral motor cortex (MI). All efferent zones to the spinal cord were clustered in the caudal half of the SMA, and we failed to detect face and ocular movements (except at one stimulation site) when microstimulating the rostral portions of the SMA. Single micropulses were also injected in efferent zones of the microexcitable cortex in order to investigate post-pulse facilitation of sustained EMG activity. For motor cortex (MI) stimulation, post-pulse facilitation was prominent and observed in 14 of 17 tested stimulation sites. The incidence of facilitation in comparable muscles obtained with SMA stimulation in comparable muscles obtained with SMA stimulation was only 20 out of 54 tests. The onset latencies of EMG modulation obtained from the two areas were in the same range but the amount of modulation in the SMA was less conspicuous than in MI. These results indicate that the SMA has oligo- or possibly even monosynaptic connections with motoneurones, but that these connections are less dense than those from MI.

Animals↗

Brachium pontis lesions in cats partly reproduce the cerebellar dysfunction of voluntary reaching movements.

The pontocerebellar pathway in the brachium pontis (BP), is known to convey signals from various cortical and subcortical visual structures to the cerebellum. Recently, a cortico-pontocerebellar pathway involving the BP has been implicated in the control of visually guided movements, on the basis of anatomical and physiological data. To further test this hypothesis, using behavioural methods, we studied the effects of a bilateral interruption of these projections in the BP, on 5 cats fully trained to perform a forepaw movement towards a moving target-light. The postoperative deficit consisted of an impairment in precision, with a strong tendency to over-reach and and increase in reaction time, contrasting with an unimpaired movement time. Although there was some initial recovery, performance soon stabilized with a permanent impairment in accuracy and reaction time. These results are discussed in relation to the various sensory signals processed at the pontine level and forwarded to the cerebellum, and compared with the effects of motor dysfunction of cerebellar origin.

Animals↗

Motor functions of the basal ganglia.

This session dealt with the structure and function of the basal ganglia and their role in motor control. The key issues discussed in the first four presentations concerned the pathophysiology of movement performance in parkinsonian patients and in animal models of this disease. Three papers were presented on neurochemically specified subsystems of the basal ganglia. Therapeutic aspects (stereoencephalotomy and chronic electrical stimulation of neural tissue) were discussed in the last two papers. A brief account is given on the highlights of each of these reports.

Animals↗

Do ipsilateral corticospinal fibers participate in the functional recovery following unilateral pyramidal lesions in monkeys?

In monkeys with a unilateral subtotal lesion of the bulbar pyramid, a partial recovery of manual dexterity occurred within 4-6 weeks. This recovery may have been due to sprouting of fibers from the intact pyramid into the partly denervated areas of the spinal gray matter. In order to test this hypothesis, small injections of radioamino acids were made in the precentral hand area of two experimental animals (3 and 18 months after pyramidotomy) and one normal control animal. The pattern of spinal labeling was analyzed in autoradiographs from the cervicothoracic segments. No statistically significant additional labeling was found in laminae VI-VIII where the majority of the ipsilateral corticospinal fibers terminate. However, in the monkey with a long survival time, many large perikarya, situated exclusively within lamina IX in segments C8 and T1, were labeled with aggregations of silver grains. On the basis of the position and size of these neurons we conclude that a postsynaptic labeling occurred selectively in those motoneurons which control hand movements and which were deprived from their contralateral pyramidal control. We tentatively suggest that such a labeling may reflect an influence of the (injected) ipsilateral cortex on these distal motoneurons via direct connections which are normally not observed in the intact monkey.

Amino Acids↗

Is the hindlimb representation of the rat's cortex a 'sensorimotor amalgam'?

In the rat, the hindlimb representation of the sensorimotor cortex is characterized by the presence of large pyramids in the fifth layer and a dense granular layer ('sensorimotor amalgam'). The objective was to investigate in the rat, whether or not the efferent zones to the gastrocnemius muscle and the proprioceptive feedback projection from that muscle to the cortex are co-extensive. To this end, the proprioceptive zone was mapped by means of field potentials and single unit discharges evoked by controlled longitudinal displacements of the gastrocnemius tendon. The efferent zones to the gastrocnemius muscle were mapped by means of intracortical microstimulation (ICMS; less than 30 microA). The proprioceptive zone occupied a territory extending from 1.0 to 2.5 mm caudal to the bregma and from 2.0 to 3.0 mm lateral from the midline. The response properties were similar to those observed previously in area 3a of monkeys. For sinusoidal displacements threshold amplitude decreased with increasing stretch frequency. The modal value of response latency was 7 ms, the shortest latency 4 ms. The ICMS zone lay 0.5 to 1.5 mm caudal to bregma having an overlap of 0.5 mm with the proprioceptive region. The proprioceptive as well as the motor areas lay within the granular cortex, but overlapped only to a small extent.

Animals↗

The thalamic connections with medial area 6 (supplementary motor cortex) in the monkey (macaca fascicularis).

The interrelationship of medial area 6 (supplementary motor area) with the thalamus was investigated by means of anterograde and retrograde tracing methods. Nine monkeys were prepared for autoradiography or histochemistry with the marker HRP conjugated to the lectin wheat germ agglutinin. Three of the monkeys received injections into the precentral cortex for comparison. Previous observations were confirmed that the thalamic relays to the motor areas are organized as crescent-shaped lamellae which transgress cytoarchitectonic boundaries. The thalamic VA-VL complex receiving fibres from areas 4 and medial area 6 also sends fibres to these same areas. The thalamic relay to medial area 6 comprised the following subdivisions: VLo, VLc, area X of Olszewski, VLm and, to a smaller extent VA. Labeling (mostly anterograde only) was also prominent in some thalamic compartments outside the 'motor' thalamus: R, CL, CM-Pf, MD, LP, PULo. It was noted that rostral and caudal injections into the medial area 6 resulted in different thalamic labeling: The rostral portion was found to be related mainly with VApc, area X and VLc, the central portion with VLo, and the caudal portion with VLc/VLo. This structural inhomogeneity may reflect also a functional rostro-caudal differentiation of the medial area 6. The thalamic territory projecting to the precentral cortex is separate from the above relay and includes principally VPLo. The present anatomical labeling study is in agreement with the conclusion of Schell and Strick (1984) that the SMA, especially its central portion, is an important target of basal ganglia outflow via the thalamic relay VLo. In addition consistent labeling was also found in thalamic subdivisions (area X, VLc) which had been found to receive cerebellar fibres.

Animals↗

Cerebello-cortical linkage in the monkey as revealed by transcellular labeling with the lectin wheat germ agglutinin conjugated to the marker horseradish peroxidase.

The possibility of a cerebellar linkage, via the thalamus with medial area 6 of the cerebral cortex was further explored in the present experiments (cf. preceding companion paper). It was found that HRP conjugated to the lectin wheat germ agglutinin injected into motor cortical areas was transported beyond the thalamus to the contralateral intracerebellar nuclei when the survival time was 4-7 days. It is suggested that the labeling in the deep cerebellar nuclei occurred via the thalamic relay where cerebellofugal fibre terminals had taken up the marker substance released by corticothalamic fibre terminals or by the retrogradely labeled thalamic perikarya. In general, transcellular labeling of perikarya was weaker than retrograde labeling in the thalamic cells. Some of the nuclear zones in the cerebellum showed relatively dense granulations of the reaction product; in other zones only cells with few granules were seen, and large parts of the nuclei were not labeled at all. The topography of secondary labeling in the cerebellar nuclei depended on the cortical injection sites. In all cases, most labeling was found in the contralateral dentate nucleus. The interposed nucleus received a fair amount of heavy labeling only in the precentral arm and face cases. Very little labeling was seen in the fastigial nucleus and in the cerebellar nuclei ipsilateral to the cortical injections. A somatotopic organization of secondary labeling was noted in the precentral cases with the face being represented caudally, the hindlimb rostrally and the arm between the face and the hindlimb representation. This is in agreement with previous anatomical and electrophysiological investigations. These observations thus lend support to the conclusion that the SMA receives a transthalamic input not only from the basal ganglia but also from the cerebellum, especially from its lateral, neo-cerebellar portion.

Animals↗

The projection of low-threshold muscle afferents of the forelimb to the main and external cuneate nuclei of the monkey.

The bulbar relay subserved by primary muscle afferents from the monkey's deep radial nerve was investigated by means of transganglionic labeling with wheatgerm agglutinin conjugated with horseradish peroxidase as well as by electrophysiological techniques. It was found that the "deep" input was confined to the pars triangularis of the main cuneate nucleus and to the ventromedial segment of the external cuneate nucleus. On the other hand, labeling occurring following incubation of the superficial (cutaneous) branch of the radial nerve was limited to the pars rotunda of the main cuneate nucleus. The cytoarchitectonic differentiation of the medullary relays is thus met by a clear-cut submodality segregation.

Afferent Pathways↗

Neuronal responses of medullary relay cells to controlled stretches of forearm muscles in the monkey.

Single units were recorded extracellularly from the external cuneate nucleus and from the main cuneate nucleus in anesthetized monkeys. The aim was to study the properties of the subpopulation of neurones which transmit "deep" (proprioceptive) information to the thalamus and the cerebral cortex, and to compare the results with previous studies in neurones of the higher "proprioceptive" centres. The neurones were characterized according to their location, their projection to the thalamus and the cerebellum, and their sensitivity to controlled displacements of the extensor digitorum communis muscle. Forty-nine neurones were allocated to the main cuneate nucleus. They occupied the pars triangularis which surrounds the pars rotunda laterally and ventrally. Fifty-six units were classified as external cuneate neurones. Among the external cuneate neurones, 14 neurones were excited antidromically by cerebellar and 8 neurones by thalamic stimulation; two further units responded antidromically to both cerebellar and thalamic stimulation. This observation is in agreement with previous anatomical evidence that part of the external cuneate neurones project to the ventrobasal complex of the thalamus. Possibly, some of these neurones may have bifurcating axons projecting to both targets. More than half of the main cuneate neurones were antidromically excited from the thalamus; three units were backfired from the cerebellum and two units were backfired from both targets. With controlled longitudinal displacements of the extensor digitorum communis tendon, the response patterns of the proprioceptive neurones were similar in both nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Pyramidal tract function and the clinical "pyramidal syndrome".

In this review, I wish to reconcile clinical usage of terminology and experimental concepts of pyramidal tract function. The traditional view, based essentially on neurological observations in stroke patients, was that this tract provides the structural basis of volitional movements. This concept is too simple and understanding of pyramidal tract function needs a considerably larger perspective. The view is discussed that the pyramidal tract is composed of subsystems with different cortical origin, fibre terminations and fibre sizes. The system shares its motor control function with other descending pathways and it also contributes to the phenomenon of descending control of sensory inflow. The pyramidal system plays a special role in the control of digital skill and speed of movements. However, there are also somewhat neglected observations that point to its function in postural control.

Adult↗

Effects of dorsal cord stimulation on stretch reflexes.

The effects of dorsal cord stimulation on phasic and tonic stretch reflex activity in extensor muscles were studied in decerebrate cats. The tonic stretch response was depressed in both fore- and hindlimb (stimulation at levels C1 and T8, respectively) and this often persisted for 5-20 min after the end of 1-10 min of dorsal cord stimulation. Depression of the phasic stretch response was only consistently seen in the forelimb during stimulation (C1) and this rarely outlasted the period of stimulation. These results support the idea that dorsal cord stimulation can reduce muscle tone but provide no explanation for the long-lasting effects of chronic, continuous stimulation in spastic man.

Animals↗

The corticopontine system in the rat. I. Mapping of corticopontine neurons.

The expanse of cerebral cortex containing corticopontine neurons was explored in rats. The retrograde tracer horseradish peroxidase (HRP) was iontophoresed into subdivisions of the pontine nuclei (PN). The densest projection was seen to originate from somatosensory and motor areas. Visual areas also provide a major contigent of corticopontine neurons, whereas auditory areas appear to have only a minor projection. Consistent labeling of cells was also seen in the granular cingulate cortex, especially in the junction region of anterior and posterior cingulate cortex. This and a sparse projection from dorsal and posterior "insular" cortex (rhinal sulcus) have not been described in detail in previous studies.

Animals↗

The corticopontine system in the rat. II. The projection pattern.

The projection from various cortical areas to the pontine nuclei (PN) of rats was investigated with anterograde tracing methods. As a general topological rule, a medial to lateral succession of the PN projection fields from the motor, somatosensory, and visual cortices was observed. Apart from the main "private" projections, each cortical area was found to send fibers also to disjunctive "extra-projection" territories which receive convergent inputs from two or more cortical areas. The sensorimotor and visual cortices provide the bulk of corticofugal fibers, but contributions from the following association areas were noted: frontal cortex, (dependent of the thalamic mediodorsal nucleus), rhinal sulcus region, and cingulate cortex.

Animals↗

Corticospinal neurones of the supplementary motor area of monkeys. A single unit study.

The direct projection from the supplementary motor area (SMA) to the spinal cord was investigated in six monkeys by means of antidromic identification of single SMA neurones. The exploration concentrated on that portion of medial area 6 from which movements were found to be elicited by stimulation at intensities of less than 30 microA in an earlier study, but also included some of medial area 4. Of 315 identified corticofugal projection neurones, 234 were found to be localized within medial area 6; of these only one third (76 cells) were corticospinal cells and the remaining two thirds were neurones which projected to the brainstem. The conduction velocities of the descending projection neurones of the SMA were slow (modal value: 10 m/s). Corticospinal cells of the SMA were found up to 6 mm rostral to the boundary between areas 4 and 6. Corticospinal neurones activated antidromically from the cervical but not from the lumbar cord ('cervico-thoracic' neurones) were concentrated in the mesial cortex; 'lumbo-sacral' neurones were found both in the dorsal cortex and the dorsal bank of the cingulate sulcus. However, there was considerable intermingling between the two types of projection neurones and there was no separation in the rostro-caudal direction. Similarly, projection neurones receiving orthodromic inputs from the somatotopical subdivisions of the precentral cortex were not segregated, but were intermingled in the entire rostro-caudal extent of the SMA. It is concluded that there is a clustering of corticospinal neurones in the SMA according to their most caudal segmental projection. However, no rostro-caudal differentiation into face, arm and leg areas was established. This observation is consistent with the results of a previous study in which corticospinal neurones in the SMA were labelled with anatomical tracers and efferent zones were investigated with intra-cortical microstimulation (Macpherson et al. 1982).

Animals↗

Anticipatory postural changes induced by active unloading and comparison with passive unloading in man.

Normal human subjects, sitting in a chair, were required to maintain stable elbow flexion against loads of 0.5 kg or 1.0 kg. Unloading was affected either 'passively' by the experimenter, or 'actively' with the subject's own contralateral arm. Elbow angle, force exerted by the load, and electromyographic activity (EMG) of biceps and triceps muscles of both arms were recorded and averaged. 'Passive' unloading was followed by a reduction of biceps EMG activity, starting 50--80 ms after weight lift, and by an upward deflection of the forearm. With 'active' unloading, however, a reduction of the biceps EMG activity slightly preceded the onset of unloading (0--30 ms). This reduction of the 'actively' unloading arm occurred at about the same time as the activity of the contralateral unloading arm. In this experiment, the unloaded forearm maintained an almost stable position. Thus, the anticipatory adjustment of elbow posture, observed when unloading was performed by the subject, appears to optimize limb stability during the mechanical perturbation.

Action Potentials↗

Microstimulation of the supplementary motor area (SMA) in the awake monkey.

The supplementary motor area of three Macaca fascicularis was mapped using intracortical microstimulation (ICMS). Both forelimb and hindlimb movements were evoked using currents of 30 microA or less. However, thresholds for evoking movements were higher than those in the primary motor cortex. Proximal motor effects predominated, but distal joint movements were also elicited. Forelimb points were clustered in mesial cortex of area 6, anterior to the precentral hindlimb and tail region. Distal joint effects were located deep in the cortex, intermingled with proximal effects. Hindlimb response which were less spatially localized, were found both ventral to the forelimb area, in the dorsal bank of the cingulate sulcus, and in mesial cortex, well anterior to area 4. No movements of facial muscles were elicited. Injections of HRP were made into the spinal cord at the cervical level in two animals and the lumbar level in the third one. An area of labelled cells was seen in mesial area 6 which corresponded closely to the region from which ICMS effects were elicited. No movements were evoked from the anterior portions of the fundal region of the cingulate sulcus which were also labelled.

Animals↗