The motor cortex of the sheep: laminar organization, projections and diffusion tensor imaging of the intracranial pyramidal and extrapyramidal tracts.

The laminar organization of the motor cortex of the sheep and other large domestic herbivores received scarce attention and is generally considered homologous to that of rodents and primates. Thickness of the cortex, subdivision into layers and organization are scarcely known. In the present study, we applied different modern morphological, mathematical and image-analyses techniques to the study of the motor area that controls movements of the forelimb in the sheep. The thickness of the cortex resulted comparable to that of other terrestrial Cetartiodactyls (but thicker than in marine Cetartiodactyls of similar body mass). The laminar organization showed marked development of layer 1, virtual absence of layer 4, and image analysis suggested prevalence of large irregular neural cells in the deeper layers. Diffusion tensor imaging revealed robust projections from the motor cortex to the pyramids in the brainstem, and well evident tracts descending to the tegmentum of the mesencephalon and dorsal pons. Our data contrast the general representation of the motor system of this species, considered to be predominantly based on extra-pyramidal tracts that originate from central pattern generators in the brainstem.

Assessment of a method to determine deep brain stimulation targets using deterministic tractography in a navigation system.

Recent advances in imaging permit radiologic identification of target structures for deep brain stimulation (DBS) for movement disorders. However, these methods cannot detect the internal subdivision and thus cannot determine the appropriate DBS target located within those subdivisions. The aim of this study is to provide a straightforward method to obtain an optimized target (OT) within DBS target nuclei using a widely available navigation system. We used T1- and T2-weighted images, fluid-attenuated inversion recovery (FLAIR) sequence, and diffusion tensor imaging (DTI) of nine patients operated for DBS in our center. Using the StealthViz® software, we segmented the targeted deep structures (subcortical targets) and the anatomically identifiable areas to which these target nuclei were connected (projection areas). We generated fiber tracts from the projection areas. By identifying their intersections with the subcortical targets, we obtained an OT within the DBS target nuclei. We computed the distances from the clinically effective electrode contacts (CEEC) to the OT obtained by our method and the targets provided by the atlas. These distances were compared using a Wilcoxon signed-rank test, with p < 0.05 considered statistically significant. We were able to identify OT coincident with the motor part of the subthalamic nucleus and the ventral intermediate nucleus. We clinically tested the results and found that the CEEC were significantly more closely related to the OT than with the targets obtained by the atlas. Our present results show that this novel method permits optimization of the stimulation site within the internal subdivisions of target nuclei for DBS.

The location of the major ascending and descending spinal cord tracts in all spinal cord segments in the mouse: actual and extrapolated.

Information on the location of the major spinal cord tracts in the mouse is sparse. We have collected published data on the position of these tracts in the mouse and have used data from other mammals to identify the most likely position of tracts for which there is no mouse data. We have plotted the position of six descending tracts (corticospinal, rubrospinal, medial and lateral vestibulospinal, rostral and caudal reticulospinal) and eight ascending tracts (gracile; cuneate; postsynaptic dorsal columns; dorsolateral, lateral, and anterior spinothalamic; dorsal and ventral spinocerebellar) on diagrams of transverse sections of all mouse spinal cord segments from the first cervical to the third coccygeal segment.

The unbearable lightness of the extrapyramidal system.

The concept of the extrapyramidal system comprises an amalgam of disparate and often conflicting ideas with a tortuous history. To the theoretical neuroscientist or practicing clinician, it promptly evokes semantic associations that are hardly reminiscent of its original meaning. The purpose of this article is to revisit the sources of the extrapyramidal concept and to examine the transformations that it went through from its inception, in the late 1890s, up to the neuroimaging revolution of the 1980s. Our review shows that the use of "extrapyramidal" as a surrogate for the basal ganglia, disorders of movement, or certain manifestations of spastic hemiplegia does not apply to humans; rather, it represents the historical product of the unwarranted translation of results of animal experimentation into the interpretation of clinical findings on human patients, misguided clinico-anatomic deductions, and fanciful phylogenetic notions. We conclude that the extrapyramidal concept is a valid and robust anatomic concept as long as it strictly refers to the collection of descending fibers originating in a few discrete brainstem tegmental motor nuclei that project to the spinal cord.

[History of the basal ganglia system. Slow development of a major cerebral system]. / Histoire du système des ganglions de la base. La lente émergence d'un système cérébral majeur.

Initially, basal ganglia was a descriptive term for onto- and phylogenetic or topographic classifications. A variable list of structures were included as basal ganglia. A major step was made when the thalamus was separated from the "striated bodies" (Vic d'Azyr, 1786) which was sometimes taken into account in the French description of the noyaux gris centraux. Even if the term is not perfect, it is preferable to "the system of basal ganglia". The subdivisions of the putamen, the distinction between the striatum and the pallidum were not really made until the beginning of the twentieth century. Modern tracing methods were needed to demonstrate the main connections. It was not until the end of the 1960s that the importance of the striato-pallido-nigral network within the basal ganglia and the cortico-striatal connections, the main afferent system, were recognized. With the description of the cortico-striatal connections, the sub-cortical system with multiple complex "loops" was questioned. The term "extra-pyramidal system" had an exaggerated success. Initially, it designated descending non-pyramidal afferents (some which do not exist) and their source. In 1992, Spatz based his separation of this heterogeneous group on the iron content. The terms of extra-pyramidal "system" and "syndrome" should be abandoned by clinicians. Physiological interpretations have varied. The role of automatic "habitual" motricity, derived from a concept of hierarchic, Jacksonian cerebral organization, was questioned when the pyramidal network was described. Clinico-pathological analysis (hemiballism, Parkinson's disease ...) has placed new emphasis on the motor role, for a time the only role accepted as real. More recently, debate has centred on other roles, particularly in cognition and motivation. An illustration of functions other than purely motor functions of the basal ganglia is given by the syndromes of loss of psychic auto-activation secondary to bilateral lesions.

Basal ganglia: functional anatomy and physiology. Part 1.

Advances in knowledge about basal ganglia structure and connectivity from 1925 to date are reviewed. Current concepts about neuronal populations, transmitters, and input and output of each of the basal ganglia nuclei are presented. The portrayal by Wilson, in 1925, of the striatum as a simple homogeneous structure has been replaced by the recognition, based on staining characteristics, connectivity, and function, that the neostriatum is compartmentalized into striosomes, matrisomes, and matrix compartments. Electrophysiologic studies have further shown the existence, in the neostriatum, of neuronal clusters that represent basic functional units much like the functional columns described much earlier for the cerebral cortex. Whereas the neostriatum is considered the major receiving area of the basal ganglia, the globus pallidus and substantia nigra pars reticulata constitute the major output nuclei. Combined neuroanatomic and neurophysiologic studies have revealed precise somatotopic organization throughout the basal ganglia system such that the leg, arm, and face areas of the cerebral cortex related to respective topographic areas within the striatum, pallidum, substantia nigra, and subthalamus. The previous concept of an inhibitory role for dopamine on striatal neurons has been modified. It is now acknowledged that dopamine exerts an inhibitory effect on striatal neurons that project to the external pallidum and a facilitatory effect on striatal neurons that project to the internal pallidum and substantia nigra pars reticulata. The previous concept of serial connectivity of the neostriatum (funnel concept) has been replaced by the concept of parallel connectivity. Within the internal connectivity of the basal ganglia, there is a fast system in which the neurotransmitter is gamma-aminobutyric acid (GABA) and a slow system modulated by neuropeptides. The slow system is believed to give identity to an otherwise homogenous GABAergic system.

N-Methyl-D-aspartate receptors mediate dopamine-induced changes in extrapyramidal and limbic dynorphin systems.

The N-methyl-D-aspartate (NMDA)-type glutamate receptor was shown to mediate dopamine-induced dynorphin A (Dyn) changes in extrapyramidal and limbic structures. MK801, a potent noncompetitive antagonist of the NMDA receptor, blocked increases in striatal and nigral Dyn content following single and multiple administrations of methamphetamine (METH). Significant attenuation of the METH-induced increases occurred with MK801 doses of 0.1 mg/kg/dose with complete blockade at 2.5 mg/kg/dose. Similar to METH, NMDA itself caused significant increases in striatal and nigral Dyn content. The NMDA-induced increase in striatal Dyn content was blocked by coadministration of an intermediate dose of MK801. The Dyn system associated with the nucleus accumbens responded in a similar manner in that MK801 totally blocked the METH-induced increases; moreover, NMDA elevated the Dyn content in this structure. The inability of MK801 to alter the quinpirole-induced decrease in striatal Dyn content suggests that the NMDA receptor is not involved in the D2 receptor regulation of striatal Dyn systems.

MR microscopy at 7.0 T: effects of brain iron.

The T2 of brain tissue is known to be field dependent, decreasing as B0 increases. Previous studies have attributed reduced T2 in the structures of the extrapyramidal motor system (EPMS) to high iron concentrations. The present study was designed to manipulate physiologic iron concentrations and study the effects on T2 and on the field dependence of T2 at 7.0 T in whole formalin-fixed brains. A rat model was devised in which iron concentrations in the structures of interest were altered by diet manipulation. Cerebral structures with different iron content were imaged and T2 measured with MR microscopy at both 2.0 and 7.0 T. T2 of all tissues was shorter by 40%-60% at 7.0 T. Although some dependence of T2 on iron concentration was evident, it was less than expected. The strongest correlation was in the substantia nigra. The highest-resolution studies, at 30 x 30 x 50 microns, show the myelin bundles in many of the EPMS structures but not in the substantia nigra. From these data, it appears that T2 at greater field strengths depends more on susceptibility-induced spin dephasing imposed by diffusion through the tissue microstructure than on the presence of iron.

Long descending direct projection from the basal ganglia to the spinal cord: a revival of the extrapyramidal concept.

Our retrograde fluorescent labeling study shows that a distinct cell group of the subthalamic nucleus, posited in the basal ganglia, directly sends long descending axons contralaterally to the upper cervical segments (C1-C5) of the spinal cord in the rat. A large population (60-70%) of these subthalamic cells projecting to contralateral spinal levels give off axonal branches innervating the ipsilateral globus pallidus. Now, the classical concept of the 'extrapyramidal' motor system needs to be reconsidered. Furthermore, our results may provide a morphological substrate for the onset of a violent form of dyskinesia, 'hemiballism', which occurs in the contralateral limbs both clinically and experimentally following discrete lesions in the subthalamic nucleus or its fiber connections with the globus pallidus.

Neuropharmacology of the extrapyramidal system.

The neuropharmacology and neuroanatomy of the extrapyramidal system are complex; however, in its most reductionistic state, this system is often described as a balance between the actions of dopamine and acetylcholine. In this paper, a thorough investigation of the neuroanatomy and neuropharmacology of the extrapyramidal system is undertaken, and an attempt is made to delineate the roles of other neurotransmitters and neuromodulators that play an important role in its functioning. To demonstrate the therapeutic complexity of extrapyramidal system movement disorders, clinical literature is briefly reviewed to show the relative efficacies of anticholinergic and prodopaminergic antiparkinsonian agents in treating neuroleptic-induced extrapyramidal side effects and to show how drugs that affect alternative neurotransmitter systems have also been used to treat these same side effects.

Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum.

The pedunculopontine tegmental nucleus (PPTn) was originally defined on cytoarchitectonic grounds in humans. We have employed cytoarchitectonic, cytochemical, and connectional criteria to define a homologous cell group in the rat. A detailed cytoarchitectonic delineation of the mesopontine tegmentum, including the PPTn, was performed employing tissue stained for Nissl substance. Choline acetyltransferase (ChAT) immunostained tissue was then analyzed in order to investigate the relationship of cholinergic perikarya, dendritic arborizations, and axonal trajectories within this cytoarchitectonic scheme. To confirm some of our cytoarchitectonic delineations, the relationships between neuronal elements staining for ChAT and tyrosine hydroxylase were investigated on tissue stained immunohistochemically for the simultaneous demonstration of these two enzymes. The PPTn consists of large, multipolar neurons, all of which stain immunohistochemically for ChAT. It is present within cross-sections that also include the A-6 through A-9 catecholamine cell groups and is traversed by catecholaminergic axons within the dorsal tegmental bundle and central tegmental tract. The dendrites of PPTn neurons respect several nuclear boundaries and are oriented perpendicularly to several well-defined fiber tracts. Cholinergic axons ascend from the mesopontine tegmentum through the dorsal tegmental bundle and a more lateral dorsal ascending pathway. A portion of the latter terminates within the lateral geniculate nucleus. It has been widely believed that the PPTn is reciprocally connected with several extrapyramidal structures, including the globus pallidus and substantia nigra pars reticulata. Therefore, the relationships of pallidotegmental and nigrotegmental pathways to the PPTn were investigated employing the anterograde autoradiographic methodology. The reciprocity of tegmental connections with the substantia nigra and entopeduncular nucleus was investigated employing combined WGA-HRP injections and ChAT immunohistochemistry. The pallido- and nigrotegmental terminal fields did not coincide with the PPTn, but, rather, were located just medial and dorsomedial to it (the midbrain extrapyramidal area). The midbrain extrapyramidal area, but not the PPTn, was reciprocally connected with the substantia nigra and entopeduncular nucleus. We discuss these results in light of other cytoarchitectonic, cytochemical, connectional, and physiologic studies of the functional anatomy of the mesopontine tegmentum.

Anatomical evidence for an ipsilateral rubrospinal pathway and for direct rubrospinal projections to motoneurons in the cat.

In 11 cases [3H]leucine injections were made in various parts of the red nucleus (NR) and surrounding area. The autoradiographical tracing results confirmed the existence of a somatotopic organization in the location of the rubrospinal neurons. Moreover the results demonstrated direct NR projections to the most dorsolaterally located motoneuronal cell group in the C8 and upper T1 spinal segments and some ipsilaterally descending rubrospinal fibers terminating in the lateral part of the cervical intermediate zone.

Monosynaptic raphespinal and reticulospinal projection to forelimb motoneurones in cats.

Wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) was injected in the nerve branches to the spino- and acromiodeltoid muscles. After injection, the cats were awake for a period of 100 h during which they performed target-reaching and/or walking movements. Transneuronally labelled neurones were found in the nucleus raphe pallidus, in the magno- and gigantocellular parts of the medial reticular formation. All neurones were located between the level of the obex and 6 mm rostrally of the obex. These results demonstrate that medullary raphespinal and reticulospinal neurones have monosynaptic connexions with deltoid motoneurones. The raphespinal projection is partly from neurones with large cell bodies assumed to be non-monoaminergic.

The adult organization and development of the rubrospinal tract. An experimental study using the orthograde transport of WGA-HRP in the North-American opossum.

We have employed the orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase to study the organization of rubrospinal connections in adult and pouch young opossums. Our results suggest that: in the adult opossum rubrospinal axons are distributed more widely than suggested by previous studies; rubrospinal projections are formed postnatally in the opossum, but much earlier than corticospinal connections; rubrospinal axons do not grow synchronously, as a massive bundle following a few leading axons, but by addition of axons over a protracted period of time; and the growth of rubral axons into the spinal gray matter follows a predictable rostral to caudal gradient as well as a proximal to distal one relative to the tract. Rubrospinal development is discussed in light of the growth of cerebellar and cortical axons into the red nucleus and the development of motor function.

[Descending pathways of the cerebral cortex to nuclear structures of the extrapyramidal system]. / O niskhodiashchikh putiakh kory golovnogo mozga k iadernym obrazovaniem ékstrapiramidnoi sistemy.

The connections of the neocortical structures in animal and human brains with the complex of nuclear formations of the extrapyramidal system have been studied. The authors present comparative characteristics and distribution of these connections in the nuclear and other formations of the extrapyramidal system. Both mediator (via the thalamus) and direct cortical projections toward the nuclei of the extrapyramidal system in primates, especially in humans, have been found to increase. It has been shown that the frontal cortex has closer connections with the complex of the extrapyramidal nuclei as compared with other brain lobes.

[The pyramidal tract. Recent anatomic and physiologic findings]. / La voie pyramidale. Données anatomiques et physiologiques récentes.

The cortical origin of the pyramidal tract is first considered. Contributions of retrograde degeneration studies as well as fiber counting method following different cortical lesions are presented and discussed. The results of these classical neuro-anatomical methods are compared with those of the more recent retrograde transport tracing method. The number and the diameter spectrum of pyramidal tract fibers differ in various mammals. In more evolved species the number of pyramidal fibers increase and their diameter span becomes wider. The thickest fibers are found in man. Along their diencephalic, mesencephalic, pontine and medullary course, axonal collaterals of corticospinal axons may terminate onto cells of origin of other descending pathways, onto relay cells of ascending pathways, and onto neurons projecting to the cerebellum. At the spinal level, the rostrocaudal extent and the termination area of corticospinal fibers may differ in various mammals. In a first group of mammals, the corticospinal fibers extend only to cervical or mid-thoracic segments and terminate in the dorsal horn. In a second group of mammals, the corticospinal fibers extend throughout the spinal cord and terminate in the dorsal horn and the intermediate zone. In a third group of mammals, the corticospinal fibers extend throughout the spinal cord and terminate in the dorsal horn, the intermediate zone and the dorsolateral part of the lateral motoneuronal cell group. In a fourth group of mammals, the corticospinal fibers also extend throughout the spinal cord and terminate in the dorsal horn, the intermediate zone and the dorsolateral as well as the ventral parts of the lateral motoneuronal cell group. A comparison is made between these different types of spinal terminations and the motor capacities of these different species. The motor deficits observed after pyramidal lesions are summarized and a comparison is made between the corticospinal tract and the descending brain stem pathways. According to electrophysiological studies in conscious animals different pyramidal units can be activated during different types of movements and at different times during the preparation or execution of a movement. Recent neuro-anatomical data suggest that the pyramidal tract is composed of many structural subsystems. Recent physiological data suggest that the pyramidal tract can be involved in various aspects of the motor control.

The distribution and origin of the ipsilateral descending limb of the brachium conjunctivum. An autoradiographic and horseradish peroxidase study in the rat.

The distribution, organization and origin of the ipsilateral descending limb of the Brachium Conjunctivum (B.C.), have been studied in the rat by using anterograde and retrograde tracing techniques. After injections of tritiated leucine/proline into the lateral cerebellar nucleus, covering both its medial part, corresponding to the dorsolateral hump (DLH) of Goodman et al. (1963) and its lateral part, (designated here as the lateral dentate, LD), and the neighboring interposed nucleus (NI), emerging fibres are numerous and leave laterally from the B.C. On the contrary, injections restricted to LD reveal very few such fibers. Within the lateral parvocellular reticular formation (LPRF) terminal labelling is heavy, and moderate to sparse within the adjacent trigeminal complex. Rostro-caudally, silver grain accumulation within the LPRF extends from the level of the motor trigeminal nucleus (VM) to the pyramidal decussation, exhibiting a cephalocaudal decrease of grain density. Within the trigeminal complex, labelling occurs in the caudal VM, the dorsal portion of the principal sensory nucleus, and within and around the trigeminal spinalis oralis. In addition, the area surrounding the VM (in part corresponding to the supratrigeminal region of Lorente de Nó 1922, 1933) is moderately labelled. After injections of HRP into various levels of the ipsilateral descending B.C.'s projection field, retrogradely labelled cells are numerous within the DLH. A slightly lesser amount of labelled cells are found in the lateral half of the NI, primarily concerning the nucleus interpositus posterior. Within the LD, only a few labelled cells are observed: these are mainly restricted to the dorsal portion at rostral levels of the nucleus. The results obtained by both the anterograde and retrograde studies suggest an absence of a topographic organization within this descending B.C. component. The possible functional meaning of these results is discussed.

Afferent and efferent relationships of the basal ganglia.

A survey of the known circuitry of the basal ganglia leads to the following conclusions. (1) No complete account can yet be given of the neural pathways by which the basal ganglia affect the bulbospinal motor apparatus. Channels of exit from the basal ganglia originate from the internal pallidal segment, the pars reticulata of the substantia nigra, and the subthalamic nucleus, and each of these is directed in part rostrally to the cerebral cortex by way of the thalamus, in part caudally to the midbrain. The postsynaptic extension of the mesencephalic channels to bulbar and spinal motor neurons is largely unknown. Since the ascending channels are collectively of greatest volume, the notion remains plausible that the basal ganglia act in considerable part by modulating motor mechanisms of the cortex. (2) Recent findings in the rat suggest that the striatum is subdivided into a ventromedial, limbic system-afferented region and a dorsolateral, 'non-limbic' region largely corresponding to the main distribution of corticostriatal fibres from the motor cortex. These two subdivisions appear to give rise to different striatofugal lines, the outflow from the limbic-afferented sector partly re-entering the circuitry of the limbic system. (3) The limbic-afferented striatal sector suggests itself as an interface between the motivational and the more strictly motor aspects of movement. This suggestion is strengthened by evidence that the 'limbic striatum' seems enabled by its striatonigral efferents to modulate not only the source of its own dopamine innervation but also that of a large additional striatal region.

Origin of the rubrospinal tract in neonatal, developing, and mature rats.

This investigation describes the origin of the rubrospinal tract in neonatal (1-10 days old), developing (15-20 days old), and mature (2-4 months old) rats studied by using the horseradish peroxidase (HRP) method of tracing neuronal connections. HRP was administered in the cervical or lumbosacral segments of the spinal cord either in the crystal or solution form. The results showed that the rubrospinal tract extended to the lumbosacral part of the spinal cord at birth. There appeared to be no difference in the pattern of labelled rubrospinal (RS) neurons following the administration of HRP in the cervical or the lumbosacral cord segment of the neonatal, developing, and mature rats. In rats of these three age groups, labelled neurons were found bilaterally in the red nucleus, with a contralateral predominance, and they were found in both the parvicellular and magnocellular portions of the red nucleus. There was a somatotopic arrangement in the labelled RS neurons: Those projecting to the cervical cord segments were located in the dorsal and dorsomedial regions of the red nucleus and those projecting to the lumbosacral cord segments were located in the ventral and ventrolateral regions of the nucleus.