Axon diameters and conduction velocities in the macaque pyramidal tract.

Small axons far outnumber larger fibers in the corticospinal tract, but the function of these small axons remains poorly understood. This is because they are difficult to identify, and therefore their physiology remains obscure. To assess the extent of the mismatch between anatomic and physiological measures, we compared conduction time and velocity in a large number of macaque corticospinal neurons with the distribution of axon diameters at the level of the medullary pyramid, using both light and electron microscopy. At the electron microscopic level, a total of 4,172 axons were sampled from 2 adult male macaque monkeys. We confirmed that there were virtually no unmyelinated fibers in the pyramidal tract. About 14% of pyramidal tract axons had a diameter smaller than 0.50 µm (including myelin sheath), most of these remaining undetected using light microscopy, and 52% were smaller than 1 µm. In the electrophysiological study, we determined the distribution of antidromic latencies of pyramidal tract neurons, recorded in primary motor cortex, ventral premotor cortex, and supplementary motor area and identified by pyramidal tract stimulation (799 pyramidal tract neurons, 7 adult awake macaques) or orthodromically from corticospinal axons recorded at the mid-cervical spinal level (192 axons, 5 adult anesthetized macaques). The distribution of antidromic and orthodromic latencies of corticospinal neurons was strongly biased toward those with large, fast-conducting axons. Axons smaller than 3 µm and with a conduction velocity below 18 m/s were grossly underrepresented in our electrophysiological recordings, and those below 1 µm (6 m/s) were probably not represented at all. The identity, location, and function of the majority of corticospinal neurons with small, slowly conducting axons remains unknown.

Normal spatial attention but impaired saccades and visual motion perception after lesions of the monkey cerebellum.

Lesions of the cerebellum produce deficits in movement and motor learning. Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar vermis. Monkeys and patients with such lesions are unable to modify the amplitude of saccades. Some have suggested that the effects on eye movements might reflect a more global cognitive deficit caused by the cerebellar lesion. We tested that idea by studying the effects of vermis lesions on attention as well as saccadic eye movements, visual motion perception, and luminance change detection. Lesions in posterior vermis of four monkeys caused the known deficits in saccadic control. Attention tested by examination of acuity threshold changes induced by prior cueing of the location of the targets remained normal after vermis lesions. Luminance change detection was also unaffected by the lesions. In one case, after a lesion restricted to lobulus VIII, the animal had impaired visual motion perception.

Cerebellum: history.

This paper will outline the history of study of the cerebellum from its beginnings to relatively recent times. Although there is no unanimous agreement about what the cerebellum does or how it does it, some principles of its structure and function are well understood. The historical approach can help to identify remaining questions and point the way to future progress. We make no effort to separate anatomical, physiological and clinical studies; rather, we hope to emphasize their interrelation. The cerebellum has always been seen as a distinct subdivision of the brain. Over the years there was an increasingly accurate description of its gross appearance and major subdivisions. By the beginning of the 19th century, the classical descriptive anatomical work was completed, and experimental study of the functions of the cerebellum began. Lesions were made in the cerebellum of experimental animals, and the behavioral deficits that were caused by the lesion were studied and described. These early animal studies powerfully influenced clinical interpretation of the symptoms seen in patients with cerebellar disease. Several questions are implicit in the anatomical and clinical studies of the nineteenth and early twentieth centuries, some of which remain incompletely answered. Many of these are addressed in other chapters in this volume. 1. Do different parts of the cerebellum do different things? The uniformity of the neuronal architecture of the cerebellar cortex suggests that each small region must operate in a similar way, but it is also clear that different regions control different functions. Is there a systematic sensory and/or body representation? 2. What are the functions of the cerebellar hemispheres? Massive in humans and very large in primates, their functions remain in dispute. Because the size of the cerebellar hemispheres parallels the development of the cerebral cortex, some have suggested that the hemispheres in humans and the higher primates may play a role in cognitive functions. 3. If one part of the cerebellum is damaged, can another part take over? A related question is whether normal motor function is possible in cases of complete or near-complete agenesis of the cerebellum. 4. What are the functions of the two distinctly different afferent systems to the cerebellum; the climbing and mossy fibers?

Whiskers, barrels, and cortical efferent pathways in gap crossing by rats.

Rats can readily be trained to jump a gap of around 16 cm in the dark and a considerably larger gap in the light for a food reward. In the light, they use vision to estimate the distance to be jumped. In the dark, they use their vibrissae at the farthest distances. Bilateral whisker shaving or barrel field lesions reduce the gap crossed in the dark by about 2 cm. Information from the barrel fields reaches motor areas via cortico-cortical, basal ganglia, or cerebellar pathways. The cells of origin of the ponto-cerebellar pathway are segregated in layer Vb of the barrel field. Efferent axons of Vb cells occupy a central position within the basis pedunculi and terminate on cells in the pontine nuclei. Pontine cells, in turn, project to the cerebellar cortex as mossy fibers. We trained normal rats to cross a gap in the light and in a dark alley that was illuminated with an infra-red source. When the performance was stable, we made unilateral lesions in the central region of the basis pedunculi, which interrupted connections from the barrel field to the pons while leaving cortico-cortical and basal ganglia pathways intact. Whisking was not affected on either side by the lesion, and the rats with unilateral peduncle lesions crossed gaps of the same distance as they did pre-operatively. Shaving the whiskers on the side of the face that retains its input to the pontine nuclei reduced the maximal gap jumped in the dark by the same amount as bilateral whisker shaving. Performance in the light was not affected. Regrowth of the shaved whiskers was associated with the recovery of the maximum distance crossed in the dark. In control cases, shaving the whiskers on the other side of the face did not reduce the distance jumped in the dark or in the light. These results suggest that the cerebellum must receive whisker information from the barrel fields for whisker-guided jumps.

Functional localisation in the cerebral cortex and cerebellum: lessons from the past.

One of the basic questions about the working of the brain is the extent to which its various functions are localised. In the nineteenth century great advances were made in the study of localisation. The control of speech, movement, and vision was identified with specific regions of the cerebral cortex. Although since the nineteenth century lesions of the cerebellum have been known to produce impaired movement, there has been rather little progress towards answering more detailed questions about the functions of the cerebellum and cerebellar localisation. The experts are still not agreed on what the cerebellum does or how and where it does it. Three examples are given of functions which probably are mediated by the cerebellum; adaptation of the vestibulo-ocular reflex, classical conditioning of the nictitating membrane response, and adaptation of saccadic eye movements. In all three cases the control of these functions has been localised to a specific region of the cerebellar cortex and/or nuclei. The success of localisation studies in the cerebral cortex can serve as a guide. Continued experimentation directed at the question of localisation should prove a fruitful approach to understanding more about the functions of the cerebellum.

How are visual areas of the brain connected to motor areas for the sensory guidance of movement?

Visual areas of the brain must be connected to motor areas for the sensory guidance of movement. The first step in the pathway from the primary visual cortex is by way of the dorsal stream of visual areas in the parietal lobe. The fact that monkeys can still guide their limbs visually after cortico-cortical fibres have been severed suggests that there are subcortical routes that link visual and motor areas of the brain. The pathway that runs from the pons and cerebellum is the largest of these. Pontine cells that receive inputs from visual cortical areas or the superior colliculus respond vigorously to appropriate visual stimuli and project widely on the cerebellar cortex. A challenge for future research is to elucidate the role of these cerebellar target areas in visuo-motor control.

Saccadic dysmetria and adaptation after lesions of the cerebellar cortex.

We studied the effects of small lesions of the oculomotor vermis of the cerebellar cortex on the ability of monkeys to execute and adapt saccadic eye movements. For saccades in one horizontal direction, the lesions led to an initial gross hypometria and a permanent abolition of the capacity for rapid adaptation. Mean saccade amplitude recovered from the initial hypometria, although variability remained high. A series of hundreds of repetitive saccades in the same direction resulted in gradual decrement of amplitude. Saccades in other directions were less strongly affected by the lesions. We suggest the following. (1) The cerebellar cortex is constantly recalibrating the saccadic system, thus compensating for rapid biomechanical changes such as might be caused by muscle fatigue. (2) A mechanism capable of slow recovery from dysmetria is revealed despite the permanent absence of rapid adaptation.

Cerebellar lesions and prism adaptation in macaque monkeys.

If a laterally displacing prism is placed in front of one eye of a person or monkey with the other eye occluded, they initially will point to one side of a target that is located directly in front of them. Normally, people and monkeys adapt easily to the displaced vision and correct their aim after a few trials. If the prism then is removed, there is a postadaptation shift in which the subject misses the target and points in the opposite direction for a few trials. We tested five Macaque monkeys for their ability to adapt to a laterally displacing prism and to show the expected postadaptation shift. When tested as normals, all five animals showed the typical pattern of adaptation and postadaptation shift. Like human subjects, the monkeys also showed complete interocular transfer of the adaptation but no transfer of the adaptation between the two arms. When preoperative training and testing was complete, we made lesions of various target areas on the cerebellar cortex. A cerebellar lesion that included the dorsal paraflocculus and uvula abolished completely the normal prism adaptation for the arm ipsilateral to the lesion in one of the five monkeys. The other four animals retained the ability to prism-adapt normally and showed the expected postadaptation shift. In the one case in which the lesion abolished prism adaptation, the damage included Crus I and II, paramedian lobule and the dorsal paraflocculus of the cerebellar hemispheres as well as lobule IX, of the vermis. Thus in this case, the lesion included virtually all the cerebellar cortex that receives mossy-fiber visual information relayed via the pontine nuclei from the cerebral cortex. The other four animals had damage to lobule V, the classical anterior lobe arm area and/or vermian lobules VI/VII, the oculomotor region. When tested postoperatively, some of these animals showed a degree of ataxia equivalent to that of the case in which prism adaptation was affected, but prism adaptation and the postadaptation shift remained normal. We conclude that in addition to its role in long-term motor learning and reflex adaptation, the region of the cerebellum that was ablated also may be a critical site for a short-term motor memory. Prism adaptation seems to involve a region of the cerebellum that receives a mossy-fiber visual error signal and probably a corollary discharge of the movement.

Visual control of the arm, the wrist and the fingers: pathways through the brain.

Sperry and his colleagues had shown that section of the corpus callosum blocks the normally strong interocular transfer of visual learning in chiasma sectioned monkeys. Although interhemispheric transfer of learning was blocked, monkeys could be readily trained to use any combination of eye and hand in a task that required rapid visually guided responses. Sperry suggested that there must be a subcortical pathway linking sensory to motor areas of the brain. We tested monkeys in a task which required them to orient their wrist and fingers correctly in order to remove a morsel of food from a slotted disc. Animals in which we made lesions of the dorsal extrastriate visual areas of the parietal lobe were profoundly impaired in performing this task, but showed no deficit in visual discrimination learning. A monkey with an extensive lesion of the ventral, temporal lobe extrastriate areas showed no deficit in the visuomotor task but was profoundly impaired in visual discrimination learning. Lesions of peri-arcuate cortex, a major cortical target of parietal lobe visual areas, produced only a mild deficit which was motor in character. We suggest that the visuomotor deficit caused by parietal lobe lesions is brought about by depriving the cerebellum of its cortical visual input.

The anatomy of the cerebellum.

Vertebrate cerebella occupy a position in the rostral roof of the 4th ventricle and share a common pattern in the structure of their cortex. They differ greatly in their external form, the disposition of the neurones of the cerebellar cortex and in the prominence of their afferent, intrinsic and efferent connections.

Cerebellum and the sensory guidance of movement.

By the end of the 19th century the locations of the primary visual and motor areas of the cerebral cortex were well recognized. At that time it was generally assumed that for the visual control of movement visual areas must be linked to motor areas by way of a series of cortico-cortical fibres. Subsequent experimental evidence showed clearly, however, that skilled visuomotor performance is still possible after complete disconnection of interhemispheric and intracortical fibre systems. Preservation of skilled visuomotor performance after such lesions has often been thought to be mediated by ipsilaterally descending motor pathways. However, the evidence indicates that there must also be subcortical pathways that link sensory to motor areas of the brain. One such pathway involves the cerebellum. There is a massive input from cortical and subcortical visual areas to the pontine nuclei. Cells in the pontine nuclei respond vigorously to appropriate visual targets and they distribute their axonal terminals bilaterally in the cerebellar cortex. A cortico-ponto-cerebellar circuit would have remained intact in all cases in the literature in which there was complete disconnection of cortico-cortical fibres between visual and motor cortex. Lesions of the cortical sensory areas that project to the pons or interruption of the fibres within the internal capsule or basis pedunculi, that link cortical sensory areas with the pontine nuclei, can severely impair the sensory guidance of movement. This paper reviews the evidence for sensory input to the cerebellum and the possible role of a cortico-ponto-cerebellar circuit in the sensory guidance of movement.

The anatomy of the cerebellum.

Vertebrate cerebella occupy a position in the rostral roof of the 4th ventricle and share a common pattern in the structure of their cortex. They differ greatly in their external form, the disposition of the neurons of the cerebellar cortex and in the prominence of their afferent, intrinsic and efferent connections.

Mossy-fibre sensory input to the cerebellum.

The role of the spinal and vestibular afferents to the cerebellum in the control of movement first began to be recognized towards the end of the 19th century. By the middle of the present century it was clear that visual and auditory information are also relayed to the cerebellum from the cerebral cortex and brainstem by way of the pontine nuclei. Pontine cells project to the cerebellar cortex where they terminate as mossy fibres. The corticopontine projection arises from cells in lamina V of the cerebral cortex. Cells in the rat primary somatosensory cortex also provide an input to the basal ganglia, but the two populations are largely segregated in distinct sub-laminae. In monkeys, and probably in humans, the cortical visual input to the pontine nuclei arises from the dorsal stream of extrastriate visual areas. Experimental and clinical evidence suggest that damage to this pathway at the cortical level, or interruption of its corticopontine fibres within the internal capsule produce profound disturbance in visuomotor guidance. One of the major pathways through the brain for the visual guidance of movement is relayed from the dorsal stream of extrastriate areas to the cerebellum by way of the pontine nuclei.

Subcortical origin of visuomotor apraxia.

Visuomotor apraxia (VMA) is a clinical syndrome characterized by a failure to make use of visual information when performing a target-directed movement. Visuomotor apraxia has traditionally been assumed to result from a disconnection of cortico-cortical fibres between visual and motor areas following occipito-parietal lesions. We describe a patient who developed a permanent contralesional and a temporary ipsilesional visuomotor apraxia as part of a complex neurological syndrome after a right [corrected] thalamic haemorrhage. MRI showed that the suprathalamic white matter was not involved but the most caudal fibres of the internal capsule appeared to be interrupted. To our knowledge this is the first case of a VMA with a lesion restricted to a deep subcortical area indicating that VMA can result from damage to subcortical projections rather than interruption of cortico-cortical fibres.

Lodewijk Bolk and the comparative anatomy of the cerebellum.

The cerebellum of mammals is histologically uniform, but it varies greatly in the relative size of its different parts. The Dutch anatomist Lodewijk Bolk studied a large series of mammalian cerebella, and put forward a general scheme of organization that can be applied to all mammals. Bolk also speculated about the functional role of different regions of the cerebellum, based on the idea that there might be a single somatotopically organized representation of the body surface on the cerebellar cortex. Although his idea of a single map is wrong, Bolk's anatomical descriptions are thorough, and his insights are profound. These descriptions formed the basis for much subsequent thinking about the structure of the cerebellum.

Visual pontocerebellar projections in the macaque.

The cerebellum plays an important role in the visual guidance of movement. In order to understand the anatomical basis of visuomotor control, we studied the projection of pontine visual cells onto the cerebellar cortex of monkeys. Wheat germ agglutinin horseradish peroxidase was injected into the dorsolateral pons two monkeys. Retrogradely labelled cells were mapped in the cerebral cortex and superior colliculus, and orthogradely labelled fibers in the cerebellar cortex. The largest number of retrogradely labelled cells in the cerebral cortex was in a group of medial extrastriate visual areas. The major cerebellar target of these dorsolateral pontine cells is the dorsal paraflocculus. There is a weaker projection to the uvula, paramedian lobe, and Crus II, and a sparse but definite projection to the ventral paraflocculus. There are virtually no projections to the flocculus. There are sparse ipsilateral pontocerebellar projections to these same regions of cerebellar cortex. In nine monkeys, we made small injections of the tracer into the cerebellar cortex and studied the location of retrogradely filled cells in the pontine nuclei and inferior olive. Injections into the dorsal paraflocculus or rostral folia of the uvula retrogradely labelled large numbers of cells in the dorsolateral region of the contralateral pontine nuclei. Labelled cells were found ipsilaterally, but in reduced numbers. Injections outside of these areas in ventral paraflocculus or paramedian lobule labelled far fewer cells in this region of the pons. We conclude that the principal source of cerebral cortical visual information arises from a medial group of extrastriate visual areas and is relayed through cells in the dorsolateral pontine nuclei. The principal target of pontine visual cells is the dorsal paraflocculus.

Cerebellar agenesis.

Lesions of the cerebellum produce profound deficits in movement. Since there is demonstrable recovery from partial lesions, some have asserted that the cerebellum may not be necessary for normal movement. It is even alleged that people may not manifest any motor symptoms despite total cerebellar agenesis. The literature points to a different conclusion. Cerebellar agenesis is always associated with profound motor deficits. A case of cerebellar agenesis of a man who died in 1951 is discussed. Evidence is presented that it is this case which gave rise to part of the oral tradition which alleges that normal movement is possible despite total cerebellar agenesis. In this brain an MRI scan revealed a small residual cerebellum. Moreover, despite an oral tradition to the contrary, there is absolutely no evidence about the motor capacities of this man during his life.

Traumatic intramyocardial dissection secondary to significant blunt chest trauma: a case report.

The case of a patient with delayed mitral regurgitation and right coronary artery traumatic injury in association with intramyocardial dissection without rupture or pseudoaneurysm is presented. These findings evolved secondary to blunt chest trauma and were confirmed by cardiac ultrasound scanning, magnetic resonance imaging, and cardiac catheterization. Successful surgical correction was facilitated with this combination of diagnostic testing.