The involvement of the human cerebellum in eyeblink conditioning

Besides its known importance for motor coordination, the cerebellum plays a major role in associative learning. The form of cerebellum-dependent associative learning, which has been examined in greatest detail, is classical conditioning of eyeblink responses. The much advanced knowledge of anatomical correlates, as well as cellular and molecular mechanisms involved in eyeblink conditioning in animal models are of particular importance because there is general acceptance that findings in humans parallel the animal data. The aim of the present review is to give an update of findings in humans. Emphasis is put on human lesion studies, which take advantage of the advances of high-resolution structural magnetic resonance imaging (MRI). In addition, findings of functional brain imaging in healthy human subjects are reviewed. The former helped to localize areas involved in eyeblink conditioning within the cerebellum, the latter was in particular helpful in delineating extracerebellar neural substrates, which may contribute to eyeblink conditioning. Human lesion studies support the importance of cortical areas of the ipsilateral superior cerebellum both in the acquisition and timing of conditioned eyeblink responses (CR). Furthermore, the ipsilateral cerebellar cortex seems to be also important in extinction of CRs. Cortical areas, which are important for CR acquisition, overlap with areas related to the control of the unconditioned eyeblink response. Likewise, cortical lesions are followed by increased amplitudes of unconditioned eyeblinks. These findings are in good accordance with the animal literature. Knowledge about contributions of the cerebellar nuclei in humans, however, is sparse. Due to methodological limitations both of human lesion and functional MRI studies, at present no clear conclusions can be drawn on the relative contributions of the cerebellar cortex and nuclei.     

Cerebellar lobules and dentate nuclei mirror cortical force‐related‐BOLD responses: Beyond all (linear) expectations

The relationship between the BOLD response and an applied force was quantified in the cerebellum using a power grip task. To investigate whether the cerebellum responds in an on/off way to motor demands or contributes to motor responses in a parametric fashion, similarly to the cortex, five grip force levels were investigated under visual feedback. Functional MRI data were acquired in 13 healthy volunteers and their responses were analyzed using a cerebellum‐optimized pipeline. This allowed us to evaluate, within the cerebellum, voxelwise linear and non‐linear associations between cerebellar activations and forces. We showed extensive non‐linear activations (with a parametric design), covering the anterior and posterior lobes of the cerebellum with a BOLD‐force relationship that is region‐dependent. Linear responses were mainly located in the anterior lobe, similarly to the cortex, where linear responses are localized in M1. Complex responses were localized in the posterior lobe, reflecting its key role in attention and executive processing, required during visually guided movement. Given the highly organized responses in the cerebellar cortex, a key question is whether deep cerebellar nuclei show similar parametric effects. We found positive correlations with force in the ipsilateral dentate nucleus and negative correlations on the contralateral side, suggesting a somatotopic organization of the dentate nucleus in line with cerebellar and cortical areas. Our results confirm that there is cerebellar organization involving all grey matter structures that reflect functional segregation in the cortex, where cerebellar lobules and dentate nuclei contribute to complex motor tasks with different BOLD response profiles in relation to the forces. Hum Brain Mapp 38:2566–2579, 2017. © 2017 Wiley Periodicals, Inc.     

Clinical manifestation of focal cerebellar disease as related to the organization of neural pathways

Neural pathways connect different parts of the cerebellum to different parts of the central nervous system. The cerebellum may be divided anatomically and functionally into three major regions. The cerebellar hemispheres and a small part of the posterior lobe vermis form the pontocerebellum, which receives inputs from the cerebral cortex via the pontine nuclei. The anterior lobe and most of the posterior lobe vermis make up the spinocerebellum, which receives afferents from the spinal cord. The nodulus and flocculus are connected with the vestibular nuclei and constitute the vestibulocerebellum. Most cases of cerebellar disease affect more than one region and different pathways. Hence, they cause generalized cerebellar symptoms dominated by impaired motor control and balance. Focal syndromes after restricted cerebellar lesions are rare. Isolated spinocerebellar affection may give gait ataxia. Vestibulocerebellar disease causes equilibrium disturbances with truncal ataxia and nystagmus. Pontocerebellar lesions typically give ipsilateral limb ataxia, but also dysartria and oculomotor dysfunction if vermal parts are involved. The clinical picture is in most cases of cerebellar disease dominated by motor disturbances, but the cerebellum also participates in the modulation of autonomic and affective responses and in cognitive functions. The cerebrocerebellar and hypothalamocerebellar circuits may be important for these tasks.     

The cerebellum in dystonia - Help or hindrance?

Dystonia has historically been considered a disorder of the basal ganglia. This review aims to critically examine the evidence for a role of the cerebellum in the pathophysiology of dystonia. We compare and attempt to link the information available from both clinical and experimental studies; work detailing cerebellar connectivity in primates; data that suggests a role for the cerebellum in the genesis of dystonia in murine models; clinical observation in humans with structural lesions and heredodegenerative disorders of the cerebellum; and imaging studies of patients with dystonia. The typical electrophysiological findings in dystonia are the converse to those found in cerebellar lesions. However, certain subtypes of dystonia mirror cerebellar patterns of increased cortical inhibition. Furthermore, altered cerebellar function can be demonstrated in adult onset focal dystonia with impaired cerebellar inhibition of motor cortex and abnormal eyeblink classical conditioning. We propose that abnormal, likely compensatory activity of the cerebellum is an important factor within pathophysiological models of dystonia. Work in this exciting area has only just begun but it is likely that the cerebellum will have a key place within future models of dystonia.     

Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.     

The human cerebellum contributes to motor, emotional and cognitive associative learning. A review

In this review results of human lesion studies are compared examining associative learning in the motor, emotional and cognitive domain. Motor and emotional learning were assessed using classical eyeblink and fear conditioning. Cerebellar patients were significantly impaired in acquisition of conditioned eyeblink and fear-related autonomic and skeletal responses. An additional finding was disordered timing of conditioned eyeblink responses. Cognitive learning was examined using stimulus-stimulus-response paradigms, with an experimental set-up closely related to classical conditioning paradigms. Cerebellar patients were impaired in the association of two visual stimuli, which could not be related to motor performance deficits.Human lesion and functional brain imaging studies in healthy subjects are in accordance with a functional compartmentalization of the cerebellum for different forms of associative learning. The medial zone appears to contribute to fear conditioning and the intermediate zone to eyeblink conditioning. The posterolateral hemispheres (that is lateral cerebellum) appear to be of additional importance in fear conditioning in humans. Future studies need to examine the reasonable assumption that the posterolateral cerebellum contributes also to higher cognitive forms of associative learning.Human cerebellar lesion studies provide evidence that the cerebellum is involved in motor, emotional and cognitive associative learning. Because of its simple and homogeneous micro-circuitry a common computation may underly cerebellar involvement in these different forms of associative learning. The overall task of the cerebellum may be the ability to provide correct predictions about the relationship between sensory stimuli.     

Resection of cerebellar tumours causes widespread and functionally relevant white matter impairments

Several diffusion tensor imaging studies reveal that white matter (WM) lesions are common in children suffering from benign cerebellar tumours who are treated with surgery only. The clinical implications of WM alterations that occur as a direct consequence of cerebellar disease have not been thoroughly studied. Here, we analysed structural and diffusion imaging data from cerebellar patients with chronic surgical lesions after resection for benign cerebellar tumours. We aimed to elucidate the impact of focal lesions of the cerebellum on WM integrity across the entire brain, and to investigate whether WM deficits were associated with behavioural impairment in three different motor tasks. Lesion symptom mapping analysis suggested that lesions in critical cerebellar regions were related to deficits in savings during an eyeblink conditioning task, as well as to deficits in motor action timing. Diffusion imaging analysis of cerebellar WM indicated that better behavioural performance was associated with higher fractional anisotropy (FA) in the superior cerebellar peduncle, cerebellum''s main outflow path. Moreover, voxel‐wise analysis revealed a global pattern of WM deficits in patients within many cerebral WM tracts critical for motor and non‐motor function. Finally, we observed a positive correlation between FA and savings within cerebello‐thalamo‐cortical pathways in patients but not in controls, showing that saving effects partly depend on extracerebellar areas, and may be recruited for compensation. These results confirm that the cerebellum has extended connections with many cerebral areas involved in motor/cognitive functions, and the observed WM changes likely contribute to long‐term clinical deficits of posterior fossa tumour survivors.     

The Cerebellum in Children with Spina Bifida and Chiari II Malformation: Quantitative Volumetrics by Region

Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction.     

Crossed cerebellar diaschisis in acute ischemic stroke: a study with serial SPECT and MRI.

This study evaluated the relationship between crossed cerebellar diaschisis (CCD) and (1) lesion volume and location in the acute phase and 1 week after stroke onset and (2) clinical outcome. Twenty-two patients with cerebral ischemic stroke underwent single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) within 48 h and on day 8 from onset. Interhemispheric asymmetric indices (AI) on SPECT were calculated for medial, intermediate, and lateral zones of the cerebellum. Lesion volumes and locations were obtained from diffusion-weighted MRI. Neurological status and 3-month clinical outcome were evaluated. Within 48 h, lesion locations in the temporal association cortex and pyramidal tract of the corona radiata were independent determinants for the AI of the medial zone (R(2)=0.439). Lesion locations in the primary, premotor, and supplementary motor cortices, primary somatosensory cortex, and anterior part of the posterior limb of the internal capsule were determinants for the AI of the intermediate zone (R(2)=0.785). Lesions in the primary motor cortex, premotor, and supplementary motor cortices and in the genu of the internal capsule were determinants for the AI of the lateral zone (R(2)=0.746). On day 8, the associations were decreased. The AIs of the intermediate and lateral zones and lesion location in the parietal association cortex were independently associated with the 3-month clinical outcome (R(2)>0.555). Acute CCD is a result of functional deafference, while in the subacute phase, transneuronal degeneration might contribute to CCD. CCD in the intermediate and later zones is a better indicator than that in the medial zone.     

Calcitonin gene-related peptide-like immunoreactivity in neuronal elements of the cat cerebellum

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was found in many mossy fiber endings in the cat cerebellum. Some fine varicose fibers within the cerebellar nuclei also showed CGRP-LI. By injecting colchicine into the lateral ventricle of the cerebrum, CGRP-LI was further visualized in perikarya of many granule cells and some small neurons in the dentate and interpositus nuclei. Among the brainstem precerebellar nuclei, the largest number of neuronal cell bodies with CGRP-LI was found in the pontine nuclei. When a lesion was placed in the pontine brachium, mossy fiber endings with CGRP-LI reduced in number in the cerebellar hemisphere of the posterior lobe ipsilateral to the lesion. Fine varicose fibers with CGRP-LI within the dentate nucleus were also decreased in number ipsilaterally to the lesion. Thus, the majority of fiber endings with CGRP-LI in the hemisphere of the posterior lobe and the dentate nucleus of the cerebellum were assumed to originate from the contralateral pontine nuclei.     

Ataxic Hemiparesis: Neurophysiological Analysis by Cerebellar Transcranial Magnetic Stimulation

The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis.     

Cerebellum Tunes the Excitability of the Motor System: Evidence from Peripheral Motor Axons

Cerebellum is highly connected with the contralateral cerebral cortex. So far, the motor deficits observed in acute focal cerebellar lesions in human have been mainly explained on the basis of a disruption of the cerebello-thalamo-cortical projections. Cerebellar circuits have also numerous anatomical and functional interactions with brainstem nuclei and projects also directly to the spinal cord. Cerebellar lesions alter the excitability of peripheral motor axons as demonstrated by peripheral motor threshold-tracking techniques in cerebellar stroke. The biophysical changes are correlated with the functional scores. Nerve excitability measurements represent an attractive tool to extract the rules underlying the tuning of excitability of the motor pathways by the cerebellum and to discover the contributions of each cerebellar nucleus in this key function, contributing to early plasticity and sensorimotor learning.     

Structural and Functional Magnetic Resonance Imaging of the Human Cerebellar Nuclei

The present review focuses on recent developments in structural and functional magnetic resonance imaging (MRI) of the deep cerebellar nuclei (DCN), the main output structure of the cerebellum. The high iron content in the DCN allows for their visibility in T2*-weighted images. Spatial resolution has improved allowing the identification of DCN in individual cerebellar patients and healthy subjects. Based on findings in larger groups of healthy subjects, probabilistic MRI-based atlases of the deep cerebellar nuclei have been developed, which are important tools in human lesion and functional imaging studies. High iron content in the DCN, on the other hand, decreases the blood oxygenation level dependent-signal making functional imaging a difficult challenge. Compared to the vast amount of studies reporting activation of the cerebellar cortex, the number of studies demonstrating activation of the DCN is much less. Most studies report activation of the dentate nucleus. Dentate activations appear to be more reliable in more complex tasks for reasons currently unknown. As yet, few studies tried to show activations of functional subunits of the dentate nucleus. Increased signal-to-noise ratio and better spatial resolution using higher MR field strength together with recent progress in dentate normalization methods will allow identification of functional subunits and their interactions with the cerebellar cortex in future studies.     

Value of Magnetic Resonance Imaging in West Syndrome of Unknown Etiology

Summary: Magnetic resonance imaging (MRI) studies of 46 patients with West syndrome (WS) of unknown etiology were reviewed retrospectively. The criteria for cryptogenic WS were met by 25 and 21 were considered symptomatic because other types of seizure or psychomotor retardation were apparent before spasm onset. Computed tomographic (CT) scans were normal in 38 patients and showed diffuse atrophy in eight symptomatic patients. In five patients, MRI was more informative than CT, demonstrating one case of delayed myelination and four cases of focal lesion. The focal lesion in 2 of these patients was similar on MRI consisting of poor gray-white matter demarcation in the parieto-occipitotemporal region. Surgical resection was performed in one because of intractable seizures, and neuropathological examination revealed cortical dysplasia. The remaining two cases with focal lesion had increased signal intensity on T₂-weighted images in the posterior frontal cortex and in the temporal lobe, respectively. Our data indicate that MRI is useful in some cases of WS, especially in demonstrating focal corticosubcortical lesions not visible on CT scan.     

Report on a workshop concerning the cerebellum and motor learning,held in St Louis October 2004

A one-day meeting on the cerebellum and motor learning was held in St Louis (October 2004), to address issues arising from a previous larger meeting (Tuebingen, June 2004). The learning tasks considered were VOR adaptation, saccadic adaptation and eyeblink conditioning. A theoretical development was reported that indicated how the cerebellum could use sensory error signals for adaptive control, by decorrelating them from an efferent copy of motor commands. The main topics for discussion were the nature of the error signals actually used by the cerebellum, and the evidence for multiple sites of synaptic plasticity. Reports of studies on VOR adaptation confirmed the presence of error signals in addition to retinal slip, in particular the eye-movement related simple-spike firing of floccular PCs. This firing appears to drive synaptic plasticity in the vestibular nuclei. From a theoretical perspective, a second site of plasticity in the brainstem has two advantages: it improves the high-frequency performance of the VOR given a delayed slip signal, and it allows VOR adaptation when smooth pursuit effectively removes the retinal slip signal. In contrast, some of the physiological data reported on saccadic adaptation seemed incompatible with current theoretical ideas about error signals. However, since other reported data were broadly consistent with those ideas, an important area of experimental disagreement was identified. Furthermore, behavioural studies indicated the presence of multiple sites of plasticity, consistent with earlier lesion studies that suggested one such site within cerebellar cortex and another outside it. Data from eyeblink conditioning suggested that the predictability of the error signal was important. Related ideas have previously emerged from studies of skeletal movement, but their theoretical implications for the cerebellar algorithm have yet to be fully explored. Finally, the long-standing controversy concerning sites of plasticity in eyeblink conditioning illustrated the technical difficulties involved in tracking down such sites.     

Role of cerebellum in learning postural tasks

For a long time, the cerebellum has been known to be a structure related to posture and equilibrium control. According to the anatomic structure of inputs and internal structure of the cerebellum, its role in learning was theoretically reasoned and experimentally proved. The hypothesis of an inverse internal model based on feedback-error learning mechanism combines feedforward control by the cerebellum and feedback control by the cerebral motor cortex. The cerebellar cortex is suggested to acquire internal models of the body and objects in the external world. During learning of a new tool the motor cortex receives feedback from the realized movement while the cerebellum produces only feedforward command. To realize a desired movement without feedback of the realized movement, the cerebellum needs to form an inverse model of the hand/ arm system. This suggestion was supported by FMRi data. The role of cerebellum in learning new postural tasks mainly concerns reorganization of natural synergies. A learned postural pattern in dogs has been shown to be disturbed after lesions of the cerebral motor cortex or cerebellar nuclei. In humans, learning voluntary control of center of pressure position is greatly disturbed after cerebellar lesions. However, motor cortex and basal ganglia are also involved in the feedback learning postural tasks.     

The spino - cerebellar tracts in rabbit.

In young mature rabbits the spinal cord was damaged within lateral funicles and adjacent parts of the dorsal and ventral funicles. After 5-8 days of survival, control examinations were performed to find the extension of the lesion of the spinal cord, as well as studies of the cerebellum by Nauta method to investigate the site of the changed nervous fibres. After injuring the spinal cord on the level of neuromer C3 the degeneration of nervous fibres was found on both side within the anterior and posterior lobes of the cerebellum. In the anterior lobe the degeneration referred to lobules I up to the anterior part of lobule V; in the posterior lobe it referred to lobule VIIIa, and VIIIb of the vermal zone, as well as to the adjacent parts of the hemispheres. When the spinal cord was damaged on the level of neuromer Th7 the degeneration of nervous fibres was seen in the same regions of the cerebellum, but mainly on the side of the lesion. When the spinal cord was damaged on the level of neuromer L2 the fibres changed by degeneration were met within the same regions of the anterior and posterior lobes of the cerebellum, but mostly on the side opposite the lesion. The changes were smaller in this region than in the two kinds of lesions discussed before. The results allow to assume that the ventral and dorsal spinocerebellar tracts end in the same regions of the cortex of the vermal zone and the intermediate zone of the anterior and posterior cerebellar lobe. The dorsal spinocerebellar tract seems to end on the same side, while the ventral spino-cerebellar tract ends almost exclusively on the opposite side of the symmetry plane.     

Atherothrombotic cerebellar infarction: vascular lesion-MRI correlation of 31 cases.

BACKGROUND AND PURPOSE: Correlation of MRI findings with atherosclerotic vascular lesions has rarely been attempted in patients with cerebellar infarction. The aim of this study was to correlate the MRI lesions with the vascular lesions seen on conventional cerebral angiography in cerebellar infarction. METHODS: The subjects included 31 patients with cerebellar infarcts who underwent both MRI and conventional cerebral angiography. We analyzed the risk factors, clinical findings, imaging study, and angiography results. We attempted to correlate MRI lesions with the vascular lesions shown in the angiograms. RESULTS: The vascular lesions seen on angiograms were subdivided into 3 groups: large-artery disease (n=22), in situ branch artery disease (n=6), and no angiographic disease with hypertension (n=3). The proximal segment (V1) lesions of vertebral artery were the most common angiographic features in patients with large-artery disease in which stroke most commonly involved the posterior inferior cerebellar artery (PICA) cerebellum. The V1 lesions with coexistent occlusive lesions of the intracranial vertebral and basilar arteries were correlated with cerebellar infarcts, which had no predilection for certain cerebellar territory. The intracranial occlusive disease without V1 lesion was usually correlated with small cerebellar lesions in PICA and superior cerebellar artery (SCA) cerebellum. The subclavian artery or brachiocephalic trunk lesion was associated with small cerebellar infarcts. The in situ branch artery disease was correlated with the PICA cerebellum lesions, which were territorial or nonterritorial infarct. No angiographic disease with hypertension was associated with small-sized cerebellar infarcts within the SCA, anterior inferior cerebellar artery, or SCA cerebellum. CONCLUSIONS: Our study indicates that the topographic heterogeneity of cerebellar infarcts are correlated with diverse angiographic findings. The result that large-artery disease, in which nonterritorial infarcts are more common than territorial infarcts, is more prevalent than in situ branch artery disease or small-artery disease, suggest that even a small cerebellar infarct can be a clue to the presence of large-artery disease.     

Excitability of the motor cortex to magnetic stimulation in patients with cerebellar lesions.

The excitability of the motor cortex to magnetic stimulation was evaluated in seven patients with cerebellar lesions (six patients with a unilateral lesion) and in 20 control subjects. Magnetic motor threshold was defined at rest. In all but one of the patients with a hemicerebellar lesion the threshold was higher in the motor cortex contralateral to the impaired hemicerebellum and the right/left threshold asymmetry was clearly greater than normal. In the patient with a lesion involving both cerebellar hemispheres the magnetic threshold was above the normal limit on both sides. The latencies of motor responses were normal in all patients. This increase in the magnetic threshold of the motor cortex functionally related to the impaired hemicerebellum suggests the existence of a facilitating tonic action of the cerebellum on central motor circuits that might act at the cortical, or spinal level, or both.     

Physiopathology of the cerebellum in the monkey: Part 2. Motor disturbances associated with partial and complete destruction of cerebellar structures

Profound truncal ataxia, dysmetria, postural tremor of the head, trunk and limbs and hypotonia and intention (acting) tremor of the limbs were displayed by 3 monkeys with total cerebellectomy and 2 monkeys with extensive damage to several structures of the cerebellum. Truncal ataxia, dysmetria, hypotonia and intention tremor gradually diminished during the immediate postoperative period whereas postural tremor became less conspicuous. The administration of harmaline, however, exaggerated or evoked postural tremor of the limbs and trunk for a period of 3–4 hr in these monkeys.On the one hand lesions of the vermis of the posterior lobe and of part of the nodulus in one animal or of the interpositus and fastigial nuclei of both sides and the nodulus in another animal or destruction of the uvula and the interpositus nuclei associated with partial involvement of dentate and fastigial nuclei of both sides in a third animal resulted in truncal ataxia and transient dysmetria. The latter animal repeatedly displayed postural tremor of the two upper limbs in response to harmaline. Harmaline, however, did not produce any peculiar effect in the 2 former animals. On the other hand unilateral or bilateral lesions of the dentate and interpositus nuclei or destruction of the left half of the posterior lobe (with or without involvement of the corresponding dentate nucleus) or interruption of the superior cerebellar peduncle did not result in any marked and/or sustained motor impairment. Nine out of 10 monkeys with such lesions, however, displayed postural tremor of the ipsilateral limbs after the administration of harmaline.Truncal ataxia predominantly involves a disturbance of the uvula and nodulus and/or the fastigial nuclei and their interconnections with the vestibular nuclei and, most likely, with the dorsal and medial accessory olives. Dysmetria (or incoordination of the limbs) is apparently related to a combined impairment of structures of the anterior and posterior lobes of the cerebellum and their corresponding interconnections with the cerebellar nuclei. Postural tremor is partly related to a disturbance at the level of a series of phylogenetically more recent structures including parts of the principal olive, neocerebellar cortex and dentate nucleus and the parvocellular division of the red nucleus as well as their nervous interconnections.