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Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although motion of the head and body has been suspected or known as the provocative cause for the production of motion sickness for centuries, it is only within the last 20 yr that the source of the signal generating motion sickness and its neural basis has been firmly established. Here, we briefly review the source of the conflicts that cause the body to generate the autonomic signs and symptoms that constitute motion sickness and provide a summary of the experimental data that have led to an understanding of how motion sickness is generated and can be controlled. Activity and structures that produce motion sickness include vestibular input through the semicircular canals, the otolith organs, and the velocity storage integrator in the vestibular nuclei. Velocity storage is produced through activity of vestibular-only (VO) neurons under control of neural structures in the nodulus of the vestibulo-cerebellum. Separate groups of nodular neurons sense orientation to gravity, roll/tilt, and translation, which provide strong inhibitory control of the VO neurons. Additionally, there are acetylcholinergic projections from the nodulus to the stomach, which along with other serotonergic inputs from the vestibular nuclei, could induce nausea and vomiting. Major inhibition is produced by the GABAB receptors, which modulate and suppress activity in the velocity storage integrator. Ingestion of the GABAB agonist baclofen causes suppression of motion sickness. Hopefully, a better understanding of the source of sensory conflict will lead to better ways to avoid and treat the autonomic signs and symptoms that constitute the syndrome. [ABSTRACT FROM AUTHOR]

The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.

The central complex, a set of neuropils in the center of the insect brain, plays a crucial role in spatial aspects of sensory integration and motor control. Stereotyped neurons interconnect these neuropils with one another and with accessory structures. We screened over 5,000 Drosophila melanogaster GAL4 lines for expression in two neuropils, the noduli (NO) of the central complex and the asymmetrical body (AB), and used multicolor stochastic labeling to analyze the morphology, polarity, and organization of individual cells in a subset of the GAL4 lines that showed expression in these neuropils. We identified nine NO and three AB cell types and describe them here. The morphology of the NO neurons suggests that they receive input primarily in the lateral accessory lobe and send output to each of the six paired noduli. We demonstrate that the AB is a bilateral structure which exhibits asymmetry in size between the left and right bodies. We show that the AB neurons directly connect the AB to the central complex and accessory neuropils, that they target both the left and right ABs, and that one cell type preferentially innervates the right AB. We propose that the AB be considered a central complex neuropil in Drosophila. Finally, we present highly restricted GAL4 lines for most identified protocerebral bridge, NO, and AB cell types. These lines, generated using the split‐GAL4 method, will facilitate anatomical studies, behavioral assays, and physiological experiments. The authors use the multicolor flip‐out strategy in Drosophila to analyze neurons in two neuropils: the noduli of the central complex and the asymmetrical body. A set of split‐GAL4 lines is provided for previously published protocerebral bridge cell types as well as cell types presented here. [ABSTRACT FROM AUTHOR]

Background: Infarction of the vermis and the tonsil in the cerebellum presents as truncal and gait ataxia. Acute rotatory vertigo is often present in infarction of the nodulus in the caudal vermis, which is closely associated with the vestibular pathway, but is minor in infarction of the rostral vermis. The rostral vermis receives input from the dorsal spinocerebellar tract (DSCT) which conveys unconsciousness proprioceptive signals from the ipsilateral lower trunk and leg. The present study investigated the characteristics of infarction of the vermis and the tonsil.Patients and Methods: Neuroradiological findings of 3 patients whose lesions were located in the vermis or the tonsil were analyzed.Results: All lesions were located in the anterior lobe in the rostral vermis, the nodulus in the caudal vermis, or the tonsil. Truncal and gait ataxia were exhibited by 3 patients. Rotatory vertigo was exhibited by 2 patients whose lesions were located in the nodulus and the tonsil, but absent in a patient with infarction of the anterior lobe. Lateropulsion opposite the lesion was apparent in a patient with infarction of the tonsil. Gaze-evoked nystagmus was observed in 2 patients with infarction of the nodulus and the tonsil.Conclusions: The tonsil and the nodulus were considered to have a close relationship with the vestibular pathway. Absence of rotatory vertigo indicated impairment of the DSCT. Our data suggested that the cause of truncal and gait ataxia differed between the rostral vermis and the caudal vermis/tonsil. [ABSTRACT FROM AUTHOR]

Here we characterize persistent apogeotropic type of central positional nystagmus, and compare it with the apogeotropic nystagmus of benign paroxysmal positional vertigo involving the lateral canal. Nystagmus was recorded in 27 patients with apogeotropic type of central positional nystagmus (22 with unilateral and five with diffuse cerebellar lesions) and 20 patients with apogeotropic nystagmus of benign paroxysmal positional vertigo. They were tested while sitting, while supine with the head straight back, and in the right and left ear-down positions. The intensity of spontaneous nystagmus was similar while sitting and supine in apogeotropic type of central positional nystagmus, but greater when supine in apogeotropic nystagmus of benign paroxysmal positional vertigo. In central positional nystagmus, when due to a focal pathology, the lesions mostly overlapped in the vestibulocerebellum (nodulus, uvula, and tonsil). We suggest a mechanism for apogeotropic type of central positional nystagmus based on the location of lesions and a model that uses the velocity-storage mechanism. During both tilt and translation, the otolith organs can relay the same gravito-inertial acceleration signal. This inherent ambiguity can be resolved by a 'tilt-estimator circuit' in which information from the semicircular canals about head rotation is combined with otolith information about linear acceleration through the velocity-storage mechanism. An example of how this mechanism works in normal subjects is the sustained horizontal nystagmus that is produced when a normal subject is rotated at a constant speed around an axis that is tilted away from the true vertical (off-vertical axis rotation). We propose that when the tilt-estimator circuit malfunctions, for example, with lesions in the vestibulocerebellum, the estimate of the direction of gravity is erroneously biased away from true vertical. If the bias is toward the nose, when the head is turned to the side while supine, there will be sustained, unwanted, horizontal positional nystagmus (apogeotropic type of central positional nystagmus) because of an inappropriate feedback signal indicating that the head is rotating when it is not. [ABSTRACT FROM AUTHOR]

The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent fights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after fights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential faws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement. [ABSTRACT FROM AUTHOR]

Tilt suppression refers to both tilting the head away from an Earth vertical axis and a reduction of an induced horizontal nystagmus. This phenomenon of reducing an induced horizontal nystagmus involves a circuitry of neurons within the vestibular nuclei and the cerebellum (collectively referred to as velocity storage) and signals from the otolith end organs. Lesions involving this circuitry can disrupt tilt suppression of induced horizontal nystagmus. We investigated the clinical value of combining the horizontal head-shaking nystagmus test with tilt suppression in 28 patients with unilateral peripheral vestibular hypofunction and 11 patients with lesions affecting the central nervous system. Each of the subjects with peripheral vestibular lesions generated an appropriately directed horizontal nystagmus after head shaking that then suppressed the induced angular slow phase velocity on average 52 ± 17.6% following tilt down of the head. In contrast, patients with central lesions had very little ability to suppress post-head-shaking nystagmus (mean 3.4 ± 56%). We recommend tilting the head after head shaking as a useful clinical test to assist in the differential diagnosis of vertiginous patients. In the case of unilateral peripheral vestibular hypofunction, head tilt suppresses the induced nystagmus via influence of the otolith organ. In the case of central pathology, the inability to suppress the nystagmus is from lesions impairing the otolith mediation on the velocity storage circuitry. [ABSTRACT FROM AUTHOR]

We sought to determine the cerebellar structures responsible for tilt suppression of post-rotatory nystagmus. We investigated ocular motor findings and MRI lesions in 73 patients with isolated cerebellar lesions who underwent recording of the vestibulo-ocular reflex (VOR) using rotatory chair tests. Tilt suppression of post-rotatory nystagmus was diminished in 27 patients (27/73, 37.0 %). The gains of the VOR and the TCs of per- and post-rotatory nystagmus did not differ between the patients with diminished and with normal tilt suppression. The patients with impaired tilt suppression showed perverted ('cross-coupled') head-shaking nystagmus (pHSN) and central positional nystagmus (CPN) more frequently than those with normal responses. Tilt suppression was impaired in five (71.4 %) of the seven patients with isolated nodulus and uvular infarction. Probabilistic lesion-mapping analysis showed that the nodulus and uvula are responsible for tilt suppression. Impaired tilt suppression may be ascribed to disruption of cerebellar contribution to the vestibular velocity-storage mechanism, which integrates information from the semicircular canals and otolith organs to help derive the brain's estimate of the head orientation relative to the pull of gravity. [ABSTRACT FROM AUTHOR]

The successful treatment of the MdDS has been carried on by Dai's colleague, Sergei Yakushin, Ph.D., Associate Professor of Neurology. 15 Dai, M, Raphan, T, Cohen, B, Prolonged reduction of motion sickness sensitivity by visual-vestibular interaction. 18 Dai, M, Cohen, B, Cho, C, Shin, S, Yakushin, SB, Treatment of the Mal de Debarquement Syndrome: a 1-year follow-up. [Extracted from the article]

We report a patient with severe and prolonged vertigo and ataxia caused by infarction of the bilateral cerebellar nodulus and uvula. Vertigo and nausea persisted for 2 weeks, causing the patient to remain bedridden. The patient showed upbeat nystagmus (UBN) on upward gaze and upon uprighting from the supine position and did not exhibit apogeotropic nystagmus characteristic of central paroxysmal positional nystagmus. Isolated positional UBN may be specific to an uvulo‐nodular lesion, and persistent and marked vertigo suggests extensive damage to the bilateral nodulus and uvula. [ABSTRACT FROM AUTHOR]

The nodulus and ventral uvula (NU) of the cerebellum play a major role in vestibular function in humans and experimental animals; however, there is almost no information about NU function in the veterinary clinical literature. In this report, we describe three canine cases diagnosed with presumptive NU hypoplasia. Of them, one adult dog presented with cervical intervertebral disk disease, and two juvenile dogs presented with signs of central vestibular disease. Interestingly, an unusual and possibly overlooked neurological sign that we called positioning head tilt was observed in these dogs. The dogs were able to turn freely in any direction at will. The head was in a level position when static or when the dog walked in a straight line. However, the head was tilted to the opposite side when the dog turned. Veterinary clinicians should be aware of this neurological sign, which has not been reported previously, and its application in lesion localization in dogs.

Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease.disease.

Periodic alternating nystagmus (PAN) is a rare oscillatory ocular motor disorder. The effects of gravity on the dynamic behavior of PAN can be studied by monitoring the nystagmus while changing head orientation. Previous studies of patients with PAN reached different conclusions about the effect of changing the orientation of the head relative to gravity on the ongoing PAN, either no effect or a damping of the nystagmus within several minutes. What neuronal circuits could account for the difference in the effects of gravity among PAN patients? We modeled how the brain resolves the tilt-translation ambiguity in normal individuals and added an unstable, oscillatory vestibular system generating PAN. PAN was suppressed in our patient in ear-down positions, in a similar pattern to that of a previously reported patient. This effect was simulated by reducing the gain of the projection of the "rotation feedback" loop to the velocity-storage integrator to approximately 5% of its normal value. With normal "rotation feedback" PAN is expected to dissipate quickly as soon as the head is rotated away from upright position. Moreover, by disconnecting the rotation feedback completely (gain = zero) the model simulated PAN that was reported to be unaffected by gravity. Thus, understanding the effect of this single parameter, the gain of the rotation feedback, can explain the observed variability among our own and previous studies. • Previous studies have shown contradicting effects of gravity on PAN. • Computational models of "rotation feedback", critical in tilt translation disambiguation, can explain the contradictions. • A very low gain of "rotation feedback" can suppress PAN in head down positions, but the effect takes a few minutes. • Understanding the role of "rotational feedback" in patients with PAN may enhance neurological localization. [ABSTRACT FROM AUTHOR]

ABSTRACT Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. J. Comp. Neurol. 523:997-1037, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Isolated vestibular syndrome may occur all along the vestibular pathways from the peripheral labyrinth to the brain. By virtue of recent developments in clinical neurotology and neuroimaging, however, diagnosis of isolated central vestibulopathy is increasing. Here, we review five distinct syndromes of isolated central vestibular syndrome from lesions restricted to the vestibular nuclei, the nucleus prepositus hypoglossi, the flocculus, the tonsil, and the nodulus, and introduce a new vestibular syndrome from isolated involvement of the inferior cerebellar peduncle. Decreased responses to head impulses do not exclude a central lesion as a cause of isolated vestibular syndrome. Brain imaging, including diffusion-weighted magnetic resonance imaging (MRI), may be falsely negative during the acute phase in patients with isolated vestibular syndrome because of a stroke. Central signs should be sought carefully in patients with isolated vertigo, even when the patients show the features of peripheral vestibulopathy and negative MRIs. Recognition of these isolated central vestibular syndromes would aid in defining the lesions responsible for various vestibular manifestations in central vestibulopathy. [ABSTRACT FROM AUTHOR]

Abstract: Intermittent positional down beat nystagmus (p-DBN) is rare. We describe an unusual case of intermittent p-DBN which was induced by rotation, anteflexion, and lateral flexion of the neck. A 59-year-old man complained of loss of consciousness and lightheadedness. Positional testing revealed the p-DBN. The evoked p-DBN had latency and the patient had a feeling of passing out while the p-DBN was present. There were no abnormal findings in the vestibular functional examinations. Findings of the MRI were negative. MRA revealed no stenosis of the vertebral artery bilaterally, but there was an anatomical difference. The p-DBN characteristics were documented by electronystagmography during the positional test. The p-DBN lasted intermittently while maintaining the provoking position. It was found that p-DBN occurred with not only the rotation of the neck, but also in the anteflexion and lateral flexion of the neck. There was no stenosis of the vertebral artery (VA) on angiography, but we speculated that the cause of the p-DBN was the VA occlusion due to rotation, anteflexion, and lateral flexion of the neck. [Copyright &y& Elsevier]

An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural-functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: 1) the flocculus/paraflocculus for high-frequency (brief) vestibular responses, sustained pursuit eye movements and gaze-holding, 2) the nodulus/ventral uvula for low-frequency (sustained) vestibular responses, and 3) the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region) for saccades and pursuit initiation.

Highlights: [&#x2022;] The calbindin expression in the ipsi and contralateral side was found to decrease 6hr after UL. [&#x2022;] Asymmetric calbindin expression was found between ipsi and contralateral nodulus 24hr after UL. [&#x2022;] Forty-eight hours after UL, calbindin expression returned to the control level. [&#x2022;] And asymmetric expression in both noduli also subsided. [ABSTRACT FROM AUTHOR]

Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease. [ABSTRACT FROM AUTHOR]

The contention of this commentary, focused on the vestibulocerebellum (particularly the flocculus), is that the great importance for our understanding of cerebellar organization in terms of climbing fiber zones, begun years ago by Voogd [, ] and Oscarsson [], needs to be matched by coming more to grips with the other fundamental geometrical organization of the cerebellum, the parallel fibers. The central issue is the selection of those parallel fiber signals to be transformed into Purkinje cell activity in the different zones. At present, in comparison to our knowledge of vestibulocerebellar climbing fiber inputs, the deficiencies in our knowledge of the zonal anatomy and physiology of vestibulocerebellar mossy fibers and granule cells are glaring. The recent emphasis on molecularly oriented investigations points to the need to reinvigorate pursuit of unanswered questions about cerebellar anatomy, the handmaiden of physiology. [ABSTRACT FROM AUTHOR]

Introduction: The cerebellum is a key structure for the control of movement. Here, we ask the question about its role in the learning and execution of sexual behavior in the male rat. The study focused on the fluctuation of cannabinoid receptors that are directly involved in the long-term depression, one of the neural mechanisms for learning and memory. Objective: To determine the density of CB1 type cannabinoid receptor at the cortex of the vermis cerebellum in male rats, during their training to acquire sexual experience. Materials and Methods: Sexually naive Wistar male rats were used. They received five training sessions, one each other day. At the end of each test, some rats were used to determine the levels of CB1 receptors by immunohistochemistry. Results: The vermis cerebellum has a basal density of cannabinoid receptors that showed a significant transitory reduction at the lobules 1, 6, 7 and 10. Once the subject became expert, the density returned to basal levels. Conclusions: The learning of sexual behavior requires the transitory reduction of CB1 receptors in four cerebellar lobules. It is proposed that it strengths synaptic connections through mechanisms of long-term depression and potentiation. Thus, the fluctuation of endocannabinoids at these cerebellar lobules at the vermis seems required for the establishment of neural circuits that allow the subject to get the experience for the appropriate execution of sexual behavior. [ABSTRACT FROM AUTHOR]

The cerebellum’s role in sensory-motor control and adaptation is undisputed. However, a key hypothesis pertaining to the function of cerebellar circuitry lacks experimental support. It is universally assumed that the discharge of mossy fibers accounts for modulation of Purkinje cell “simple spikes” (SSs). This assumption acts as a prism through which all other functions of cerebellar circuitry are viewed. The vestibulo-cerebellum (nodulus and uvula) receives a large, unilateral, vestibular primary afferent mossy fiber projection. We can test its role in modulating Purkinje cell SSs by recording the modulated activity of both mossy fiber terminals and Purkinje cell SSs evoked by identical natural vestibular stimulation. Sinusoidal rotation about the longitudinal axis (roll) modulates the activity of vestibular primary afferent mossy and climbing fibers as well as Purkinje cell SSs and complex spikes (CSs). Remarkably, vestibular primary afferent mossy fibers discharge 180 degrees out of phase with SSs. This indicates that mossy fibers cannot account for SS modulation unless an inhibitory synapse is interposed between mossy fibers or vestibular climbing fibers and Purkinje cells. The authors review several experiments that address the relative contributions of mossy and climbing fiber afferents to the modulation of SSs. They conclude that climbing fibers, not mossy fibers, are primarily responsible for the modulation of SSs as well as CSs and they propose revised functions for these two afferent systems. [ABSTRACT FROM PUBLISHER]

The nodulus and uvula (lobules X and IX of the vermis) receive mossy fibers from both vestibular afferents and vestibular nuclei neurons and are thought to play a role in spatial orientation. Their properties relate to a sensory ambiguity of the vestibular periphery: otolith afferents respond identically to translational (inertial) accelerations and changes in orientation relative to gravity. Based on theoretical and behavioral evidence, this sensory ambiguity is resolved using rotational cues from the semicircular canals. Recordings from the cerebellar cortex have identified a neural correlate of the brain's ability to resolve this ambiguity in the simple spike activities of nodulus/uvula Purkinje cells. This computation, which likely involves the cerebellar circuitry and its reciprocal connections with the vestibular nuclei, results from a remarkable convergence of spatially- and temporally-aligned otolith-driven and semicircular canal-driven signals. Such convergence requires a spatio-temporal transformation of head-centered canal-driven signals into an estimate of head reorientation relative to gravity. This signal must then be subtracted from the otolith-driven estimate of net acceleration to compute inertial motion. At present, Purkinje cells in the nodulus/uvula appear to encode the output of this computation. However, how the required spatio-temporal matching takes place within the cerebellar circuitry and what role complex spikes play in spatial orientation and disorientation remains unknown. In addition, the role of visual cues in driving and/or modifying simple and complex spike activity, a process potentially critical for long-term adaptation, constitutes another important direction for future studies. [ABSTRACT FROM AUTHOR]

Nodular infarctions are a rare cause of vertigo and may imitate vestibular neuritis. We report on two patients with acute positional vertigo due to nodular infarction, a clinical presentation is not reported so far. High-resolution MR imaging using thin slices is required to identify isolated nodular infarctions. [ABSTRACT FROM AUTHOR]

Mechanisms of head-shaking nystagmus (HSN) require further exploration in central vestibular disorders. To determine whether impaired uvulonodular inhibition over the velocity storage of the vestibulo-ocular reflex (VOR) is the mechanism of ipsilesional HSN in lateral medullary infarction (LMI), 17 patients with ipsilesional HSN and LMI underwent measurements of the VOR gains during low-frequency sinusoidal harmonic accelerations, and the time constants (TC) of the VOR and tilt suppression of the post-otatory nystagmus during step-velocity rotation. Compared with normal controls, the patients showed increased VOR gains without difference between ipsi- and contralesional rotations, while the VOR TCs were decreased without directional asymmetry during step-velocity rotation. In contrast, the patients showed impaired tilt suppression of the postrotatory nystagmus, and the impairment of tilt suppression was more severe after contralesional than ipsilesional rotation. The asymmetric tilt suppression may generate ipsilesional HSN by increasing contralesional velocity storage during head shaking, and may be ascribed to disruption of ipsilesional nodulo-uvular inhibition of the velocity storage mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Mossy and climbing fibers convey a broad array of signals from vestibular end organs to Purkinje cells in the vestibulo-cerebellum. We have shown previously that Purkinje cell simple spikes (SSs) and climbing fiber–evoked complex spikes (CSs) in the mouse uvula-nodulus are arrayed in 400 μm wide sagittal climbing fiber zones corresponding to the rotational axes of the vertical semicircular canals. It is often assumed that mossy fibers modulate a higher frequency of SSs through the intermediary action of granule cells whose parallel fibers course through the Purkinje cell dendritic tree. This assumption is complicated by the diffuse topography of vestibular primary afferent mossy fiber projections to the uvula-nodulus and the dispersion of mossy fiber signals along folial axes by parallel fibers. Here we measure this parallel fiber dispersion. We made microinjections of neurobiotin into the molecular layers of different folia within the mouse vestibulo-cerebellum and measured the distribution of granule cells retrogradely labeled by the injected neurobiotin. Sixty-two percent of labeled granule cells were located outside a 400 μm sagittal zone flanking the injection site. The dispersion of labeled granule cells was ∼2.5 mm along folial axes that were 2.7–2.9 mm wide. Our data suggest that topographic specificity of SSs could not be attributed to the topography of vestibular primary afferent mossy fiber–granule cell projections. Rather the response specificity of SSs must be attributed to other mechanisms related to climbing fiber–evoked Purkinje cell and interneuronal activity. [Copyright &y& Elsevier]

The output signal of Purkinje cells is conveyed by the modulated discharge of simple spikes (SSs) often ascribed to mossy fiber-granule cell-parallel fiber inputs to Purkinje cell dendrites. Although generally accepted, this view lacks experimental support. We can address this view by controlling afferent signals that reach the cerebellum over climbing and mossy fiber pathways. Vestibular primary afferents constitute the largest mossy fiber projection to the uvula-nodulus. The discharge of vestibular primary afferent mossy fibers increases during ipsilateral roll tilt. The discharge of SSs decreases during ipsilateral roll tilt. Climbing fiber discharge [complex spikes (CSs)] increases during ipsilateral roll tilt. These observations suggest that the modulation of SSs during vestibular stimulation cannot be attributed directly to vestibular mossy fiber afferents. Rather we suggest that interneurons driven by vestibular climbing fibers may determine SS modulation. We recorded from cerebellar interneurons (granule, unipolar brush, Golgi, stellate, basket, and Lugaro cells) and Purkinje cells in the uvula-nodulus of anesthetized mice during vestibular stimulation. We identified all neuronal types by juxtacellular labeling with neurobiotin. Granule, unipolar brush, stellate, and basket cells discharge in phase with ipsilateral roll tilt and in phase with CSs. Golgi cells discharge out of phase with ipsilateral roll tilt and out of phase with CSs. The phases of stellate and basket cell discharge suggests that their activity could account for the antiphasic behavior of CSs and SSs. Because Golgi cells discharge in phase with SSs, Golgi cell activity cannot account for SS modulation. The sagittal array of Golgi cell axon terminals suggests that they contribute to the organization of discrete parasagittal vestibular zones. [ABSTRACT FROM AUTHOR]

The vestibular nuclear complex (VNC) is classically divided into four nuclei on the basis of cytoarchitectonics. However, anatomical data on the distribution of afferents to the VNC and the distribution of cells of origin of different efferent pathways suggest a more complex internal organization. Immunoreactivity for calcium-binding proteins has proven useful in many areas of the brain for revealing structure not visible with cell, fiber or Golgi stains. We have looked at the VNC of the cat using immunoreactivity for the calcium-binding proteins calbindin, calretinin and parvalbumin. Immunoreactivity for calretinin revealed a small, intensely stained region of cell bodies and processes just beneath the fourth ventricle in the medial vestibular nucleus. A presumably homologous region has been described in rodents. The calretinin-immunoreactive cells in this region were also immunoreactive for choline acetyltransferase. Evidence from other studies suggests that the calretinin region contributes to pathways involved in eye movement modulation but not generation. There were focal dense regions of fibers immunoreactive to calbindin in the medial and inferior nuclei, with an especially dense region of label at the border of the medial nucleus and the nucleus prepositus hypoglossi. There is anatomical evidence that suggests that the likely source of these calbindin-immunoreactive fibers is the flocculus of the cerebellum. The distribution of calbindin-immunoreactive fibers in the lateral and superior nuclei was much more uniform. Immunoreactivity to parvalbumin was widespread in fibers distributed throughout the VNC. The results suggest that neurochemical techniques may help to reveal the internal complexity in VNC organization. [ABSTRACT FROM AUTHOR]

The vestibular nuclei and posterior cerebellum are the destination of vestibular primary afferents and the subject of this review. The vestibular nuclei include four major nuclei (medial, descending, superior and lateral). In addition, smaller vestibular nuclei include: Y-group, parasolitary nucleus, and nucleus intercalatus. Each of the major nuclei can be subdivided further based primarily on cytological and immunohistochemical histological criteria or differences in afferent and/or efferent projections. The primary afferent projections of vestibular end organs are distributed to several ipsilateral vestibular nuclei. Vestibular nuclei communicate bilaterally through a commissural system that is predominantly inhibitory. Secondary vestibular neurons also receive convergent sensory information from optokinetic circuitry, central visual system and neck proprioceptive systems. Secondary vestibular neurons cannot distinguish between sources of afferent activity. However, the discharge of secondary vestibular neurons can distinguish between “active” and “passive” movements.The posterior cerebellum has extensive afferent and efferent connections with vestibular nuclei. Vestibular primary afferents are distributed to the ipsilateral uvula-nodulus as mossy fibers. Vestibular secondary afferents are distributed bilaterally. Climbing fibers to the cerebellum originate from two subnuclei of the contralateral inferior olive; the dorsomedial cell column and β-nucleus. Vestibular climbing fibers carry information only from the vertical semicircular canals and otoliths. They establish a coordinate map, arrayed in sagittal zones on the surface of the uvula-nodulus. Purkinje cells respond to vestibular stimulation with antiphasic modulation of climbing fiber responses (CFRs) and simple spikes (SSs). The modulation of SSs is out of phase with the modulation of vestibular primary afferents. Modulation of SSs persists, even after vestibular primary afferents are destroyed by a unilateral labyrinthectomy, suggesting that an interneuronal network, triggered by CFRs is responsible for SS modulation. The vestibulo-cerebellum, imposes a vestibular coordinate system on postural responses and permits adaptive guidance of movement. [Copyright &y& Elsevier]

Protein kinase C isoforms PKC-δ and PKC-γ are expressed in Purkinje cells in the uvula-nodulus of the cerebellum. We examined the effect of Purkinje cell activity on the transcription, expression and intracellular distribution of PKC-δ and PKC-γ. Relative changes in activity were induced by unilateral labyrinthectomy (UL), decreasing the activity of Purkinje cells on the side of the labyrinthectomy relative to the contralateral side with intact vestibular input. After a UL, there was decreased immunolabeling of Purkinje cell axon terminals in the ipsilateral caudal vestibular complex by antisera to PKC-δ, but not PKC-γ. Western blots prepared from the uvula-nodulus and caudal vestibular complex showed an increase in the cytosolic PKC-δ and a decrease in membrane-associated PKC-δ in the ipsilateral uvula-nodulus 12–48 h after the UL. Hybridization histochemistry and semiquantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated no change in transcription of PKC-δ mRNA in the uvula-nodulus 1–240 h after unilateral labyrinthectomy. We conclude that both PKC-δ and PKC-γ are constitutively expressed in Purkinje cells. The targeting of PKC-δ, but not PKC-γ, to Purkinje neuron synaptic terminals is influenced by activity. [ABSTRACT FROM AUTHOR]

We investigated the orientation of quick phases (QPs) of vestibularly-induced eye movements in rabbits in response to ''off-vertical'' sinusoidal vestibular stimulation. We also examined the possible role of the cerebellar nodulus and ventral uvula in controlling QP spatial orientation and modification. During ''off-vertical'' vestibular stimulation QPs remained aligned with the earth's horizontal plane, while the slow phases (SPs) were aligned with the plane of vestibular stimulation. This suggests that QPs are coded in gravito-inertial coordinates and SPs in head coordinates. When rabbits were oscillated in the light (20° peak-to-peak; 0.2 Hz) about an ''off-vertical'' axis for 2 h, the QPs changed their trajectory, abandoning the earth's horizontal plane to approach the plane of the stimulus. By contrast, in the absence of conjunctive optokinetic stimulation, QPs remained fixed in the earth's horizontal plane even after 2 h of ''off-vertical'' stimulation. The conjunctive combination of optokinetic and vestibular stimulation caused QPs to change their plane of rotation. After lesion of the nodulus-uvula the ability of rabbits to reorient QPs during conjoint vestibular-optokinetic stimulation was maintained. We conclude that the space orientation and adaptation of QPs do not require cerebellar control. [ABSTRACT FROM AUTHOR]

Properties of otolith inputs to vestibulocerebellar neurons were investigated in 14 adult cats. In the vestibular nuclei, we recorded single-unit activities that responded orthodromically after stimulation of the utricular and/or saccular nerves and antidromically after stimulation of the cerebellum (uvula-nodulus and anterior vermis). Descending axonal projections to the spinal cord were also examined by antidromic stimulation of the caudal end of the C1 segment. Forty-seven otolith-activated neurons that projected to the uvula-nodulus were recorded. Thirteen (28%) of the 47 neurons received convergent inputs from the utriculus and sacculus. The remaining 34 (72%) vestibular neurons were non-convergent neurons: 18 (38%) received utricular input alone, and 16 (34%) received saccular input alone. Most (35/47) vestibulocerebellar neurons were located in the descending vestibular nucleus and only one of these projected to the spinal cord. Seven of the 47 vestibulocerebellar neurons were located in the lateral vestibular nucleus and most of these neurons projected to the spinal cord. The remaining neurons were located in group X (two neurons) and the superior vestibular nucleus (three neurons). In a different series of experiments, 37 otolith-activated vestibular neurons were tested to determine whether they projected to the uvula-nodulus and/or the anterior vermis. Nineteen of the 37 neurons projected to the anterior vermis, 13/37 projected to the uvula-nodulus, and 5/37 projected to both. The utricular and/or saccular nerve-activated vestibulocerebellar neurons projected to not only the uvula-nodulus, but also to the anterior vermis. In summary, the results of this study showed that vestibular neurons receiving inputs from the utriculus and/or sacculus projected to the cerebellar cortex. This indirect otolith-cerebellar pathway terminated both in the anterior lobe and in the uvula/nodulus. [ABSTRACT FROM AUTHOR]

Connections of Purkinje cell axons of lobule X (nodulus) with vestibulocerebellar neurons projecting to lobule X or IX (uvula) were revealed in the rat. Purkinje cell axons were anterogradely labeled with biotinylated dextran (BD) injected into sublobule Xa while vestibular neurons were retrogradely labeled with cholera toxin subunit B (CTB) injected into sublobule Xa or IXc. Labeled terminals of Purkinje cell axons of lobule X were numerous in the superior vestibular nucleus (SV), medial parts of the parvocellular (MVpc) and the caudal part (MVc) of the medial vestibular nucleus (MV), and group y. These subdivisions of the vestibular nuclei contained many neurons projecting to lobule X or IX. Lobule-X-projecting and lobule-IX-projecting neurons were in contact with terminals of Purkinje cell axons of lobule X in the MVpc and MVc. They were distributed dorsally to medially in medial parts of the MVpc and MVc. The present study suggests that Purkinje cells in lobule X regulate the output of a population of lobule-X-projecting or lobule-IX-projecting neurons of the MVpc and MVc. [ABSTRACT FROM AUTHOR]

Connections of Purkinje cell axons of lobule X (nodulus vermis) with vestibulospinal neurons have been demonstrated in the rat, by anterograde labeling of axons with biotinylated dextran (BD) injected into sublobule Xa and by retrograde labeling of neurons with cholera toxin subunit B (CTB) injected into cervical segments. Labeled terminals of Purkinje cell axons were numerous in the superior vestibular nucleus, the parvocellular (MVpc) and the caudal part (MVc) of the medial vestibular nucleus (MV), and group y. A limited number of labeled terminals were seen in the caudal part of the descending vestibular nucleus (DV). Occasional labeled terminals were seen in the lateral part of the lateral vestibular nucleus (LV) whereas few labeled terminals were seen in the magnocellular part of the MV (MVmc). Vestibulospinal neurons labeled from the C2 and C3 segments were seen bilaterally in the MVmc, MVpc, MVc, and DV, and ipsilaterally in the LV. CTB-labeled vestibulospinal neurons in contact with BD-labeled terminals of Purkinje cell axons were identified in the lateral part of the MVpc, near the border between the MVpc and MVmc, or close to the dorsal acoustic stria, and in the middle part of the MVc at its rostral level. The present study suggests that Purkinje cells of lobule X regulate the output of cervical-projecting vestibulospinal neurons in the MVpc and MVc. [ABSTRACT FROM AUTHOR]

We report two patients with an ocular tilt reaction (OTR) due to unilateral caudal cerebellar lesion. One patient had a caudal cerebellar hemorrhage, the other a posterior inferior cerebellar artery territory infarct. There was head tilt in both patients which had not been reported previously. These findings support the previous proposal that the mechanism of a tonic contraversive OTR with unilateral cerebellar lesion is an increased tonic resting activity in the ipsilesional vestibular nucleus due to a loss of inhibition from the lesioned nodulus. [ABSTRACT FROM AUTHOR]

The nodulus and sublobule d of the uvula of rhesus and cynomolgus monkeys were electrically stimulated with short trains of pulses to study changes in horizontal slow-phase eye velocity. Nodulus and uvula stimulation produced a rapid decline in horizontal slow phase velocity, one aspect of the spatial reorientation of the axis of eye rotation that occurs when the head is tilted with regard to gravity during per- and post-rotatory nystagmus and optokinetic after-nystagmus (OKAN). Nodulus and uvula stimulation also reproduced the reduction of the horizontal time constant of post-rotatory nystagmus and OKAN that occurs during visual suppression. The brief electric stimuli (4-5 s) induced little slow-phase velocity and had no effect on the initial jump in eye velocity at the onset or the end of angular rotation. Effects of stimulation were unilateral, suggesting specificity of the output pathways. Activation of more caudal sites in the uvula produced nystagmus with a rapid rise in eye velocity, but the effects did not outlast the stimulus and did not affect VOR or OKAN time constants. Thus, stimulation of caudal parts of the uvula did not affect eye velocity produced by velocity storage. We postulate that the nodulus and sublobule d of the uvula control the time constant of the yaw axis (horizontal) component of slow-phase eye velocity produced by velocity storage. [ABSTRACT FROM AUTHOR]

We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (≈5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6-8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/ h). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h, thereby increasing the VOR time constant. Small values of h would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g, without altering the coupling to velocity storage g or its time constant (1/ h). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum. [ABSTRACT FROM AUTHOR]

Under anesthesia with NO (70%) and halothane (2-4%), Purkinje cell activities were extracellularly recorded in the flocculus and nodulus of immobilized pigmented rabbits. Large field (60° × 60°) optokinetic stimulation (OKS) was delivered to the central visual field of one eye with a constant velocity (0.1-4.0 °/S) at 0°, 45°, 90° or 135° to the horizontal plane of the eye. Most of the Purkinje cells in the flocculus and the nodulus showed significant simple spike modulations to OKS delivered to either eye. As a whole, the preferred directions of simple spike responses in the flocculus had the same orientation as those of complex spike responses. However, the preferred directions and amplitudes of modulation of simple spike responses did not necessarily correlate with those of complex spike responses in individual flocculus Purkinje cells. On the other hand, the preferred directions of simple and complex spike responses were not necessarily in the same orientation in the nodulus. The optimum velocity for simple spike responses was in the range 0.1-2.0°/s for Purkinje cells in both the flocculus and the nodulus. The amplitude and time to peak of the simple spike responses of nodulus Purkinje cells were significantly smaller and longer, respectively, than those of flocculus Purkinje cells. In both the flocculus and the nodulus, Purkinje cells whose simple spikes preferred the horizontal orientation (H cells) and the vertical orientation (V cells) showed clustering. In particular, zonal organization was noted in the flocculus. H cells were localized in a dorso-ventral zone in the rostral one third of the flocculus, and V cells were in two distinct zones rostral and caudal to the H cell zone. The locations of H and V cells in the flocculus correspond to the H zone and V zones, respectively, determined on the basis of the preferred directions of complex spike responses to OKS. This indicates that the same subdivisions of the flocculus are supplied with optokinetic signals with the same orientation selectivity through both mossy and climbing fibers, and suggest that such subdivisions of the flocculus are functional units which control horizontal and vertical components of optokinetic eye movements. The present results indicate that the flocculus and the nodulus are supplied with distinct optokinetic signals through mossy fibers and play different roles in controlling optokinetic eye movements. [ABSTRACT FROM AUTHOR]

Under anesthesia with NO (70%) and halothane (2-4%), complex spikes of Purkinje cells were extracellularly recorded in the nodulus and flocculus of immobilized pigmented rabbits. Optokinetic stimulation (OKS) was delivered to each eye as repetitive movements of a random dot pattern. The visual field of each eye was divided into anterior, central and posterior fields at axes 45° and 135° along the horizon. With OKS of the ipsilateral eye, the preferred direction of complex spike responses was: (1) forward (F) in all visual fields (F response), (2) upward (U) in both the anterior and central visual fields but downward (D) in the posterior visual field (U response), or (3) no response (N) in any of the visual fields (N response). With OKS of the contralateral eye, the preferred direction was: (1) backward (B) in both the anterior and central visual fields but N in the posterior visual field (B response), (2) U in the anterior but D in both the central and posterior visual fields (D response), or (3) N in all visual fields. Purkinje cells were classified into five categories in terms of the complex spike responses to OKS to the central visual fields of the ipsi-/contralateral eyes: F/B, F/N, U/D, U/N and N/D types. In cells with ipsi-F and/or contra-B responses, OKS delivered above the horizon induced F and/or B responses, but OKS below the horizon induced no response. In cells with contra-D response, OKS both above and below the horizon induced D responses. Cells with ipsi-U responses showed unusually complex direction selectivity: in the anterior, central and posterior fields, the preferred direction was U, U and D, respectively, above the horizon, as opposed to N, D and D below the horizon. In the nodulus, F/B and F/N type cells were localized in the ventral lamella within two distinct longitudinal zones about 0.5-1.5 and 2.5-3.5 mm from the midline, while U/D, U/N and N/D type cells were found in both the ventral and dorsal lamellae within a longitudinal zone about 1.5-2.5 mm from the midline. In the flocculus, the locations of F/N (or F/B), U/N and N/D type cells roughly corresponded to H, anterior V and R zones, respectively, as previously reported on the basis of the direction of eye movements induced by microstimulation. The receptive field of visual climbing fiber inputs to the nodulus and flocculus is organized such that complex spike activity is best modulated with retinal image slips caused by head rotation around the axis of either the horizontal (F/B, F/N types) or the anterior canal (U/D, U/N, N/D types) on the ipsilateral side. [ABSTRACT FROM AUTHOR]

In pigmented rabbits anesthetized with NO (70%) and halothane (2-4%), Purkinje cells were extracellularly recorded in the nodulus. Large field (60°×60°) optokinetic stimulation (OKS) with constant velocity was delivered to either the ipsi- or contralateral eye, and the direction and velocity selectivities of complex spike responses were examined. To ipsilateral OKS ( n = 181), the preferred direction was forward (F, n = 72), upward (U, n = 38) or downward (D, n = 10), while the remaining cells ( n = 61) showed no response (N). To contralateral OKS ( n = 117), the preferred direction was backward (B, n = 22), upward (U, n = 7) or downward (D, n = 22), while the rest ( n = 66) showed N. Cells tested with both eyes ( n = 95) fell into 8 categories based on the preferred direction to ipsi- and contralateral OKS: (1) ipsi-F and contra-B (F/B type, n = 20), (2) ipsi-F but contra-N (F/N type, n = 12), (3) ipsi-U and contra-D (U/D type, n = 15), (4) ipsi-U but contra-N (U/N type, n = 13), (5) ipsi-N but contra-D (N/D type, n = 1), (6) ipsi-D but contra-N (D/N type, n = 5), (7) ipsi-N but contra-U (N/U type, n = 6), and (8) N to both eyes (N/N type, n = 23). The optimum velocity was in the range 0.1-2.0°/s for all cells responsive to OKS. In the ventral lamella, four medio-laterally aligned zones were demonstrated. In the most medial zone (0-0.5 mm from the midline), the majority of cells showed ipsi-N or contra-N responses. In the second zone (0.5-1.5 mm), most cells preferred ipsi-F or contra-B directions. In the third zone (1.5-2.5 mm), most cells preferred ipsi-U or contra-D directions. In the most lateral zone (2.5-3.5 mm), most cells preferred ipsi-F or contra-B directions. In the dorsal lamella, a longitudinal zone characterized with cells preferring ipsi-U or contra-D directions was found about 1.5-2.5 mm from the midline. This zone seemed to be the continuation of the third zone in the ventral lamella. Cells preferring ipsi-D or contra-U directions were scattered in the medial half of both the dorsal and ventral lamellae. Most cells responsive to electrical stimulation of the contralateral optic tract (OT) preferred the ipsi-F direction and were localized in the second and the most lateral zones of the ventral lamella. As for cells activated by a climbing fiber with a branching axon to the flocculus, no characteristic feature was found in terms of the preferred direction to OKS, except that none of the cells preferring ipsi-D or contra-U directions were activated by such branching climbing fibers. The results indicate that the nodulus consists of at least four functionally distinct zones in terms of direction selectivity of visual climbing fiber afferents. [ABSTRACT FROM AUTHOR]

The distribution of vestibular neurons projecting to the flocculus and the nodulus and uvula of the caudal vermis (Larsell's lobules X and IX) was investigated with retrograde axonal transport of horseradish peroxidase and the fluorescent tracers Fast Blue, Nuclear Yellow and Diamidino Yellow. The presence of collateral axons innervating the flocculus on one hand and the nodulus and uvula on the other was studied with simultaneous injection of the different fluorescent tracers. The distribution of vestibular neurons projecting to either flocculus or caudal vermis is rather similar and has a bilateral symmetry. The projection from the magnocellular medial vestibular nucleus is very sparse, while that from the lateral vestibular nucleus is absent. The majority of labeled neurons was found in the medial, superior, and descending vestibular nuclei, in that order. Double labeled neurons were distributed in a similar way as the single labeled ones. Labeled neurons project to the nodulus and uvula, the flocculus, and to both parts of the cerebellum simultaneously in a ratio of 12:4:1. Five different populations of vestibulocerebellar neurons can be distinguished on the basis of their projection to the: (1) ipsilateral flocculus, (2) contralateral flocculus, (3) ipsilateral flocculus and nodulus/uvula, (4) contralateral flocculus and nodulus/uvula, and (5) nodulus/uvula. [ABSTRACT FROM AUTHOR]

The occurrence and distribution of labeled cells in the pontine nuclei were mapped following injections of small amounts of horseradish peroxidase (0.05-0.5 μl, 50% suspension) in the flocculus, nodulus and the dorsal and ventral paraflocculus in adult albino rabbits. While no labeled cells were found in the pontine nuclei following injections in the nodulus, some were present following injections in the flocculus and a great number following injections in the paraflocculus. The projections onto the flocculus and paraflocculus are precisely organized. Following injections in the paraflocculus labeled neurons are arranged in four columns (E and G in the paramedian pontine nucleus, F in the peduncular and H in the dorsolateral nucleus). Following injections in the ventral paraflocculus labeled cells are present only in parts of column E and F, while columns G and H and parts of E and F project onto the dorsal paraflocculus. Following injections in the flocculus labeled cells occur in the rostral part of column E only. A comparison between the sites of termination of pontine afferents and the areas giving origin to floccular and parafloccular fibers shows that only few fibers mediating visual impulses end in these pontine areas, while they receive numerous fibers from gyrus cinguli and areas 18 and 19 of the cerebral cortex. [ABSTRACT FROM AUTHOR]

Positioning head tilt is a neurological sign that has recently been described in dogs with congenital cerebellar malformations. This head tilt is triggered in response to head movement and is believed to be caused by a lack of inhibition of the vestibular nuclei by the cerebellar nodulus and ventral uvula (NU), as originally reported cases were dogs with NU hypoplasia. We hypothesized that other diseases, such as lysosomal storage diseases that cause degeneration in the whole brain, including NU, may cause NU dysfunction and positioning head tilt. Videos of the clinical signs of canine lysosomal storage disease were retrospectively evaluated. In addition, post-mortem NU specimens from each dog were histopathologically evaluated. Nine dogs were included, five with lysosomal storage disease, two Chihuahuas with neuronal ceroid lipofuscinosis (NCL), two Border Collies with NCL, one Shikoku Inu with NCL, two Toy Poodles with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Twenty-eight videos recorded the clinical signs of the dogs. In these videos, positioning head tilt was observed in seven of nine dogs, two Chihuahuas with NCL, one Border Collie with NCL, one Shikoku Inu with NCL, one Toy Poodle with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Neuronal degeneration and loss of NU were histopathologically confirmed in all diseases. As positioning head tilt had not been described until 2016, it may have been overlooked and may be a common clinical sign and pathophysiology in dogs with NU dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tamura, Tamura, Nakamoto, Hasegawa, Tsuboi, Uchida, Yabuki and Yamato.)

Cerebellar nodulus (lobule X) is an anterior and inferior structure of the vermis and is the epicenter of locculonodular lobe (vestibulocerebellum). Nodulus coordinates with the vestibular nuclei through afferent Mossy and efferent Purkinje fibers and plays a pivotal role in maintaining balance and is responsible for vestibulo-ocular reflex. Any lesion disrupting these fiber tracts impairs the person's ability to control ocular movements during head tilting and posture while standing and walking. Isolated infarction of nodulus is extremely rare with only few cases been reported earlier. In this article, the authors present a case of an elderly female with severe giddiness and cerebellar signs and were diagnosed to have an isolated cerebellar nodulus infarction on imaging studies. Conservative management to which our patient responded well is also discussed. [ABSTRACT FROM AUTHOR]

Positional vertigo and nystagmus without associated neurological symptoms and signs are characteristic features of benign paroxysmal positional vertigo (BPPV). Although positional nystagmus may occur with caudal cerebellar infarction including the nodulus, positional nystagmus is usually associated with other neurological signs such as spontaneous or gaze-evoked nystagmus, perverted head-shaking nystagmus, cerebellar dysmetria, or severe gait ataxia with falling. We present a patient with nodular infarction who had positional vertigo with nystagmus as a sole manifestation. Video-oculography showed apogeotropic positional horizontal nystagmus during head turning while supine, which was consistent with apogeotropic BPPV involving the horizontal canal. MRI disclosed acute infarct in the nodulus. Nodulus infarction should be considered in a patient with positional nystagmus, especially when the presenting symptoms and signs are consistent with BPPV involving the horizontal canal. [ABSTRACT FROM AUTHOR]

We reported a patient with cerebellar infarction who presented with purely isolated vertigo, ipsilesional spontaneous nystagmus, and contralesional axial lateropulsion without usual symptoms or signs of cerebellar dysfunction. An MRI of the brain showed a small left cerebellar infarct selectively involving the nodulus. A pure vestibular syndrome in our patient may be explained by ipsilateral involvement of nodulo-vestibular inhibitory projection to vestibular nucleus. Clinicians should be aware of the possibility of a nodulus infarction in patient with acute vestibular syndrome, even if the pattern of nystagmus and lateropulsion is typical of a vestibular neuritis. [Copyright &y& Elsevier]

Introduction and aim: Although percutaneous ethanol sclerotherapy for the treatment of benign thyroid nodules (PEI) has been used for more than 30 years, there are only two studies in thyroid cysts (THCY) and 2 in autonomously functioning nodule (AFN) in which the mean follow-up reaches at least five years, while in the event of non-autonomously functioning solid nodules (NAS), there is not any study with at least 5-year mean follow-up. Our study focuses on the long-term efficacy of PEI in benign thyroid nodules. Method: We analyzed the long-term success of PEI in 254 patients treated for more than 10 years. The success was defined as 50% or greater reduction in nodule volume. In addition, the patient had to remain euthyroid without thyrostatic therapy in AFN. Results: The 10-year success rate was 79.4%, 37.1% and 69.4% in THCY, AFN and NAS, respectively. In 23.3% of unsuccessful PEIs, the failure could be revealed only after 5 years of follow-up. The mean nodule volume at 10-year follow-up related to the initial size was 29.8%, 39.6% and 48.9% in THCY, NAS and AFN, respectively. In THCY, PEI proved to be significantly more effective in older patients while other parameters (size of the nodule, amount of the injected alcohol and the ratio of these) did not correlate significantly with the success rate. Conclusions: Our study which presents the longest follow-up in all 3 types of benign thyroid nodules confirms that PEI has a minimal role in AFN, is recommendable in THCY and might have a role in NAS. The success rate decreases over time which emphasizes the importance of the long-term follow-up in the judgement of PEI. Orv Hetil. 2020; 161(6): 224-231.