Reversed Corrective Saccades during Head Impulse Test in Acute Cerebellar Dysfunction

Patients with cerebellar lesions may show horizontal (positive)- or downward (perverted)-corrective saccades during horizontal head impulse test (HIT). However, corrective saccades in the direction of head rotation (reversed corrective saccades) have not been reported during HIT. We present two patients who showed reversed corrective saccades during horizontal HIT as an initial sign of acute cerebellitis. In contrast to the corrective saccades mostly observed in peripheral vestibular paresis, this paradoxical response indicates abnormally increased vestibulo-ocular responses due to cerebellar disinhibition over the vestibulo-ocular reflex. This paradoxical response should be considered an additional bedside cerebellar sign.     

Language Disorder in a Child with Early Left Thalamic Lesion

The present paper describes two patients, AB and FS, whose deficit in transcoding verbal to Arabic numerals was greatly affected by the format of the input. Despite intact comprehension of written verbal numerals and otherwise intact production of Arabic numerals they both transcode inefficiently the former into the latter. Yet, their ability to write the same Arabic numerals on dictation was fully preserved. Moreover, in both patients’ performance, a systematic error pattern emerged reflecting the influence of the lexico-syntactic structure of the input numerals in the transcoding processes. Current models of number transcoding may not easily account for this pattern of dissociation without postulating different code-dependent pathways for verbal to Arabic transcoding. Within a more parsimonious approach, it is tentatively suggested that spoken and written verbal codes activate with different efficiency the same transcoding algorithm.     

After Effects of Cerebellar Continuous Theta Burst Stimulation on Reflexive Saccades and Smooth Pursuit in Humans

The use of cerebellar repetitive transcranial magnetic stimulation has been attempted for perturbing reflexive and voluntary eye movements, but discrepancies are seen between the results of distinct studies possibly due to the different stimulation sites, intensities, and paradigms. We describe the after effects of 20 and 40 s continuous Theta Burst Stimulation (cTBS) as compared to sham stimulation, applied over the lateral cerebellar vermis and paravermis on Reflexive Saccades (RS) and Smooth Pursuit (SP) eye movements, recorded in the 30 min following stimulation. The experiments were carried out in eight healthy volunteers, and eye movements were recorded monocularly with video-oculography. The 40 s cTBS significantly increased the amplitude of ipsilateral RS and the acceleration of the ipsilateral SP, and this effect was detectable all over the 30-min recording period; 40 s cTBS did not modify the other parameters, namely the peak velocity, the duration and the latency of RS, and the latency and the velocity of SP. The 20 s cTBS was ineffective on all RS and SP parameters. Finally, we detected a significant quite-linear reduction of RS peak velocity over time, but this was independent from cTBS and was probably caused by fatigue. The effects of 40 s cTBS in our experiments mimic the disorder of ocular motility in Wallenberg’s syndrome and could result from functional impairment of cerebellopontine pathways. This effect lasts 30 min at least, and can provide a useful framework for adaptive ocular motor studies.     

Abnormal Head Impulse Test in a Unilateral Cerebellar Lesion

Background

The findings of head impulse tests (HIT) are usually normal in cerebellar lesions.

Case Report

A 46-year-old male presented with progressive dizziness and imbalance of 3 weeks duration. The patient exhibited catch-up saccades during bedside horizontal HIT to either side, which was more evident during the rightward HIT. However, results of bithermal caloric tests and rotatory chair test were normal. MRI revealed a lesion in the inferior cerebellum near the flocculus.

Conclusions

This case provides additional evidence that damage to the flocculus or its connections may impair the vestibulo-ocular reflex only during high-speed stimuli, especially when the stimuli are applied to the contralesional side. By observing accompanying cerebellar signs, the abnormal HIT findings caused by a cerebellar disorder can be distinguished from those produced by peripheral vestibular disorders.     

Paroxysmal Sympathetic Hyperactivity with Dystonia Following Non-traumatic Bilateral Thalamic and Cerebellar Hemorrhage

Neurocritical Care -     

Spontaneous Saccades and Gaze-Holding Ability in the Pigmented Rat. II. Effects of Localized Cerebellar Lesions

We have studied the effects of the ablation of the cerebellar vermal area corresponding to lobules VI - VIII and of the flocculus - paraflocculus of both sides on the spontaneous eye movements performed in the light and in the dark in head-restrained pigmented rats. These effects have been compared with those already described for the inferior olive lesion. The cerebellar lesions were performed 1 week to 6 months in advance. Eye movements were recorded through a phase detection search coil apparatus. Following vermal topectomy, the main characteristics of the spontaneous saccades are unmodified. Following the ablation of the flocculus - paraflocculus there is no change in the saccadic main sequence. However, the spontaneous saccades in the dark present a postsaccadic drift made up of two components with different time courses, the first one being fast and the second one slow. The former is due in part to a mismatch between the phasic (the pulse) and the tonic (the step) components of the eye movements; the latter to the leakage of the neural integrator. In light only the first component is present and the eye maintains a steady position. The time constant of the neural integrator is considerably reduced to approximately 600 - 900 ms from a value of approximately 1600 - 4000 ms in the intact rats. The amplitude of the postsaccadic drift in the light depends on both the mismatch between the pulse and the step of innervation of the extraocular muscles and the increased leakiness of the neural integrator. The gain of the pulse to step transformation is reduced to approximately 0.79 at all saccadic amplitudes and eccentricities and such a reduction is due to a decreased step amplitude, while the pulse amplitude remains unchanged. The contribution of the leakage of the neural integrator to the postsaccadic drift in the light is a function of the eccentricity with a slope of 0.23. The deficits described after flocculus - paraflocculus ablation are also very similar to those described following inferior olive lesion from a quantitative point of view. The possible mechanisms of the visually activated olivocerebellar system in the control of saccadic performance and in maintaining its calibration are discussed.     

Spontaneous Saccades and Gaze-Holding Ability in the Pigmented Rat. I. Effects of Inferior Olive Lesion

We have studied the effects of lesion of the inferior olive on the spontaneous eye movements performed both in the light and dark in head restrained pigmented rats. The inferior olive lesion was made at least 1 month before study with 3-acetylpyridine and eye movements were recorded through a phase detection search coil apparatus. Following lesion, the spontaneous saccades performed in the dark present a postsaccadic drift which is made up of two components characterized by their different time courses, the first one being fast and the second one slow. The latter component is due to the leakage of the neural integrator and the former is mainly the consequence of a mismatch between the phasic and the tonic component of the ocular movement. In the light only the first component is present and then the eye maintains a steady position. After the lesion the saccades in the dark present a time constant of the slow component of the postsaccadic drift which is significantly reduced to approximately 600 - 900 ms from a value of 1600 - 4000 ms of the intact rats. This means that the integrity of the inferior olive is necessary to keep the time constant of the neural integrator within the physiological range. In the light, the amplitude of the postsaccadic drift depends on two factors. First, there is a mismatch between the phasic and the tonic components of the ocular movement, which are due to the pulse and the step of innervation of the extraocular muscles respectively. Different types of analysis have shown that the gain of the pulse to step transformation is about 0.77 at all saccadic amplitudes and eccentricities. Second, there is an increased leakiness of the neural integrator. Such a contribution increases linearly as a function of the eccentricity with a slope of 0.21. The main sequence of the saccades is not appreciably affected by the olivary lesion. Thus, the consequence of the inferior olive lesion may be interpreted as a general disruption of the integration process which, in physiological conditions, generates a proper and sustained oculomotor signal. More generally, it may be viewed as a loss of coordination between phasic and tonic motor commands.     

The Recognition Memory Deficit Caused by Mediodorsal Thalamic Lesion in Non-human Primates: A Comparison with Rhinal Cortex Lesion

Two earlier studies found that rhinal cortex ablations in the monkey ( Macaca fascicularis ) impaired delayed matching-to-sample (DMS) when the stimuli in the experiment came from a large population of possible stimuli, but not when the stimulus population was small, while uncinate fascicle section had no effect on DMS whatever the stimulus population size. The mediodorsal thalamus receives a large projection from the rhinal cortex, and has been implicated in recognition memory performance. We trained monkeys preoperatively in delayed matching-to-sample with large and small stimulus populations, exactly as in the earlier studies, then examined the effect of bilaterally ablating the medial portion of the mediodorsal thalamic nucleus. Mediodorsal lesion impaired postoperative delayed matching-to-sample performance with a large stimulus set, but had no effect on performance of DMS with a small stimulus population. In comparison with the earlier data from rhinal cortex lesions with the same methods, wherever a deficit was seen in the rhinal-lesioned animals the mediodorsal thalamic nucleus-lesioned animals showed a smaller deficit. We conclude that other efferents from the rhinal cortex, possibly those to the adjacent inferior temporal cortex, enable better performance in the mediodorsal thalamic nucleus-lesioned animals than in the animals with rhinal cortex ablation.     

Mediodorsal Thalamic Lesions Impair Long-Term Visual Associative Memory in Macaques

Six cynomolgus monkeys (Macaca fascicularis) were trained to associate visual stimuli with the delivery of various amounts of food reward. The animals had to choose correctly between pairs of stimuli drawn from a population of 16. Four of these stimuli were associated with 0 reward pellets, four with 1 pellet, four with 2 pellets and four with 4 pellets. Mediodorsal thalamic lesions including the medial part of the mediodorsal nucleus, similar to those which are frequently seen in Korsakoff amnesia, produced a severe impairment in this task. The impairment was seen both in memory for the quantity of reward, as expressed in choices between 1-pellet and 2-pellet stimuli or choices between 2-pellet and 4-pellet stimuli, and also in memory for the qualitative absence or presence of reward, as expressed in choices between 0-pellet and 1-pellet stimuli. The deficit in this task establishes that mediodorsal thalamic lesions in monkeys can impair long-term memory tasks, in addition to their known effects on several short-term memory tasks. The contrast between the present results and those of previous experiments on visual long-term memory in the monkey following mediodorsal thalamic lesions can be related to similar contrasts in studies of lesions in the amygdala, suggesting that the functions of these two structures are related.     

Brief Report: Typical Visual Updating in Autism

Journal of Autism and Developmental Disorders - Individuals with Autism Spectrum Disorder (ASD) can struggle with visual updating. In a previous picture morphing study (Burnett and Jellema 2012)...     

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor.     

Organization of the Visual Reticular Thalamic Nucleus of the Rat

The visual sector of the reticular thalamic nucleus has come under some intense scrutiny over recent years, principally because of the key role that the nucleus plays in the processing of visual information. Despite this scrutiny, we know very little of how the connections between the reticular nucleus and the different areas of visual cortex and the different visual dorsal thalamic nuclei are organized. This study examines the patterns of reticular connections with the visual cortex and the dorsal thalamus in the rat, a species where the visual pathways have been well documented. Biotinylated dextran, an anterograde and retrograde tracer, was injected into different visual cortical areas [17; rostral 18a: presumed area AL (anterolateral); caudal 18a: presumed area LM (lateromedial); rostral 18b: presumed area AM (anteromedial); caudal 18b: presumed area PM (posteromedial)] and into the different visual dorsal thalamic nuclei (posterior thalamic, lateral posterior, lateral geniculate nuclei), and the patterns of anterograde and retrograde labelling in the reticular nucleus were examined. From the cortical injections, we find that the visual sector of the reticular nucleus is divided into subsectors that each receive an input from a distinct visual cortical area, with little or no overlap. Further, the resulting pattern of cortical terminations in the reticular nucleus reflects largely the patterns of termination in the dorsal thalamus. That is, each cortical area projects to a largely distinct subsector of the reticular nucleus, as it does to a largely distinct dorsal thalamic nucleus. As with each of the visual cortical areas, each of the visual dorsal thalamic (lateral geniculate, lateral posterior, posterior thalamic) nuclei relate to a separate territory of the reticular nucleus, with little or no overlap. Each of these dorsal thalamic territories within the reticular nucleus receives inputs from one or more of the visual cortical areas. For instance, the region of the reticular nucleus that is labelled after an injection into the lateral geniculate nucleus encompasses the reticular regions which receive afferents from cortical areas 17, rostral 18b and caudal 18b. These results suggest that individual cortical areas may influence the activity of different dorsal thalamic nuclei through their reticular connections.     

Organization of the Visual Sector of the Thalamic Reticular Nucleus in Galago

Projections to and from the visual sector of the thalamic reticular nucleus were studied in the prosimian primate genus Galago by anterograde and retrograde transport of WGA-HRP injected into the dorsal lateral geniculate nucleus (GLd), pulvinar nucleus, and their cortical targets. Contrary to the idea that thalamic connections with the reticular nucleus are not delimited sharply between nuclei associated with the same modality, our results show a distinct laminar segregation of the projections from the GLd and pulvinar nuclei. The GLd is connected reciprocally with the lateral {frsol|2/3} of the caudal part of the reticular nucleus, and the striate cortex sends projections to the same lateral tier. Both sets of projections are organized topographically, lines of projection taking the form of slender elongated strips that run from caudo-dorsal to rostro-ventral within the nucleus. The pulvinar nucleus, which projects to several areas of the temporal, parietal, and occipital lobes, including the striate cortex, is connected reciprocally with the medial {frsol|1/3} of the caudal part of the reticular nucleus. Every injection into the pulvinar nucleus labelled a wide area of the medial tier, with no indication of visuotopic organization. The projections from the middle temporal area, one of the principal targets of the pulvinar nucleus, also terminate only in the medial tier of the visual sector. And we would expect that, in general, a thalamic nucleus and its cortical target would project to the same part of the reticular nucleus. The case of the striate area is an exception but only in the sense that it projects to the pulvinar nucleus as well as GLd. Thus an injection into a single locus in area 17 produces two parallel strips in the visual sector of the reticular nucleus, but both are in the lateral tier. We propose that each strip arises from a separate population of cells with cortical layer VI, one with an allegiance to the GLd and the other to the pulvinar nucleus.     

Humor and Laughter in Patients with Cerebellar Degeneration

Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.     

Sudden Stopping in Patients with Cerebellar Ataxia

Stopping during walking, a dynamic motor task frequent in everyday life, is very challenging for ataxic patients, as it reduces their gait stability and increases the incidence of falls. This study was conducted to analyse the biomechanical characteristics of upper and lower body segments during abrupt stopping in ataxic patients in order to identify possible strategies used to counteract the instability in the sagittal and frontal plane. Twelve patients with primary degenerative cerebellar ataxia and 12 age- and sex-matched healthy subjects were studied. Time–distance parameters, dynamic stability of the centre of mass, upper body measures and lower joint kinematic and kinetic parameters were analysed. The results indicate that ataxic patients have a great difficulty in stopping abruptly during walking and adopt a multi-step stopping strategy, occasionally with feet parallel, to compensate for their inability to coordinate the upper body and to generate a well-coordinated lower limb joint flexor–extensor pattern and appropriate braking forces for progressively decelerating the progression of the body in the sagittal plane. A specific rehabilitation treatment designed to improve the ability of ataxic patients to transform unplanned stopping into planned stopping, to coordinate upper body and to execute an effective flexion–extension pattern of the hip and knee joints may be useful in these patients in order to improve their stopping performance and prevent falls.     

Smooth Pursuit Eye Movements and Voluntary Control of Saccades in the Antisaccade Task in Schizophrenic Patients

Abstract: It has been hypothesized that a saccade control dysfunction is one cause of a smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. We studied the voluntary control of saccades in schizophrenic patients with the SPEM dysfunction using an antisaccade task. The mean error rate in the antisaccade task was significantly higher in the two schizophrenic groups with and without a SPEM dysfunction than in the normal control group. Furthermore, the schizophrenic group with the SPEM dysfunction showed significantly more errors than the schizophrenic group without the SPEM dysfunction. These findings seem to suggest a close relationship between the SPEM dysfunction and the appearance of errors which indicates an inability to inhibit reflexive saccades voluntarily in the antisaccade task. However, 4 of 10 subjects with the SPEM dysfunction showed an error rate less than the mean error rate of the schizophrenic group without the SPEM dysfunction. So, a voluntary control disorder of saccades as the main cause of the SPEM dysfunction appeared to be unlikely. An interesting finding of this study was that many schizophrenic subjects with the SPEM dysfunction showed errors with the latencies similar to those in express saccades², particularly in the rightward direction. This finding may suggest a close relationship between the SPEM dysfunction in schizophrenic patients and some pathological conditions of express saccades such as disinhibition of express saccades.