Detection of floccular hypometabolism in downbeat nystagmus by fMRI

Kalla, Roger; Deutschländer, Angela; Hüfner, Katharina; Stephan, Thomas; Jahn, Klaus; Glasauer, Stefan; Brandt, Thomas; Strupp, Michael

doi:10.1212/01.wnl.0000194242.28018.d9

Cited by 96 publications

(59 citation statements)

References 8 publications

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“…Furthermore, it is associated with impaired smooth pursuit eye movements, especially in the downward direction [22], which would be expected from a deficit of floccular PCs with downward on-directions. For a population of DBN patients with cerebellar atrophy, we recently showed that, in comparison to healthy controls, BOLD activation in the floccular lobe was decreased during downward pursuit [23]. The present study thus supports our hypothesis on the pathogenesis of DBN, which is based on a asymmetric distribution of the on-directions of vertical gaze-velocity PCs [16,17].…”

Section: Discussionsupporting

confidence: 89%

Up–Down Asymmetry of Cerebellar Activation During Vertical Pursuit Eye Movements

et al. 2009

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Purkinje cells in the cerebellar floccular lobe, whose firing rate is modulated during vertical smooth pursuit eye movements, show a preference for downward pursuit. Here we validate the functional vertical asymmetry of the cerebellar flocculus in humans using functional magnetic resonance imaging (fMRI) by demonstrating a significantly higher activation of the floccular lobe for downward than for upward pursuit. The findings corroborate our recent hypothesis on the pathogenesis of cerebellar downbeat nystagmus.Suggested Reviewers:Response to Reviewers: We thank both reviewers for their helpful comments. Below you find a point-to-point response to all questions and comments. Following the suggestion of reviewer 1, we changed the title of the manuscript, and have rewritten large parts of the discussion in response to both reviewers. We hope that the manuscript will now satisfy the reviewers.point-to-point-responseReviewer 1Reviewer 1: The authors first suggest that this experiment demonstrates a selective activation of the floccular lobe for downward, but not upward pursuit. This is clearly enontiated in the title and in the abstract. However, the objective result, using their paradigm, is that there is a positive difference of activation during downward as compared to upward, and no positive difference of activation during upward as compared to downward. Since the paradigm did not compare pursuit to a rest condition (such as fixation), it can not be ruled out that there may be some activation during upward smooth pursuit. Therefore, it can not be concluded that there is no activation of flocculus during upward pursuit.Answer: We completely agree with reviewer 1 that the objective result of this study is not a selective activation of the cerebellar flocculus during downward pursuit. Therefore, we changed the title to: Up-down asymmetry of cerebellar activation during vertical pursuit eye movements. We also changed the respective sentence in the abstract, which now reads:"Here we validate the functional vertical asymmetry of the cerebellar flocculus in humans using functional magnetic resonance imaging (fMRI) by demonstrating a significantly higher activation of the floccular lobe for downward than for upward pursuit."Reviewer 1: The paradigm elicited vertical pursuit for 20° followed by a saccadic reset in the opposite direction. There is no control experiment that can eliminate the possibility of a saccadic and not a pursuit activation of flocculus during the task. This notion is very briefly discussed (page 7, line 4-11) and ruled out based on the electrophysiological data in monkeys. This would have been the good time to validate these animal data and in the same time obtain a good control study, by using vertical saccadic blocks in the same subjects.Answer: We agree with reviewer 1 that theoretically, the floccular activation may have been caused by the saccadic jump and not by the pursuit eye movement. As stated in the discussion, electrophysiological studies in the monkey showed that most floccular PCs paus...

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Section: Discussionsupporting

confidence: 89%

Up–Down Asymmetry of Cerebellar Activation During Vertical Pursuit Eye Movements

et al. 2009

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“…This supports the view that a functional deficiency of the flocculi causes not only a defect in downward pursuit but also DBN [Marti et al 2005]. More recent studies using voxel-based morphometry demonstrated an atrophy in certain areas of the cerebellum, which are mainly related to ocular motor function [Hufner et al 2007;Kalla et al 2006].…”

Section: Therapeutic Advances In Neurological Disorders 2 (4)supporting

confidence: 72%

“…These cells are predominantly activated with ipsiversive and downward gaze velocity, but only $10% of them show on-directions for upward-gaze velocity [Partsalis et al 1995]. With functional magnetic resonance imaging (fMRI) and F-fluorodeoxyglucose-positron emission tomography, it was recently shown that patients with DBN have diminished activation/metabolism of both floccular lobes (Figure 3) [Bense et al 2006;Kalla et al 2006]. This supports the view that a functional deficiency of the flocculi causes not only a defect in downward pursuit but also DBN [Marti et al 2005].…”

Section: Therapeutic Advances In Neurological Disorders 2 (4)mentioning

confidence: 99%

Review: Current treatment of vestibular, ocular motor disorders and nystagmus

Strupp

Brandt²

2009

Ther Adv Neurol Disord

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Vertigo and dizziness are among the most common complaints with a lifetime prevalence of about 30%. The various forms of vestibular disorders can be treated with pharmacological therapy, physical therapy, psychotherapeutic measures or, rarely, surgery. In this review, the current pharmacological treatment options for peripheral and central vestibular, cerebellar and ocular motor disorders will be described. They are as follows for peripheral vestibular disorders. In vestibular neuritis recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease a recent study showed long-term high-dose treatment with betahistine has a significant effect on the frequency of the attacks. The use of aminopyridines introduced a new therapeutic principle in the treatment of downbeat and upbeat nystagmus and episodic ataxia type 2 (EA 2). These potassium channel blockers presumably increase the activity and excitability of cerebellar Purkinje cells, thereby augmenting the inhibitory influence of these cells on vestibular and cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus, and gabapentin and memantine, pendular nystagmus. However, many other eye movement disorders such as ocular flutter opsoclonus, central positioning, or see-saw nystagmus are still difficult to treat. Although progress has been made in the treatment of vestibular neuritis, downbeat and upbeat nystagmus, as well as EA 2, stateof-the-art trials must still be performed on many vestibular and ocular motor disorders, namely Menière's disease, bilateral vestibular failure, vestibular paroxysmia, vestibular migraine, and many forms of central eye movement disorders.

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“…Similarly the cerbellar vermis, also has been found to be active in patients with bipolar disorder while performing SPEM (Martin et al, 2011). fMRI activation during downward smooth pursuit was less in both flocculi of the cerebellum for patients with DBN than controls (Kalla et al, 2006). Reduced activation in the paraflocular lobule and in the ponto-medullary brainstem of the patients was also seen (Hüfner et al, 2007).…”

Section: Fmri and Visual Dysfunctionmentioning

confidence: 80%

Current Trends of fMRI in Vision Science: A Review

Kashou¹

2012

Functional Magnetic Resonance Imaging - Advanced Neuroimaging Applications

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Detection of floccular hypometabolism in downbeat nystagmus by fMRI

Cited by 96 publications

References 8 publications

Up–Down Asymmetry of Cerebellar Activation During Vertical Pursuit Eye Movements

Up–Down Asymmetry of Cerebellar Activation During Vertical Pursuit Eye Movements

Review: Current treatment of vestibular, ocular motor disorders and nystagmus

Current Trends of fMRI in Vision Science: A Review

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