Cerebellum and Ocular Motor Control

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

Pearls & Oy-sters: Positional vertigo and vertical nystagmus in medulloblastoma

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Structure of amyloid-β (20-34) with Alzheimer's-associated isomerization at Asp23 reveals a distinct protofilament interface.

Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20-34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20-34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD

Visual Fixation and Continuous Head Rotations Have Minimal Effect on Set-Point Adaptation to Magnetic Vestibular Stimulation

Background: Strong static magnetic fields such as those in an MRI machine can induce sensations of self-motion and nystagmus. The proposed mechanism is a Lorentz force resulting from the interaction between strong static magnetic fields and ionic currents in the inner ear endolymph that causes displacement of the semicircular canal cupulae. Nystagmus persists throughout an individual's exposure to the magnetic field, though its slow-phase velocity partially declines due to adaptation. After leaving the magnetic field an after effect occurs in which the nystagmus and sensations of rotation reverse direction, reflecting the adaptation that occurred while inside the MRI. However, the effects of visual fixation and of head shaking on this early type of vestibular adaptation are unknown.Methods: Three-dimensional infrared video-oculography was performed in six individuals just before, during (5, 20, or 60 min) and after (4, 15, or 20 min) lying supine inside a 7T MRI scanner. Trials began by entering the magnetic field in darkness followed 60 s later, either by light with visual fixation and head still, or by continuous yaw head rotations (2 Hz) in either darkness or light with visual fixation. Subjects were always placed in darkness 10 or 30 s before exiting the bore. In control conditions subjects remained in the dark with the head still for the entire duration.Results: In darkness with head still all subjects developed horizontal nystagmus inside the magnetic field, with slow-phase velocity partially decreasing over time. An after effect followed on exiting the magnet, with nystagmus in the opposite direction. Nystagmus was suppressed during visual fixation; however, after resuming darkness just before exiting the magnet, nystagmus returned with velocity close to the control condition and with a comparable after effect. Similar after effects occurred with continuous yaw head rotations while in the scanner whether in darkness or light.Conclusions: Visual fixation and sustained head shaking either in the dark or with fixation inside a strong static magnetic field have minimal impact on the short-term mechanisms that attempt to null unwanted spontaneous nystagmus when the head is still, so called VOR set-point adaptation. This contrasts with the critical influence of vision and slippage of images on the retina on the dynamic (gain and direction) components of VOR adaptation

Pharmacological and Behavioral Strategies to Improve Vision in Acquired Pendular Nystagmus.

BACKGROUND Acquired pendular nystagmus (APN) is a back and forth, oscillatory eye movement in which the 2 oppositely directed slow phases have similar waveforms. APN occurs commonly in multiple sclerosis and causes a disabling oscillopsia that impairs vision. Previous studies have proven that symptomatic therapy with gabapentin or memantine can reduce the nystagmus amplitude or frequency. However, the effect of these medications on visual acuity (VA) is less known and to our knowledge the impact of non-pharmacological strategies such as blinking on VA has not been reported. This is a single observational study without controls (Class IV) and is meant to suggest a future strategy for study of vision in patients with disabling nystagmus and impaired vision. CASE REPORT A 49-year-old woman with primary progressive multiple sclerosis with spastic paraparesis and a history of optic atrophy presented with asymmetrical binocular APN and bothersome oscillopsia. We found that in the eye with greater APN her visual acuity improved by 1 line (from 0.063 to 0.08 decimals) immediately after blinking. During treatment with memantine, her VA without blinking increased by 2 lines, from 0.063 to 0.12, but improved even more (from 0.12 to 0.16) after blinking. In the contralateral eye with a barely visible nystagmus, VA was reduced by 1 line briefly (~500 ms) after blinking. CONCLUSIONS In a patient with APN, blinking transiently improved vision. The combination of pharmacological treatment with memantine and the blinking strategy may induce better VA and less oscillopsia than either alone

Fluctuations in the Site Disordered Traveling Salesman Problem

We extend a previous statistical mechanical treatment of the traveling salesman problem by defining a discrete "site disordered'' problem in which fluctuations about saddle points can be computed. The results clarify the basis of our original treatment, and illuminate but do not resolve the difficulties of taking the zero temperature limit to obtain minimal path lengths.Comment: 17 pages, 3 eps figures, revte

Longer duration entry mitigates nystagmus and vertigo in 7-Tesla MRI

IntroductionPatients and technologists commonly describe vertigo, dizziness, and imbalance near high-field magnets, e.g., 7-Tesla (T) magnetic resonance imaging (MRI) scanners. We sought a simple way to alleviate vertigo and dizziness in high-field MRI scanners by applying the understanding of the mechanisms behind magnetic vestibular stimulation and the innate characteristics of vestibular adaptation.MethodsWe first created a three-dimensional (3D) control systems model of the direct and indirect vestibulo-ocular reflex (VOR) pathways, including adaptation mechanisms. The goal was to develop a paradigm for human participants undergoing a 7T MRI scan to optimize the speed and acceleration of entry into and exit from the MRI bore to minimize unwanted vertigo. We then applied this paradigm from the model by recording 3D binocular eye movements (horizontal, vertical, and torsion) and the subjective experience of eight normal individuals within a 7T MRI. The independent variables were the duration of entry into and exit from the MRI bore, the time inside the MRI bore, and the magnetic field strength; the dependent variables were nystagmus slow-phase eye velocity (SPV) and the sensation of vertigo.ResultsIn the model, when the participant was exposed to a linearly increasing magnetic field strength, the per-peak (after entry into the MRI bore) and post-peak (after exiting the MRI bore) responses of nystagmus SPV were reduced with increasing duration of entry and exit, respectively. There was a greater effect on the per-peak response. The entry/exit duration and peak response were inversely related, and the nystagmus was decreased the most with the 5-min duration paradigm (the longest duration modeled). The experimental nystagmus pattern of the eight normal participants matched the model, with increasing entry duration having the strongest effect on the per-peak response of nystagmus SPV. Similarly, all participants described less vertigo with the longer duration entries.ConclusionIncreasing the duration of entry into and exit out of a 7T MRI scanner reduced or eliminated vertigo symptoms and reduced nystagmus peak SPV. Model simulations suggest that central processes of vestibular adaptation account for these effects. Therefore, 2-min entry and 20-s exit durations are a practical solution to mitigate vertigo and other discomforting symptoms associated with undergoing 7T MRI scans. In principle, these findings also apply to different magnet strengths

Influence of magnetic vestibular stimulation on self-motion perception

Ultrahigh magnetic fields (UHF) induce dizziness, vertigo and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called magnetic vestibular stimulation (MVS) (Roberts et al., 2011; Ward et al., 2015). As the effect of the magnetic field on the cupula remains constant throughout the exposure, MVS is specifically suitable for studying cognitive performance under vestibular stimulation. The effect of MVS can be set near to zero by tilting the head 30° forward towards the body, allowing to compare different strengths of MVS within subjects (Mian et al., 2016). Furthermore, MVS serves as a suitable non-invasive model for unilateral failure of the vestibular system, which enables studying compensatory processes (Ertl and Boegle, 2019). We conducted our study in a Siemens Terra 7 Tesla Scanner and tested 8 young, healthy participants and plan to include 30 more. The study had two main goals. First, to investigate the process of perception-reflex uncoupling, as under MVS self-motion perception differs from measured nystagmus in direction as well as time course. While horizontal nystagmus was predominant, most participants report a percept of roll rotation, and less frequent a percept of yaw rotation or a mixture of both when moving in to and out of the magnetic field. This matches previous studies (Mian et al., 2013). Reported percepts did not correspond fully to measured reflexive eye-movements. Overall, stronger nystagmus indicated stronger percepts. Roll percepts make sense because the brain integrates the prior knowledge and sensory evidence. In supine position, yaw but not roll rotation would also elicit change in direction of gravity. Second, to quantify influence of continuous vestibular stimulation on cognitive functions with spatial components. Behavioral and neuroimaging studies have shown repeatedly that caloric, galvanic and motion platform-induced vestibular stimulation can affect performance in spatial tasks, such as mental rotation (Klaus et al., 2019; Falconer & Mast, 2012). The influence of MVS on spatial cognition is relevant for fMRI studies as MVS can be a confounder, especially in studies using UHFs. In our study, we did not find a meaningful effect of MVS on mental body rotation performance, neither in allocentric nor in egocentric strategy. In the future, we aim to compare healthy participants and patients with vestibular disorders to investigate adaption and habituation mechanisms

Benign Paroxysmal Positional Vertigo

A 58-year-old woman seeks care from her primary physician after the occurrence of sudden vertigo and imbalance with nausea and vomiting, which began that morning when she got out of bed. The vertigo lasted less than a minute but recurred when she lay back down in bed, rolled over in bed, or got up again. She reports no tinnitus or hearing loss. How should this patient be evaluated and treated?OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000004487/21SEQ:21PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000004487ADJUST_YN:YEMP_ID:A075641DEPT_CD:801CITE_RATE:54.42FILENAME:kimjs-bppv-nejm-2014.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM: