Gerald Wiest

New Tests of Vestibular Function

Abstract: The vestibulo‐ocular reflex (VOR) is the only drive for short‐latency eye movements stabilizing the retina during externally imposed, sudden, high‐head accelerations. New strategies can exploit this unique VOR feature to study it under conditions relevant to the daily lives of patients, and to exclude the contributions from confounding nonvestibular mechanisms. Testing of the yaw vestibulo‐ocular reflex (VOR) during random, whole‐body rotational transients at ≤2800°/s2 delivered about centered and eccentric axes enables measurement of gains and millisecond latencies of the canal and otolith VORs in humans. Repeated measurements in acute unilateral deafferentation show sequential recovery of canal and otolith VORs to contralesional rotation, but severe and permanent deficits to ipsilesional rotation. Patients with bilateral loss of caloric responses show severe bilateral loss of VORs to transient rotation, suggesting that the apparent preservation of their VORs during sinusoidal rotations at moderate frequencies may be due instead to somatosensory inputs.

Vestibular function in severe bilateral vestibulopathy

OBJECTIVES To assess residual vestibular function in patients with severe bilateral vestibulopathy comparing low frequency sinusoidal rotation with the novel technique of random, high acceleration rotation of the whole body. METHODS Eye movements were recorded by electro-oculography in darkness during passive, whole body sinusoidal yaw rotations at frequencies between 0.05 and 1.6 Hz in four patients who had absent caloric vestibular responses. These were compared with recordings using magnetic search coils during the first 100 ms after onset of whole body yaw rotation at peak accelerations of 2800°/s2. Off centre rotations added novel information about otolithic function. RESULTS Sinusoidal yaw rotations at 0.05 Hz, peak veocity 240°/s yielded minimal responses, with gain (eye velocity/head velocity)<0.02, but gain increased and phase decreased at frequencies between 0.2 and 1.6 Hz in a manner resembling the vestibulo-ocular reflex. By contrast, the patients had profoundly attenuated responses to both centred and eccentric high acceleration transients, representing virtually absent responses to this powerful vestibular stimulus. CONCLUSION The analysis of the early ocular response to random, high acceleration rotation of the whole body disclosed a profound deficit of semicircular canal and otolith function in patients for whom higher frequency sinusoidal testing was only modestly abnormal. This suggests that the high frequency responses during sinusoidal rotation were of extravestibular origin. Contributions from the somatosensory or central predictor mechanisms, might account for the generation of these responses. Random, transient rotation is better suited than steady state rotation for quantifying vestibular function in vestibulopathic patients.

Sigmund Freud and the VIIIth Cranial Nerve.

This report focuses on Sigmund Freud’s previously untranslated neuroanatomic articles on the brainstem connections of the VIIIth cranial nerve. Freud erroneously concluded in all 3 reports that the vestibular nucleus of Deiters was a third acoustic nucleus, despite prior studies showing that fibers to Deiters nucleus remain intact after sectioning the peripheral acoustic nerve. Furthermore, Freud had a close personal and professional relationship with Josef Breuer, a pioneer in neurophysiologic studies of the vestibular system. Freud’s “neglect” of the vestibular part of the VIIIth cranial nerve is discussed in the context of the late 19th century, which represented a pivotal time in our understanding of the brain and the vestibular system. Sigmund Freud was not only the founder of psychoanalysis, but he also made important contributions to clinical neurology, a science that was rapidly developing in the last decades of the 19th century. Of his neurologic writings, the monograph entitled Zur Auffassung der Aphasien (1) is usually regarded as his most important work. Far less known are Freud’s neuroanatomic studies (2). Among these, 3 previously untranslated publications dealing with the origin of the VIIIth cranial nerve are the subject of this report (3). Ernst von Bruecke, head of physiology at the University of Vienna, first encouraged Freud to investigate the histology of nerve cells. Bruecke came to Vienna in 1849, where he established the first chair of physiology in Austria. Freud, who received his medical degree in Vienna in 1881, worked in Bruecke’s laboratory from 1876 to 1882. Despite being miserably housed in a dark, old gun factory, the laboratory was the pride of the Viennese medical school. During this period, Freud published several histologic studies on invertebrate nerve cells and nerve fibers (2). Theodor Meynert, who was one of Freud’s mentors at the time, was also head of psychiatry and one of the leading neuroanatomists. He encouraged Freud to devote himself to brain anatomy. It was in Meynert’s laboratory where Freud began his studies on the medulla oblongata. It is unclear whether Meynert stimulated Freud’s interest in the origin of the acoustic nerve or whether it was Freud’s own idea. Freud’s biographer, Ernest Jones, suggested that Josef Breuer, whom Freud first met at Bruecke’s laboratory in the late 1870s, was the one who persuaded Freud to address this topic. Breuer was also a graduate of the University of Vienna medical school and a disciple of Bruecke. It was Breuer’s private patient, Anna O. or Bertha Pappenheim, who would later be a focus of their famous book Studien über Hysterie (4). According to Jones, the only academic advice Breuer seems ever to have given Freud was “a suggestion for a piece of anatomic research . . . one wonders if this was not the starting point of Freud’s important work on the root fibers of the acoustic nerve, the most valuable of all his histologic researches. If so, it was a piece of advice worth having” (5, p 168). Freud’s passion for neuroanatomy at that time is reflected in a letter from May 1885 to his wife to be in which he assured her that anatomy of the brain was the only serious rival she had ever had or was likely to have (5). The first of these 3 papers is a brief 2-page report on the interolivary tract in the medulla of fetuses of 5 to 6 months and was published in the Neurologisches Centralblatt in June 1885 (6). In the introduction, Freud notes that he performed his studies in Meynert’s laboratory using Weigert’s staining technique, a standard method to stain the myelin sheath. Before describing the anatomic connections between the acoustic nerve and the interolivary tract, and the latter with the crossed trapezoid body, Freud outlined his findings on the origin of the acoustic nerve. Freud differentiates between the most external acoustic roots that terminate in the anterior acoustic nucleus (which he also calls acoustic ganglion) and the medial or inner roots that terminate in the posterior or inner acoustic nucleus. The description of an anterior and posterior acoustic nucleus is consistent with our current concept of central auditory pathways (i.e., the ventral [anterior] and dorsal [posterior] cochlear nuclei.) The most striking finding in Freud’s report is that he proposed a third acoustic nucleus, which he called the external acoustic nucleus (also referred to as Deiters’ nucleus). The second paper, which Freud wrote during his felAddress correspondence and reprint requests to Dr. Robert W. Baloh, Reed Neurologic Research Center, Department of Neurology, UCLA School of Medicine, 710 Westwood Plaza, Room C-246A, Los Angeles, CA 90095-1769, U.S.A. Email: rwbaloh@ucla.edu This article was supported by the Austrian Science Fund. Dr. Baloh is supported by National Institutes of Health Grants AG09693 and DC02952. Otology & Neurotology 23:228–232

Impaired Linear Vestibulo-Ocular Reflex Initiation and Vestibular Catch-Up Saccades in Older Persons

The vestibulo-ocular reflex, which stabilizes gaze to reduce retinal slip during head perturbations, has two components: the angular (AVOR), mediated by the semicircular canals, and the linear (LVOR), mediated by the otoliths. Progressive losses in vestibular sensory cells and primary neurons begins at about age 40 yrs,1 and are associated with age-related impairments in the steady-state1–3 and transient AVOR.4 However, little is known about possible age-related impairments of the LVOR. Vestibular catch-up saccades (VCUS) cued by the semicircular canals during transient rotations can supplement the hypometric AVOR to assist people with vestibular deafferentation to stabilize gaze.5 However, VCUS cued by otolith organs have not been previously studied, especially in terms of a possible association with aging. This study sought to characterize LVOR initiation and VCUS in older humans. We investigated nine younger subjects 24 ± 5 years of age (mean ± SD, range 18– 31) and eight older subjects 65 ± 7 years of age (range 56–75) who gave written informed consent to a protocol approved by the UCLA Human Subject Protection Committee. Random lateral (“heave”) translations were delivered by a pneumatic position servo at peak acceleration of 0.5 G over a distance of ± 25 cm. Subjects were firmly secured to a chair-mounted head-holder. Eye and head movements were sampled at 1200 Hz using binocular magnetic search coils and a cranial accelerometer. Ten responses were averaged for each condition. Subjects fixed targets at 200, 50, or 15 cm distant immediately before unpredictable onset of randomly directed translation in dark (LVOR) or light (visually enhanced LVOR, LVVOR). All older subjects maintained ideal vergence of 1.5–2 deg for the 200-cm target, 6–8 deg for the 50-cm target, and 21–26 deg for the 15-cm target, with actual vergences depending on individual interpupillary distances. Search coil recording of head rotation showed it to be negligible (< 0.5°)for the first 250 ms after onset of head translation, excluding a role for the AVOR in the responses studied. The typical

Initiation of the Linear Vestibulo‐Ocular Reflex in Cerebellar Dysfunction

The linear vestibulo-ocular reflex (LVOR) is an otolith-mediated reflex that reduces retinal image slip during translation. A characteristic feature of the LVOR is that it depends on the distance to the visual or imagined target.1 Previous studies used eccentric axis rotation, which combined angular and linear stimulation, to determine the effects of cerebellar disorders on otolithic function.2 However, sensitivity and the effects of viewing distance on the initial LVOR have not yet been established in patients with hereditary cerebellar ataxia. In the present study we examined the LVOR by means of transient high linear acceleration, a powerful method for the assessment of pure otolithic signals. Spinocerebellar ataxia type 6 (SCA-6) and episodic ataxia type 2 (EA-2) result from mutations in the calcium channel CACNA1A that codes for the main transmembrane component of a calcium channel expressed most heavily in the cerebellum.3 Since SCA-6 and EA-2 are not associated with primary vestibular pathology or deficient convergence, they represent ideal conditions to study the role of the cerebellum in modulating the LVOR for target distance.4

The origins of vestibular science

The vestibular system conveys information about body motion and gravity. It was one of the first sensory systems to emerge in evolution; however, it was also the last to be discovered. The causal relationship between diseases of the ear and the symptom of vertigo was not recognized until the mid‐19th century. Only a few years later, the basic principle of semicircular canal function was elucidated almost simultaneously by three scientists with completely different backgrounds. This historical review describes the major milestones in the discoveries of the anatomy and the physiology of the vestibular system that paved the way for the establishment of neurotology as a clinical subspecialty.

The personal and scientific feud between Ernst Brücke and Josef Hyrtl.

Objective: To describe the events surrounding the personal and professional feud between Josef Hyrtl and Ernst Brücke and its impact on early investigations into the function of the semicircular canals of the inner ear. Data Sources: Published data in scientific journals and news media, documents at the Vienna Institute for the History of Medicine, published personal letters, and an interview with Brückes great-grandson, Dr. Thomas Brücke. Conclusion: Although Hyrtl was instrumental in recruiting Brücke to the University of Vienna, the two professors soon became embroiled in a feud that persisted throughout their academic careers. The difference in approach of these two giants in their field is well illustrated by their views on the function of the semicircular canals of the inner ear. Based on their shape, Hyrtl concluded that they were important for directional hearing, whereas based on animal experiments, Brücke concluded that they were sense organs for equilibrium.

Free Will, Agency, and the Synthetic Function of the Ego: An Investigation Using Cortical Stimulation

The experience that I feel myself to be the agent of my own movements is inherent to any volitional action. Impairments of this basic experience both in normal subjects and in patients with focal brain lesions may help to shed light on the nature of this perceptual mechanism, entitled authorship processing. We here report a perceptual illusion during invasive electrical cortical stimulation in a patient who underwent presurgical evaluation for epilepsy surgery. While stimulating the right frontal eye field electrically, which induced a contralateral eye and head deviation, the patient repeatedly had the illusion of performing this movement volitionally. Our observation suggests that ambiguous contextual situations may produce impairment of authorship processing. The findings are in line with current neuroscientific data, suggesting that authorship knowledge is not inherent to any volitional act, but requires information and inference for any given action. This notion also shows striking similarities to the Freudian concept of the synthetic function of the ego. By harmonizing conflicting elements, the synthetic function of the ego ensures unanimity of action and—as shown in our patient—also of authorship and free will.

Die biologischen und philosophischen Grundlagen einer Theorie

Nach den Anschauungen der modernen Biologie unterscheidet sich die organische Welt von der anorganischen vor allem durch die Entwicklung von Hierarchien (Mayr, 1997). Hierarchische biologische Prinzipien finden folglich sowohl in der Ontogenese als auch in der Phylogenese ihren Niederschlag. Die aktuellen Vorstellungen zur Evolution des Gehirns korrelieren mit den gegenwartigen Konzepten der allgemeinen Evolution. Demnach geht die (Gehirn-) Evolution von einem fruhen, einfachen Zustand aus, der sich zunehmend in mehrere Bauplane kompliziert. Die weitere Entwicklung ist durch Verzweigung bzw. Radiation und Konstanz, sowie durch Komplexitatszunahme (punktuell auch durch Vereinfachungen) gekennzeichnet (Roth, 1996).

Hierarchische Prinzipien im Nervensystem

John Hughlings Jackson, der spater als einer der Grundungsvater der klinischen Neurologie in die Geschichte der Medizin eingehen sollte, wurde entscheidend von den Ideen Herbert Spencers beeinflusst (Abb. 9). Jackson war bereits am Beginn seiner Karriere als Assistent am Londoner National Hospital for the Paralysed and the Insane von den teils befremdenden Symptomen neurologischer Patienten beeindruckt. Open image in new window Abb. 9 John Hughlings Jackson (1834–1911) Copyright: Royal College of Physicians of London