bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Flexible Manufacturing Capacity in Pharmaceutical Product Introductions*
Authors: Chambers Chester G. , Snir Eli M. , Ata Asad
Published: May 2009

This work considers the value of the flexibility offered by production facilities that can easily be configured to produce new products. We focus on technical uncertainty as the driver of this value, while prior works focused only on demand uncertainty. Specifically, we evaluate the use of process flexibility in the context of risky new product development in the pharmaceutical industry. Flexibility has value in this setting due to the time required to build dedicated capacity, the finite duration of patent protection, and the probability that the new product will not reach the market due to technical or regulatory reasons. Having flexible capacity generates real options, which enables firms to delay the decision about constructing product‐specific capacity until the technical uncertainty is resolved. In addition, initiating production in a flexible facility can enable the firm to optimize production processes in dedicated facilities. The stochastic dynamic optimization problem is formulated to analyze the optimal capacity and allocation decisions for a flexible facility, using data from existing literature. A solution to this problem is obtained using linear programming. The result of this analysis shows both the value of flexible capacity and the optimal capacity allocation. Due to the substantial costs involved with flexibility in this context, the optimal level of flexible capacity is relatively small, suggesting products be produced for only short periods before initiating construction of dedicated facilities.
Health Care Supply Chain Design: Toward Linking the Development and Delivery of Care Globally*
Authors: Sinha Kingshuk K. , Kohnke Emily J.
Published: May 2009

This article is motivated by the gap between the growing demand and available supply of high‐quality, cost‐effective, and timely health care, a problem faced not only by developing and underdeveloped countries but also by developed countries. The significance of this problem is heightened when the economy is in recession. In an attempt to address the problem, in this article, first, we conceptualize care as a bundle of goods, services, and experiences—including diet and exercise, drugs, devices, invasive procedures, new biologics, travel and lodging, and payment and reimbursement. We then adopt a macro, end‐to‐end, supply chain–centric view of the health care sector to link the development of care with the delivery of care. This macro, supply chain–centric view sheds light on the interdependencies between key industries from the upstream to the downstream of the health care supply chain. We propose a framework, the 3A‐framework, that is founded on three constructs—affordability, access, and awareness—to inform the design of supply chain for the health care sector. We present an illustrative example of the framework toward designing the supply chain for implantable device–based care for cardiovascular diseases in developing countries. Specifically, the framework provides a lens for identifying an integrated system of continuous improvement and innovation initiatives relevant to bridging the gap between the demand and supply for high‐quality, cost‐effective, and timely care. Finally, we delineate directions of future research that are anchored in and follow from the developments documented in the article.
Anthropology in the Public Sphere, 2008: Emerging Trends and Significant Impacts
Authors: Checker Melissa
Published: May 2009

ABSTRACT  The themes, trends, and significant events of 2008 demonstrate that anthropology has established a new foothold in the public sphere—one that makes the most of novel forms of communication to reach far beyond the ivory tower to disseminate knowledge widely and freely. This review focuses on six topical areas of robust anthropological research in 2008 that also addressed some of the year's most pressing problems and issues, including the following: (1) war and peace; (2) climate change; (3) natural, industrial, and development‐induced disaster recovery; (4) human rights; (5) health disparities; and (6) racial understanding, politics, and equity in the United States. It concludes by addressing some emerging issues in 2009 that especially require anthropological attention and insight, if we are to move beyond “business as usual.”[Keywords: practicing anthropology, public anthropology, 2009 trends, anthropological impacts]
DELINQUENCY BALANCE: REVISITING PEER INFLUENCE*
Authors: MCGLOIN JEAN MARIE
Published: May 2009

An impressive number of inquiries across an array of methodological specifications has demonstrated that deviant peers are an important correlate of various criminological outcomes, which include within‐ individual change and stability in offending behavior. Still, the causal mechanisms of peer influence arguably remain underdeveloped (Giordano, 2003; Warr, 2002). In an attempt to expand the dialogue on the nature of peer influence, this inquiry proposes that scholars would benefit from considering relative peer deviance in addition to exposure to deviant peers. Specifically, it argues that an imbalance in delinquency between friends helps to explain delinquency change/stability; therefore, exposure to deviant peers is not always risky and exposure to less deviant peers is not always protective. The analysis uses the Add Health data to construct within‐individual and across‐individual (delinquency) difference scores and relies on self‐reports rather than on perceptions for the best friends' delinquency. The results provide support for the premise that adolescents attempt to achieve delinquency “balance” with their best friend by changing behavior, net of raw peer deviance levels (i.e., objective exposure). The findings also suggest that balance is not achieved through selection, given that the deviance gap between the respondent and his or her best friend does not predict friendship stability. The discussion considers these results from a theoretical and empirical perspective and offers several avenues for future research.
UNRAVELING THE CONTEXTUAL EFFECTS ON STUDENT SUSPENSION AND JUVENILE ARREST: THE INDEPENDENT AND INTERDEPENDENT INFLUENCES OF SCHOOL, NEIGHBORHOOD, AND FAMILY SOCIAL CONTROLS*
Authors: KIRK DAVID S.
Published: May 2009

Scholars of human development argue that a variety of social contexts affect youth development and that the interdependency of these contexts bears on the shape of human lives. However, few studies of contextual effects have attempted to model the effects of school, neighborhood, and family context at the same time, or to explore the relative and interdependent impact of these contexts on youth outcomes. This study provides an examination of the independent and interdependent influences of school, neighborhood, and familial contexts through an analysis of student suspension and juvenile arrest. Findings reveal that school‐based and family‐based informal social controls additively combine to reduce the likelihood of suspension and arrest. Moreover, for suspension, results support the hypothesis that an interdependent compensatory relation is present between the extent of collective efficacy in schools and in the surrounding neighborhood; school collective efficacy has a controlling influence on the likelihood of suspension that becomes even stronger in the absence of neighborhood collective efficacy. However, for arrest, an accentuating effect of school‐based social controls exists rather than a compensatory effect. A lack of neighborhood collective efficacy and a lack of school‐based social controls combine to exert a substantial increase in the likelihood of arrest.
Evaluation of cytotoxicity of two root canal filling materials by MTT assay
Authors: Ashraf Hengameh , Taherian Ali , Kerdar Alireza N.
Published: May 2009

The aim of this study was to assess the cytotoxicity of two root filling materials GuttaFlow (GF) and gutta‐percha (GP) on mouse fibroblasts cell line L‐929. In this study there were four groups: GP and GF were considered as study groups and the other two were negative control groups. GP and GF were prepared according to manufacturer's instruction. L‐929 fibroblast cells of mouse were passaged with trypsin (Merck, Germany) after elimination of freeze phase. Adequate trypsin was added to cells and they were prepared with 95% of cell vitality. After 24 h, 150 000 cells were put in each well. The cell and dimethyl methacrylate were used as negative and positive controls. Ten specimens from each group were brought into contact with the culture medium and were incubated under sterilised conditions 24 h later. The cytotoxicity of all samples was assessed by dimethylthiazol diphenyltetrazolium bromide test after 1 h, 24 h and 72 h. The results showed that cytotoxicity of GF was less than GP when assessed at 24 h and 72 h, but there was no significant difference at 1 h. In GF, the most and least cytotoxicity were observed at 24 h and 72 h while cytotoxicity of GP increased with time.
Use of a natural tooth crown as a pontic following cervical root fracture: a case report
Authors: Parolia Abhishek , Shenoy Kundabala M. , Thomas Manuel S. , Mohan Mandakini
Published: May 2009

The loss of anterior teeth can be psychologically and socially damaging to the patient. Despite a wide range of treatment options available, traumatised teeth may be inevitably lost on certain occasions. This paper describes the immediate replacement of a right central incisor using a fibre‐composite resin with the natural tooth crown as a pontic. The abutment teeth can be conserved with minimal or no preparation, thus keeping the technique reversible, and can be completed at chair side thereby avoiding laboratory costs. It can be used as an interim measure or a definitive prosthesis.
Stimulus Profile and Modeling of Continuous Galvanic Vestibular Stimulation in Functional Magnetic Resonance Imaging
Authors: Stephan Thomas , Hüfner Katharina , Brandt Thomas
Published: May 2009

Both direct current (DC) and alternating current (AC) have been used for galvanic vestibular stimulation (GVS) during functional MRI (fMRI). The perceptual effects of apparent rotation persist while the current is being applied, but there is a subjective decay over the entire stimulation period. Particularly during DC–GVS in a supine position, subjects report a strong vestibular sensation related to the onset and offset of the stimulus, and weaker effects during constant DC–GVS stimulation. In the present study, we analyzed DC–GVS fMRI data from a group of volunteers with two different statistical models. In model I, the effects of GVS were modeled as a single regressor that described the periods during which the current was switched on. In model II, an additional regressor describing the onset and offset of the stimulation was included. The activation pattern found by using model I included only a subset of the activation patterns known to respond to vestibular stimulation from previous imaging studies. Model II revealed two different activation maps: block effects similar to the results obtained in model I and additional transient GVS effects with larger activation clusters and higher t‐values. This extended activation pattern resembled the results obtained during AC–GVS, including multisensory vestibular projection areas. We show that the major part of the blood oxygenation level dependent (BOLD) responses elicited by DC–GVS is related to the on‐ and offset of stimulation currents and reflects the perceptual experience just‐described. In addition, the separate modeling of transient and persistent effects of DC–GVS can identify distinct cortical correlates of those effects.
Applying Knowledge—Challenges in Bringing Scientific Advances to Dizzy Patients
Authors: Haslwanter Thomas , Ong James
Published: May 2009

Simple diagnostic or therapeutic procedures can produce tremendous benefits for dizzy patients. To see how new ideas in the laboratory evolve into benefits for patients, an attempt to analyze how the corresponding information is distributed was made. To quantify that flow of information, a number of new scientific publications, citation numbers, and a number of new books on relevant subjects were looked at. For vertigo, this approach was facilitated by the fact that the diagnostic procedures for benign paroxysmal positioning vertigo (BPPV) and for canal paresis can be traced back to seminal publications. Results indicate that the current way of disseminating new information used here is working well, and that new ideas on diagnosis and treatment are readily available to practitioners. However, the application of new methods is limited by the availability of the required technology. It is conjectured that the technological requirements have become more complex over time, leading to a slower uptake of new technology.
Long‐Term Follow‐up of Vestibular Neuritis
Authors: Mandalà Marco , Nuti Daniele
Published: May 2009

The long‐term outcome of vestibular neuritis was evaluated in 35 patients using 4 bedside tests (head impulse, head heave, head shake, vibration), the caloric test and two surveys that explored the degree of disability (Dizziness Handicap Inventory [DHI]) and the anxiety and depression levels (Hospital Anxiety and Depression Scale [HADS]). Sixty‐six percent of patients showed a positive bedside clinical test or calorics abnormalities. DHI scores were significantly higher in the patients group, while HADS scores were comparable between patients and controls. Disability from vestibular neuritis is primarily due to the vestibular disturbance itself, rather than purely psychological factors.
Posture Control in Vestibular‐Loss Patients
Authors: Mergner Thomas , Schweigart Georg , Fennell Luminous , Maurer Christoph
Published: May 2009

Patients with chronic bilateral loss of vestibular functions normally replace these by visual or haptic referencing to stationary surroundings, resulting in an almost normal stance control. But with eyes closed, they show abnormally large body sway, and may tend to fall when there are external disturbances to the body or when standing on an unstable support surface. Patients’ postural responses depend on joint angle proprioception and ground reaction–force cues (occasionally referred to as “somatosensory graviception”). It is asked why the force cues do not allow patients to fully substitute loss of the vestibular cues. In recent years, four sets of observations of experimental situations where patients, eyes closed, show impaired stance control or even may fall were identified: (1) with unstable or compliant support (“inevitable falls”); (2) with large external disturbances such as support surface tilts or pull stimuli impacting on their bodies (leading to abnormally large body movements); (3) with fast body–support tilts (also abnormally large body movements); and (4) with transient support tilt (overshooting body–support stabilization and abnormaly late body–space [BS] stabilization). When patients’ data were modeled, it was found that their problems stem mainly from the force cues. It was hypothesized that patients have difficulties decomposing this sensory information into its constituents in order to be able to get rid of an active force component. Normals do not have this difficulty, because the vestibular system performs the decomposition.
Anxiety‐Related Behavior and Biogenic Amine Pathways in the Rat following Bilateral Vestibular Lesions
Authors: Darlington Cynthia L. , Goddard Matthew , Zheng Yiwen , Smith Paul F.
Published: May 2009

Many clinical studies have reported that patients with vestibular disorders have a high rate of anxiety disorders and depression. By contrast, there have been few studies of affective behavior in animals following vestibular lesions. Recent studies using the vestibular impaired ci2/ci2 mutant rat strain have shown that rather than preferring the closed arm of the elevated plus maze, as rats would normally, they make more open‐arm entries and spend more time on the open arms compared to wild‐type controls. In the open‐field maze, rather than preferring to explore the outer zone near the walls (“thigmotaxis”), ci2/ci2 rats prefer the inner region of the maze. In rats with bilateral vestibular deafferentation (BVD), similar results were obtained. Compared to sham controls, at 3 and 5 months post‐op, BVD rats spent more time on the open arms of the elevated plus maze, more time in the inner zone of the open‐field maze, and failed to learn inhibitory avoidance in the elevated T maze. They did not display increased hyponeophagia; however, they did exhibit a decrease in social interaction. Blood corticosterone levels were not significantly different from sham controls. At 6 months post‐op, BVD rats demonstrated circumscribed changes in the expression of tyrosine hydroxylase, the serotonin transporter, and tryptophan hydroxylase, in various regions of the medial temporal and frontal lobes, suggesting changes in biogenic amine pathways.
Balance before Reason in Rats and Humans
Authors: Smith Paul F. , Brandt Thomas , Strupp Michael , Darlington Cynthia L. , Zheng Yiwen
Published: May 2009

Considerable clinical and experimental evidence indicates that loss of vestibular function results in cognitive deficits, especially deficits in spatial memory. These studies demonstrate the importance of balance for the most fundamental of cognitive processes and suggest that information about head acceleration and orientation must have been critical to the evolution of brain structures such as the hippocampus. Studies of animals with bilateral vestibular lesions have shown that theta rhythm and the activity of hippocampal place cells are severely disrupted; recent human studies show that bilateral vestibular loss is even associated with hippocampal atrophy. While it is conceivable that the effects of vestibular lesions on the hippocampus are due to chronic stress and increased glucocorticoid levels, at present there is little evidence to support this hypothesis. It is also possible that the hippocampal changes are due to a reduction in exploration and active behavior; however, in rats, at least, bilateral vestibular lesions cause hyperactivity rather than hypoactivity. Alternatively, the hippocampus may have developed a special dependence upon the vestibular system during evolution, since it was the first sensory system to reliably indicate gravitational vertical.
Vestibular Critical Period, Maturation of Central Vestibular Neurons, and Locomotor Control
Authors: Eugène Daniel , Deforges Sèverine , Vibert Nicolas , Vidal Pierre‐Paul
Published: May 2009

Mutant mice are a good model to study to what extent the postnatal activity of sensory afferents is necessary for the maturation of central neurons. In particular, the question arises whether the signals carried by the first‐order vestibular neurons, which encode information on the head movement of pups, are necessary for the maturation of second‐order vestibular neurons. To address that question, juvenile and adult transgenic, vestibular‐deficient mutants where a null mutation of the KCNE1 potassium‐channel gene leads to degeneration of all hair cells of the inner ear just after birth were studied. These KCNE1−/− mutants are deaf and show quasi‐constant head bobbing and a permanent shaker/waltzer phenotype. This behavior is not due to persistent abnormalities of the membrane properties of central vestibular neurons, because their maturation is delayed but not impaired by the absence of sensory vestibular information. On the other hand, the data shed light on how the membrane properties of vestibular neurons might be modified according to functional requirements or following lesions. The expression levels of the protein calretinin that regulates the intracellular free‐calcium concentration in central vestibular neurons could play a major role both in intact animals and following labyrinthectomy. By comparing the KCNE1−/− mutant mice to other vestibular‐deficient animals, it was concluded that the suppression of vestibular inputs during a “critical period” of postnatal development can induce a permanent circling behavior, but that this phenotype is not always due to congenital vestibular deficiency.
Impulsive Testing of Semicircular‐Canal Function Using Video‐oculography
Authors: Weber Konrad P. , MacDougall Hamish G. , Halmagyi G. Michael , Curthoys Ian S.
Published: May 2009

The head impulse test (HIT) is a safe, quick way of assessing horizontal semicircular‐canal function in patients with peripheral vestibular loss. At the bedside, the clinician identifies “overt” catch‐up saccades back to the target after brisk passive head rotation as an indirect sign of canal paresis. However, saccades during head rotation (“covert” saccades) may not be detectable by the naked eye, and so lead to incorrect diagnosis. Up to now, the scleral search coil technique has been the standard for HIT measurement, but that technique is not practical for routine diagnostic use. A new lightweight, nonslip, high‐speed video‐oculography system (vHIT) that measures eye velocity during horizontal head impulses has been developed. This system is easy to use in a clinical setting, provides an objective measure of the vestibulo‐ocular reflex (VOR), and detects both overt and covert catch‐up saccades in patients with vestibular loss.
On‐Road Assessment of Driving Performance in Bilateral Vestibular‐Deficient Patients
Authors: MacDougall Hamish G. , Moore Steven T. , Black Ross A. , Jolly Neryla , Curthoys Ian S.
Published: May 2009

This study measured on‐road driving behavior in subjects with bilateral vestibular loss (BVL). Data included point‐of‐regard (what the driver is looking at and attending to), gaze stability (the performance of the vestibulo‐ocular reflex), and head movement, during complex maneuvers such as changing lanes, cornering, pulling into traffic, and parking. Subjective and objective measures showed few differences between BVL subjects and age‐matched controls, and that it is possible to drive well with little or no peripheral vestibular function. This has important implications for driver licensing, road‐safety policy, and for the potential successful rehabilitation of vestibular patients. Patients with unilateral vestibular dysfunction may have more difficulty driving than their bilateral counterparts.
Respiratory Impact on Motion Sickness Induced by Linear Motion
Authors: Mert Agali , Klopping‐Ketelaars Ineke , Bles Willem
Published: May 2009

Motion sickness incidence (MSI) for vertical sinusoidal motion reaches a maximum at 0.167 Hz. Normal breathing frequency is close to this frequency. There is some evidence for synchronization of breathing with this stimulus frequency. If this enforced breathing takes place over a larger frequency range (0.05–0.8 Hz) and whether this contributes to the high MSI at 0.167 Hz was investigated. Sinusoidal motion (amplitude 0.3 g, frequencies 0.05, 0.1, 0.2, 0.4, and 0.8 Hz) was applied. Nausea with the MISC‐scores and respiratory parameters, such as tidal volume, respiratory frequency, end‐tidal CO2 (PetCO2), and respiratory minute volume, were measured. Control conditions included rest and the hyperventilation provocation test. The nausea scores were highest at 0.2 Hz. With increasing frequencies the respiratory minute volume increased and the PetCO2 values decreased. The hyperventilation provocation test did not cause nausea. The main conclusion is that the high MSI at 0.167 Hz is not due to enforced breathing, since enforced breathing still increases with higher stimulus frequencies.
Saccadometry of Conditional Rules in Presymptomatic Huntington's Disease
Authors: Robert Matthieu P.A. , Nachev Parashkev C. , Hicks Stephen L. , Golding Charlotte V.P. , Tabrizi Sarah J. , Kennard Christopher
Published: May 2009

The promise of new treatments for Huntington's disease (HD) has intensified interest in markers of preclinical onset and progression. Recent research has shown that elementary saccadic tasks may exhibit subtle preclinical abnormalities. Other studies have shown cognitive dysfunction to be a major component of early‐HD phenotype. It was hypothesized that the synergistic combination of an oculomotor response with a cognitively demanding paradigm might therefore offer a functional marker that could be superior both to simpler saccadic paradigms and to conventional cognitive tests. The performance of 12 early‐symptomatic HD patients and 17 presymptomatic gene carriers on three saccadic paradigms were studied: prosaccades, color‐cued centrally triggered saccades and a second‐order conditional rule task on which the direction of the saccade was cued by the combination of central and peripheral cues. Eye movements were recorded using a highly portable, patient‐friendly infrared recording device. The analysis of the latency distributions showed that the second‐order conditional rule task could discriminate between clinical groups, had a predictive potential within the presymptomatic group and appeared to be more sensitive than easier tasks. The simplicity of portable saccadometry, combined with the sensitivity of a complex oculomotor task, may therefore offer a promising functional marker in HD.
Bilateral Vestibular Failure as an Early Sign in Creutzfeldt‐Jakob Disease
Authors: Jahn Klaus , Arbusow Viktor , Zingler Vera C. , Strupp Michael , Kretzschmar Hans A. , Brandt Thomas
Published: May 2009

Bilateral vestibular failure causes dysfunction of the vestibulo‐ocular reflex with consecutive symptoms like apparent movements of the visual environment during head movements (oscillopsia) and unsteady gait in darkness or on uneven ground. A definite case of Creutzfeldt‐Jakob disease in which bilateral vestibular loss was one of the first clinical signs is reported. Further, in a series of 9 consecutive patients with Creutzfeldt‐Jakob disease (6 probable, 3 definite), 3 had bilateral vestibular loss at initial presentation. The vestibular nuclei are known to be severely affected in animal spongiform encephalopathies. They might also be a vulnerable target in human prion diseases.
Structural Changes in the Human Brain following Vestibular Neuritis Indicate Central Vestibular Compensation
Authors: Helmchen Christoph , Klinkenstein Jan , Machner Björn , Rambold Holger , Mohr Christian , Sander Thurid
Published: May 2009

Vestibular neuritis (VN) is a sudden unilateral vestibular failure (UVF) with a variable course. Caloric hyporesponsiveness often persists, and it is largely unknown why patients with the same degree of hyporesponsiveness show different functional recovery. As the peripheral vestibular deficit alone does not seem to determine functional recovery, it was the aim of this study to elucidate whether structural (morphological) brain changes (1) contribute to central vestibular compensation, and (2) account for the variability of clinical recovery in VN. Structural global gray‐matter volume (GMV) changes in 15 VN patients were compared with age‐matched controls. Morphometric changes in multisensory vestibular cortices, which may be related to functional disability scores, were hypothesized. Patients were examined with neuro‐otological tests and clinical scores to assess vestibular disability. Using voxel‐based morphometry (VBM, SPM2), categorical comparison revealed GMV increase in patients’ multisensory vestibular cortices [insula, inferior parietal lobe (IPL), superior temporal gyrus (STG)], cerebellum, and motion‐sensitive areas in the middle temporal area (MT). GMV decrease was found in the midline pontomedullary junction. Simple regression analysis revealed (1) GMV increase in insula and retroinsular vestibular cortex and STG with improving clinically assessed vestibular deficits, and (2) GMV increase in insula vestibular cortex and STG with improving self‐assessed vestibular impairment. For the first time, these data suggest structural cortical plasticity in multisensory vestibular‐cortex areas in VN that are related to clinical vestibular function and vertigo. As increase of GMV was related to an improvement of vestibular function, structural alterations may be related to central vestibular compensation.
Modeling of Intrinsic and Synaptic Properties to Reveal the Cellular and Network Contribution for Vestibular Signal Processing
Authors: Rössert Christian , Pfanzelt Sandra , Straka Hans , Glasauer Stefan
Published: May 2009

Computational modeling of cellular and network properties of central vestibular neurons is necessary for understanding the mechanisms of sensory–motor transformation for gaze stabilization. As a first step to mathematically describe vestibular signal processing, the available physiological data of the synaptic and intrinsic properties of frog second‐order vestibular neurons (2°VN) were used to create a model that combines cellular and network parameters. With this approach it is now possible to reveal the particular contributions of intrinsic membrane versus emerging network properties in shaping labyrinthine afferent‐evoked synaptic responses in 2°VN, to simulate perturbations, and to generate hypotheses that are testable in empiric experiments.
Electrotactile Feedback of Sway Position Improves Postural Performance during Galvanic Vestibular Stimulation
Authors: Wood Scott J. , Black F. Owen , MacDougall Hamish G. , Moore Steven T.
Published: May 2009

The purpose of this study was to assess the influence of electrotactile feedback on postural control performance during binaural galvanic vestibular stimulation (GVS). Postural equilibrium was measured with a computerized hydraulic platform in 10 healthy adults (6M, 4F, 24–65 y). Feedback of anterior–posterior (AP) and mediallateral (ML) body sway was derived from a 2‐axis linear accelerometer mounted on a torso belt and displayed on a 144‐point electrotactile array held against the anterior dorsal tongue. Subjects were trained to use the tongue electrotactile feedback (TEF) by voluntarily swaying to draw figures on their tongue, both with and without GVS. Subjects performed 24 randomized trials (20‐s duration with eyes closed, 2 trials per condition), including 4 support surface conditions (fixed, rotational sway‐referenced, translating the support surface proportional to AP sway, and combined rotational–translational support‐platform sway referencing), and 3 feedback conditions (baseline, GVS, and GVS with TEF). Postural performance was assessed using deviations from upright (peak‐to‐peak and root‐mean‐square sway) and convergence toward stability limits (time and distance to limit of support boundaries). Postural stability was impaired (with respect to baseline) during GVS in all platform conditions, with larger decrements in performance during trials with rotation sway‐referencing. Electrotactile feedback improved performance with GVS toward non‐GVS levels, especially during trials with rotation sway‐referencing. These results demonstrate the effectiveness of TEF in providing sensory substitution to maintain postural stability during vestibular disturbances.
Visual Search Disorders in Acute and Chronic Homonymous Hemianopia
Authors: Machner Björn , Sprenger Andreas , Sander Thurid , Heide Wolfgang , Kimmig Hubert , Helmchen Christoph , Kömpf Detlef
Published: May 2009

Patients with homonymous hemianopia due to occipital brain lesions show disorders of visual search. In everyday life this leads to difficulties in reading and spatial orientation. It is a matter of debate whether these disorders are due to the brain lesion or rather reflect compensatory eye movement strategies developing over time. For the first time, eye movements of acute hemianopic patients (n= 9) were recorded during the first days following stroke while they performed an exploratory visual‐search task. Compared to age‐matched control subjects their search duration was prolonged due to increased fixations and refixations, that is, repeated scanning of previously searched locations. Saccadic amplitudes were smaller in patients. Right hemianopic patients were more impaired than left hemianopic patients. The number of fixations and refixations did not differ significantly between both hemifields in the patients. Follow‐up of one patient revealed changes of visual search over 18 months. By using more structured scanpaths with fewer saccades his search duration decreased. Furthermore, he developed a more efficient eye‐movement strategy by making larger but less frequent saccades toward his blind side. In summary, visual‐search behavior of acute hemianopic patients differs from healthy control subjects and from chronic hemianopic patients. We conclude that abnormal visual search in acute hemianopic patients is related to the brain lesion. We provide some evidence for adaptive eye‐movement strategies developed over time. These adaptive strategies make the visual search more efficient and may help to compensate for the persisting visual‐field loss.
Displacement of Listing's Plane by Galvanic Vestibular Stimulation Measured by 3‐Dimensional Video‐oculography
Authors: Dera Thomas
Published: May 2009

Saccadic eye movements are located in Listings plane (LP). Activation of the semicircular canals moves the eye positions out of LP, whereas activation of the otolith organs shifts LP. Bipolar galvanic vestibular stimulation (GVS) with DC current stimulates the vestibular periphery, and it is thought to resemble virtual rotations mainly in roll. Eye positions were measured with 3‐dimensional (3‐D) video‐oculography, using sclera markers to determine the ocular torsion. The subjects were seated in darkness, with the head fixed in the upright position, and instructed to perform a saccade when the visual target appeared. GVS was applied in blocks of 10 s. During GVS, subjects showed nystagmus. Eye positions moved out of LP and returned with a torsional offset. Only positions after saccadic eye movements were selected to evaluate that offset. In a group of four healthy subjects, the mean offset to LP was 0.4° (mean current 2.5 mA), with a SD that was greater for GVS (1.0°) than for the control condition (0.4°).
Vestibular “PREHAB”
Authors: Magnusson Måns , Kahlon Babar , Karlberg Mikael , Lindberg Sven , Siesjö Peter , Tjernström Fredrik
Published: May 2009

A sudden unilateral loss or impairment of vestibular function causes vertigo, dizziness, and impaired postural function. In most occasions, everyday activities supported or not by vestibular rehabilitation programs will promote a compensation and the symptoms subside. As the compensatory process requires sensory input, matching performed motor activity, both motor learning of exercises and matching to sensory input are required. If there is a simultaneous cerebellar lesion caused by the tumor or the surgery of the posterior cranial fossa, there may be a risk of a combined vestibulocerebellar lesion, with reduced compensatory abilities and with prolonged or sometimes permanent disability. On the other hand, a slow gradual loss of unilateral function occurring as the subject continues well‐learned everyday activities may go without any prominent symptoms. A pretreatment plan was therefore implemented before planned vestibular lesions, that is, “PREHAB.” This was first done in subjects undergoing gentamicin treatment for morbus Ménière. Subjects would perform vestibular exercises for 14 days before the first gentamicin installation, and then continue doing so until free of symptoms. Most subjects would only experience slight dizziness while losing vestibular function. The approach—which is reported here—was then expanded to patients with pontine‐angle tumors requiring surgery, but with remaining vestibular function to ease postoperative symptoms and reduce risk of combined cerebellovestibular lesions. Twelve patients were treated with PREHAB and had gentamicin installations transtympanically. In all cases there was a caloric loss, loss of VOR in head impulse tests, and impaired subjective vertical and horizontal. Spontaneous, positional nystagmus, subjective symptoms, and postural function were normalized before surgery and postoperative recovery was swift. Pretreatment training with vestibular exercises continued during the successive loss of vestibular function during gentamicin treatment, and pre‐op gentamicin ablation of vestibular function offers a possibility to reduce malaise and speed up recovery.
Effect of Canal Plugging on Quadrupedal Locomotion in Monkey
Authors: Cohen Bernard , Xiang Yongqing , Yakushin Sergei B. , Kunin Mikhail , Raphan Theodore , Minor Lloyd , Della Santina Charles C.
Published: May 2009

The vestibular system plays an important role in controling gait, but where in the labyrinths relevant activity arises is largely unknown. After the semicircular canals are plugged, low frequency (0.01–2 Hz) components of the angular vestibulo‐ocular reflex (aVOR) and angular vestibulo‐collic reflex (aVCR) are lost, but high frequency (3–20 Hz) components remain. We determined how loss of low frequency canal afference affects limb and head movements during quadrupedal locomotion. Head, body, and limb movements were recorded in three dimensions (3‐D) in a cynomolgus monkey with a motion detection system, while the animal walked on a treadmill. All six canals were plugged, reducing the canal time constants from ≈4.0 sec to ≈0.07 sec. Major changes in the control of the limbs occurred after surgery. Fore and hind limbs were held farther from the body, producing a broad‐based gait. Swing‐phase trajectories were inaccurate, and control of medial‐lateral limb movement was erratic. These changes in gait were present immediately after surgery, as well as 15 months later, when the animal had essentially recovered. Thus, control of the limbs in the horizontal plane was defective after loss of the low‐frequency semicircular canal input and never recovered. Cycle‐averaged pitch and roll head rotations, and 3‐D head translations were also significantly larger and more erratic after than before surgery. Head rotations in yaw could not be quantified due to intrusion of voluntary head turns. These findings indicate that the semicircular canals provide critical low frequency information to maximize the accuracy of stepping and stabilize the head during normal quadrupedal locomotion.
Why Do Subjective Vertigo and Dizziness Persist over One Year after a Vestibular Vertigo Syndrome?
Authors: Best Christoph , Eckhardt‐Henn Annegret , Tschan Regine , Dieterich Marianne
Published: May 2009

The overlap and interlinkage of dizzy symptoms in patients with psychiatric and vestibular vertigo/dizziness disorders is the subject of an ongoing debate. In a one‐year follow up in 68 patients with vestibular vertigo syndromes, the persistency of vertigo and dizziness symptoms was examined and correlated with vestibular parameters and results from a psychiatric evaluation. Patients with vestibular migraine showed poorest improvement of vertigo and dizziness symptoms over time. In addition, patients who developed anxiety or depressive disorder after the onset of the vestibular disorder showed poor improvement and high persistency of symptoms.
Adaptation of Orientation of Central Otolith‐only Neurons
Authors: Eron Julia N. , Cohen Bernard , Raphan Theodore , Yakushin Sergei B.
Published: May 2009

Otolith‐only neurons were recorded extracellularly in the vestibular nuclei before and after cynomolgus monkeys were held on‐side for up to 3 hr. The aim was to determine whether the polarization vectors of these neurons reorient toward the spatial vertical as do canal‐otolith convergent neurons. Otolith input was characterized by tilting the animal 30° from the upright position while positioning the head in different directions in yaw. This determined the response vector orientation (RVO), that is, the projection of the otolith polarization vector onto the head horizontal plane. Changes in the RVO of otolith‐only neurons ranged from 2°–16°, which was on average considerably less than the changes previously noted in canal‐otolith convergent vestibulo‐only (VO) and vestibular plus saccade (VPS) neurons, which ranged up to 109°. Some of the otolith‐only neurons had marked sensitivity changes. These findings suggest that otolith‐only neurons tend to maintain a head‐fixed orientation during prolonged head tilts relative to gravity. In contrast, canal‐convergent VO and VPS neurons optimize their response vector orientation to gravity when the head is oriented for prolonged periods.
Head Impulse Testing Using Video‐oculography
Authors: Bartl Klaus , Lehnen Nadine , Kohlbecher Stefan , Schneider Erich
Published: May 2009

Head impulses are a routine clinical test of semicircular canal function. At the bedside, they are used to detect malfunctioning of the horizontal semicircular canals. So far, 3‐D‐search‐coil recording is required to reliably test anterior and posterior canal function and to determine the gain of the vestibulo‐ocular reflex (VOR). Search‐coil recording cannot be done at the bedside. Here we tested whether video‐oculography (VOG) is suitable to assess VOR gain for individual canals at the bedside. We recorded head impulses in healthy subjects using a mobile high‐frame‐rate, head‐mounted VOG‐device and compared the results with those obtained with standard search‐coil recording. Our preliminary results indicate that high‐frame‐rate VOG is a promising tool to measure and quantify individual semicircular canal function not only at the bedside.
Some Perspectives on Saccade Adaptation
Authors: Tian Jing , Ethier Vincent , Shadmehr Reza , Fujita Masahiko , Zee David S.
Published: May 2009

The saccadic system is an ideal model for the study of how the brain optimizes its motor behavior. Here we review some recent research that points to exciting new areas of investigation relative to the multiple time scales of and the influence of context and consolidation on motor learning. These findings suggest new ways of thinking about the processes that underlie the short‐term adaptive mechanisms that maintain accuracy of eye movements and so ensure optimal vision.
The Edinger–Westphal Nucleus Represents Different Functional Cell Groups in Different Species
Authors: Horn Anja K.E. , Schulze Christina , Radtke‐Schuller Susanne
Published: May 2009

In all vertebrates, including humans, the Edinger–Westphal nucleus (EW) forms a circumscribed cell group dorsomedial to the oculomotor nucleus (nIII). Traditionally the EW is considered the location of parasympathetic preganglionic neurons of the ciliary ganglion, mediating pupillary constriction and accommodation. In a comparative study in rat, ferret, monkey, and human, the location of cholinergic neurons within and around the nIII, which includes motoneurons of the extra‐ocular muscles and the preganglionic neurons of the ciliary ganglion, was compared to the location of urocortin‐positive neurons. Irrespective of the species, the cholinergic and urocortin‐positive neurons form largely separated cell populations adjacent to each other. Only in monkey, cholinergic putative preganglionic neurons were found within the cytoarchitecturally defined EW, whereas in rat, ferret, and human the EW is almost exclusively composed of urocortin‐positive neurons. In humans, the presumed preganglionic neurons are located as an inconspicuous group of choline acetyltransferase‐positive neurons dorsal to the urocortin‐positive EW.
Abnormal Connection between Lateral and Posterior Semicircular Canal Revealed by a New Modeling Process
Authors: Rousie Dominique Louise , Deroubaix Jean Paul , Joly Olivier , Baudrillard Jean Claude , Berthoz Alain
Published: May 2009

We developed a modeling procedure using CT scans or MRI data for exploring the bony and lymphatic canals of vestibular patients. We submitted 445 patients with instability and spatial de‐orientation to this procedure. Out of the 445 patients, 95 had scoliosis, some of them, because malformations were suspected also had CT‐scan modeling and functional tests. We focused on a never described, abnormal connection between the lymphatic lateral and posterior canal (LPCC) with a frequency of 67/445 (15%). In the scoliosis subgroup, the frequency was 52/95 (55%). Three scoliotic patients had CT scans. For each of them, the modeling revealed that LPCC was present on the bony canals. LPCC has pathognomic signs: no rotatory vertigo but frequent instability, transport sickness head tilt on the side of the anomaly, and spatial disorientation in new environment. We evaluated the functional impact of LPCC by testing the vestibulo‐ocular reflex (VOR) in horizontal and vertical planes and found reproducible abnormal responses: in the case of left LPCC, during a counterclockwise horizontal rotation or a post clockwise horizontal rotation, added to the expected horizontal nystagmus, we found an unexpected upbeat nystagmus induced by the ampullofugal displacement of the fluid in the posterior canal. As LPCC was found in CT scans and MRI modeling for a same subject, we suggest that it could be a congenital abnormal process of ossification of the canals. The responses to the vestibular tests highlighting constant unexpected nystagmus underline the potential functional consequences of LPCC on vestibular perception and scoliosis.
EyeSeeCam: An Eye Movement–Driven Head Camera for the Examination of Natural Visual Exploration
Authors: Schneider Erich , Villgrattner Thomas , Vockeroth Johannes , Bartl Klaus , Kohlbecher Stefan , Bardins Stanislavs , Ulbrich Heinz , Brandt Thomas
Published: May 2009

The prototype of a gaze‐controlled, head‐mounted camera (EyeSeeCam) was developed that provides the functionality for fundamental studies on human gaze behavior even under dynamic conditions like locomotion. EyeSeeCam incorporates active visual exploration by saccades with image stabilization during head, object, and surround motion just as occurs in human ocular motor control. This prototype is a first attempt to combine free user mobility with image stabilization and unrestricted exploration of the visual surround in a man‐made technical vision system. The gaze‐driven camera is supplemented by an additional wide‐angle, head‐fixed scene camera. In this scene view, the focused gaze view is embedded with picture‐in‐picture functionality, which provides an approximation of the foveated retinal content. Such a combined video clip can be viewed more comfortably than the saccade‐pervaded image of the gaze camera alone. EyeSeeCam consists of a video‐oculography (VOG) device and a camera motion device. The benchmark for the evaluation of such a device is the vestibulo‐ocular reflex (VOR), which requires a latency on the order of 10 msec between head and eye (camera) movements for proper image stabilization. A new lightweight VOG was developed that is able to synchronously measure binocular eye positions at up to 600 Hz. The camera motion device consists of a parallel kinematics setup with a backlash‐free gimbal joint that is driven by piezo actuators with no reduction gears. As a result, the latency between the rotations of an artificial eye and the camera was 10 msec, which is VOR‐like.
The Effect of Dual Tasks in Locomotor Path Integration
Authors: Glasauer Stefan , Stein Alexandra , Günther Anna L. , Flanagin Virginia L. , Jahn Klaus , Brandt Thomas
Published: May 2009

Without landmarks, navigation is based on information about self‐velocity, which is transformed to position or orientation by a process called path integration. Simple path integration tasks, such as reaching a previously seen goal by blindfolded locomotion, were often considered to be automatic and not influenced by unrelated cognitive activity. However, we recently showed that reproduction of self‐motion without landmark cues exhibits systematic dual‐task interference. Since these experiments did not exclude that the dual task only interferes with memory for self‐motion, we performed two additional experiments testing generic path integration. We show that locomotor homing and reaching predefined goals by active self‐motion are affected systematically by a concurrent mental task. The similarity of the effects we found to those reported for duration estimation led us to the hypothesis that subjective time may be used as a temporal basis of path integration. Alternatively, path integration and duration estimation may be based on similar underlying neuronal mechanisms, for example, coincidence detection in neural oscillators.