Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

The functional relationship between yawning and vigilance

BACKGROUND: Although yawning is a ubiquitous and phylogenetically old phenomenon, its origin and purpose remain unclear. The study aimed at testing the widely held hypothesis that yawning is triggered by drowsiness and brings about a reversal or suspension of the process of falling asleep. METHODS: Subjects complaining of excessive sleepiness were spontaneously yawning while trying to stay awake in a quiet and darkened room. Changes in their electroencephalogram (EEG) and heart rate variability (HRV) associated with yawning were compared to changes associated with isolated voluntary body movements. Special care was taken to remove eye blink- and movement-artefacts from the recorded signals. RESULTS: Yawns were preceded and followed by a significantly greater delta activity in EEG than movements (p< or =0.008). After yawning, alpha rhythms were attenuated, decelerated, and shifted towards central brain regions (p< or =0.01), whereas after movements, they were attenuated and accelerated (p<0.02). A significant transient increase of HRV occurred after the onset of yawning and movements, which was followed by a significant slow decrease peaking 17s after onset (p<0.0001). No difference in HRV changes was found between yawns and movements. CONCLUSIONS: Yawning occurred during periods with increased drowsiness and sleep pressure, but was not followed by a measurable increase of the arousal level of the brain. It was neither triggered nor followed by a specific autonomic activation. Our results therefore confirm that yawns occur due to sleepiness, but do not provide evidence for an arousing effect of yawning.

Sight-reading of violinists: eye movements anticipate the musical flow

When sight-reading a piece of music the eyes constantly scan the score slightly ahead of music execution. This separation between reading and acting is commonly termed eye-hand span and can be expressed in two ways: as anticipation in notes or in time. Previous research, predominantly in piano players, found skill-dependent differences of eye-hand span. To date no study has explored visual anticipation in violinists. The present study investigated how structural properties of a piece of music affect the eye-hand span in a group of violinists. To this end eye movements and bow reversals were recorded synchronously while musicians sight-read a piece of music. The results suggest that structural differences of the score are reflected in the eye-hand span in a way similar to skill level. Specifically, the piece with higher complexity was associated with lower anticipation in notes, longer fixation duration and a tendency for more regressive fixations. Anticipation in time, however, remained the same (approximately 1 s) independently of the score played but was correlated with playing tempo. We conclude that the eye-hand span is not only influenced by the experience of the musician, but also by the structure of the score to be played.

Zielinstruktionen, räumliche Quiet-Eye-Verankerung und Bewegungsparametrisierung: Hinweise auf einen Wirkmechanismus

Die motorikwissenschaftliche Befundlage zum sogenannten „Quiet Eye“ weist darauf hin, dass hohe sportmotorische Leistungen, insbesondere in Präzisionsaufgaben, mit einer langen finalen Fixation vor der Bewegungsentfaltung einhergehen. Ein Mechanismus, der diesen Zusammenhang aus einer kognitionspsychologischen Perspektive erklären könnte, ist die Optimierung von Informationsverarbeitungsprozessen der Bewegungsparametrisierung. Diese Annahme wurde durch eine experimentelle Manipulation von Zielinstruktionen in einer Ballwurfaufgabe untersucht. Zum einen zeigen die Ergebnisse, dass sich die räumliche Verankerung des Quiet Eye in Abhängigkeit der variierten Aufgabenziele verändert; zum anderen deuten die Befunde darauf hin, dass sich Veränderungen der Verankerung im Bewegungsresultat niederschlagen. Damit wird ein kognitiver Wirkmechanismus plausibilisiert, nach dem die Bewegungsgenauigkeit durch Zielinstruktion via räumliche Quiet-Eye-Verankerung bestimmt wird.

Effects of task modality, length and complexity on time for activities in lucid dreams

Introduction: Nocturnal dreams can be considered as a kind of simulation of the real world on a higher cognitive level (Erlacher & Schredl, 2008). Within lucid dreams, the dreamer is aware of the dream state and thus able to control the ongoing dream content. Previous studies could demonstrate that it is possible to practice motor tasks during lucid dreams and doing so improved performance while awake (Erlacher & Schredl, 2010). Even though lucid dream practice might be a promising kind of cognitive rehearsal in sports, little is known about the characteristics of actions in lucid dreams. The purpose of the present study was to explore the relationship between time in dreams and wakefulness because in an earlier study (Erlacher & Schredl, 2004) we found that performing squads took lucid dreamers 44.5 % more time than in the waking state while for counting the same participants showed no differences between dreaming and wakefulness. To find out if the task modality, the task length or the task complexity require longer times in lucid dreams than in wakefulness three experiments were conducted. Methods: In the first experiment five proficient lucid dreamers spent two to three non-consecutive nights in the sleep laboratory with polysomnographic recording to control for REM sleep and determine eye signals. Participants counted from 1-10, 1-20 and 1-30 in wakefulness and in their lucid dreams. While dreaming they marked onset of lucidity as well as beginning and end of the counting task with a Left-Right-Left-Right eye movement and reported their dreams after being awakened. The same procedure was used for the second experiment with seven lucid dreamers except that they had to walk 10, 20 or 30 steps. In the third experiment nine participants performed an exercise involving gymnastics elements such as various jumps and a roll. To control for length of the task the gymnastic exercise in the waking state lasted about the same time as walking 10 steps. Results: As a general result we found – as in the study before – that performing a task in the lucid dream requires more time than in wakefulness. This tendency was found for all three tasks. However, there was no difference for the task modality (counting vs. motor task). Also the relative time for the different lengths of the tasks showed no difference. And finally, the more complex motor task (gymnastic routine) did not require more time in lucid dreams than the simple motor task. Discussion/Conclusion: The results showed that there is a robust effect of time in lucid dreams compared to wakefulness. The three experiments could not explain that those differences are caused by task modality, task length or task complexity. Therefore further possible candidates needs to be investigated e.g. experience in lucid dreaming or psychological variables. References: Erlacher, D. & Schredl, M. (2010). Practicing a motor task in a lucid dream enhances subsequent performance: A pilot study. The Sport Psychologist, 24(2), 157-167. Erlacher, D. & Schredl, M. (2008). Do REM (lucid) dreamed and executed actions share the same neural substrate? International Journal of Dream Research, 1(1), 7-13. Erlacher, D. & Schredl, M. (2004). Time required for motor activity in lucid dreams. Perceptual and Motor Skills, 99, 1239-1242.

The role of brand marketing in snowboarding: A comparative study of Switzerland and New Zealand

Introduction: Brands play an essential role in the organizational structure of snowboarding by sponsoring athletes, arranging events, contributing to product development and developing long-term partnerships with other key actors. However, the specialities of their role in scene sports, such as creating identities, networking and brand marketing strategies, have not been extensively researched. This study aims to provide an analysis of the function of brands within the snowboarding subculture by comparing how the sport is organized in Switzerland and New Zealand. Sociological theories of subcultures (Hitzler & Niederbacher, 2010) and social networks (Stegbauer, 2008) are used to defi ne the structures of the sport, whereas marketing and branding theories (Adjouri & Stastny, 2006) help to understand the role of the brands. Snowboarding will be defi ned as an alternative sports subculture based on characteristics such as aesthetics, adventure and new resources of performance (Schwier, 2006). Such a defi nition also begs for a novel form of analyzing its organization. Unlike more conventional structures, the organization of snowboarding allows a variety of actors to get involved in leading the sport. By portraying and encouraging differentiated identities and lifestyles, athletes provide a space for other actors to fi nd their place within the sport (Wheaton, 2005). According to Stegbauers network theory, individual actors are able to obtain high positions and defi ne their identity depending on their ties to actors and networks within the subculture (Stegbauer, 2008). For example, social capital, contacts within the sport and insider knowledge on subculture-related information enable actors to get closer to the core (Hitzler & Niederbacher, 2010). Actors who do not have close networks and allies within the subculture are less likely to engage successfully in the culture, whether as an individual or as a commercial actor (Thorpe, 2011). This study focuses on the organizational structure of snowboarding by comparing the development of the sport in Switzerland and New Zealand. An analysis of snowboarding in two nations with diverse cultures and economic systems allows a further defi nition of the structural organization of the sport and explains how brands play an important role in the sport. Methods: The structural organization of the sport will be analyzed through an ethnographic approach, using participant observation at various leading events in Switzerland (Freestyle.ch, European Open) and New Zealand (World Heli Challenge, New Zealand Open, New Zealand Winter Games). The data is analyzed using grounded theory (Glaser & Strauss 1967) and gives an overview of the actors that are playing an important role in the local development of snowboarding. Participant observation was also used as a tool to get inside the sport culture and opened up the possibility to make over 40 semi-structured qualitative expert interviews with international core actors from 11 countries. Obtaining access to one actor as a partner early on helped to get inside the local sport culture. The ‘snowball effect’ allowed the researcher to acquire access, build trust and conduct interviews with experts within the core scene. All the interviewed actors have a direct infl uence on the sport in one or both countries, which permit a cross-analysis. The data of the interviews was evaluated through content analysis (Mayring 2010). The two methods together provided suffi cient data to analyze the organizational structure and discuss the role of brand marketing within snowboarding. Results: An actors mapping by means of a center-periphery framework has identifi ed fi ve main core groups: athletes, media representatives, brand-marketing managers, resort managers and event organizers. In both countries the same grouping of actors were found. Despite possessing different and frequently multiple roles and responsibilities, core actors appear to have a strong common identifi cation as ‘snowboarders’, are considered to be part of the organizational elite of the sport and tend to advocate similar goals. The author has found that brands in Switzerland tend to have a larger impact on the broader snowboarding culture due to a number of factors discussed below. Due to a larger amount of snowboarders and stronger economic power in Europe, snowboarders are making attempts to differentiate themselves from other winter sports, while competing with each other to develop niche markets. In New Zealand, on the other hand, the smaller market enables more cooperation and mutual respect within snowboarders. Further they are more closely linked to other winter sports and are satisfi ed with being lumped together. In both countries, brands have taken up the role of supporting young athletes, organizing competitions and feeding media with subculture-related content. Brands build their image and identity through the collaboration with particular athletes who can represent the values of the brand. Local and global communities with similar lifestyles and interests are being built around brands that share a common vision of the sport. The dominance of brands in snowboarding has enabled them with the power to organize and rule the sport through its fan base and supporters. Brands were defi ned by interviewees as independent institutions led by insiders who know the codes and symbols of the sport and were given trust and credibility. The brands identify themselves as the engines of the sport by providing the equipment, opportunities for athletes to get exposure, allowing media to get exclusive information on activities, events and sport-related stories. Differences between the two countries are more related to the economic system. While Switzerland is well integrated in the broader European market, New Zealand’s geographical isolation and close proximity to Australia tends to limit its market. Further, due to different cultural lifestyles, access to resorts and seasonal restrictions, to name a few, the amount of people practicing winter sports in New Zealand is much smaller than in Switzerland. However, this also presents numerous advantages. For example, the short southern hemisphere winter season in New Zealand enables them to attract international sports athletes, brands and representatives in a period when Europe and North America is in summer. Further, the unique snow conditions in New Zealand and majestic landscape is popular for attracting world renowned photo- and cinematographers. Another advantage is the less populated network as it provides the opportunity for individuals to gain easier access to the core of the sport, obtain diverse positions and form a unique identity and market. In Switzerland, on the other hand, the snowboarding network is dense with few positions available for the taking. Homegrown brands with core recognition are found in both countries. It was found that the Swiss brands tend to have a larger impact on the market, whereas in New Zealand, the sport is more dependent on import products by foreign brands. Further, athletes, events and resorts in New Zealand are often dependent on large brand sponsorships from abroad such as from brand headquarters in the Unites States. Thus, due to its location in the centre of Europe, Swiss brands can take advantage of brands which are closer in proximity and culture to sponsor athletes and events. In terms of media coverage, winter sports in New Zealand tend to have a minor coverage and tradition in local mass media, which leads to less exposure, recognition and investment into the sport. This is also related to how snowboarding is more integrated into other winter sports in New Zealand. Another difference is the accessibility of the ski resort by the population. While in Switzerland the resorts are mostly being visited by day-travelers, ‘weekend warriors’ and holiday makers, the location of the resorts in New Zealand make it diffi cult to visit for one day. This is in part due to the fact that Swiss ski resorts and villages are usually the same location and are accessible through public transportation, while the ski resorts in New Zealand have been built separately from the villages. Further, the villages have not been built to accommodate to high tourist arrivals. Thus, accommodation and food facilities are limited and there is a lack of public transportation to the resorts. Discussion: The fi ndings show that networks and social relations combined with specifi c knowledge on scene-related attributes are crucial in obtaining opportunities within the sport. Partnerships as well as competition between these different actors are necessary for core acceptance, peer credibility and successful commercial interests. Brands need to maintain effective marketing strategies and identities which incorporate subcultural forms of behavior and communication. In order to sustain credibility from its fans, athletes and other snowboarding actors, brands need to maintain their insider status through social networks and commercial branding strategies. The interaction between all actors is a reciprocated process, where social capital, networks and identities are being shared. While the overall structure of snowboard subcultures in Europe and New Zealand are similar, there are some distinct characteristics which make each one unique. References Adjouri, N. & Stastny, P. (2006). Sport-Branding: Mit Sport-Sponsoring zum Markenerfolg. Wiesbaden: Gabler. Glaser, B. & Strauss, K. (1967). The discovery of grounded theory: Strategies for qualitative research. Chicago: Aldine. Hebdige, D. (2009). Subculture; The meaning of style. New York: Routledge. Hitzler, R. & Niederbacher, A. (2010). Leben in Szenen: Formen juveniler Vergemeinschaftung heute. Wiesbaden: Verlag für Sozialwissenschaften. Mayring, P. (2010). Qualitative Inhaltsanalyse: Grundlagen und Techniken. Weinheim: Beltz. Schwier, J. (2006). Repräsentationen des Trendsports. Jugendliche Bewegungskulturen, Medien und Marketing. In: Gugutzer, R. (Hrsg.). body turn. Perspektiven der Soziologie des Körpers und des Sports. Bielefeld: transcript (S. 321-340). Stegbauer, C. (2008). Netzwerkanalyse und Netzwerktheorie. Ein neues Paradigma in den Sozialwissenschaften. Wiesbaden: VS Verlag für Sozialwissenschaften. Thorpe, H. (2011). Snowboarding bodies in theory and practice. Basingstoke: Palgrave Macmillan. Wheaton, B. (2005). Understanding lifestyle sports; consumption, identity and difference. New York: Routledge.

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A novel Statistical Shape Model for treatment planning of Retinoblastoma

Purpose: Proper delineation of ocular anatomy in 3D imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic Resonance Imaging (MRI) is nowadays utilized in clinical practice for the diagnosis confirmation and treatment planning of retinoblastoma in infants, where it serves as a source of information, complementary to the Fundus or Ultrasound imaging. Here we present a framework to fully automatically segment the eye anatomy in the MRI based on 3D Active Shape Models (ASM), we validate the results and present a proof of concept to automatically segment pathological eyes. Material and Methods: Manual and automatic segmentation were performed on 24 images of healthy children eyes (3.29±2.15 years). Imaging was performed using a 3T MRI scanner. The ASM comprises the lens, the vitreous humor, the sclera and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens and the optic nerve, then aligning the model and fitting it to the patient. We validated our segmentation method using a leave-one-out cross validation. The segmentation results were evaluated by measuring the overlap using the Dice Similarity Coefficient (DSC) and the mean distance error. Results: We obtained a DSC of 94.90±2.12% for the sclera and the cornea, 94.72±1.89% for the vitreous humor and 85.16±4.91% for the lens. The mean distance error was 0.26±0.09mm. The entire process took 14s on average per eye. Conclusion: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor and the lens using MRI. We additionally present a proof of concept for fully automatically segmenting pathological eyes. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

Quantifying the vestibulo-ocular reflex with video-oculography: nature and frequency of artifacts

Video-oculography devices are now used to quantify the vestibulo-ocular reflex (VOR) at the bedside using the head impulse test (HIT). Little is known about the impact of disruptive phenomena (e.g. corrective saccades, nystagmus, fixation losses, eye-blink artifacts) on quantitative VOR assessment in acute vertigo. This study systematically characterized the frequency, nature, and impact of artifacts on HIT VOR measures. From a prospective study of 26 patients with acute vestibular syndrome (16 vestibular neuritis, 10 stroke), we classified findings using a structured coding manual. Of 1,358 individual HIT traces, 72% had abnormal disruptive saccades, 44% had at least one artifact, and 42% were uninterpretable. Physicians using quantitative recording devices to measure head impulse VOR responses for clinical diagnosis should be aware of the potential impact of disruptive eye movements and measurement artifacts.

Impairments of peripheral motion change detection during smooth pursuit eye movements

Introduction: In team sports the ability to use peripheral vision is essential to track a number of players and the ball. By using eye-tracking devices it was found that players either use fixations and saccades to process information on the pitch or use smooth pursuit eye movements (SPEM) to keep track of single objects (Schütz, Braun, & Gegenfurtner, 2011). However, it is assumed that peripheral vision can be used best when the gaze is stable while it is unknown whether motion changes can be equally well detected when SPEM are used especially because contrast sensitivity is reduced during SPEM (Schütz, Delipetkose, Braun, Kerzel, & Gegenfurtner, 2007). Therefore, peripheral motion change detection will be examined by contrasting a fixation condition with a SPEM condition. Methods: 13 participants (7 male, 6 female) were presented with a visual display consisting of 15 white and 1 red square. Participants were instructed to follow the red square with their eyes and press a button as soon as a white square begins to move. White square movements occurred either when the red square was still (fixation condition) or moving in a circular manner with 6 °/s (pursuit condition). The to-be-detected white square movements varied in eccentricity (4 °, 8 °, 16 °) and speed (1 °/s, 2 °/s, 4 °/s) while movement time of white squares was constant at 500 ms. 180 events should be detected in total. A Vicon-integrated eye-tracking system and a button press (1000 Hz) was used to control for eye-movements and measure detection rates and response times. Response times (ms) and missed detections (%) were measured as dependent variables and analysed with a 2 (manipulation) x 3 (eccentricity) x 3 (speed) ANOVA with repeated measures on all factors. Results: Significant response time effects were found for manipulation, F(1,12) = 224.31, p < .01, ηp2 = .95, eccentricity, F(2,24) = 56.43; p < .01, ηp2 = .83, and the interaction between the two factors, F(2,24) = 64.43; p < .01, ηp2 = .84. Response times increased as a function of eccentricity for SPEM only and were overall higher than in the fixation condition. Results further showed missed events effects for manipulation, F(1,12) = 37.14; p < .01, ηp2 = .76, eccentricity, F(2,24) = 44.90; p < .01, ηp2 = .79, the interaction between the two factors, F(2,24) = 39.52; p < .01, ηp2 = .77 and the three-way interaction manipulation x eccentricity x speed, F(2,24) = 3.01; p = .03, ηp2 = .20. While less than 2% of events were missed on average in the fixation condition as well as at 4° and 8° eccentricity in the SPEM condition, missed events increased for SPEM at 16 ° eccentricity with significantly more missed events in the 4 °/s speed condition (1 °/s: M = 34.69, SD = 20.52; 2 °/s: M = 33.34, SD = 19.40; 4 °/s: M = 39.67, SD = 19.40). Discussion: It could be shown that using SPEM impairs the ability to detect peripheral motion changes at the far periphery and that fixations not only help to detect these motion changes but also to respond faster. Due to high temporal constraints especially in team sports like soccer or basketball, fast reaction are necessary for successful anticipation and decision making. Thus, it is advised to anchor gaze at a specific location if peripheral changes (e.g. movements of other players) that require a motor response have to be detected. In contrast, SPEM should only be used if a single object, like the ball in cricket or baseball, is necessary for a successful motor response. References: Schütz, A. C., Braun, D. I., & Gegenfurtner, K. R. (2011). Eye movements and perception: A selective review. Journal of Vision, 11, 1-30. Schütz, A. C., Delipetkose, E., Braun, D. I., Kerzel, D., & Gegenfurtner, K. R. (2007). Temporal contrast sensitivity during smooth pursuit eye movements. Journal of Vision, 7, 1-15.

Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

Vertical bias in neglect: A question of time?

Neglect is defined as the failure to attend and to orient to the contralesional side of space. A horizontal bias towards the right visual field is a classical finding in patients who suffered from a right-hemispheric stroke. The vertical dimension of spatial attention orienting has only sparsely been investigated so far. The aim of this study was to investigate the specificity of this vertical bias by means of a search task, which taps a more pronounced top-down attentional component. Eye movements and behavioural search performance were measured in thirteen patients with left-sided neglect after right hemispheric stroke and in thirteen age-matched controls. Concerning behavioural performance, patients found significantly less targets than healthy controls in both the upper and lower left quadrant. However, when targets were located in the lower left quadrant, patients needed more visual fixations (and therefore longer search time) to find them, suggesting a time-dependent vertical bias.

Vestibular deficits do not underlie looping behavior in achiasmatic fish

Zebrafish belladonna (bel) mutants carry a mutation in the lhx2 gene that encodes a Lim domain homeobox transcription factor, leading to a defect in the retinotectal axon pathfinding. As a result, a large fraction of homozygous bel mutants is achiasmatic. Achiasmatic bel mutants display ocular motor instabilities, both reserved optokinetic response (OKR) and spontaneous eye oscillations, and an unstable swimming behavior, described as looping. All these unstable behaviors have been linked to the underlying optic nerve projection defect. Looping has been investigated under different visual stimuli and shown to be vision dependent and contrast sensitive. In addition, looping correlates perfectly with reversed OKR and the spontaneous oscillations of the eyes. Hence, it has been hypothesized that looping is a compensatory response to the perception of self-motion induced by the spontaneous eye oscillations. However, both ocular and postural instabilities could also be caused by a yet unidentified vestibular deficit. Here, we performed a preliminary test of the vestibular function in achiasmatic bel larval mutants in order to clarify the potential role of a vestibular deficit in looping. We found that the vestibular ocular reflex (VOR) is normally directed in both bel mutants and wild types and therefore exclude the possibility that nystagmus and looping in reverse to the rotating optokinetic drum can be attributed to an underlying vestibular deficit.

Ocular penetration of caspofungin in a rabbit uveitis model

BACKGROUND: Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. METHODS: Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses. RESULTS: The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 +/- 0.39 mug/ml and 1.12 +/- 0.34 mug/ml, respectively. Drug concentrations decreased to 0.24 +/- 0.09 mug/ml at 16 h and 0.26 +/- 0.14 mug/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 +/- 0.48 mug/g at 4 h, peaked at 2.16 +/- 1.14 mug/g at 8 h, and declined to 1.87 +/- 0.52 mug/g and 1.49 +/- 0.48 mug/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 mug/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. CONCLUSIONS: In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis.

Evaluation of cavitations in proximal caries lesions at various magnification levels in vitro

OBJECTIVES: The aim of this study was to evaluate the cavitation rate of proximal caries using different magnification aids in vitro. METHODS: Radiographs of 285 extracted teeth were taken and the proximal surfaces were graded to the criteria R0 (no radiolucency), R1 (radiolucency confined to the outer half of enamel), R2 (inner half of enamel) and R3 (outer half of dentin). Subsequently, the proximal surfaces were checked for the presence of cavitations with the naked eye (NE), and by using 4.3 x magnification eyeglasses (ME), a stereo microscope (SM, 10x), or a scanning electron microscope (SEM, up to 2000 x magnification). RESULTS: In surfaces with R3 caries, cavitations were visible in 56 of 59 cases with the naked eye. When using SEM, all surfaces revealed cavitations (100%). Regarding the surfaces with R2 lesion, 36 of 46 cases showed cavitations (NE); the corresponding values were 39/46 (ME), 41/46 (SM), and 46/46 (SEM); in the latter, in most cases deep defects could be observed. With regard to R1 lesions, 36/60 (NE), 43/60 (ME), 45/60 (SM), and 58/60 (SEM) cases revealed cavitations. A breakdown of radiographically sound surfaces (R0) was present in some 10% of the examined surfaces (24/261, NE; 33/261, SEM). CONCLUSIONS: Cavitations (defined as breakdown of the surface) are present in significantly more cases than previously reported. This might be an explanation why even small radiolucencies tend to progress, albeit slowly. Thus, close follow-ups should strongly be recommended when considering a preventive treatment regimen with small radiolucencies.

Theta burst transcranial magnetic stimulation is associated with increased EEG synchronization in the stimulated relative to unstimulated cerebral hemisphere

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies, we set out to test whether TBS is associated with changes of neuronal synchronization as assessed by surface EEG. In four healthy subjects one TBS train of 600 pulses (200 bursts, each burst consisting of 3 pulses at 30 Hz, repeated at intervals of 100 ms) was applied over the right frontal eye field and EEG synchronization was assessed in a time-resolved manner over 60 min by using a non-overlapping moving window. For each time step the linear cross-correlation matrix for six EEG channels of the right and for the six homotopic EEG channels of the left hemisphere were computed and their largest eigenvalues used to assess changes of synchronization. Synchronization was computed for broadband EEG and for the delta, theta, alpha, beta and gamma frequency bands. In all subjects EEG synchronization of the stimulated hemisphere was significantly and persistently increased relative to EEG synchronization of the unstimulated hemisphere. This effect occurred immediately after TBS for the theta, alpha, beta and gamma frequency bands and 10-20 min after TBS for broadband and delta frequency band EEG. Our results demonstrate that TBS is associated with increased neuronal synchronization of the cerebral hemisphere ipsilateral to the stimulation site relative to the unstimulated hemisphere. We speculate that enhanced synchronization interferes with cortical information processing and thus may be a neurophysiological correlate of the impaired behavioural performance detected previously.